%PDF-1.3
%
6 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
13 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
4 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
7 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
10 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
11 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
9 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
3 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
8 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
1 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
5 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
12 0 obj
<>>>/BBox[0 0 612 792]/Length 131>>stream
xM =eǏ\7'P1ibPC}a3w2>Jؙ H<$:
vaW*kLn
U?
IEƜӂR
o!S; WaL[{Z]Ĺ5^f5mޖ&
endstream
endobj
15 0 obj
<>stream
Acrobat Distiller 8.1.0 (Windows); modified using iText 4.2.0 by 1T3XT
Arbortext Advanced Print Publisher 9.0.114/W
2018-07-23T08:33:01-07:00
2018-07-11T22:40:36+05:30
application/pdf
CMB-2017-0249-ver9-Ahn_3P 637..648
uuid:3e162326-6c76-4b3b-9ba0-d1ba97a3e199
uuid:33cde1fe-3e33-46dc-9303-7b10c805fda6
endstream
endobj
16 0 obj
<>stream
x+ |
endstream
endobj
17 0 obj
<>stream
xS**T0T0 Bi yA$
endstream
endobj
18 0 obj
<>stream
x+ |
endstream
endobj
19 0 obj
<>stream
xS**T0T0 Bi y+
endstream
endobj
20 0 obj
<>stream
x+ |
endstream
endobj
21 0 obj
<>stream
xS**T0T0 Bi y,
endstream
endobj
22 0 obj
<>stream
x+ |
endstream
endobj
23 0 obj
<>stream
xS**T0T0 Bih lT
endstream
endobj
24 0 obj
<>stream
x+ |
endstream
endobj
25 0 obj
<>stream
xS**T0T0 Bi yJ%
endstream
endobj
26 0 obj
<>stream
x+ |
endstream
endobj
27 0 obj
<>stream
xS**T0T0 Bi y\'
endstream
endobj
28 0 obj
<>stream
x+ |
endstream
endobj
29 0 obj
<>stream
xS**T0T0 Bi ye(
endstream
endobj
30 0 obj
<>stream
x+ |
endstream
endobj
31 0 obj
<>stream
xS**T0T0 Bih uU
endstream
endobj
32 0 obj
<>stream
x+ |
endstream
endobj
33 0 obj
<>stream
xS**T0T0 Bi yS&
endstream
endobj
34 0 obj
<>stream
x+ |
endstream
endobj
35 0 obj
<>stream
xS**T0T0 Bi y8#
endstream
endobj
36 0 obj
<>stream
x+ |
endstream
endobj
37 0 obj
<>stream
xS**T0T0 Bi yn)
endstream
endobj
38 0 obj
<>stream
x+ |
endstream
endobj
39 0 obj
<>stream
xS**T0T0 Bi yw*
endstream
endobj
41 0 obj
<>stream
/GS1 gs
BT
/F1 1 Tf
9.9626 0 0 9.9626 74.0976 715.4644 Tm
0 0 0 rg
0 Tc
0 Tw
[(sophi)-7.8(sticated)-220.1(repa)-8.6(ir)-211.1(mech)-10.2(anisms)-214.2(\(D)-7.4(uarte)-217(et)-216.6(al.,)-211.7(1994\).)-216.7(Con)-7(seque)-8.6(ntly,)-213.8(they)-218.2(rapidly)-219.5(evolve)-215.8(and)-220.3(exist)-217.2(as)-215.1(a)-213.1(set)-212.9(of)]TJ
0 -1.195 TD
[(no)-7.2(nidentical)-217.5(but)-209.9(clos)-8.8(ely)-211.7(related)-217.4(genetic)-215.4(variant)-10.7(s,)-207.2(know)-7(n)-211.3(a)0(s)-209.4(a)-213.1(viral)-212.3(quasispe)-9.1(cies.)-215.8(Viral)-216.2(populations)-218.8(can)-210.7(read)-8.6(ily)]TJ
0 -1.2007 TD
[(adapt)-357.3(to)-357.1(dynamic)-356.6(envi)-7.6(ronment)-9.7(s)-349.1(and)-356.9(develop)-358.8(resistanc)-10.7(e)-355.4(t)0(o)-351.4(antiviral)-359.2(drugs)-359.8(and)-351.2(vaccines)-11.5(,)-353.2(which)-359.4(makes)-359.2(the)]TJ
T*
[(desi)-8.8(gn)-331.6(o)-6.5(f)-332.8(effective)-347.8(and)-334.1(long-)-8.6(lasting)-341(treatmen)-11.1(ts)-335.5(for)-336.3(RNA)-339.2(viral)-337.5(dise)-8.8(ases)-339.1(exceedin)-10.3(gly)-335.1(dif)-7(cult)-334.7(\(Laur)-9.4(ing)-335.1(and)]TJ
T*
[(Andi)-9.7(no,)-263.7(2010\).)-267.9(Deter)-10.4(mining)-269.7(the)-268.6(structure)-271.5(of)-265.3(vir)-7(al)-262.1(popul)-6.6(ations)-269.2(help)-7.6(s)-263.7(the)-268.6(understa)-9.9(nding)-268.3(of)-265.3(viral)-269.2(disease)-10.2(s)-263.7(and)]TJ
T*
[(provi)-8.5(des)-432.1(guida)-8.4(nce)-432.7(in)-431.1(the)-439.3(developm)-10.3(ent)-433.6(of)-430.3(effect)-11(ive)-433.6(medica)-10.5(l)-430.3(therape)-9.7(utics.)-433.8(Qua)-8(sispecies)-442.4(spectrum)-440.2(recon-)]TJ
T*
[(str)-8.2(uction)-307.8(\(QS)-7.4(R\))-304.1(aims)-313.9(to)-305.9(asse)-9(mble)-307(indi)-8.6(vidual)-307.8(hapl)-7.6(otype)-310(seque)-8.6(nces)-309.4(in)-305.9(a)-309.8(popul)-6.6(ation)-307(and)-311.4(estimat)-10.5(e)-304.2(their)-314.7(prev-)]TJ
T*
[(ale)-8.6(nce)-284.7(usin)-7(g)-285.3(sequenci)-9.7(ng)-286.1(reads)-289.4(gener)-9.4(ated)-288.2(from)-289.4(a)-287.1(sample)-288.8(cont)-7.6(aining)-290.7(a)-281.4(set)-292.6(of)-282.3(viral)-291.9(variants.)-291.9(High-th)-11.1(roughput)]TJ
T*
[(next)-7.6(-generati)-10.3(on)-445.4(seque)-8.6(ncing)-452.2(\(NGS\))-453(technologie)-10.6(s)-445.8(have)-450.5(enabled)-451.6(aff)-8(ordable)-451.8(acquisi)-9.9(tion)-446.8(of)-447.4(data)-447.6(neede)-9.2(d)-444.6(t)0(o)]TJ
0 -1.195 TD
[(asse)-9(mble)-381(quasispe)-9.1(cies.)-386.5(Howeve)-10.3(r,)-378.7(relatively)-384.5(short)-385.3(length)-381.8(of)-379.1(the)-382.4(NGS)-379.3(read)-8.6(s)-377.5(and)-379.7(the)-382.4(presence)-386.3(of)-379.1(erro)-8.8(rs)-374.6(in)]TJ
0 -1.2007 TD
[(seque)-8.6(ncin)-7.6(g)-296.7(data)-305.3(rende)-9.4(r)-298.7(the)-308.4(QSR)-306.1(problem)-305.6(dif)-7(cult.)-301(Th)-7(e)-298.5(QSR)-306.1(probl)-8.6(em)-302.8(is)-301.4(partic)-10(ularly)-304.1(challe)-9.8(nging)-302.5(whe)-8(n)-296.7(the)]TJ
T*
[(str)-8.2(ains)-225(in)-226.2(a)-224.5(viral)-229.3(popul)-6.6(ation)-227.4(are)-229.8(highly)-226.3(simi)-7.6(lar,)-225.4(that)-226.6(is,)-227.8(the)-228.8(sequences)-232.6(are)-229.8(charact)-11.5(erized)-230.9(by)-223.5(low)-225.2(mut)-8.6(ual)-223.1(genet)-10.1(ic)]TJ
T*
[(distanc)-9.9(es,)-238.2(and)-237.4(further)-243.4(exacerba)-11.3(ted)-234.5(if)-239.6(some)-237.2(of)-236.8(those)-237.2(strai)-8.6(ns)-236(are)-235.5(relat)-9.2(ively)-238.8(rare)-238.2(\(Posa)-8(da-Cespede)-11.3(s)-235.3(e)0(t)-239.4(al.,)-234.5(2016\).)]TJ
1.0015 -1.2007 TD
[(Sever)-8.6(al)-387.3(soft)-9(ware)-393.8(tools)-391.8(for)-393.2(solving)-393.3(the)-393.8(QSR)-391.4(problem)-396.7(by)-388.5(anal)-9.4(yzing)-395.3(NGS)-390.6(data)-396.3(have)-393.6(been)-393.6(developed)-396.2(in)]TJ
-1.0015 -1.2007 TD
[(rece)-10.4(nt)-311.6(years.)-312.5(ShoR)-7(AH)-311(\(Zagor)-10.1(di)-305.9(et)-313.4(al.,)-314.1(2011\),)-313.5(the)-314.1(earliest)-318.8(publicly)-312.1(avai)-9.4(lable)-314.5(such)-313.3(software)-10.1(,)-307.7(was)-316.5(developed)]TJ
T*
[(by)-473.8(com)-7.6(bining)-476.7(a)-474.9(path)-474.2(cover)-9.4(-based)-477.9(appro)-7.6(ach)-472.5(and)-476.4(proba)-7.6(bilistic)-478.1(clus)-8.8(tering)-474.8(in)-476.6(Eriksson)-479.7(et)-472.7(al.)-473.1(\(2008\))-480.8(and)]TJ
T*
[(Za)-8.8(gordi)-241.9(et)-245.1(al.)-239.8(\(2010a)-8.3(\),)-242.1(respect)-10.9(ively,)-244.8(and)-243.1(applied)-247.7(to)-243.3(analysis)-245.2(o)-6.5(f)-236.1(HI)-7.4(V)-238(data)-248.4(\(Zagordi)-247.7(et)-245.1(al.,)-240.2(201)-8(0b\).)-238(Re)-8(ad-graph)]TJ
0 -1.195 TD
[(appro)-7.6(ach)-330.2(was)-333.6(the)-325.5(b)-6.5(asis)-328.6(for)-330.6(ViSpA)-332.3(\(Astrovsk)-8.5(aya)-330.2(et)-330.4(al.,)-331.2(2011\),)-330.5(developed)-333.7(as)-328.9(a)-332.6(variant)-329.4(of)-327.9(the)-331.2(networ)-9.3(k)-325.1(ow)]TJ
0 -1.2007 TD
[(method)-319.9(propos)-7.7(ed)-316.3(in)-311.6(Westbr)-9.1(ooks)-317.2(et)-313.4(al.)-313.7(\(2008\))-8.5(.)-307.7(Prospe)-8.7(ri)-313.6(et)-313.4(al.)-313.7(\(2011\))-321.5(proposed)-318.3(a)-315.5(combina)-9.5(torial)-318.2(method)-319.9(for)]TJ
T*
[(QSR)-340.2(and)-339.8(the)-331.2(resu)-8(lting)-336.5(softw)-8(are,)-338.3(QuRe,)-338.2(was)-339.2(provided)-342.7(by)-331.6(Prospe)-8.7(ri)-336.3(and)-334.1(Salemi)-340.8(\(2012\))-8.5(.)]TJ
1.0015 -1.2007 TD
[(An)-346.9(approach)-349.2(that)-346.1(resu)-8(lted)-346.1(in)-340(the)-348.3(softw)-8(are)-343.6(packa)-9.2(ge)-344.7(PredictHa)-11.5(plo)-340.8(\(Pra)-8(bhakaran)-349.2(et)-347.5(al.,)-342.6(201)-8(4\))-339.3(relie)-9.2(d)-342.2(o)0(n)-343(a)]TJ
-1.0015 -1.2007 TD
[(Di)-8.2(richlet)-326.5(proce)-9.4(ss)-328.3(mixture)-331.1(model)-330.6(and)-322.7(was)-333.6(developed)-333.7(specica)-10.7(lly)-326.5(targeting)-333.7(HIV)-325.1(popu)-8.7(lation)-327.6(reconst)-9.1(ruction;)]TJ
T*
[(Qua)-8(siRecom)-9.7(b)-365(\(To)]TJ
7.0904 .0228 TD
()Tj
.4154 -.0228 TD
[(pfer)-367.3(et)-364.6(al.,)-371(2013\))-370(is)-364(based)-372.8(on)-365.7(a)-366.7(hidden)-367.6(Marko)-9.5(v)-365(model)-364.7(that)-368.9(expl)-7.6(icitly)-370.2(models)-372.3(recombi-)]TJ
-7.5058 -1.2007 TD
[(nation)-341.9(events.)-336.8(In)-333.6(Sch)-9(irmer)-334.5(et)-336.1(al.)-336.5(\(2012\),)-339(a)-332.6(benchmar)-11.3(king)-335.9(study)-332.1(that)-340.4(compare)-10.5(s)-332(the)-336.9(performanc)-11.1(e)-332.6(o)0(f)-333.5(sever)-10.6(al)]TJ
T*
[(pu)-7.2(blicly)-310.6(availa)-9.8(ble)-308.4(quasispe)-9.1(cies)-312.2(reconst)-9.1(ruction)-310.5(softw)-8(ares)-311.4(was)-310.8(pres)-8(ented.)-312.1(The)-311.2(study)-309.4(dem)-7.6(onstrated)-315(that)-312(none)]TJ
0 -1.195 TD
[(of)-379.1(the)-371(tes)-8(ted)-371(methods)-384.5(could)-372.6(reco)-8.6(nstruct)-380(populations)-383.8(characterize)-14.1(d)-370.7(b)0(y)-377.1(low)-373.2(pairw)-8.6(ise)-377.9(distance)-376.7(betwee)-10.9(n)-376.3(the)]TJ
0 -1.2007 TD
[(hapl)-7.6(otype)-355.5(seque)-8.6(nces.)-355.3(Follow)-7.6(ing)-352.2(this)-356.9(study,)-355.3(other)-351.8(soft)-9(wares,)-356.3(includi)-9.7(ng)-348.7(Hap)-8(loClique)-356.6(\(To)]TJ
35.5659 .0171 TD
()Tj
.4154 -.0171 TD
[(pfer)-355.9(et)-353.2(al.,)-354(2014\),)]TJ
-35.9813 -1.2007 TD
[(based)-287.4(on)-280.4(max)-7.6(-clique)-283.9(enum)-8.4(eration)-283.9(of)-282.3(a)-281.4(read)-281.8(alignm)-9.7(ent)-280(graph)-7.6(,)-279.2(and)-282.9(viral)-286.3(genome)-284.8(assembl)-11.9(er)-278.4(\(VGA)-11.1(\))-275.9(\()-88.1(Mangul)]TJ
T*
[(et)-290.6(al.,)-285.7(2014\),)-285(a)-287.1(graph-colo)-12.2(ring)-280.9(b)-6.5(ased)-286.7(heuristic)-289.3(method,)-291.9(were)-291.4(developed)-9.3(.)-284.9(Most)-287.8(recently,)-292.5(a)-287.1(reference-)-13.1(assisted)]TJ
T*
[(de)-242.3(novo)-242.1(assembly)-246(pipe)-7.6(line,)-238.4(ViQu)-8(aS,)-241.9(was)-242.5(propos)-7.7(ed)-236.6(in)-237.6(Jayas)-9.8(undar)-7.6(a)-235.9(e)0(t)-239.4(al.)-239.8(\(2014\))-8.5(.)-239.4(ViQuaS)-243.8(extends)-246.2(an)-242.3(existing)]TJ
T*
[(algo)-7.6(rithm,)-237.1(QuRe)-241.1(\(Prosper)-8.5(i)-236.8(e)0(t)-233.7(al.,)-234.5(2011\),)-239.5(an)19.4(d)-222.7(o)0(u)26.9(t)0(p)18.5(e)0(r)23.2(f)0(o)19.3(r)14.3(ms)-211.1(va)19.4(ri)22.2(ou)21.2(s)-223.9(o)0(t)24.2(h)0(e)19.4(r)-219(te)22.4(ch)19.4(ni)24.2(qu)21.2(es)-215.1(on)-212.1(a)-218.8(w)0(i)20.2(d)0(e)-213.9(r)14.3(an)19.4(ge)-213.9(of)-208.4(da)19.4(t)13.5(a)-224.5(se)18.3(t)13.5(.)]TJ
T*
[(Ho)17.3(w)12.4(e)0(v)19.4(e)0(r)23.2(,)-393(pe)19.4(r)14.3(f)0(o)19.3(r)14.3(ma)15.9(nc)25.1(e)-395.2(o)0(f)-379.1(t)0(h)18.5(e)14.5(se)-385.8(m)12.8(o)0(r)19.3(e)-389.5(re)17.5(c)14.5(e)0(n)19.4(t)-390.5(me)15.9(t)13.5(h)0(o)21.2(d)0(s)-378.3(d)0(e)19.4(t)13.5(er)17.5(i)13.5(o)0(r)19.3(a)0(t)22.4(e)0(s)-380.1(d)0(r)19.3(a)0(m)21.6(a)0(t)22.4(i)0(c)22.4(a)0(l)16.7(l)13.5(y)-393.4(i)13.5(n)-393.4(t)13.5(he)-384.6(sc)23.9(en)19.5(ar)23.2(io)18.5(s)-388.9(w)0(h)17.3(e)0(r)23.2(e)-395.2(t)13.5(h)0(e)]TJ
T*
[(ge)19.4(ne)19.4(t)13.5(i)0(c)-313.4(d)0(i)24.2(v)0(e)19.4(r)0(s)23.8(i)0(t)21.4(y)-325.1(o)16.3(f)-327.1(a)-321.2(p)0(o)21.2(p)0(u)21.2(l)13.5(at)22.4(io)18.5(n)-319.4(i)13.5(s)-326.3(l)13.5(ow)-312.8(\(P)20(os)25.7(ad)19.4(a-)23.2(Ce)20.4(sp)20(ed)19.4(es)-311.8(et)-307.7(al)16.7(.,)-308.1(20)21.2(16)21.2(\))14.3(.)]TJ
1.0015 -1.195 TD
[(Both)-243.8(Po)-6.4(sada-Cespe)-12.5(des)-244.3(et)-245.1(al.)-245.5(\(2016\))-241.8(and)-248.8(Schirm)-8.2(er)-244.3(et)-239.4(al.)-245.5(\(2012\))-247.5(have)-245.6(pointed)-246(out)-244.1(that)-249.4(the)-240.2(exis)-8.8(ting)-241.9(methods)]TJ
-1.0015 -1.2007 TD
[(for)-347.7(viral)-348.8(quasispe)-9.1(cies)-346.3(recon)-9.4(struction)-350.2(struggle)-346.6(in)-345.7(the)-348.3(scenarios)-349.4(whe)-8(re)-341(the)-348.3(popul)-6.6(ations)-348.8(are)-343.6(char)-8.6(acterize)-11.2(d)-342.2(b)0(y)]TJ
T*
[(low)-356.1(dive)-7.6(rsity.)-354.3(This,)-354.3(in)-351.4(part,)-357.1(is)-352.6(due)-351.2(to)-351.4(the)-354(pres)-8(ence)-355.5(of)-350.6(relat)-9.2(ively)-352.6(long)-352.9(genet)-10.1(ic)-353.2(regions)-354.5(that)-357.5(are)-355(common)-354.8(to)]TJ
T*
[(pair)-9.6(s)-252.3(o)0(f)-259.6(closel)-9.2(y)-251.2(rel)-8.8(ated)-259.8(viral)-257.8(seque)-8.6(nces;)-261.7(clearly,)-263.3(this)-260.2(mak)-7.6(es)-254.9(disti)-7.6(nguishin)-7.1(g)-256.8(different)-260.9(strai)-8.6(ns)-258.8(challengin)-9.9(g.)-257.2(The)]TJ
T*
[(probl)-8.5(em)-331.2(becomes)-339.8(even)-331(mor)-7.8(e)-326.9(dif)-7(cult)-334.7(when)-333.1(the)-331.2(frequenc)-9.7(y)-330.8(o)0(f)-327.9(o)-6.5(ne)-327.7(\(or)-330.6(mor)-7.8(e\))-329.7(of)-333.6(the)-331.2(close)-335.7(strains)-335.7(is)-329.8(low;)-331.2(in)]TJ
T*
[(such)-273.5(settings,)-275(small)-271.9(genetic)-278(distances)-276.2(may)-269.4(be)-270.8(confused)-274.6(for)-268(seque)-8.6(ncing)-270.1(errors)-275.2(and)-271.5(hence)-270.9(remai)-10(n)-262.5(undet)-8.4(ected.)]TJ
T*
[(Su)-6.4(ch)-447.2(failur)-10.1(es)-448.4(to)-448.2(dete)-9.4(ct)-449.9(may)-451.5(have)-456.2(serious)-452.4(conse)-8.6(quence)-9.9(s)-445.8(i)0(n)-448.2(antivi)-9(ral)-452.7(treatme)-10.3(nt)-448.2(studies)-453.2(sinc)-8.8(e)-446.4(undet)-8.4(ected)]TJ
T*
[(str)-8.2(ains)-242.1(cannot)-249.9(be)-242.3(properl)-8.1(y)-239.8(targeted)-246.6(for)-245.2(drug)-244(and)-243.1(vaccine)-248.6(desi)-8.8(gn.)-240.9(It)-239.6(has)-244.3(been)-245.6(show)-8.2(n)-239.8(that)-243.7(even)-245.6(the)-245.8(viral)-246.4(strains)]TJ
0 -1.195 TD
[(exis)-8.8(ting)-293.1(at)-296.3(low)-293.5(frequenc)-9.7(ies)-292.6(can)-296.1(cause)-300.6(a)-292.8(drug)-295.3(treatme)-10.3(nt)-294.5(failure)-297.2(due)-294.3(to)-294.5(their)-297.6(resistanc)-10.7(e)-292.8(t)0(o)-288.8(the)-297.1(drug)-295.2(\(Le)-296.1(et)-296.3(al.,)]TJ
0 -1.2007 TD
[(20)-7.2(09;)-431.8(Simen)-437.9(et)-432.9(al.,)-433.6(2009\).)-433(Th)-7(erefore,)-438.1(com)-7.6(plete)-434(reco)-8.6(very)-433.6(of)-430.3(the)-433.6(com)-7.6(position)-436.7(of)-436(viral)-434.2(popul)-6.6(ations)-434.2(is)-432.3(of)]TJ
T*
[(cri)-8.8(tical)-334.3(import)-9.9(ance)-338.5(for)-336.3(effective)-342.2(antivi)-9(ral)-333.2(therapi)-10.7(es.)]TJ
1.0015 -1.2007 TD
-.0192 Tc
[(In)-190.7(this)-191.9(article,)-190.3(w)-1.1(e)-192.5(p)2.8(ropose)-192.5(a)-192.5(n)-2.9(ovel)-193.4(QSR)-195.4(a)]TJ
15.3417 0 TD
-.0188 Tc
[(lgorithm,)-189.9(aBayes)-3.7(QR)-189.3(\(c)-4.3(ombining)-190.3(agglom)]TJ
15.5693 0 TD
[(erative)-192.1(h)3.2(ierarchical)-193(c)1.4(lustering)]TJ
-31.9126 -1.2007 TD
-.0196 Tc
[(a)-5.1(n)2.4(d)-196.8(B)-2.3(aye)-5.1(s)1.2(ian)-196.8(i)-.4(nfe)-5.1(r).4(ence)-5.1(\),)-190.7(that)-193.8(overc)-5.1(o)2.4(me)]TJ
15.0401 0 TD
-.0188 Tc
[(s)-191.5(limitations)-191.5(of)-192.3(the)-192.1(e)1.4(xisting)-196(m)-.3(ethods)-191.5(and)-190.3(r)]TJ
15.7571 0 TD
-.0197 Tc
[(e)-5.2(liably)-191.2(r).3(ec)-5.2(onstructs)-192.4(q)-3.4(ua)-5.2(sis)-4.6(p)2.3(ec)-5.2(ies)]TJ
-30.7973 -1.2007 TD
[(c)-5.2(h)2.3(a)-5.2(r).3(ac)-5.2(terize)-5.2(d)-287.9(b)-3.4(y)-287.9(l)-.5(ow)-291.9(diver)-5.4(s)1.1(ity.)-293.2(T)2.5(he)-289.7(al)]TJ
14.7271 0 TD
-.0193 Tc
[(gorithm)-291.1(p)2.7(e)-4.8(rfor)-5(m)-.8(s)-288.7(r).7(ec)-4.8(onstruction)-287.5(o)]TJ
13.3216 0 TD
-.0185 Tc
[(f)-288.7(a)-288.5(quasispecies)-287.9(from)-284.6(NGS)-291.6(data)-288.5(in)-286.7(two)]TJ
-28.0487 -1.2007 TD
-.0192 Tc
[(stages.)-258.6(I).8(n)-253.3(t)0(he)-255.1(rst)-256(sta)-4.7(g)2.8(e)-4.7(,)-252.9(conic)-4.7(t-free)-260.8(s)1.6(hort)-256(re)-4.7(ads)-254.5(a)1(re)-255.1(hier)]TJ
21.7607 0 TD
-.0195 Tc
[(archica)-5(lly)-253.6(mer)-5.2(g)2.5(e)-5(d)-253.6(and)-253.6(a).7(sse)-5(m)-1(bled)-259.3(into)-259.3(longe)-5(r)-255.6(seque)-5(n)2.5(c)-5(e).7(s)]TJ
-21.7607 -1.2007 TD
[(\()-5.3(c).6(ontigs\),)-361.4(w)-1.5(hic)-5.1(h)-356.1(we)-363.6(re)-5.1(fer)-358.1(t)-.4(o)-361.8(a).6(s)-363(s)1.2(upe)-5.1(r-re)-5.1(ads.)-361.4(In)-356.1(the)-363.6(s)1.2(ec)-5.1(on)]TJ
22.4663 0 TD
-.0192 Tc
[(d)-355.7(s)-4.1(tage,)-361(likel)-5.7(ihoods)-356.9(of)-357.7(the)-357.5(p)-2.9(robable)-357.5(q)-2.9(ua)-4.7(sispec)-4.7(ies)-356.9(a)-4.7(re)]TJ
-22.4663 -1.195 TD
[(c)-4.7(o)2.8(mpute)-4.7(d)-185(using)-185(t)0(he)-186.8(assembled)-185(s)1.6(upe)-4.7(r-re)-4.7(ads)-186.2(\().8(r)-4.9(a)1(ther)-187(than)-185(usin)]TJ
22.5403 0 TD
-.0199 Tc
[(g)-185.7(t)-.7(he)-187.5(original)-188.5(se)-5.4(t)-182.8(o)-3.6(f)-182(s)-4.8(hort)-182.8(re)-5.4(ads\),)-185.3(a)-5.4(nd)-185.7(the)-181.8(m)-7.1(ost)-188.5(like)-5.4(l)-.7(y)-185.7(s).9(e)-5.4(t)]TJ
-22.5403 -1.2007 TD
-.0192 Tc
[(of)-380.4(viral)-381.2(s)-4.1(trains)-379.7(is)-379.7(selec)-4.7(t)0(ed.)-378.1(N)-1.1(ote)-380.3(t)0(hat)-381.2(t)0(he)-385.9(supe)-4.7(r-rea)-4.7(d)2.8(s)-385.3(s)1.6(ynthesiz)-4.7(ed)-384.2(in)-378.5(the)-380.3()-2.1(rst)-381.2(s)1.6(ta)-4.7(ge)-386(of)-380.4(a)-4.7(B)-1.9(ayesQR)-383.2(allow)-382.4(u)-2.9(s)-379.7(t)0(o)]TJ
T*
-.0187 Tc
[(distinguish)-173.1(b)3.3(etween)-167.4(closely)-173.1(r)1.3(elated)-173.1(strains,)-172.7(which)-173.1(s)2.1(hare)]TJ
20.9981 0 TD
-.0184 Tc
[(lo)3.6(ng)-167.1(genetic)-174.6(regio)3.6(n)-2.1(s,)-172.4(as)-174(well)-169.9(as)-168.3(red)3.6(u)-2.1(ce)-174.6(th)3.6(e)-174.6(s)2.4(earch)-172.8(s)2.4(pace)-168.9(and)]TJ
-20.9981 -1.2007 TD
-.0186 Tc
[(enable)-248.8(computational)-249.7(t).6(ractability)-247(of)-249(the)-248.8(B)-1.3(ayes)]TJ
17.7147 0 TD
-.0181 Tc
[(ian)-246.5(i)1.1(nference)-248.3(conducted)-252.2(i)1.1(n)-246.5(t)1.1(he)-248.3(second)-246.5(stage.)]TJ
-16.7131 -1.2007 TD
0 Tc
[(The)-260(secon)-8.6(d)-251.2(sta)-8(ge)-253.7(of)-259.6(aBayesQR)-265(involves)-265(sequential)-261.5(pruni)-8.6(ng)-251.9(of)-259.6(the)-257.2(solution)-260.3(space)-10.4(;)-253.9(i)0(n)-254.7(partic)-10(ular,)-254.7(the)-257.2(li)-7.1(kely)]TJ
-1.0015 -1.2007 TD
[(set)-503.1(of)-498.6(part)-9.6(ial)-499(viral)-502.5(strain)-9.4(s)-497(compri)-8.9(sing)]TJ
/F5 1 Tf
16.5083 0 TD
(n)Tj
/F1 1 Tf
.9958 0 TD
[(single-)-10.1(nucleotide)-505(variant)-10.7(s)-497(\(SN)-7.4(Vs\))-498.8(is)-500.6(gener)-9.4(ated)-498.8(by)-502.3(extendi)-8.7(ng)]TJ
/F2 1 Tf
-17.5041 67.0005 TD
[(63)-7.2(8)]TJ
34.0921 0 TD
[(AHN)-338(AND)-344.1(VIKALO)]TJ
ET
endstream
endobj
50 0 obj
<>stream
/GS1 gs
BT
/F1 1 Tf
9.9626 0 0 9.9626 107.6031 715.4644 Tm
0 0 0 rg
0 Tc
0 Tw
[(previous)-8.1(ly)-294.5(inferred)-297.2(partial)-298(viral)-297.6(strains)-295.8(having)]TJ
/F5 1 Tf
18.9438 0 TD
(n)Tj
/F6 1 Tf
.5008 0 TD
(-)Tj
/F1 1 Tf
.552 0 TD
[(1)-291(SNVs.)-296.2(T)-12(h)-12.1(e)-298.5(n)-12.1(u)-12.1(m)-10(b)-12.1(e)-13.9(r)-298.7(o)-12.1(f)-298.7(s)-13.3(e)-13.9(q)-6.5(u)-12.2(e)-13.9(n)-12.2(c)-8.2(e)-13.9(s)-303.6(i)-9.2(n)-302.4(a)-298.5(s)-13.3(e)-8.2(t)-305.1(\()-8.4(i)-9.2(.)-11.8(e)-13.9(.)-11.8(,)-296.3(t)-14.9(h)-6.5(e)-304.2(s)-13.3(i)-9.2(z)-13.9(e)]TJ
-19.9966 -1.195 TD
.0122 Tc
[(of)-360.4(a)-360.2(v).1(ir)3.8(al)-361.2(po)5.7(pulation\))-360.4(is)-365.3(dyn)5.7(a)-1.7(mic)4(a)-1.7(lly)-364.1(upd)5.7(ated)-358.5(at)-361.2(ea)4(ch)]TJ
22.8931 0 TD
.0097 Tc
[(st)-5.2(ep)-366.6(by)-361(eval)-5.2(uati)-5.2(ng)-366.6(qual)-5.2(ity)-366.6(of)-368.6(the)-362.7(s)-3.6(et)-363.7(of)-368.6(partially)]TJ
-22.8931 -1.2007 TD
.0109 Tc
[(reconstructed)-274.4(v)-1.2(iral)-277.2(strains)-275.6(a)-3(nd)-274.4(ulti)]TJ
14.1069 0 TD
.0106 Tc
[(mately)-274.7(precisely)-280.4(inferred)-280.4(at)-277.5(the)-276.5(e)-3.3(nd)]TJ
14.9377 0 TD
.0128 Tc
[(of)-274.5(the)-274.3(s)-.5(e)4.5(a)-1.1(rc)4.6(h)-272.5(p).7(roc)4.6(e)-1.1(s)5.1(s)-.5(.)-272.1(T).8(he)-274.3(re)4.6(la)4.6(tive)]TJ
-29.0446 -1.2007 TD
.009 Tc
[(fr)-5.1(eque)-4.9(nc)-4.9(ie)-4.9(s)-351.5(o)-3.1(f)-352.2(e)-4.9(ac)-4.9(h)-350.3(s)-4.3(tr)-5.1(ai)]TJ
10.3227 0 TD
.012 Tc
[(n)-347.3(a)-1.9(re)-349.1(determin)5.5(ed)-347.3(by)-353(counting)-347.3(t)-2.9(h)5.5(e)-354.8(n)5.5(u)-.1(mb)5.5(er)]TJ
17.5098 0 TD
.0114 Tc
[(s)-354.8(o)4.9(f)-355.5(r)3(eads)-349.1(unambigu)4.9(ously)-347.9(a)-2.5(ssociated)]TJ
-27.8325 -1.2007 TD
[(with)-353.5(each)-359.2(o)-.6(f)-355.4(t)2.3(he)-360.9(reconstruc)]TJ
11.5461 0 TD
.0105 Tc
[(ted)-360.2(s)-2.8(trains.)-354.1(O)-5.6(ur)-362.1(test)-4.4(s)-355.7(o)-1.6(n)-360.2(b)4(oth)-360.2(s)-2.8(imulated)-354.5(and)-360.2(e)2.3(xperimental)-357.2(d)-1.6(at)-4.4(a)-356.2(d)-1.6(em)-5.2(onstrat)-4.4(e)]TJ
-11.5461 -1.2007 TD
.0114 Tc
[(su)4.9(perior)-264.5(performance)-258.6(c)-2.5(ompared)-256.8(t)-3.5(o)-262.5(s)3.8(ta)]TJ
15.6035 0 TD
.0128 Tc
[(te-)4.4(o).6(f-)4.4(the-)4.4(ar)4.4(t)-263.9(m)2.8(etho)6.3(ds)-262.3(f)4.4(o).6(r)-263.1(q)6.3(uas)5.2(i)-2.1(s)5.1(p).7(ec)4.6(ie)4.6(s)-262.3(r)4.4(eco)6.3(nstru)6.3(c)-1.1(tio)6.3(n).7(.)-260.7(I)4.4(n)-261.1(p).7(ar)4.4(tic)4.6(u).7(lar)4.4(,)]TJ
-15.6035 -1.2007 TD
.0118 Tc
[(it)-481.1(is)-479.5(shown)-478.4(t)2.6(hat)-475.4(unlike)-480.1(t)2.6(he)-480.1(co)5.3(mp)5.3(etin)5.3(g)-478.4(m)-3.9(eth)5.3(o)-.4(ds,)-478(a)3.6(Ba)]TJ
22.8191 0 TD
.0107 Tc
[(yesQR)-484.2(i)1.5(s)-480.6(c)2.5(apable)-481.2(of)-481.4(detecting)-479.5(a)-3.2(nd)-479.5(rel)-4.2(i)1.5(abl)-4.2(y)-479.5(re-)]TJ
-22.8191 -1.2007 TD
.0119 Tc
[(co)5.4(nstructing)-330.3(v)-.2(iral)-327.4(haplotypes)-331.5(h)-.2(av)5.4(ing)-330.3(v)]TJ
16.0758 0 TD
.0106 Tc
[(ery)-331.6(s)-2.7(mall)-334.4(mutual)-334.4(ge)]TJ
8.3708 0 TD
.0143 Tc
[(n)7.8(e).4(t)5.1(i)-.6(c)-329.7(d)7.8(is)6.6(ta)6.1(nce)6.1(s)1(.)]TJ
/F2 1 Tf
10.959 0 0 10.959 259.37 590.9668 Tm
0 Tc
[(2.)-496.7(PROPOSED)-329.3(METHOD)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 567.0424 Tm
[(O)12.4(u)0(r)-356.3(a)0(l)22.4(g)0(o)15.5(r)0(i)16.5(t)13.5(hm)-357.9(f)14.3(o)0(r)-356.3(i)13.5(nf)13.6(er)17.5(ri)22.2(ng)-354.3(sp)20(ec)17.7(tr)16.5(um)-352.2(of)-350.6(a)-361.1(v)0(i)18.5(r)0(a)17.5(l)-362(po)15.5(pu)21.2(la)16.7(ti)15.7(on)-348.7(co)13.8(ns)20(is)17.3(ts)-352.6(of)-350.6(th)18.5(e)-361.1(f)0(o)19.3(l)0(l)15.7(o)0(w)17.3(i)0(n)18.5(g)-359.3(tw)14.5(o)-359.3(s)0(t)17.3(e)0(p)19.4(s)0(:)-352.6(\()0(1)19.3(\))-361.2(co)19.5(n-)]TJ
-1.0015 -1.2007 TD
[(st)17.3(ru)19.3(ct)16.7(in)18.5(g)-336.5(s)0(u)20(p)0(e)13.8(r)0(-)17.3(r)0(e)17.5(a)0(d)19.4(s)-337.7(by)-325.9(hi)18.5(er)17.5(ar)17.5(ch)13.8(ic)16.7(al)16.7(l)13.5(y)-336.5(cl)16.7(us)14.4(te)16.7(ri)22.2(ng)-331.6(al)16.7(i)13.5(g)0(n)15.5(e)0(d)-327.7(p)0(a)13.8(i)13.5(re)17.5(d-)13.6(en)19.4(d)-336.5(r)0(e)17.5(a)0(d)19.4(s)-337.7(an)13.8(d)-336.5(\()0(2)19.3(\))-338.5(in)18.5(fe)17.5(rr)17.3(in)18.5(g)-336.5(t)0(h)18.5(e)-338.3(mo)17.7(st)-329.8(l)13.5(i)0(k)18.5(e)0(l)16.7(y)]TJ
T*
[(qu)21.2(as)12.6(i)13.5(s)0(p)14.4(e)0(c)17.7(i)0(e)16.7(s)-326.3(f)14.3(r)0(o)13.6(m)-323(th)18.5(e)-326.9(s)0(e)18.3(t)-322.2(of)-316.5(su)20(pe)13.8(r-)17.3(r)14.3(e)0(a)12(d)0(s)-315.7(a)0(n)19.4(d)-325.1(es)18.3(ti)15.7(m)12.8(a)0(t)16.7(i)0(n)18.5(g)-325.1(th)18.5(e)-326.9(f)0(r)17.3(e)0(q)19.4(u)0(e)19.4(n)0(c)13.8(i)0(e)16.7(s)-320.6(of)-316.5(th)18.5(e)-326.9(s)0(t)17.3(r)14.3(ai)16.7(ns)-315.7(in)-317.3(th)18.5(e)-321.2(q)0(u)15.5(a)0(s)18.3(i)0(s)17.3(p)0(e)19.4(c)0(i)16.7(e)0(s)12.6(.)]TJ
/F5 1 Tf
10.959 0 0 10.959 107.6031 519.2502 Tm
[(2.1.)-496.9(Super-read)-329.6(construction)-331.8(via)-334.3(agglomerat)7.8(ive)-335.6(clustering)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 501.2786 Tm
[(In)-236.8(the)-240.1(rst)-235.8(sta)-8(ge)-236.6(of)-236.8(aBayes)-10.1(QR,)-238.2(paired-)-9.9(end)-237.4(read)-8.6(s)-235.3(uniqu)-6.6(ely)-240.2(mapped)-239.3(to)-237.6(a)-241.6(reference)-249.3(genome)-239.3(are)-241.1(groupe)-8.3(d)-234.1(into)]TJ
-1.0015 -1.2007 TD
[(super-r)-8.6(eads)-372(via)-376.7(agglomerat)-12.6(ive)-371(hierar)-9.2(chical)-374(cluste)-9.2(ring.)-372.4(This)-371(is)-375.4(facilitat)-10.9(ed)-367.5(by)-371.4(a)-372.4(weight)-10.1(ed)-367.5(graph)]TJ
/F5 1 Tf
38.9347 0 TD
(G)Tj
/F6 1 Tf
.8877 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
(\()Tj
/F7 1 Tf
.3357 0 TD
(V)Tj
/F1 1 Tf
.6658 0 TD
()Tj
/F7 1 Tf
.5008 0 TD
(E)Tj
/F1 1 Tf
.5747 0 TD
(\),)Tj
-42.6165 -1.2007 TD
[(which)-313.9(is)-312.8(const)-9.6(ructed)-314.5(and)-311.4(recu)-8.6(rsively)-317.4(updated)-319(as)-311.8(the)-314.1(clusteri)-9.7(ng)-308.8(proce)-9.4(eds.)-312.9(In)-310.8(partic)-10(ular,)-311.6(each)-315.7(vertex)-320.2(of)]TJ
/F5 1 Tf
41.5012 0 TD
(G)Tj
/F1 1 Tf
1.03 0 TD
(is)Tj
-42.5312 -1.195 TD
[(associa)-10.1(ted)-251.5(with)-251.5(a)-247.2(cluste)-9.2(r)-247.4(collecting)-257.3(read)-253.3(that)-249.4(origina)-8.9(ted)-245.8(from)-255.2(a)-247.2(sing)-7(le)-245.1(strai)-8.6(n)-245.5(i)0(n)-249(a)-247.2(quasi)-9.6(species)-10.2(;)-242.5(w)0(e)-251.9(denot)-8.4(e)-247.3(the)]TJ
0 -1.2007 TD
[(set)-298.2(of)-293.7(read)-8.6(s)-292.2(i)0(n)-300.2(the)]TJ
/F5 1 Tf
7.557 0 TD
(i)Tj
6.9738 0 0 6.9738 185.7259 457.0581 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 194.57 453.4865 Tm
[(clus)-8.8(ter)-299(\(i.e.,)-294.5(the)-302.7(cluster)-302.1(associa)-10.2(ted)-297.1(with)-297(the)]TJ
/F5 1 Tf
17.6236 0 TD
(i)Tj
6.9738 0 0 6.9738 372.9825 457.0581 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 381.8834 453.4865 Tm
[(vertex\))-300.1(as)]TJ
/F5 1 Tf
4.2736 0 TD
(V)Tj
6.9738 0 0 6.9738 430.5826 451.9558 Tm
(i)Tj
/F6 1 Tf
9.9626 0 0 9.9626 434.7211 453.4865 Tm
(=)Tj
/F7 1 Tf
.717 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(v)Tj
6.9738 0 0 6.9738 451.3322 458.3054 Tm
(j)Tj
0 -1.0731 TD
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 453.8267 453.4865 Tm
()Tj
/F5 1 Tf
.4951 0 TD
(j)Tj
/F6 1 Tf
.4496 0 TD
(=)Tj
/F1 1 Tf
.7227 0 TD
(1)Tj
/F8 1 Tf
1.1666 0 TD
.1682 Tc
(...)Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(V)Tj
6.9738 0 0 6.9738 508.9889 451.9558 Tm
(i)Tj
/F7 1 Tf
9.9626 0 0 9.9626 511.4266 453.4865 Tm
(jg)Tj
/F1 1 Tf
.7739 0 TD
[(.)-296.3(Let)]TJ
/F5 1 Tf
-41.3077 -1.2007 TD
(sr)Tj
6.9738 0 0 6.9738 115.3133 439.9936 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 120.1322 441.5243 Tm
[(denot)-8.4(e)-241.6(a)-235.9(conse)-8.6(nsus)-244.4(seque)-8.6(nce)-239.2(\(i.)-6.6(e.,)-242.3(a)-241.6(super-read\))-250.5(construc)-9.9(ted)-240.2(from)-243.8(the)-245.8(reads)-243.9(in)]TJ
/F5 1 Tf
31.3037 0 TD
(V)Tj
7.4718 0 0 6.641 438.1227 439.8802 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 440.2203 441.5243 Tm
[(.)-239.4(The)]TJ
/F5 1 Tf
2.2933 0 TD
(i)Tj
6.9738 0 0 6.9738 465.9022 445.1526 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 474.2361 441.5243 Tm
(and)Tj
/F5 1 Tf
1.6901 0 TD
(j)Tj
6.9738 0 0 6.9738 493.9085 445.1526 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 502.2424 441.5243 Tm
[(vertex)-246.2(of)]TJ
/F5 1 Tf
-39.6119 -1.2007 TD
(G)Tj
/F1 1 Tf
.9674 0 TD
[(are)-258.2(connecte)-10.3(d)-245.5(b)0(y)-251.9(a)0(n)-253.7(edge)]TJ
/F5 1 Tf
10.4137 0 TD
(e)Tj
6.9738 0 0 6.9738 225.4677 428.0881 Tm
(ij)Tj
/F7 1 Tf
9.9626 0 0 9.9626 232.611 429.5621 Tm
.2829 Tc
(2E)Tj
/F1 1 Tf
1.7584 0 TD
0 Tc
[(if)-251(all)-254.3(the)-251.5(read)-8.6(s)-246.7(i)0(n)]TJ
/F5 1 Tf
7.0108 0 TD
(V)Tj
7.4718 0 0 6.641 326.0975 427.918 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 330.6897 429.5621 Tm
(and)Tj
/F5 1 Tf
1.7015 0 TD
(V)Tj
7.4718 0 0 6.641 353.7637 427.918 Tm
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 358.3558 429.5621 Tm
[(\(or,)-251.3(equi)-7.6(valently,)]TJ
/F5 1 Tf
7.1473 0 TD
(sr)Tj
6.9738 0 0 6.9738 437.2723 428.0881 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 442.2046 429.5621 Tm
(and)Tj
/F5 1 Tf
1.7015 0 TD
(sr)Tj
6.9738 0 0 6.9738 466.8093 428.0881 Tm
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 469.3038 429.5621 Tm
[(\))-247.4(are)-258.2(conict)-252.7(fre)-8(e)]TJ
-36.3057 -1.2007 TD
[(and)-339.8(an)-344.7(overlap)-343.7(cri)-8.8(terion,)-344.3(specied)-350.4(later)-344.9(in)-340(this)-339.8(subse)-8(ction,)-341.6(is)-341.2(sat)-8(ised.)-344.9(The)-339.6(weight)]TJ
/F5 1 Tf
34.075 0 TD
(w)Tj
6.9738 0 0 6.9738 453.77 416.1259 Tm
(ij)Tj
/F1 1 Tf
9.9626 0 0 9.9626 461.5369 417.5999 Tm
[(of)-344.9(the)-342.6(edge)]TJ
/F5 1 Tf
4.9849 0 TD
(e)Tj
6.9738 0 0 6.9738 515.6786 416.1259 Tm
(ij)Tj
/F1 1 Tf
9.9626 0 0 9.9626 523.5022 417.5999 Tm
[(is)-335.5(a)]TJ
-41.7459 -1.2007 TD
[(measur)-9.1(e)-287.1(o)0(f)-288(similarity)-297.4(between)]TJ
/F5 1 Tf
12.542 0 TD
(V)Tj
7.4718 0 0 6.641 238.6771 403.9936 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 243.6094 405.6377 Tm
(and)Tj
/F5 1 Tf
1.7356 0 TD
(V)Tj
7.4718 0 0 6.641 267.0236 403.9936 Tm
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 272.0125 405.6377 Tm
[(at)-284.9(each)-292.9(step,)-293.7(the)-285.7(algo)-7.6(rithm)-288(merges)-293.7(a)-287.1(pair)-294.1(of)-288(vertices)-293.3(connec)-9.9(ted)-285.7(by)]TJ
-16.5026 -1.2007 TD
[(the)-336.9(edge)-336.7(havi)-7.6(ng)-331.6(the)-336.9(largest)-342(weight)-340.2(to)-334.3(form)-340.6(a)-332.6(new)-338.1(vertex)-337.2(and)-339.8(agglome)-9.5(rates)-337.7(the)-336.9(correspo)-9.1(nding)-336.6(clus)-8.8(ters.)]TJ
1.0015 -1.2007 TD
[(The)-277(alleles)-281.9(at)-279.2(homozygous)-281.6(sites,)-281.3(com)-7.6(mon)-273.3(to)-277.4(all)-277.1(the)-280(component)-11(s)-275.1(o)0(f)-276.6(a)-275.7(quasispe)-9.1(cies,)-278.4(are)-281(not)-272.5(utilize)-8.6(d)-273.9(i)0(n)-277.4(the)]TJ
-1.0015 -1.195 TD
[(reconst)-9.1(ruction)-310.5(procedure)-10.5(.)-302(Instead)-9.1(,)-302(w)0(e)-303.2(separat)-10.9(e)-304.2(reads)-306.5(havi)-7.6(ng)-303.1(originate)-9.3(d)-302.4(from)-306.4(different)-312.1(strains)-307.2(by)-308.8(clustering)]TJ
0 -1.2007 TD
[(them)-284.3(using)-280.9(heteroge)-10.5(neous)-285.6(sites)-281(with)-285.7(reliable)-283.5(SNV)-282.5(inf)-7(ormation.)-286.7(An)-278.6(SNV)-282.5(inf)-7(ormation)-286.4(is)-278.6(consider)-9.9(ed)-282.2(reliable)]TJ
T*
[(if)-245.3(the)-245.8(relative)-249.3(abunda)-8.1(nce)-244.9(o)-6.5(f)-241.7(the)-245.8(allele)-251.5(is)-244.5(above)-246.4(a)-247.2(predeterm)-11.1(ined)-246.6(threshold,)-251(as)-243.5(in)-243.3(Di)-247.2(Gial)-8.6(lonardo)-245.2(et)-245.1(al.)-245.5(\(2014\))-8.5(;)]TJ
T*
[(alleles)-401.4(whose)-392(abunda)-8.1(nce)-398.5(is)-392.4(below)-393.6(the)-393.8(thr)-7(eshold)-397.3(are)-394.8(treated)-399.5(as)-391.5(seque)-8.6(ncing)-395.3(errors)-394.8(and)-396.7(disrega)-9.1(rded)-393.8(in)-391.3(the)]TJ
T*
[(process)-582.3(of)-578.3(cluste)-9.2(ring.)-577.2(For)-578.2(conven)-8.2(ience,)-581.4(let)-578.7(us)-577.5(denote)-580(the)-581.6(set)-577.1(of)-578.2(preproce)-9.7(ssed)-576.3(paired-)-9.9(end)-578.8(reads)-579.6(by)]TJ
/F5 1 Tf
T*
(R)Tj
/F6 1 Tf
.7796 0 TD
(=)Tj
/F7 1 Tf
.7227 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(r)Tj
6.9738 0 0 6.9738 131.4141 308.5228 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 133.8519 309.9968 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(i)Tj
/F6 1 Tf
.4496 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
.0065 Tc
(1)Tj
/F7 1 Tf
1.1723 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2675 0 TD
(R)Tj
/F7 1 Tf
.6203 0 TD
(jg)Tj
/F1 1 Tf
.7682 0 TD
[(.)-347.5(The)-345.3(aggl)-7.6(omerativ)-9.3(e)-344(clus)-8.8(tering)-349.6(is)-346.9(initializ)-9.9(ed)-344.7(with)]TJ
/F7 1 Tf
20.4461 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(R)Tj
/F7 1 Tf
.6146 0 TD
(j)Tj
/F1 1 Tf
.6146 0 TD
[(cluste)-9.2(rs,)-346.5(one)-345.5(for)-347.7(each)-349.8(read)-8.6(;)-345(i)0(n)]TJ
-30.894 -2.0998 TD
[(ot)24.2(he)19.4(r)-338.5(w)12.4(or)19.3(ds)20(,)-336.1(w)12.4(e)-338.3(s)0(t)17.3(a)14.5(rt)-330.6(w)12.4(i)0(t)21.4(h)]TJ
/F5 1 Tf
10.9259 0 TD
(V)Tj
/F1 1 Tf
6.9738 0 0 6.9738 222.633 287.5464 Tm
(1)Tj
/F6 1 Tf
9.9626 0 0 9.9626 228.2456 289.0771 Tm
(=)Tj
/F5 1 Tf
.7227 0 TD
(r)Tj
/F1 1 Tf
6.9738 0 0 6.9738 239.3007 287.5464 Tm
(1)Tj
9.9626 0 0 9.9626 243.2692 289.0771 Tm
()Tj
/F8 1 Tf
.6658 0 TD
.1568 Tc
(...)Tj
/F1 1 Tf
1.2918 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(V)Tj
/F7 1 Tf
6.9738 0 0 6.9738 273.8834 287.2629 Tm
(j)Tj
/F5 1 Tf
.2764 0 TD
(R)Tj
/F7 1 Tf
.6097 0 TD
(j)Tj
/F6 1 Tf
9.9626 0 0 9.9626 284.1448 289.0771 Tm
(=)Tj
/F5 1 Tf
.717 0 TD
(r)Tj
/F7 1 Tf
6.9738 0 0 6.9738 295.1432 287.2629 Tm
(j)Tj
/F5 1 Tf
.2683 0 TD
(R)Tj
/F7 1 Tf
.6178 0 TD
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 303.7039 289.0771 Tm
[(,)-341.8(i)13.5(mp)17.7(l)13.5(y)0(i)24.2(n)0(g)-331.6(t)13.5(ha)19.4(t)]TJ
/F7 1 Tf
6.2881 0 TD
[(jV)-64.9(j)]TJ
/F6 1 Tf
1.3771 0 TD
(=)Tj
/F9 1 Tf
.9446 .7455 TD
(P)Tj
/F7 1 Tf
6.9738 0 0 6.9738 390.5007 299.2818 Tm
[(jV)-69(j)]TJ
/F5 1 Tf
-.2276 -2.7315 TD
(i)Tj
/F6 1 Tf
.4471 0 TD
(=)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F7 1 Tf
9.9626 0 0 9.9626 402.2361 289.0771 Tm
(j)Tj
/F5 1 Tf
.2675 0 TD
(V)Tj
6.9738 0 0 6.9738 411.0802 287.5464 Tm
(i)Tj
/F7 1 Tf
9.9626 0 0 9.9626 413.518 289.0771 Tm
(j)Tj
/F6 1 Tf
.4382 0 TD
(=)Tj
/F7 1 Tf
.717 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(R)Tj
/F7 1 Tf
.6146 0 TD
(j)Tj
/F1 1 Tf
.2731 0 TD
[(,)-336.1(a)0(n)19.4(d)-336.5(pr)19.3(oc)19.5(e)14.5(e)0(d)-327.7(b)0(y)-331.6(s)15.1(eq)19.4(ue)19.4(n-)]TJ
-33.0223 -1.9348 TD
-.0188 Tc
[(t)-5.3(i)-18.8(al)-18.8(ly)-275.6(m)-18.8(e)2.8(r)-18.8(g).5(i)-5.3(n)-18.8(g)-265(j)-5.3(u)-18.8(d)2.4(i)-18.8(c)3.6(i)-18.8(o)-.3(u)-18.8(s)6.9(l)-18.8(y)-267.8(ch)-18.8(os)-18.8(en)-275.6(pa)-18.8(irs)-276.8(o)-18.8(f)-261.3(v)-18.8(ert)-18.8(i)2.6(c)-18.8(e)-1.1(s)-271.1(\()-18.8(i.)-18.8(e.)]TJ
21.4416 0 TD
[(,)-264.4(a)-18.9(g)6.2(g)-18.9(lo)-18.9(me)-18.9(rat)-18.9(i)2.5(n)-18.9(g)-265.1(t)-5.4(h)-18.9(e)-266.9(c)-18.9(o)6.2(r)-18.9(res)-18.9(p)1.1(o)-18.9(n)2.3(d)-18.9(i)5.3(n)-18.9(g)-265.1(c)-18.9(l)3.5(u)-18.9(s)1.1(t)-5.4(e)-18.9(rs\))-18.9(.)-266.7(Intuitively,)]TJ
-21.4416 -1.2007 TD
-.0193 Tc
[(it)-341.5(is)-345.6(me)-4.8(aningful)-347.2(to)-344.4(reduc)-4.8(e)-340.5(the)-346.2(n)2.7(umbe)-4.8(r)-340.7(o)-3(f)-346.4(v)2.7(er)-5(tices)-345.6(in)-344.4(the)-346.2(g)2.7(ra)-4.8(ph)-344.4(by)-344.4(merging)-344.4(t)-.1(hose)-340.5(a)-4.8(s)1.5(socia)-4.8(t)-.1(ed)-344.4(with)-344.4(c)-4.8(o)2.7(nic)-4.8(t-fre)-4.8(e)]TJ
T*
[(cons)-4.3(ensus)-214.8(s)-4.3(equence)-4.9(s)-209.1(that)-216.4(ha)-4.9(ve)-215.4(a)-215.4(l)-.2(arge)-209.7(overlap.)-213.3(T)-2.9(o)-213.6(f).6(orm)-6.6(a).8(lize)-215.4(t)-.2(his,)-213.3(let)]TJ
/F5 1 Tf
26.131 0 TD
0 Tc
(L)Tj
6.9738 0 0 6.9738 373.4361 244.4031 Tm
(i)Tj
/F6 1 Tf
9.9626 0 0 9.9626 377.5747 245.8771 Tm
(=)Tj
/F7 1 Tf
.717 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(l)Tj
/F1 1 Tf
6.9738 0 0 6.9738 392.5416 244.4031 Tm
(1)Tj
9.9626 0 0 9.9626 396.5101 245.8771 Tm
()Tj
/F7 1 Tf
.6658 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(l)Tj
/F7 1 Tf
6.9738 0 0 6.9738 424.0629 244.0629 Tm
(j)Tj
/F5 1 Tf
.2683 0 TD
(L)Tj
4.9813 0 0 4.9813 429.7888 243.0424 Tm
(i)Tj
/F7 1 Tf
6.9738 0 0 6.9738 431.7164 244.0629 Tm
(j)Tj
9.9626 0 0 9.9626 434.0975 245.8771 Tm
(g)Tj
/F1 1 Tf
.7113 0 TD
-.0192 Tc
[(denote)-215.2(an)-213.4(index)-213.4(s)1.6(et)-216.2(of)-215.4(the)]TJ
-33.4832 -1.2974 TD
-.019 Tc
[(SNV)-211.5(p)3(ositions)-214.4(covered)-213.2(b)3(y)]TJ
/F5 1 Tf
10.2259 0 TD
-.0208 Tc
(sr)Tj
6.9738 0 0 6.9738 216.9637 231.4771 Tm
0 Tc
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 219.4582 232.9511 Tm
.1882 Tc
[(,l)207.4(e)202.7(t)]TJ
/F5 1 Tf
1.6047 0 TD
0 Tc
(L)Tj
6.9738 0 0 6.9738 240.9448 231.4771 Tm
(i)Tj
/F7 1 Tf
.2845 0 TD
(\\)Tj
/F5 1 Tf
.6504 0 TD
(j)Tj
/F6 1 Tf
9.9626 0 0 9.9626 251.6031 232.9511 Tm
(=)Tj
/F7 1 Tf
.7227 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(l)Tj
/F1 1 Tf
6.9738 0 0 6.9738 266.57 231.4771 Tm
(1)Tj
9.9626 0 0 9.9626 270.5952 232.9511 Tm
()Tj
/F7 1 Tf
.6658 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(l)Tj
/F7 1 Tf
6.9738 0 0 6.9738 298.0912 231.1369 Tm
(j)Tj
/F5 1 Tf
.2764 0 TD
(L)Tj
4.9813 0 0 4.9813 303.8739 230.1165 Tm
(i)Tj
/F7 1 Tf
.2845 0 TD
(\\)Tj
/F5 1 Tf
.6487 0 TD
(j)Tj
/F7 1 Tf
6.9738 0 0 6.9738 310.4503 231.1369 Tm
(j)Tj
9.9626 0 0 9.9626 312.8314 232.9511 Tm
(g)Tj
/F1 1 Tf
.7113 0 TD
-.0186 Tc
[(be)-208.9(the)-208.9(i).6(ndex)-207.2(set)-209.9(o)-2.3(f)-209.1(S)-1.5(NV)-211.1(positions)-214(covered)-212.9(b)3.4(y)-212.8(b)-2.3(oth)]TJ
/F5 1 Tf
19.2682 0 TD
-.0208 Tc
(sr)Tj
6.9738 0 0 6.9738 519.3636 231.4771 Tm
0 Tc
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 523.9557 232.9511 Tm
-.0211 Tc
(and)Tj
/F5 1 Tf
-41.7914 -1.3316 TD
-.0208 Tc
(sr)Tj
6.9738 0 0 6.9738 115.0866 218.1543 Tm
0 Tc
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 219.685 Tm
.2109 Tc
[(,a)225.4(n)232.9(d)-6.1(l)230.1(e)231.1(t)]TJ
/F5 1 Tf
3.2778 0 TD
0 Tc
(L)Tj
6.9738 0 0 6.9738 155.7354 218.1543 Tm
(i)Tj
/F7 1 Tf
.2764 0 TD
([)Tj
/F5 1 Tf
.6585 0 TD
(j)Tj
/F6 1 Tf
9.9626 0 0 9.9626 166.3936 219.685 Tm
(=)Tj
/F7 1 Tf
.7227 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(l)Tj
/F1 1 Tf
6.9738 0 0 6.9738 181.3606 218.1543 Tm
(1)Tj
9.9626 0 0 9.9626 185.3291 219.685 Tm
()Tj
/F8 1 Tf
.6715 0 TD
.1454 Tc
[(..)-5.7(.)]TJ
/F1 1 Tf
1.2747 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(l)Tj
/F7 1 Tf
6.9738 0 0 6.9738 212.485 217.8708 Tm
(j)Tj
/F5 1 Tf
.2683 0 TD
(L)Tj
4.9813 0 0 4.9813 218.2676 216.8503 Tm
(i)Tj
/F7 1 Tf
.2732 0 TD
([)Tj
/F5 1 Tf
.6601 0 TD
(j)Tj
/F7 1 Tf
6.9738 0 0 6.9738 224.844 217.8708 Tm
(j)Tj
9.9626 0 0 9.9626 227.2251 219.685 Tm
(g)Tj
/F1 1 Tf
.7341 0 TD
-.0171 Tc
[(be)-230.2(the)-230.2(i)2.1(ndex)-228.4(set)-231.2(o)-.8(f)-230.4(S)0(NV)-232.4(po)]TJ
10.3682 0 TD
-.0183 Tc
[(sitions)-230.8(covered)-229.6(b)-2(y)-235.3(e)1.9(ither)]TJ
/F5 1 Tf
9.6 0 TD
-.0151 Tc
(sr)Tj
6.9738 0 0 6.9738 441.014 218.1543 Tm
0 Tc
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 445.7762 219.685 Tm
-.0163 Tc
(or)Tj
/F5 1 Tf
1.03 0 TD
-.0151 Tc
(sr)Tj
6.9738 0 0 6.9738 463.5211 218.1543 Tm
0 Tc
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 466.0156 219.685 Tm
-.0169 Tc
[(.)-233.5(T)5.3(hen,)-227.8(th)5.1(e)-235.7(p)5.1(airs)-229.4(of)]TJ
-35.9757 -1.3373 TD
-.018 Tc
[(vertices)-259(\()]TJ
/F5 1 Tf
3.5623 0 TD
0 Tc
(i)Tj
/F1 1 Tf
.2845 0 TD
()Tj
/F5 1 Tf
.5008 0 TD
(j)Tj
/F1 1 Tf
.2788 0 TD
-.0204 Tc
[(\))-284.9(t)-1.2(ha)-5.9(t)-257.2(w)-2.3(e)-262(c)-5.9(on)-4.1(sid)-4.1(e)-.2(r)-262.1(a)-.2(s)-261.4(c)-5.9(an)-4.1(did)-4.1(a)-.2(tes)-261.4(f)-6.1(or)-262.1(mer)-6.1(g)1.6(in)-4.1(g)-260.2(a)-.2(n)-4.1(d)-260.2(th)]TJ
19.7747 0 TD
-.0184 Tc
[(us)-259.4(connect)-255.2(b)-2.1(y)-258.2(a)1.8(n)-263.9(e)1.8(dge)-260(a)1.8(re)-260(those)-260(s)2.4(atisfying)-263.9(e)1.8(ither)]TJ
/F7 1 Tf
-12.064 -1.9177 TD
0 Tc
(j)Tj
/F5 1 Tf
.2731 0 TD
(L)Tj
6.9738 0 0 6.9738 238.7338 185.7259 Tm
(i)Tj
/F7 1 Tf
.2845 0 TD
(\\)Tj
/F5 1 Tf
.6585 0 TD
(j)Tj
/F7 1 Tf
9.9626 0 0 9.9626 247.748 187.2567 Tm
.282 Tc
(j)Tj
/F10 1 Tf
1.599 0 TD
0 Tc
(h)Tj
/F7 1 Tf
.7227 0 TD
.2251 Tc
(j)Tj
/F5 1 Tf
.7682 0 TD
0 Tc
(L)Tj
6.9738 0 0 6.9738 284.0314 185.7259 Tm
(i)Tj
/F7 1 Tf
.2764 0 TD
([)Tj
/F5 1 Tf
.6585 0 TD
(j)Tj
/F7 1 Tf
9.9626 0 0 9.9626 293.0456 187.2567 Tm
(j)Tj
/F1 1 Tf
1.269 0 TD
(or)Tj
/F7 1 Tf
1.838 0 TD
(j)Tj
/F5 1 Tf
.2675 0 TD
(L)Tj
6.9738 0 0 6.9738 332.2204 185.7259 Tm
(i)Tj
/F7 1 Tf
.2764 0 TD
(\\)Tj
/F5 1 Tf
.6585 0 TD
(j)Tj
/F7 1 Tf
9.9626 0 0 9.9626 341.2346 187.2567 Tm
(j)Tj
/F6 1 Tf
.4382 0 TD
(=)Tj
/F1 1 Tf
.882 0 TD
[(min)-173.6(\()]TJ
/F7 1 Tf
2.0657 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(L)Tj
6.9738 0 0 6.9738 383.1873 185.7259 Tm
(i)Tj
/F7 1 Tf
9.9626 0 0 9.9626 385.6818 187.2567 Tm
(j)Tj
/F1 1 Tf
.2675 0 TD
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(L)Tj
6.9738 0 0 6.9738 401.5558 185.7259 Tm
(j)Tj
/F7 1 Tf
9.9626 0 0 9.9626 404.0503 187.2567 Tm
(j)Tj
/F1 1 Tf
.2675 0 TD
(\))Tj
-30.0233 -1.9405 TD
[(where)-303.5(the)-302.7(secon)-8.6(d)-296.7(condi)-8.4(tion)-298.8(prom)-8.6(otes)-299(merger)-305.8(of)-299.4(short)-305.7(super)-8.8(-reads,)-303.9(and)-300(the)-302.8(choi)-7.6(ce)-301(of)]TJ
/F10 1 Tf
34.5928 0 TD
(h)Tj
/F1 1 Tf
.7967 0 TD
[(is)-301.4(discusse)-10.3(d)-296.7(belo)-7.6(w.)]TJ
-35.3895 -1.2007 TD
[(To)-445.2(quantify)-447.9(uncerta)-9.7(inty)-441.1(inhe)-7.6(rent)-442.1(to)-442.5(a)-446.4(clusteri)-9.7(ng)-439.7(solu)-7(tion)-441.1(due)-447.9(to)-442.5(existence)-447.5(o)-6.5(f)-440.9(nonoverla)-9.5(pping)-444.8(positions)]TJ
T*
[(among)-339.2(the)-336.9(reads)-340.6(in)-334.3(each)-338.5(cluste)-9.2(r,)-333.2(we)-337.3(dene)-336.7(a)-338.3(position-s)-8.9(pecic)-342(conden)-8.1(ce)-335.2(score)-340.6(as)-334.6(follows:)]TJ
/F5 1 Tf
17.0204 -2.5266 TD
(score)Tj
6.9738 0 0 6.9738 298.8283 117.3543 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 301.2661 118.8283 Tm
([)Tj
/F5 1 Tf
.3357 0 TD
(l)Tj
/F1 1 Tf
.2788 0 TD
(])Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
ET
321.222 121.153 47.168 .39685 re
f
BT
/F5 1 Tf
9.9626 0 0 9.9626 321.222 125.6314 Tm
(cr)Tj
6.9738 0 0 6.9738 329.5558 124.1575 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 331.9936 125.6314 Tm
([)Tj
/F5 1 Tf
.3357 0 TD
(l)Tj
/F1 1 Tf
.2845 0 TD
(])Tj
/F6 1 Tf
.5008 0 TD
(-)Tj
/F5 1 Tf
.717 0 TD
(cr)Tj
/F1 1 Tf
.865 0 TD
([)Tj
/F5 1 Tf
.3357 0 TD
(l)Tj
/F1 1 Tf
.2788 0 TD
(])Tj
-3.6306 -1.3657 TD
(1)Tj
/F6 1 Tf
.6658 0 TD
(-)Tj
/F5 1 Tf
.7227 0 TD
(cr)Tj
/F1 1 Tf
.865 0 TD
([)Tj
/F5 1 Tf
.3301 0 TD
(l)Tj
/F1 1 Tf
.2845 0 TD
(])Tj
-25.0783 -1.7982 TD
(where)Tj
/F5 1 Tf
2.6916 0 TD
(l)Tj
/F1 1 Tf
.5292 0 TD
[(denotes)-246.2(the)-245.8(p)-6.5(osition,)]TJ
/F5 1 Tf
8.5131 0 TD
(cr)Tj
/F1 1 Tf
.865 0 TD
([)Tj
/F7 1 Tf
.552 0 TD
()Tj
/F1 1 Tf
.4951 0 TD
[(])-241.7(i)0(s)-244.5(the)-245.8(o)-6.5(verall)-249(coverage)-248.5(rat)-8.8(e,)-241.9(and)]TJ
/F5 1 Tf
13.5776 0 TD
(cr)Tj
6.9738 0 0 6.9738 387.0991 92.6362 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 389.5936 94.1102 Tm
([)Tj
/F7 1 Tf
.5577 0 TD
()Tj
/F1 1 Tf
.4894 0 TD
[(])-247.4(denotes)-246.2(clus)-8.8(ter-speci)-11.5(c)-241.5(cover)-9.4(age)]TJ
-29.3519 -1.2007 TD
[(rate)-358.5(for)]TJ
/F5 1 Tf
3.3916 0 TD
(V)Tj
7.4718 0 0 6.641 147.5716 80.5039 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 153.1842 82.148 Tm
(\(i.e.,)Tj
/F5 1 Tf
2.1738 0 TD
(cr)Tj
6.9738 0 0 6.9738 183.1747 80.674 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 185.6125 82.148 Tm
([)Tj
/F5 1 Tf
.3357 0 TD
(l)Tj
/F1 1 Tf
.2788 0 TD
[(])-355.6(i)0(s)-358.3(the)-359.7(fraction)-366.3(of)-356.3(read)-8.6(s)-354.8(i)0(n)]TJ
/F5 1 Tf
11.5916 0 TD
(V)Tj
6.9738 0 0 6.9738 313.3416 80.674 Tm
(i)Tj
/F6 1 Tf
9.9626 0 0 9.9626 317.4802 82.148 Tm
(=)Tj
/F7 1 Tf
.7227 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(v)Tj
6.9738 0 0 6.9738 334.0912 86.9669 Tm
(j)Tj
0 -1.0731 TD
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 336.5857 82.148 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(j)Tj
/F6 1 Tf
.4496 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
/F7 1 Tf
1.1666 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(V)Tj
6.9738 0 0 6.9738 391.7479 80.674 Tm
(i)Tj
/F7 1 Tf
9.9626 0 0 9.9626 394.2424 82.148 Tm
(jg)Tj
/F1 1 Tf
1.1267 0 TD
[(covering)-367.2(position)]TJ
/F5 1 Tf
7.466 0 TD
(l)Tj
/F1 1 Tf
.2788 0 TD
[(\).)-355.9(On)-364(the)-354(on)-7.2(e)]TJ
-37.643 -1.2007 TD
[(hand,)-249.9(this)-254.5(score)-255.2(is)-244.5(penal)-10.1(ized)-248.4(at)-250.8(a)-252.9(site)-250.6(where)-252.3(the)-251.5(fraction)-258.2(of)-248.2(cluste)-9.2(r)-247.4(membe)-8.7(rs)-249.4(\(short)-251.5(reads\))-252.3(cover)-9.4(ing)-249.7(the)-251.5(site)-250.6(is)]TJ
/F2 1 Tf
0 66.9721 TD
[(A)-334.8(BAYE)-9(SIAN)-341.4(METHOD)-340.5(FOR)-339.6(QUA)-8(SISP)-8.2(ECIES)-336.3(REC)-9.2(ONST)-8.7(RUCTI)-10.1(ON)-10587.7(639)]TJ
ET
endstream
endobj
59 0 obj
<>stream
0 0 0 rg
/GS1 gs
74.098 435.515 430.413 .51022 re
f
74.098 300.075 430.413 .45358 re
f
74.098 417.09 430.413 .45355 re
f
BT
/F1 1 Tf
9.9626 0 0 9.9626 74.0976 715.4644 Tm
0 Tc
0 Tw
[(low)-9(;)-384.8(the)-388.1(scor)-8(e)-389.5(i)0(s)-386.7(negativ)-8.7(e)-389.5(i)0(f)-387.5(the)-393.8(cluster-speci)-14.6(c)-389.5(coverage)-396.5(rate)-392.6(is)-386.7(belo)-7.6(w)-386(the)-393.8(global)-393.2(coverage)-396.5(rate,)-393(which)]TJ
0 -1.195 TD
[(im)-7.8(plies)-239.9(uncerta)-9.7(inty)-236.2(o)-6.5(f)-236.1(the)-240.2(clusteri)-9.7(ng)-234.8(deci)-9.4(sion.)-240.7(On)-238.8(the)-240.2(other)-243.7(hand,)-238.5(posi)-7(tive)-238(scor)-8(es)-237.8(indicate)-247.4(high)-239.1(conden)-8.1(ce)-238.4(in)]TJ
0 -1.2007 TD
[(the)-245.8(d)-6.5(ecision)-248.9(to)-243.3(group)-250.5(the)-245.8(reads)-249.6(into)-241.9(the)-245.8(sam)-8.8(e)-241.6(cluste)-9.2(r.)-242.1(Note)-250.5(that)-243.7(the)-245.8(highe)-8.4(st)-244.5(possibl)-7.6(e)-241.6(scor)-8(e)-241.6(o)0(f)-248.2(1)-239.8(at)-245.1(posi)-7(tion)]TJ
/F5 1 Tf
42.0133 0 TD
(l)Tj
/F1 1 Tf
.5235 0 TD
(is)Tj
-42.5369 -1.2007 TD
[(achi)-9.4(eved)-325.3(when)-321.7(all)-328.3(the)-319.8(read)-8.6(s)-320.6(i)0(n)-323(a)-321.2(cluster)-324.9(cover)-328(the)]TJ
/F5 1 Tf
20.6965 0 TD
(l)Tj
6.9738 0 0 6.9738 283.0676 683.2628 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 292.1952 679.6345 Tm
[(p)-6.5(osition.)-322.5(Using)-330.4(the)-319.8(conden)-8.1(ce)-323.8(scor)-8(es,)-323.6(we)-320.2(dene)-331(the)]TJ
-21.8915 -1.2007 TD
(weight)Tj
/F5 1 Tf
3.0672 0 TD
(w)Tj
6.9738 0 0 6.9738 111.3448 666.1982 Tm
(ij)Tj
/F1 1 Tf
9.9626 0 0 9.9626 119.0551 667.6722 Tm
[(assi)-10(gned)-334.9(to)-334.3(an)-339.1(edge)]TJ
/F5 1 Tf
8.422 0 TD
(e)Tj
6.9738 0 0 6.9738 207.4393 666.1982 Tm
(ij)Tj
/F1 1 Tf
9.9626 0 0 9.9626 215.1495 667.6722 Tm
[(to)-334.3(quant)-8.4(ify)-337.1(similarity)-342.9(between)]TJ
/F5 1 Tf
12.6785 0 TD
(V)Tj
7.4718 0 0 6.641 347.5842 666.0282 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 353.0267 667.6722 Tm
(and)Tj
/F5 1 Tf
1.7811 0 TD
(V)Tj
7.4718 0 0 6.641 376.9511 666.0282 Tm
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 382.3369 667.6722 Tm
(as)Tj
/F5 1 Tf
-14.5849 -2.5152 TD
(w)Tj
6.9738 0 0 6.9738 243.6661 641.0833 Tm
(ij)Tj
/F6 1 Tf
9.9626 0 0 9.9626 249.7322 642.614 Tm
(=)Tj
ET
258.576 644.882 19.956 .39685 re
f
BT
/F1 1 Tf
9.9626 0 0 9.9626 266.0598 649.3605 Tm
(1)Tj
/F7 1 Tf
-.7512 -1.3657 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(L)Tj
6.9738 0 0 6.9738 266.7968 634.2802 Tm
(i)Tj
/F7 1 Tf
.2845 0 TD
([)Tj
/F5 1 Tf
.6504 0 TD
(j)Tj
/F7 1 Tf
9.9626 0 0 9.9626 275.8109 635.7542 Tm
(j)Tj
/F9 1 Tf
.5691 1.6332 TD
(X)Tj
/F5 1 Tf
6.9738 0 0 6.9738 280.1763 631.7289 Tm
(l)Tj
/F7 1 Tf
.2845 0 TD
(2)Tj
/F5 1 Tf
.6503 0 TD
(L)Tj
4.9813 0 0 4.9813 290.5511 630.7085 Tm
(i)Tj
/F7 1 Tf
.2845 0 TD
([)Tj
/F5 1 Tf
.6601 0 TD
(j)Tj
9.9626 0 0 9.9626 298.8283 642.614 Tm
(score)Tj
6.9738 0 0 6.9738 320.4283 641.0833 Tm
(i)Tj
/F7 1 Tf
.2845 0 TD
([)Tj
/F5 1 Tf
.6585 0 TD
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 329.4424 642.614 Tm
([)Tj
/F5 1 Tf
.3357 0 TD
(l)Tj
/F1 1 Tf
.2845 0 TD
(])Tj
/F11 1 Tf
.3301 0 TD
(:)Tj
/F1 1 Tf
-25.579 -3.0444 TD
[(Given)-365.1(the)-359.7(weights)]TJ
/F5 1 Tf
7.8757 0 TD
(w)Tj
6.9738 0 0 6.9738 169.1716 610.8093 Tm
(ij)Tj
/F1 1 Tf
9.9626 0 0 9.9626 173.5936 612.2833 Tm
[(,)-358.9(w)0(e)-360.1(can)-364.4(now)-359(specify)-362(the)-359.7(clus)-8.8(tering)-361(proce)-9.4(dure.)-360(In)-356.3(each)-366.9(step,)-356.3(the)-365.3(pair)-356.7(of)-362(vertices)]TJ
-9.9869 -1.2007 TD
[(connec)-9.9(ted)-291.4(by)-291.7(the)-291.4(edge)-296.8(with)-291.3(max)-7.6(imum)-291.7(weight)-294.6(is)-295.7(merged;)-296(the)-291.4(new)-8(ly)-288.8(construc)-9.9(ted)-291.4(vertex)-297.4(inherits)-298.2(edges)-293.1(from)]TJ
T*
[(the)-262.9(merged)-264(vertic)-10(es)-260.6(and)-260.2(the)-257.2(weight)-10.1(s)-258(o)0(n)-257.6(thos)-7(e)-258.6(edges)-264.7(are)-258.2(re-eval)-11.7(uated.)-260.9(A)-260.8(new)-264.1(\(longer\))-261.3(conse)-8.6(nsus)-261.5(seque)-8.6(nce)-261.9(is)]TJ
T*
[(const)-9.6(ructed)-291.7(by)-291.7(com)-7.6(bining)-288.9(the)-291.4(tw)-8.2(o)-285.3(super)-8.8(-reads)-292.1(assoc)-9.8(iated)-291.7(with)-297(the)-291.4(merged)-292.5(vertic)-10(es;)-292.6(recall)-296.3(that)-289.2(there)-296.7(are)-292.4(no)]TJ
0 -1.195 TD
[(con)-9.7(icts)-387.1(betwee)-10.9(n)-387.7(the)-388.1(super-r)-8.6(eads)-389.1(being)-389.6(merged.)-395.3(If)-386.7(after)-395.4(such)-387.3(an)-390.3(update)-392.2(step)-390.1(no)-388.5(edges)-389.8(connec)-9.9(t)-384.8(the)-388.1(n)-6.5(e)0(w)]TJ
0 -1.2007 TD
[(vert)-9.6(ex)-441.5(with)-450.7(the)-445(rest)-448.9(of)-447.4(the)-445(graph)-451.4(\(because)-454.6(no)-445.4(inhe)-7.6(rited)-445.6(edges)-452.4(satisfy)-449.5(the)-445(connec)-9.9(tivity)-448.1(condi)-8.4(tion\),)]TJ
/F10 1 Tf
41.5922 0 TD
(h)Tj
/F1 1 Tf
.9446 0 TD
(is)Tj
-42.5369 -1.2007 TD
[(decr)-8.6(eased)-260.7(and)-260.2(the)-257.2(above)-257.8(proce)-9.4(ss)-254.3(is)-255.9(repe)-8.6(ated.)-260.1(We)-256.2(initi)-9.2(ally)-255.1(set)]TJ
/F10 1 Tf
24.5889 0 TD
(h)Tj
/F1 1 Tf
.7568 0 TD
[(to)-254.7(0.9)-258(and)-260.2(gradually)-262.6(decrease)-268.6(it)-251.7(by)-257.6(0)]TJ
/F11 1 Tf
14.5963 0 TD
(:)Tj
/F1 1 Tf
.2731 0 TD
[(1)-256.8(while)]TJ
/F10 1 Tf
-40.2151 -1.2007 TD
(h)Tj
/F6 1 Tf
.7796 0 TD
(>)Tj
/F1 1 Tf
.8308 0 TD
[(0.)-280(The)-282.7(above)-286.2(procedure)-289.3(is)-278.6(repeate)-11.5(d)-279.6(until)-279.6(no)-280.4(pairs)-284.7(of)-276.7(vertic)-10(es)-277.7(satisf)-10.5(y)-273.9(the)-285.7(connectivi)-9.9(ty)-277.4(condi)-8.4(tion.)-282.1(By)-279.4(that)]TJ
-1.6104 -1.2007 TD
[(po)-7.2(int,)-287(a)-292.8(set)-292.6(of)-293.7(long)-290.3(conse)-8.6(nsus)-295.7(sequences)-300.9(\(the)-294.1(nal)-291.3(super)-8.8(-reads\))-294.9(has)-295.5(been)-291.2(formed)-298.4(from)-295.1(the)-291.4(cluste)-9.2(rs)-289.2(of)-293.7(reads)]TJ
T*
[(assoc)-9.8(iated)-462.5(with)-462.1(the)-456.4(nodes)-462(of)-458.7(the)-456.4(n)-6.4(al)-455.6(graph)-7.6(.)-455.6(While)-463.2(the)-456.4(com)-7.6(plexity)-459.3(of)-458.7(aggl)-7.6(omerativ)-9.3(e)-457.8(clusteri)-9.7(ng)-456.8(is,)-455.4(in)]TJ
T*
[(gener)-9.4(al,)]TJ
/F5 1 Tf
3.5054 0 TD
(O)Tj
/F1 1 Tf
.7227 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(N)Tj
/F1 1 Tf
6.9738 0 0 6.9738 126.822 496.3463 Tm
(3)Tj
9.9626 0 0 9.9626 130.7905 492.718 Tm
[(\))-293(where)]TJ
/F5 1 Tf
3.3688 0 TD
(N)Tj
/F1 1 Tf
.956 0 TD
[(denotes)-297.4(the)-291.4(input)-299.6(data)-293.9(size)-295.1(\(Sasire)-10.3(kha)-288.6(and)-294.3(Ba)-8(by,)-292.1(2013\),)-290.7(it)-291.6(has)-295.5(been)-296.8(shown)-293.5(that)-294.9(its)]TJ
-10.0154 -1.2007 TD
[(time)-241.5(com)-7.6(plexity)-243(can)-239.2(be)-236.6(reduc)-9.4(ed)-236.6(to)]TJ
/F5 1 Tf
14.0557 0 TD
(O)Tj
/F1 1 Tf
.7227 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(N)Tj
/F1 1 Tf
6.9738 0 0 6.9738 231.9306 484.3841 Tm
(2)Tj
9.9626 0 0 9.9626 235.8991 480.7558 Tm
[(\))-236.1(with)-240.1(accur)-11.1(acy)-239.2(equal)-243.5(to)-237.6(that)-238(of)-236.8(the)-240.2(brute-f)-10.1(orce)-241.9(method)-240.3(by)-240.5(using)-241.1(the)]TJ
-16.2408 -1.195 TD
[(part)-9.6(ial)-390.9(maximum)-396(array)-398.3(technique)-399(\()-122.2(Jung)-396.9(and)-391(Kim,)-394.2(2001\).)-393.1(We)-392.8(exploit)-396.7(this)-391(to)-391.3(efcientl)-10.3(y)-387.7(construc)-9.9(t)-390.5(super-)]TJ
0 -1.2007 TD
[(read)-8.6(s.)-332.4(Th)-7(e)-332.6(algori)-8.2(thm)-332.9(for)-336.3(super)-8.8(-read)-335.7(const)-9.6(ruction)-339(is)-335.5(formali)-8.7(zed)-335.9(as)-334.6(Algorit)-8.1(hm)-335.1(1.)]TJ
/F2 1 Tf
8.9663 0 0 8.9663 74.0976 423.5526 Tm
[(Algorithm)-335.1(1:)]TJ
/F1 1 Tf
5.9499 0 TD
[(Agglomerative)-338.6(clustering)-332(for)-338.9(super-read)-333.8(construction)]TJ
/F2 1 Tf
-5.9499 -2.0802 TD
(Input:)Tj
/F1 1 Tf
3.0413 0 TD
[(Set)-338.7(of)-330.4(reads)-335(aligned)-338.2(to)-331.8(the)-333.8(reference)-338(genome)]TJ
/F2 1 Tf
-3.0413 -1.2203 TD
(Output:)Tj
/F1 1 Tf
3.7748 0 TD
[(Set)-332.3(of)-336.7(super-reads)-334.5(and)-336.1(the)-333.8(corresponding)-331.4(condence)-339(scores)]TJ
/F2 1 Tf
-3.7748 -1.2203 TD
(for)Tj
/F10 1 Tf
1.6187 0 TD
(h)Tj
/F11 1 Tf
.7777 0 TD
(>)Tj
/F1 1 Tf
1.0496 0 TD
(0)Tj
/F2 1 Tf
.8283 0 TD
(do)Tj
/F1 1 Tf
-2.2699 -1.2266 TD
[(Build)-332.8(a)-330.7(weighted)-341.1(graph)]TJ
/F5 1 Tf
9.9649 0 TD
(G)Tj
/F6 1 Tf
.8852 0 TD
(=)Tj
/F1 1 Tf
.7208 0 TD
(\()Tj
/F7 1 Tf
.3288 0 TD
(V)Tj
/F1 1 Tf
.6702 0 TD
()Tj
/F7 1 Tf
.4995 0 TD
(E)Tj
/F1 1 Tf
.5691 0 TD
(\))Tj
/F2 1 Tf
-13.6385 -1.2203 TD
(while)Tj
/F1 1 Tf
2.6114 0 TD
(E)Tj
/F7 1 Tf
.9484 0 TD
(6)Tj
T*
.3365 Tc
(;)Tj
/F2 1 Tf
1.9348 0 TD
0 Tc
(do)Tj
/F1 1 Tf
-3.4966 -1.2203 TD
[(Merge)-334.5(two)-334.6(clusters)-336.4(connected)-338.1(with)-331.9(the)-333.8(largest)-335.7(weight)]TJ
0 -1.2266 TD
(Update)Tj
/F5 1 Tf
3.231 0 TD
(G)Tj
/F6 1 Tf
.8852 0 TD
(=)Tj
/F1 1 Tf
.7145 0 TD
(\()Tj
/F7 1 Tf
.3351 0 TD
(V)Tj
/F1 1 Tf
.6639 0 TD
()Tj
/F7 1 Tf
.4995 0 TD
(E)Tj
/F1 1 Tf
.5754 0 TD
[(\))-330.9(and)-336.1(weights)-334(using)-331.6(partial)-338.6(maximum)-336.1(array)]TJ
/F2 1 Tf
-8.9027 -1.2203 TD
[(end)-333.2(while)]TJ
/F10 1 Tf
T*
(h)Tj
/F6 1 Tf
.6639 0 TD
(=)Tj
/F10 1 Tf
.7208 0 TD
(h)Tj
/F6 1 Tf
.6639 0 TD
(-)Tj
/F1 1 Tf
.7208 0 TD
(0)Tj
/F11 1 Tf
.4995 0 TD
(:)Tj
/F1 1 Tf
.2719 0 TD
(1)Tj
/F2 1 Tf
-5.5452 -1.2267 TD
[(end)-339.6(for)]TJ
/F5 1 Tf
10.959 0 0 10.959 74.0976 267.1936 Tm
[(2.2.)-502(Maximum)-327.8(likely)-335.4(\(MA\))-333.9(reconstruction)-327.5(of)-331.2(quasispecies)-332.5(from)-330.1(super-reads)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 84.0755 249.222 Tm
[(Here)-354(we)-354.4(describ)-9.1(e)-349.7(how)-353.3(to)-351.4(recon)-9.4(struct)-350.8(the)-354(mos)-7(t)-345(likel)-8.2(y)-347.9(set)-355.1(of)-350.6(strains)-352.7(in)-351.4(a)-349.7(v)-6.5(iral)-348.1(quasi)-9.6(species)-357.3(using)-354.9(super-)]TJ
-1.0015 -1.195 TD
[(read)-8.6(s)-314.9(from)-317.8(Section)-320.9(2.1)-314.9(and)-311.4(their)-320.4(conden)-8.1(ce)-318.1(scores.)-320.2(While)-321(in)-311.6(princi)-8.2(ple)-314.1(the)-314.1(method)-319.9(ou)-7.2(tlined)-316.2(in)-311.6(thi)-7.8(s)-309.2(sectio)-9.2(n)]TJ
0 -1.2007 TD
[(coul)-7.6(d)-285.3(b)0(e)-287.8(applied)-287.6(dir)-7(ectly)-286.1(to)-288.8(the)-285.7(short)-288.6(reads)-289.4(provided)-291.5(by)-286.1(a)-287.1(seque)-8.6(ncing)-287.2(platfo)-8.2(rm,)-286.2(such)-284.9(an)-287.8(appro)-7.6(ach)-284.7(woul)-9.7(d)-279.6(i)0(n)]TJ
T*
[(gener)-9.4(al)-262.1(not)-266.8(only)-261.9(be)-265.1(com)-7.6(putational)-10.9(ly)-260.4(prohi)-8.6(bitive)-265(due)-265.8(to)-260.4(a)-264.3(very)-268.6(large)-268.2(numb)-6.6(er)-261.4(of)-265.3(short)-265.8(reads)-266.6(but)-266.8(also)-264.9(limit)-268.8(the)]TJ
T*
[(abili)-8.2(ty)-448.2(of)-453.1(the)-450.7(algori)-8.2(thm)-446.8(to)-453.8(distingui)-7.7(sh)-446.6(str)-8.2(ains)-452.7(with)-450.7(small)-454(mutual)-453.6(genet)-10.1(ic)-449.9(distances)-458.3(due)-453.6(to)-448.2(having)-453(long)]TJ
T*
[(conse)-8.6(rved)-308.4(regi)-9.6(ons.)-305.5(Re)-8(lying)-305.3(on)-308.8(a)-309.8(relative)-10.3(ly)-305.9(small)-311.7(numb)-6.6(er)-306.9(of)-305.1(long)-313.1(super-r)-8.6(eads)-309.4(construc)-9.9(ted)-308.4(from)-312.1(short)-311.3(reads)]TJ
T*
[(cir)-8.8(cumvents)-341.5(both)-335.9(of)-339.2(these)-341.4(problems)-341.7(and)-339.8(makes)-336.5(the)-342.6(reconstruct)-13(ion)-335.1(more)-340.4(accurate)-344.1(and)-339.8(practicall)-10.7(y)-336.5(feasible.)]TJ
T*
[(Not)-9(e)-452.1(that)-459.9(seque)-8.6(ncing)-457.9(err)-8(ors)-455(may)-457.2(un)-7.2(desirably)-463(prevent)-463.2(cluste)-9.2(rs)-454.3(of)-458.7(reads)-460.1(from)-460.1(being)-457.9(merged)-463.2(with)-462.1(other)]TJ
T*
[(clus)-8.8(ters)-283.9(due)-288.6(to)-283.1(a)-287.1(violation)-287.2(of)-288(conict-fr)-10.5(ee)-283.9(require)-9.9(ment;)-287.8(conse)-8.6(quently,)-286.2(a)-287.1(set)-286.9(of)-282.3(short)-288.6(reads)-289.4(in)-283.1(a)-287.1(small)-289(cluster)]TJ
0 -1.195 TD
[(is)-335.5(likely)-333.3(to)-328.7(have)-336.7(a)-332.6(disproportio)-11.2(nate)-333.7(amount)-331.3(of)-333.6(seque)-8.6(ncing)-332.7(errors.)-338.2(For)-327.8(this)-334.1(reason,)-336.1(we)-331.6(ignor)-8.6(e)-326.9(clus)-8.8(ters)-329.4(with)]TJ
0 -1.2007 TD
[(very)-427.9(small)-419.9(membe)-8.7(rships)-427.1(\(in)-416.8(partic)-10(ular,)-419.7(thos)-7(e)-418(cont)-7.6(aining)-421.6(fewer)-425(than)-423(0)]TJ
/F11 1 Tf
29.1982 0 TD
(:)Tj
/F1 1 Tf
.2731 0 TD
(001)Tj
/F7 1 Tf
1.7242 0 TD
.2251 Tc
(j)Tj
/F5 1 Tf
.7625 0 TD
0 Tc
(R)Tj
/F7 1 Tf
.6203 0 TD
(j)Tj
/F1 1 Tf
.6886 0 TD
[(reads\),)-423.4(which)-427.7(limits)-424.4(the)]TJ
-33.267 -1.2007 TD
[(dete)-9.4(ction)-335.5(of)-333.6(str)-8.2(ains)-333.2(to)-334.3(thos)-7(e)-332.6(const)-9.6(ituting)-335.1(mor)-7.8(e)-332.6(than)-337.7(0)]TJ
/F11 1 Tf
21.7663 0 TD
(:)Tj
/F1 1 Tf
.2731 0 TD
(1)Tj
/F5 1 Tf
.5008 0 TD
(%)Tj
/F1 1 Tf
1.1666 0 TD
[(of)-333.6(the)-336.9(quasispe)-9.1(cies.)]TJ
-22.7053 -1.2007 TD
-.0108 Tc
[(Le)-10.8(t)]TJ
/F7 1 Tf
1.5706 0 TD
0 Tc
(C)Tj
/F6 1 Tf
.7056 0 TD
(=)Tj
/F7 1 Tf
.7227 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(C)Tj
6.9738 0 0 6.9738 125.5748 104.3149 Tm
(m)Tj
/F1 1 Tf
9.9626 0 0 9.9626 131.074 105.789 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(m)Tj
/F6 1 Tf
.8877 0 TD
(=)Tj
/F1 1 Tf
.7227 0 TD
(1)Tj
/F8 1 Tf
1.1666 0 TD
.1568 Tc
(...)Tj
/F1 1 Tf
1.2918 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(M)Tj
/F7 1 Tf
.8707 0 TD
(g)Tj
/F1 1 Tf
.7568 0 TD
[(de)19.4(no)21.2(t)13.5(e)-247.2(th)18.5(e)-247.2(c)14.5(ol)18.5(l)13.5(e)0(c)17.7(t)13.5(i)13.5(o)0(n)-234.8(o)0(f)-236.8(c)0(l)22.4(u)0(s)20(t)13.5(er)17.5(s)-246.7(t)13.5(ha)19.4(t)-242.5(r)0(e)17.5(m)12.8(ai)22.4(n)-245.5(a)0(f)17.5(t)13.5(er)-232.9(de)19.4(le)22.4(ti)21.4(ng)-234.8(cl)22.4(us)20(t)13.5(e)0(r)17.5(s)-246.7(ha)25.1(vi)18.5(ng)-234.8(on)21.2(l)13.5(y)]TJ
-12.4168 -1.2007 TD
[(fe)17.5(w)-289.2(r)14.3(ea)17.7(ds)25.7(;)-288.1(m)0(o)17.7(r)14.3(eo)19.4(ve)19.4(r)14.3(,)-290.6(f)14.3(o)0(r)-276.7(c)0(o)19.4(n)0(v)21.2(e)14.5(ni)18.5(en)19.4(c)14.5(e)-287.1(le)16.7(t)-288.1(u)16.3(s)-292.2(r)14.3(el)22.4(ab)19.4(el)-279.2(t)13.5(h)0(e)-276.5(r)0(e)17.5(a)14.5(ds)-281.6(i)13.5(n)]TJ
/F5 1 Tf
25.6189 0 TD
(C)Tj
7.4718 0 0 6.641 335.9054 92.1826 Tm
(m)Tj
/F1 1 Tf
9.9626 0 0 9.9626 344.1259 93.8268 Tm
(as)Tj
/F5 1 Tf
1.1097 0 TD
(c)Tj
6.9738 0 0 6.9738 359.6598 97.455 Tm
(j)Tj
0 -.9186 TD
(m)Tj
/F1 1 Tf
9.9626 0 0 9.9626 365.1589 93.8268 Tm
.2865 Tc
[(,t)286.5(h)305(a)301(ti)286.5(s)309.5(,)]TJ
/F5 1 Tf
3.4826 0 TD
0 Tc
(C)Tj
6.9738 0 0 6.9738 406.4881 92.3527 Tm
(m)Tj
/F6 1 Tf
9.9626 0 0 9.9626 413.6881 93.8268 Tm
(=)Tj
/F7 1 Tf
.717 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(c)Tj
6.9738 0 0 6.9738 430.2991 97.455 Tm
(j)Tj
0 -.9186 TD
(m)Tj
/F1 1 Tf
9.9626 0 0 9.9626 435.855 93.8268 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(j)Tj
/F6 1 Tf
.4439 0 TD
(=)Tj
/F1 1 Tf
.7227 0 TD
(1)Tj
/F8 1 Tf
1.1666 0 TD
.1568 Tc
(...)Tj
/F1 1 Tf
1.2918 0 TD
0 Tc
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2732 0 TD
(C)Tj
6.9738 0 0 6.9738 491.3007 92.3527 Tm
(m)Tj
/F7 1 Tf
9.9626 0 0 9.9626 496.7999 93.8268 Tm
(jg)Tj
/F1 1 Tf
-42.4287 -1.2007 TD
[(wh)17.3(er)23.2(e)]TJ
/F5 1 Tf
2.7372 0 TD
(c)Tj
6.9738 0 0 6.9738 105.8456 85.4929 Tm
(j)Tj
0 -.9186 TD
(m)Tj
/F7 1 Tf
9.9626 0 0 9.9626 114.1228 81.8646 Tm
(2)Tj
/F5 1 Tf
.9389 0 TD
(R)Tj
/F1 1 Tf
.6146 0 TD
[(.)-330.4(W)0(e)-324.5(o)0(r)19.3(g)0(a)19.4(n)16.3(iz)16.7(e)-332.6(t)13.5(he)-322(su)20(pe)19.4(r)14.3(-)0(r)23(e)0(a)17.7(d)0(s)-321.4(o)0(b)21.2(t)13.5(ai)16.7(n)16.3(e)0(d)-327.7(b)0(y)-320.2(A)12.4(lg)18.5(or)24.9(it)21.4(hm)-323.7(1)-330.8(i)0(n)-323(S)11.4(ec)17.7(t)13.5(i)13.5(o)0(n)-325.9(2)0(.)21.6(1)-330.8(i)13.5(n)0(t)18.5(o)-330.8(ro)19.3(w)12.4(s)-332(of)-322.2(an)]TJ
/F5 1 Tf
35.1391 0 TD
(M)Tj
/F6 1 Tf
1.0414 0 TD
()Tj
/F5 1 Tf
.7227 0 TD
(N)Tj
/F1 1 Tf
-42.4743 -1.2007 TD
[(matri)-10.9(x)]TJ
/F2 1 Tf
3.016 0 TD
(S)Tj
/F6 1 Tf
.717 0 TD
(=)Tj
/F7 1 Tf
.7227 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(s)Tj
6.9738 0 0 6.9738 127.3322 68.4283 Tm
(mn)Tj
/F1 1 Tf
9.9626 0 0 9.9626 136.2897 69.9023 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(m)Tj
/F6 1 Tf
.8877 0 TD
(=)Tj
/F1 1 Tf
.7227 0 TD
(1)Tj
/F8 1 Tf
1.1666 0 TD
.1682 Tc
(...)Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(M)Tj
/F1 1 Tf
.8763 0 TD
()Tj
/F5 1 Tf
.5008 0 TD
(n)Tj
/F6 1 Tf
.6658 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
.0065 Tc
(1)Tj
/F8 1 Tf
1.1723 0 TD
.1682 Tc
(...)Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(N)Tj
/F7 1 Tf
.7284 0 TD
(g)Tj
/F1 1 Tf
.882 0 TD
[(with)-382.4(entr)-9.6(ies)]TJ
/F5 1 Tf
5.2296 0 TD
(s)Tj
6.9738 0 0 6.9738 316.2897 68.4283 Tm
(mn)Tj
/F7 1 Tf
9.9626 0 0 9.9626 328.0251 69.9023 Tm
.2829 Tc
(2f)Tj
/F1 1 Tf
1.4397 0 TD
0 Tc
[(A)-166.8(C)-173.2(G)-166.8(T)]TJ
/F6 1 Tf
4.8939 0 TD
(-)Tj
/F7 1 Tf
.717 0 TD
(g)Tj
/F1 1 Tf
.882 0 TD
[(whe)-8(re)]TJ
/F6 1 Tf
3.0046 0 TD
(-)Tj
/F1 1 Tf
1.0983 0 TD
[(denot)-8.4(es)-380.1(a)-383.8(site)]TJ
/F2 1 Tf
-37.5235 67.0005 TD
[(64)-7.2(0)]TJ
34.0921 0 TD
[(AHN)-338(AND)-344.1(VIKALO)]TJ
ET
endstream
endobj
64 0 obj
<>stream
/GS1 gs
BT
/F1 1 Tf
9.9626 0 0 9.9626 107.6031 715.4644 Tm
0 0 0 rg
0 Tc
0 Tw
[(not)-318(covered)-320(by)-314.5(a)-315.5(super)-8.8(-read)-318.6(and)]TJ
/F5 1 Tf
13.4866 0 TD
(N)Tj
/F1 1 Tf
.9845 0 TD
[(denotes)-320.2(the)-319.8(total)-315.5(numb)-6.6(er)-318.3(of)-310.8(SNV)-322.3(sites)-320.8(in)-311.6(the)-319.8(strains)-318.6(of)-316.5(a)-315.5(quasi)-9.6(species.)]TJ
-14.4711 -1.195 TD
[(A)-289.2(nucleot)-8.7(ide)-285.7(in)-288.8(the)-291.4(\()]TJ
/F5 1 Tf
8.4106 0 TD
(m)Tj
/F1 1 Tf
.717 0 TD
()Tj
/F5 1 Tf
.5008 0 TD
(n)Tj
/F1 1 Tf
.5008 0 TD
[(\))-287.3(posi)-7(tion)-287.4(of)]TJ
/F2 1 Tf
5.2638 0 TD
(S)Tj
/F1 1 Tf
.8365 0 TD
[(is)-290(assigned)-293.7(con)-9.8(dence)]TJ
/F5 1 Tf
9.3382 0 TD
(score)Tj
6.9738 0 0 6.9738 383.9243 702.0281 Tm
(m)Tj
/F1 1 Tf
9.9626 0 0 9.9626 389.4235 703.5588 Tm
([)Tj
/F5 1 Tf
.3357 0 TD
(n)Tj
/F1 1 Tf
.5008 0 TD
[(])-287.3(dened)-291.9(in)-288.8(Sect)-8.6(ion)-289.6(2.1;)-290(the)-285.7(scor)-8(es)]TJ
-29.1242 -1.2007 TD
[(for)-262.3(the)-262.9(entire)-271.7(matrix)-267.8(are)-263.9(normaliz)-9.3(ed)-259.4(so)-264.5(that)-266.4(they)-263.7(fall)-262.7(b)-6.5(etween)-267(0)-262.5(and)-265.8(1)-256.8(t)0(o)-266.1(use)-261.3(them)-267.2(in)-260.4(our)-266(Bayesian)-270.5(appro)-7.6(ach)]TJ
T*
[(to)-283.1(assembl)-11.9(y.)-280(Let)]TJ
/F10 1 Tf
6.9595 0 TD
(e)Tj
/F5 1 Tf
6.9738 0 0 6.9738 180.7936 678.1038 Tm
(mn)Tj
/F1 1 Tf
9.9626 0 0 9.9626 192.6425 679.6345 Tm
[(be)-282.2(the)-285.7(probab)-8.3(ility)-282.3(that)]TJ
/F5 1 Tf
9.2358 0 TD
(s)Tj
6.9738 0 0 6.9738 288.4535 678.1038 Tm
(mn)Tj
/F1 1 Tf
9.9626 0 0 9.9626 300.3023 679.6345 Tm
[(was)-288(estimated)-292.7(erroneous)-9.9(ly)-283.1(due)-282.9(to)-283.1(either)-288.8(a)-287.1(sequen)-9.3(cing)-280.8(err)-8(or)]TJ
-19.3422 -1.2007 TD
[(in)-345.7(read)-8.6(s)-343.4(o)0(n)-348.7(the)]TJ
/F5 1 Tf
6.5157 0 TD
(n)Tj
6.9738 0 0 6.9738 177.5054 671.3007 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 186.9165 667.6722 Tm
[(SNV)-350.8(posi)-7(tion)-350(or)-344.9(the)-348.3(u)-6.5(ncertainty)-353.3(induc)-8.4(ed)-344.7(by)-348.7(read)-8.6(s)-343.4(not)-352.2(covering)-355.8(the)]TJ
/F5 1 Tf
27.969 0 TD
(n)Tj
6.9738 0 0 6.9738 470.5511 671.3007 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 479.9621 667.6722 Tm
[(SNV)-350.8(position.)]TJ
-37.3755 -1.2007 TD
[(Note)-279(that)-277.8(negat)-10.1(ive)-280(scores)-280(indicate)-287.2(low)-276.4(conden)-8.1(ce)-278.2(resu)-8(lting)-279.6(from)-278(insufci)-10.1(ent)-274.3(clus)-8.8(ter-speci)-11.5(c)-275.7(coverage)-282.7(rat)-8.8(e,)]TJ
T*
[(while)-259.8(posi)-7(tive)-255.1(scor)-8(es)-260.6(imply)-257.6(relat)-9.2(ively)-255.8(con)-9.7(dent)-258(informat)-9.5(ion.)-255.8(To)-257.4(map)]TJ
/F5 1 Tf
27.9634 0 TD
(score)Tj
6.9738 0 0 6.9738 407.792 642.2738 Tm
(m)Tj
/F1 1 Tf
9.9626 0 0 9.9626 413.2912 643.7479 Tm
([)Tj
/F5 1 Tf
.3357 0 TD
(n)Tj
/F1 1 Tf
.5008 0 TD
(])Tj
/F7 1 Tf
.6146 0 TD
(2)Tj
/F1 1 Tf
.9332 0 TD
(\()Tj
/F6 1 Tf
.5008 0 TD
(-)Tj
/F7 1 Tf
.7227 0 TD
(1)Tj
/F1 1 Tf
1.0015 0 TD
[()-167.8(1)0(])-253.9(t)0(o)-260.4(the)-257.2(set)-258.4([0)-171.3(1],)]TJ
-35.2928 -1.2007 TD
[(we)-297.5(set)]TJ
/F10 1 Tf
2.868 0 TD
(e)Tj
/F5 1 Tf
6.9738 0 0 6.9738 140.0314 630.3116 Tm
(mn)Tj
/F6 1 Tf
9.9626 0 0 9.9626 150.6897 631.7856 Tm
(=)Tj
/F1 1 Tf
.7227 0 TD
(1)Tj
/F6 1 Tf
.6658 0 TD
(-)Tj
/F5 1 Tf
.7227 0 TD
(e)Tj
6.9738 0 0 6.9738 176.2015 635.414 Tm
(score)Tj
4.9813 0 0 4.9813 191.3385 634.3936 Tm
(m)Tj
/F1 1 Tf
6.9738 0 0 6.9738 195.4204 635.414 Tm
([)Tj
/F5 1 Tf
.3333 0 TD
(n)Tj
/F1 1 Tf
.4959 0 TD
(])Tj
9.9626 0 0 9.9626 206.9857 631.7856 Tm
(for)Tj
/F5 1 Tf
1.4568 0 TD
(score)Tj
6.9738 0 0 6.9738 243.1558 630.3116 Tm
(m)Tj
/F1 1 Tf
9.9626 0 0 9.9626 248.6551 631.7856 Tm
([)Tj
/F5 1 Tf
.3357 0 TD
(n)Tj
/F1 1 Tf
.5008 0 TD
(])Tj
/F11 1 Tf
.6146 0 TD
(<)Tj
/F5 1 Tf
1.0471 0 TD
(ln)Tj
/F1 1 Tf
.7853 0 TD
(\(1)Tj
/F6 1 Tf
1.0015 0 TD
(-)Tj
/F11 1 Tf
.717 0 TD
()Tj
/F1 1 Tf
.3983 0 TD
[(\),)-293.3(where)]TJ
/F11 1 Tf
3.6192 0 TD
()Tj
/F1 1 Tf
.6886 0 TD
[(denot)-8.4(es)-294.7(the)-297.1(error)-296.1(rate)-301.6(of)-293.7(a)-292.8(seque)-8.6(ncing)-298.6(platform.)]TJ
-23.8662 -1.2007 TD
[(Other)-8.6(wise,)-337.5(we)-337.3(set)]TJ
/F10 1 Tf
7.6595 0 TD
(e)Tj
/F5 1 Tf
6.9738 0 0 6.9738 187.7102 618.3494 Tm
(mn)Tj
/F6 1 Tf
9.9626 0 0 9.9626 198.4251 619.8235 Tm
(=)Tj
/F11 1 Tf
.717 0 TD
()Tj
/F1 1 Tf
.3983 0 TD
(.)Tj
-9.2301 -1.195 TD
-.0108 Tc
[(Le)-10.8(t)]TJ
/F5 1 Tf
1.599 0 TD
0 Tc
(Q)Tj
/F6 1 Tf
.882 0 TD
(=)Tj
/F7 1 Tf
.7227 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(q)Tj
6.9738 0 0 6.9738 159.4771 606.3872 Tm
(k)Tj
/F1 1 Tf
9.9626 0 0 9.9626 163.2188 607.918 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(k)Tj
/F6 1 Tf
.6373 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
/F8 1 Tf
1.1723 0 TD
.1568 Tc
(...)Tj
/F1 1 Tf
1.2918 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(K)Tj
/F7 1 Tf
.7284 0 TD
(g)Tj
/F1 1 Tf
.7853 0 TD
[(de)19.4(no)21.2(te)-267.8(t)13.5(h)0(e)-270.8(s)0(e)18.3(t)-271(of)]TJ
/F5 1 Tf
6.8514 0 TD
(K)Tj
/F1 1 Tf
.9446 0 TD
[(st)23(ra)17.5(in)18.5(s)-275.1(o)0(f)-265.3(a)-275.7(vi)24.2(ra)17.5(l)-276.7(q)0(u)21.2(a)0(s)18.3(i)13.5(sp)14.4(e)14.5(c)0(i)16.7(e)0(s)18.3(.)-273.5(T)10.8(h)0(e)-265.1(g)0(o)15.5(a)0(l)-262.1(i)0(n)-266.1(t)0(h)18.5(e)-275.7(se)18.3(co)19.4(nd)-263.3(st)17.3(ag)19.5(e)]TJ
-19.7121 -1.2007 TD
[(of)-236.8(ou)21.2(r)-247.4(m)0(e)21.6(t)0(h)18.5(o)0(d)-234.8(i)0(s)-238.8(t)0(o)-237.6(d)0(e)19.4(t)13.5(er)17.5(mi)20.6(ne)]TJ
/F5 1 Tf
11.9388 0 TD
(Q)Tj
/F1 1 Tf
.9674 0 TD
[(fr)17.3(om)-232.7(th)18.5(e)-247.2(s)0(u)20(p)0(e)19.4(r)0(-)17.3(r)0(e)23.2(a)0(d)-242.3(m)12.8(at)16.7(ri)22.2(x)]TJ
/F2 1 Tf
10.8234 0 TD
(S)Tj
/F1 1 Tf
.8024 0 TD
[(us)20(i)13.5(n)0(g)-240.5(a)-247.2(pr)24.9(ob)15.5(ab)19.4(i)13.5(l)0(i)21.4(s)0(t)17.3(i)0(c)-239.4(f)14.3(ra)17.5(me)15.9(w)12.4(o)0(r)19.3(k)0(.)-234.5(A)0(n)-238.8(e)0(x)19.5(h)0(a)19.4(u)0(s)20(t)0(i)21.4(v)0(e)]TJ
-24.532 -1.2007 TD
[(se)18.3(ar)23.2(ch)-287.8(ov)15.5(e)14.5(r)-298.7(th)18.5(e)-292.8(e)0(n)13.8(t)13.5(ir)22.2(e)-298.5(s)0(o)20(l)0(u)18.5(t)0(i)21.4(o)0(n)-286.1(s)0(p)20(a)0(c)17.7(e)-298.5(i)13.5(s)-297.9(co)19.4(mp)17.7(ut)18.5(at)22.4(io)18.5(na)19.4(l)13.5(l)0(y)-288.8(i)0(n)18.5(t)13.5(ra)17.5(ct)22.4(ab)19.4(le)-290.6(ev)19.4(en)-287.8(f)14.3(o)0(r)-288(s)0(m)16.5(a)0(l)22.4(l)]TJ
/F2 1 Tf
32.954 0 TD
(S)Tj
/F1 1 Tf
.5406 0 TD
[(;)-293.7(i)0(n)18.5(s)0(t)17.3(e)14.5(ad)13.8(,)-290.6(w)0(e)-291.8(r)0(e)23.2(c)0(o)13.8(n)0(s)20(t)13.5(ru)19.3(ct)]TJ
-33.4946 -1.2007 TD
-.0159 Tc
[(th)-15.9(e)-241.1(s)-15.9(et)-247(o)-15.9(f)]TJ
/F5 1 Tf
3.8184 0 TD
0 Tc
(K)Tj
/F1 1 Tf
.8991 0 TD
[(vi)18.5(r)14.3(a)0(l)-222.3(s)0(t)17.3(r)0(a)17.5(i)13.5(ns)-224.6(se)18.3(qu)21.2(en)19.4(t)13.5(i)0(a)16.7(l)13.5(ly)18.5(,)-233.7(e)0(x)19.4(t)13.5(en)19.4(di)18.5(ng)-223.5(pa)19.4(r)14.3(t)0(i)15.7(a)0(l)22.4(l)0(y)-220.5(e)0(s)18.3(t)0(i)21.4(m)0(a)15.9(t)0(e)22.4(d)-234.1(st)23(ra)17.5(in)18.5(s)-229.6(o)0(n)-223.5(S)11.4(NV)-225.6(po)21.2(si)17.3(t)13.5(i)0(o)18.5(n)-228.4(at)-222.3(ea)17.7(ch)-225.3(st)23(ep)19.4(.)-233.7(S)11.4(in)18.5(ce)]TJ
-4.7175 -1.2007 TD
[(ma)21.6(in)18.5(ta)16.7(i)13.5(n)0(i)18.5(n)0(g)-251.9(a)0(n)19.4(d)-262.5(ex)19.4(te)16.7(nd)21.2(in)18.5(g)-262.5(a)0(l)16.7(l)-259.6(po)21.2(ss)18.9(ib)18.5(le)-250.8(pa)13.8(r)14.3(t)0(i)21.4(a)0(l)-256.5(s)0(t)17.3(r)14.3(ai)16.7(ns)-253.1(in)18.5(ev)19.4(i)13.5(t)0(a)16.7(b)0(l)24.2(y)-268.2(i)13.5(n)0(c)19.4(r)0(e)17.5(a)0(s)18.3(e)-264.3(t)13.5(h)0(e)19.4(i)0(r)-256.6(n)0(u)21.2(m)0(b)17.7(e)0(r)-250(e)0(x)13.8(p)0(o)21.2(n)0(e)19.4(n)0(t)24.2(i)0(a)16.7(l)0(l)21.4(y)0(,)-251.5(u)0(n)15.5(l)13.5(ik)18.5(el)22.4(y)]TJ
T*
[(se)18.3(t)13.5(s)-303.6(of)-288(ca)17.7(nd)21.2(id)18.5(at)22.4(e)-304.2(s)0(t)23(r)0(a)17.5(i)0(n)18.5(s)-297.9(ar)17.5(e)-298.5(p)0(r)19.3(u)0(n)21.2(e)0(d)-293.5(i)13.5(n)-302.4(e)0(a)17.7(c)0(h)-287.8(s)0(t)17.3(e)0(p)19.4(.)-296.3(E)10.8(a)0(c)17.7(h)-302.4(st)23(ep)-293.5(co)19.4(ns)20(is)17.3(t)13.5(s)-297.9(of)-293.7(t)13.5(h)0(r)19.3(e)0(e)-295.3(b)0(a)19.4(s)0(i)23(c)-304.2(pa)19.4(r)14.3(t)0(s)17.3(:)-299.4(\(a)17.5(\))-298.6(e)0(x)19.4(t)13.5(en)19.4(si)17.3(on)-291.8(of)-288(th)18.5(e)]TJ
T*
[(pa)19.4(rt)22.2(ia)16.7(l)13.5(l)0(y)-482.3(r)14.3(ec)17.7(on)15.5(s)15.1(t)0(r)16.5(u)0(c)19.4(t)13.5(ed)-481.3(st)17.3(r)14.3(a)0(i)16.7(n)0(s)20(,)-489.8(\()14.3(b)0(\))-481.5(s)0(e)18.3(l)13.5(ec)17.7(ti)21.4(on)-479.5(of)-481.5(pr)25(ob)15.5(ab)19.4(l)13.5(e)-491.9(se)18.3(t)13.5(s)-491.3(co)19.4(m)12.8(p)0(r)19.3(i)0(s)17.3(i)13.5(ng)]TJ
/F5 1 Tf
30.5298 0 TD
(K)Tj
/F1 1 Tf
1.1552 0 TD
[(st)17.3(r)14.3(a)0(i)16.7(n)0(s)-480.7(c)0(h)19.4(o)0(s)20(e)0(n)-475.6(a)0(m)15.9(o)0(n)21.2(g)-490.2(t)13.5(h)0(o)15.5(s)0(e)]TJ
-31.685 -1.2007 TD
[(ge)19.4(ne)19.4(ra)17.5(t)13.5(e)0(d)-276.5(i)0(n)-277.4(s)0(t)23(e)0(p)-276.5(\()0(a)17.5(\))0(,)-276.3(a)0(n)19.4(d)-285.3(\(c)17.5(\))-281.6(e)0(v)19.4(a)0(l)16.7(u)0(a)19.4(t)0(i)21.4(o)0(n)-274.7(o)0(f)-276.7(t)0(h)18.5(e)-287.1(qu)21.2(al)16.7(i)13.5(t)0(y)-277.4(o)0(f)-276.6(t)13.5(he)-276.5(se)18.3(le)16.7(ct)22.4(ed)-276.5(se)18.3(ts)-272.9(of)-276.6(st)17.3(ra)17.5(i)13.5(n)0(s)-275.9(a)0(n)19.4(d)-285.3(an)-276.5(up)21.2(da)19.4(te)-279.2(of)]TJ
/F5 1 Tf
40.4655 0 TD
(K)Tj
/F1 1 Tf
.6544 0 TD
.2849 Tc
[(.T)284.9(h)300.6(e)]TJ
-41.1199 -1.195 TD
0 Tc
[(se)18.3(qu)21.2(en)19.4(ti)21.4(al)-313.4(Ba)14.7(ye)19.4(si)23(an)-316.3(i)13.5(n)0(f)19.3(e)0(r)17.5(e)0(n)19.4(c)0(e)-312.4(p)0(r)19.3(o)0(c)19.4(e)0(d)19.4(u)0(r)19.3(e)-326.9(i)13.5(n)-325.1(st)23(ep)]TJ
/F5 1 Tf
19.4674 0 TD
(t)Tj
/F1 1 Tf
.6032 0 TD
[(is)-312.8(il)21.4(lu)18.5(st)23(ra)17.5(te)16.7(d)-319.4(i)0(n)-311.6(S)0(u)16.3(p)0(p)21.2(l)0(e)16.7(m)12.8(en)19.5(ta)16.7(r)14.3(y)-325.1(F)11.4(i)0(g)18.5(.)-324.7(S)11.4(1)-325.1(i)13.5(n)-325.1(A)12.4(p)0(p)15.5(e)0(n)19.4(d)0(i)24.2(x)-325.1(A.)]TJ
/F5 1 Tf
10.959 0 0 10.959 117.5811 488.3526 Tm
[(2.2.1.)-497(Extending)-487.6(partially)-491.2(reconstructed)-490.8(strains.)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 349.0015 488.3526 Tm
[(Le)-8.8(t)]TJ
/F5 1 Tf
1.8551 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 373.6062 486.8219 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F6 1 Tf
9.9626 0 0 9.9626 392.9385 488.3526 Tm
(=)Tj
/F7 1 Tf
.7227 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(f)Tj
6.9738 0 0 6.9738 409.3794 491.981 Tm
(i)Tj
/F1 1 Tf
-.2114 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 425.5936 488.3526 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(i)Tj
/F6 1 Tf
.4495 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
/F7 1 Tf
1.1723 0 TD
.1682 Tc
[()5.7()]TJ
/F1 1 Tf
1.3088 0 TD
0 Tc
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 480.7558 486.8219 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F7 1 Tf
9.9626 0 0 9.9626 498.444 488.3526 Tm
(jg)Tj
/F1 1 Tf
1.2804 0 TD
[(be)-509.8(the)]TJ
-40.511 -1.2007 TD
[(collec)-9.8(tion)-241.9(of)-248.2(partially)-251.1(recon)-9.4(structed)-251.7(strains)-250.3(covering)-247.7(the)-245.8(rst)]TJ
/F5 1 Tf
24.4523 0 TD
(t)Tj
/F6 1 Tf
.4723 0 TD
(-)Tj
/F1 1 Tf
.717 0 TD
[(1)-245.5(SNV)-248.4(sites)-246.8(and)-248.8(let)]TJ
/F5 1 Tf
7.9611 0 TD
(B)Tj
6.9738 0 0 6.9738 448.4975 474.9164 Tm
(t)Tj
/F6 1 Tf
9.9626 0 0 9.9626 452.7495 476.3904 Tm
(=)Tj
/F7 1 Tf
.717 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(b)Tj
6.9738 0 0 6.9738 469.9274 481.2094 Tm
(j)Tj
0 -.9674 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 472.4786 476.3904 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(j)Tj
/F6 1 Tf
.4496 0 TD
(=)Tj
/F1 1 Tf
.7227 0 TD
(1)Tj
/F7 1 Tf
1.1666 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2732 0 TD
(B)Tj
6.9738 0 0 6.9738 527.6975 474.9164 Tm
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 530.3054 476.3904 Tm
(jg)Tj
/F1 1 Tf
-42.4287 -1.2007 TD
[(be)-270.8(the)-274.3(lists)-276.2(of)-271(disti)-7.6(nct)-274.3(bases)-277.2(in)-271.7(the)]TJ
/F5 1 Tf
13.9475 0 TD
(t)Tj
6.9738 0 0 6.9738 249.5621 468.0565 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 258.1794 464.4282 Tm
[(colu)-7.6(mn)-272.5(of)]TJ
/F2 1 Tf
4.3931 0 TD
(S)Tj
/F1 1 Tf
.552 0 TD
[(,)-273.5(where)]TJ
/F5 1 Tf
3.2436 0 TD
(b)Tj
6.9738 0 0 6.9738 344.7495 468.0565 Tm
(i)Tj
0 -.9186 TD
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 350.1353 464.4282 Tm
.2829 Tc
(2f)Tj
/F1 1 Tf
1.4397 0 TD
0 Tc
[(A)-166.8(C)-167.6(G)-172.5(T)]TJ
/F7 1 Tf
4.2224 0 TD
(g)Tj
/F1 1 Tf
.7739 0 TD
[(and)-271.5(2)]TJ
/F7 1 Tf
2.4981 0 TD
.2827 Tc
(j)Tj
/F5 1 Tf
1.3202 0 TD
0 Tc
(B)Tj
6.9738 0 0 6.9738 458.4188 462.9542 Tm
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 461.0266 464.4282 Tm
.282 Tc
(j)Tj
/F1 1 Tf
1.599 0 TD
0 Tc
[(4.)-274.3(Then,)-278.2(all)-271.4(the)]TJ
-37.0739 -1.2007 TD
[(possibl)-7.6(e)-372.4(exten)-10.2(sions)-373.2(of)]TJ
/F5 1 Tf
9.4805 0 TD
(f)Tj
6.9738 0 0 6.9738 206.3055 456.0944 Tm
(i)Tj
/F1 1 Tf
-.2114 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 226.2047 452.466 Tm
[(to)-379.9(the)-376.7(SNV)-373.6(site)]TJ
/F5 1 Tf
6.9026 0 TD
(t)Tj
/F1 1 Tf
.6544 0 TD
[(can)-375.8(be)-378.9(enumera)-10.5(ted)-376.7(as)]TJ
/F7 1 Tf
9.3723 0 TD
(f)Tj
/F1 1 Tf
.5008 0 TD
([)Tj
/F5 1 Tf
.3357 0 TD
(f)Tj
6.9738 0 0 6.9738 407.4518 456.0944 Tm
(i)Tj
/F1 1 Tf
-.2114 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 423.666 452.466 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(b)Tj
/F1 1 Tf
6.9738 0 0 6.9738 433.644 456.0944 Tm
(1)Tj
/F5 1 Tf
0 -.9186 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 437.6125 452.466 Tm
(])Tj
/F7 1 Tf
1.0015 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
.1678 Tc
([)Tj
/F5 1 Tf
.8365 0 TD
0 Tc
(f)Tj
6.9738 0 0 6.9738 473.2723 456.0944 Tm
(i)Tj
/F1 1 Tf
-.2114 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 489.4865 452.466 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(b)Tj
/F7 1 Tf
6.9738 0 0 6.9738 499.4644 457.5684 Tm
(j)Tj
/F5 1 Tf
.2683 0 TD
(B)Tj
4.9813 0 0 4.9813 505.644 456.5479 Tm
(t)Tj
/F7 1 Tf
6.9738 0 0 6.9738 507.6282 457.5684 Tm
(j)Tj
/F5 1 Tf
-1.1706 -1.008 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 510.0093 452.466 Tm
(])Tj
/F7 1 Tf
.3357 0 TD
(g)Tj
/F1 1 Tf
.5008 0 TD
[(.)-376(Let)]TJ
/F5 1 Tf
-41.228 -1.2007 TD
(S)Tj
6.9738 0 0 6.9738 112.5921 444.1322 Tm
(i)Tj
/F1 1 Tf
0 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F6 1 Tf
9.9626 0 0 9.9626 131.9244 440.5038 Tm
(=)Tj
/F7 1 Tf
.717 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(s)Tj
6.9738 0 0 6.9738 147.9118 445.7196 Tm
(i)Tj
4.9813 0 0 4.9813 149.896 443.9621 Tm
(c)Tj
/F7 1 Tf
.4439 .2845 TD
(0)Tj
/F1 1 Tf
6.9738 0 0 6.9738 147.9118 437.7259 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 165.5999 440.5038 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(c)Tj
/F7 1 Tf
6.9738 0 0 6.9738 175.0677 444.1322 Tm
(0)Tj
/F6 1 Tf
9.9626 0 0 9.9626 179.0929 440.5038 Tm
(=)Tj
/F1 1 Tf
.7227 0 TD
(1)Tj
/F7 1 Tf
1.1666 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2675 0 TD
(S)Tj
6.9738 0 0 6.9738 223.6535 444.1322 Tm
(i)Tj
/F1 1 Tf
0 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F7 1 Tf
9.9626 0 0 9.9626 241.3417 440.5038 Tm
(jg)Tj
/F1 1 Tf
1.0641 0 TD
[(be)-299.2(the)-297.1(collec)-9.8(tion)-293.1(of)-299.4(super-r)-8.6(eads)-298(covering)-304.6(some)-294.1(of)-299.4(the)-297.1(rst)]TJ
/F5 1 Tf
23.8149 0 TD
(t)Tj
/F1 1 Tf
.5747 0 TD
[(SNV)-299.6(sites,)]TJ
-38.8778 -1.2007 TD
[(which)-308.2(are)-303.7(consist)-9.3(ent)-302.7(with)]TJ
/F5 1 Tf
10.6869 0 TD
(f)Tj
6.9738 0 0 6.9738 218.3243 432.17 Tm
(i)Tj
/F1 1 Tf
-.2032 -.9105 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 237.5432 428.5416 Tm
[(\(ig)-7(noring)-305.2()48.5()]TJ
/F6 1 Tf
4.8256 0 TD
(-)Tj
/F1 1 Tf
.717 0 TD
-.0485 Tc
[()-347.2(i)-48.5(n)]TJ
/F5 1 Tf
2.0031 0 TD
0 Tc
(s)Tj
6.9738 0 0 6.9738 316.5731 433.7574 Tm
(i)Tj
4.9813 0 0 4.9813 318.5007 431.9999 Tm
(c)Tj
/F7 1 Tf
.4552 .2845 TD
(0)Tj
/F1 1 Tf
6.9738 0 0 6.9738 316.5731 425.7637 Tm
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 334.2046 428.5416 Tm
[(\))-304.3(where)]TJ
/F7 1 Tf
3.3916 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(i)Tj
6.9738 0 0 6.9738 375.7605 427.0676 Tm
(c)Tj
/F7 1 Tf
4.9813 0 0 4.9813 378.8787 429.1086 Tm
(0)Tj
9.9626 0 0 9.9626 381.2598 428.5416 Tm
(g)Tj
/F1 1 Tf
.8024 0 TD
[(denotes)-308.8(indices)-305.8(of)-305.1(rows)-306.1(of)]TJ
/F2 1 Tf
11.0283 0 TD
(S)Tj
/F1 1 Tf
.8536 0 TD
[(that)-306.3(are)]TJ
-40.1525 -1.195 TD
[(placed)-359.8(in)]TJ
/F5 1 Tf
4.1143 0 TD
(S)Tj
6.9738 0 0 6.9738 153.6377 420.2078 Tm
(i)Tj
/F1 1 Tf
0 -.9105 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 171.2692 416.6361 Tm
[(,)-353.2(and)-356.9(let)]TJ
/F5 1 Tf
3.7728 0 TD
(S)Tj
6.9738 0 0 6.9738 213.8456 420.2078 Tm
(i)Tj
0 -.9105 TD
(t)Tj
/F6 1 Tf
9.9626 0 0 9.9626 218.0976 416.6361 Tm
(=)Tj
/F7 1 Tf
.7227 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(s)Tj
6.9738 0 0 6.9738 234.085 421.1148 Tm
(i)Tj
4.9813 0 0 4.9813 236.0692 420.0377 Tm
(c)Tj
6.9738 0 0 6.9738 234.085 414.6519 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 239.3007 416.6361 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(c)Tj
/F6 1 Tf
.6146 0 TD
(=)Tj
/F1 1 Tf
.7227 0 TD
(1)Tj
/F7 1 Tf
1.1666 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(S)Tj
6.9738 0 0 6.9738 295.0298 420.2078 Tm
(i)Tj
0 -.9105 TD
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 297.6377 416.6361 Tm
(jg)Tj
/F1 1 Tf
1.121 0 TD
[(denot)-8.4(e)-349.7(the)-359.7(collecti)-11.1(on)-354.3(of)-350.6(nucl)-7.6(eotides)-357.1(\()]TJ
/F5 1 Tf
15.4043 0 TD
(s)Tj
6.9738 0 0 6.9738 466.129 421.1148 Tm
(i)Tj
4.9813 0 0 4.9813 468.0566 420.0377 Tm
(c)Tj
6.9738 0 0 6.9738 466.129 414.6519 Tm
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 474.066 416.6361 Tm
.2829 Tc
(2f)Tj
/F1 1 Tf
1.4397 0 TD
0 Tc
[(A)-166.8(C)-173.3(G)-166.8(T)]TJ
/F7 1 Tf
4.2224 0 TD
(g)Tj
/F1 1 Tf
.5008 0 TD
(,)Tj
-42.9466 -1.2007 TD
[(not)-272.5()54.2()]TJ
/F6 1 Tf
2.1681 0 TD
(-)Tj
/F1 1 Tf
.552 0 TD
[()48.5()0(\))-272.9(observed)-274.6(at)-273.5(the)]TJ
/F5 1 Tf
7.6083 0 TD
(t)Tj
6.9738 0 0 6.9738 213.5054 408.2455 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 222.1794 404.6739 Tm
[(SNV)-271.1(site)-273.3(of)-271(the)-268.6(super)-8.8(-reads)-275.1(in)]TJ
/F5 1 Tf
12.4737 0 TD
(S)Tj
6.9738 0 0 6.9738 351.4393 408.2455 Tm
(i)Tj
/F1 1 Tf
0 -.9105 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 371.7354 404.6739 Tm
[(whe)-8(re)]TJ
/F7 1 Tf
2.7201 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(i)Tj
6.9738 0 0 6.9738 406.6581 403.1432 Tm
(c)Tj
/F7 1 Tf
9.9626 0 0 9.9626 410.2865 404.6739 Tm
(g)Tj
/F1 1 Tf
.7682 0 TD
[(denot)-8.4(es)-266.3(the)-274.3(indices)-277.4(of)-271(rows)-271.9(in)]TJ
/F2 1 Tf
-31.1501 -1.2007 TD
(S)Tj
/F1 1 Tf
.8593 0 TD
[(that)-312(contri)-8.2(bute)-309.2(to)]TJ
/F5 1 Tf
7.2953 0 TD
(S)Tj
6.9738 0 0 6.9738 193.833 396.3401 Tm
(i)Tj
0 -.9186 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 196.4409 392.7117 Tm
[(.)-307.7(Given)]TJ
/F5 1 Tf
3.3176 0 TD
(S)Tj
6.9738 0 0 6.9738 234.4818 396.3401 Tm
(i)Tj
/F1 1 Tf
0 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 252.17 392.7117 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(S)Tj
6.9738 0 0 6.9738 262.148 396.3401 Tm
(i)Tj
0 -.9186 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 267.8172 392.7117 Tm
(and)Tj
/F5 1 Tf
1.7527 0 TD
(f)Tj
6.9738 0 0 6.9738 289.5306 396.3401 Tm
(i)Tj
/F1 1 Tf
-.2032 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 305.8015 392.7117 Tm
[(,)-302(the)-314.1(probabil)-9.7(ity)-309.4(of)]TJ
/F5 1 Tf
7.9554 0 TD
(b)Tj
6.9738 0 0 6.9738 390.0471 397.5306 Tm
(j)Tj
0 -.9674 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 395.7164 392.7117 Tm
[(being)-310(the)-314.1(true)-311.2(extension)-313.1(of)]TJ
/F5 1 Tf
11.2502 0 TD
(f)Tj
6.9738 0 0 6.9738 512.0503 396.3401 Tm
(i)Tj
/F1 1 Tf
-.2032 -.9186 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 531.3259 392.7117 Tm
(is)Tj
-42.5312 -1.2007 TD
[(given)-338.4(by)-331.6(the)-336.9(fol)-7(lowing:)]TJ
/F5 1 Tf
14.2776 -3.1013 TD
(P)Tj
/F1 1 Tf
.6146 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(S)Tj
6.9738 0 0 6.9738 264.3023 353.9905 Tm
(i)Tj
0 -.9918 TD
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 266.9102 349.8519 Tm
(j)Tj
/F5 1 Tf
.2731 0 TD
(b)Tj
6.9738 0 0 6.9738 274.6204 353.9905 Tm
(j)Tj
0 -.9918 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 277.2283 349.8519 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(S)Tj
6.9738 0 0 6.9738 287.2062 353.9905 Tm
(i)Tj
/F1 1 Tf
0 -.9918 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 304.8377 349.8519 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(f)Tj
6.9738 0 0 6.9738 314.0786 353.9905 Tm
(i)Tj
/F1 1 Tf
-.2032 -.9918 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 330.2928 349.8519 Tm
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
/F9 1 Tf
.8934 .9503 TD
(Y)Tj
/F7 1 Tf
6.9738 0 0 6.9738 345.8834 362.3243 Tm
(j)Tj
/F5 1 Tf
.2764 0 TD
(S)Tj
4.9813 0 0 4.9813 351.2692 364.8755 Tm
(i)Tj
0 -.8991 TD
(t)Tj
/F7 1 Tf
6.9738 0 0 6.9738 353.3102 362.3243 Tm
(j)Tj
/F5 1 Tf
-1.317 -3.3331 TD
(c)Tj
/F6 1 Tf
.6178 0 TD
(=)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
9.9626 0 0 9.9626 358.5826 349.8519 Tm
(P)Tj
/F1 1 Tf
.6203 0 TD
(\()Tj
/F5 1 Tf
.3301 0 TD
(s)Tj
6.9738 0 0 6.9738 371.9054 353.9905 Tm
(i)Tj
4.9813 0 0 4.9813 373.8896 352.9133 Tm
(c)Tj
6.9738 0 0 6.9738 371.9054 347.0739 Tm
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 377.1212 349.8519 Tm
(j)Tj
/F5 1 Tf
.2675 0 TD
(b)Tj
6.9738 0 0 6.9738 384.7747 353.9905 Tm
(j)Tj
0 -.9918 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 387.3826 349.8519 Tm
(\))Tj
/F5 1 Tf
-13.1964 -3.5737 TD
(P)Tj
/F1 1 Tf
.6146 0 TD
(\()Tj
/F5 1 Tf
.3301 0 TD
(s)Tj
6.9738 0 0 6.9738 269.1779 318.3306 Tm
(i)Tj
4.9813 0 0 4.9813 271.1621 317.3102 Tm
(c)Tj
6.9738 0 0 6.9738 269.1779 311.4708 Tm
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 274.3936 314.2487 Tm
(j)Tj
/F5 1 Tf
.2731 0 TD
(b)Tj
6.9738 0 0 6.9738 282.1039 318.3306 Tm
(j)Tj
0 -.9837 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 284.7117 314.2487 Tm
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
/F1 1 Tf
1.6901 .6373 TD
(1)Tj
/F6 1 Tf
.6658 0 TD
(-)Tj
/F10 1 Tf
.717 0 TD
(e)Tj
/F5 1 Tf
6.9738 0 0 6.9738 324.17 319.0676 Tm
(i)Tj
4.9813 0 0 4.9813 326.1542 318.0471 Tm
(c)Tj
6.9738 0 0 6.9738 328.8755 319.0676 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 331.4834 320.5984 Tm
1.2262 Tc
[(i)1226.2(f)]TJ
/F5 1 Tf
2.5607 0 TD
0 Tc
(b)Tj
6.9738 0 0 6.9738 361.9842 325.4172 Tm
(j)Tj
0 -.9674 TD
(t)Tj
/F6 1 Tf
9.9626 0 0 9.9626 366.2361 320.5984 Tm
(=)Tj
/F5 1 Tf
.7227 0 TD
(s)Tj
6.9738 0 0 6.9738 377.2912 325.0771 Tm
(i)Tj
4.9813 0 0 4.9813 379.2188 323.9999 Tm
(c)Tj
6.9738 0 0 6.9738 377.2912 318.6708 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 382.4503 320.5984 Tm
()Tj
ET
313.115 310.904 10.091 .39685 re
f
BT
/F10 1 Tf
6.9738 0 0 6.9738 313.7385 313.5117 Tm
(e)Tj
/F5 1 Tf
4.9813 0 0 4.9813 316.4597 312.4346 Tm
(i)Tj
.2845 -.148 TD
(c)Tj
.5463 .148 TD
(t)Tj
/F7 1 Tf
6.9738 0 0 6.9738 313.1149 305.2346 Tm
(j)Tj
/F5 1 Tf
.2764 0 TD
(B)Tj
4.9813 0 0 4.9813 319.2944 304.1574 Tm
(t)Tj
/F7 1 Tf
6.9738 0 0 6.9738 321.3353 305.2346 Tm
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 324.8503 308.6361 Tm
[()-1835.1(otherw)-9.3(ise)]TJ
/F11 1 Tf
6.0718 0 TD
(:)Tj
/F9 1 Tf
-8.8829 2.2762 TD
(\()Tj
/F1 1 Tf
-17.9935 -4.6093 TD
[(We)-182.3(ex)19.4(te)16.7(nd)]TJ
/F5 1 Tf
4.3931 0 TD
(f)Tj
6.9738 0 0 6.9738 165.5999 289.0204 Tm
(i)Tj
/F1 1 Tf
-.2032 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 183.7984 285.3921 Tm
[(to)-180.7([)]TJ
/F5 1 Tf
1.2974 0 TD
(f)Tj
6.9738 0 0 6.9738 200.9763 289.0204 Tm
(i)Tj
/F1 1 Tf
-.2114 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 217.1905 285.3921 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(b)Tj
6.9738 0 0 6.9738 227.1684 290.2109 Tm
(j)Tj
0 -.9674 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 229.7763 285.3921 Tm
(])Tj
/F7 1 Tf
.6146 0 TD
(2)Tj
/F5 1 Tf
.9333 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 251.3196 283.918 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 276.5479 285.3921 Tm
[(by)-183.6(ap)19.4(pe)19.4(nd)15.5(in)18.5(g)-188.6(t)0(h)18.5(e)]TJ
/F5 1 Tf
6.8742 0 TD
(b)Tj
6.9738 0 0 6.9738 350.0219 290.2109 Tm
(j)Tj
0 -.9674 TD
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 355.4078 285.3921 Tm
(2)Tj
/F5 1 Tf
.9333 0 TD
(B)Tj
6.9738 0 0 6.9738 370.8849 283.918 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 375.4203 285.3921 Tm
[(wh)17.3(ic)16.7(h)-188.6(s)0(a)12.6(t)13.5(is)17.3(e)14.5(s)]TJ
ET
434.154 287.716 79.143 .39685 re
f
BT
/F5 1 Tf
6.9738 0 0 6.9738 439.9369 290.8913 Tm
(P)Tj
/F1 1 Tf
.6178 0 TD
(\()Tj
/F5 1 Tf
.3333 0 TD
(S)Tj
4.9813 0 0 4.9813 450.0849 293.3858 Tm
(i)Tj
0 -.8991 TD
(t)Tj
/F7 1 Tf
6.9738 0 0 6.9738 452.0692 290.8913 Tm
(j)Tj
/F5 1 Tf
.2764 0 TD
(b)Tj
4.9813 0 0 4.9813 457.455 294.2361 Tm
(j)Tj
0 -1.0584 TD
(t)Tj
/F1 1 Tf
6.9738 0 0 6.9738 459.4959 290.8913 Tm
()Tj
/F5 1 Tf
.4959 0 TD
(S)Tj
4.9813 0 0 4.9813 466.4692 293.3858 Tm
(i)Tj
/F1 1 Tf
0 -.9788 TD
(1)Tj
/F8 1 Tf
.5008 0 TD
(:)Tj
/F5 1 Tf
.2731 0 TD
(t)Tj
/F6 1 Tf
.4666 0 TD
(-)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
6.9738 0 0 6.9738 479.2251 290.8913 Tm
()Tj
/F5 1 Tf
.4959 0 TD
(f)Tj
4.9813 0 0 4.9813 485.688 293.3858 Tm
(i)Tj
/F1 1 Tf
-.2049 -.9788 TD
(1)Tj
/F8 1 Tf
.5008 0 TD
(:)Tj
/F5 1 Tf
.2732 0 TD
(t)Tj
/F6 1 Tf
.4666 0 TD
(-)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
6.9738 0 0 6.9738 497.4235 290.8913 Tm
(\))Tj
ET
499.748 299.509 7.2 .39685 re
f
BT
4.9813 0 0 4.9813 502.129 300.3023 Tm
(1)Tj
/F7 1 Tf
-.478 -1.2292 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(S)Tj
.5008 .3528 TD
(i)Tj
0 -.865 TD
(t)Tj
/F7 1 Tf
.3983 .5122 TD
(j)Tj
/F9 1 Tf
9.9626 0 0 9.9626 434.1542 281.2535 Tm
(P)Tj
/F5 1 Tf
4.9813 0 0 4.9813 436.8188 266.9102 Tm
(B)Tj
.626 -.1935 TD
(t)Tj
6.9738 0 0 6.9738 445.7762 274.507 Tm
(P)Tj
/F1 1 Tf
.6178 0 TD
(\()Tj
/F5 1 Tf
.3333 0 TD
(S)Tj
4.9813 0 0 4.9813 455.9243 276.9448 Tm
(i)Tj
0 -.865 TD
(t)Tj
/F7 1 Tf
6.9738 0 0 6.9738 457.9085 274.507 Tm
(j)Tj
/F5 1 Tf
.2683 0 TD
(b)Tj
4.9813 0 0 4.9813 463.2944 277.9086 Tm
(j)Tj
0 -1.0584 TD
(t)Tj
/F1 1 Tf
6.9738 0 0 6.9738 465.2786 274.507 Tm
()Tj
/F5 1 Tf
.504 0 TD
(S)Tj
4.9813 0 0 4.9813 472.2518 276.9448 Tm
(i)Tj
/F1 1 Tf
0 -.9902 TD
(1)Tj
/F8 1 Tf
.5008 0 TD
(:)Tj
/F5 1 Tf
.2731 0 TD
(t)Tj
/F6 1 Tf
.4666 0 TD
(-)Tj
/F1 1 Tf
.7284 0 TD
(1)Tj
6.9738 0 0 6.9738 485.0078 274.507 Tm
()Tj
/F5 1 Tf
.504 0 TD
(f)Tj
4.9813 0 0 4.9813 491.5275 276.9448 Tm
(i)Tj
/F1 1 Tf
-.2049 -.9902 TD
(1)Tj
/F8 1 Tf
.5008 0 TD
(:)Tj
/F5 1 Tf
.2732 0 TD
(t)Tj
/F6 1 Tf
.4666 0 TD
(-)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
6.9738 0 0 6.9738 503.2628 274.507 Tm
(\))Tj
ET
505.587 283.181 7.2 .39685 re
f
BT
4.9813 0 0 4.9813 507.9117 283.9747 Tm
(1)Tj
/F7 1 Tf
-.4666 -1.2292 TD
(j)Tj
/F5 1 Tf
.2732 0 TD
(S)Tj
.5008 .3414 TD
(i)Tj
0 -.865 TD
(t)Tj
/F7 1 Tf
.3983 .5235 TD
(j)Tj
9.9626 0 0 9.9626 516.0187 285.3921 Tm
()Tj
/F10 1 Tf
1.0528 0 TD
(d)Tj
/F1 1 Tf
6.9738 0 0 6.9738 531.496 283.918 Tm
(0)Tj
9.9626 0 0 9.9626 535.4645 285.3921 Tm
(,)Tj
-42.9466 -2.8623 TD
-.0151 Tc
[(where)-233.9(t)-1.6(he)-228.2(ex)-15.1(p)11.8(o)1.2(n)-15.1(e)10(nt)-229.2(e)-15.1(n)10(su)-15.1(r)9.9(e)-.6(s)-227.6(p)1.2(ro)-15.1(p)11.8(e)-.6(r)-228.4(n)-15.1(o)11.8(r)-.8(maliza)-15.1(t)7.3(io)-15.1(n)-215.8(a)-.6(n)-15.1(d)-215.8(is)-227.6(ne)-15.1(e)8.3(d)1.2(e)-15.1(d)-217.6(sinc)-15.1(e)-219.4(t)-1.6(he)-228.2(n)-15.1(u)11.8(mber)-228.4(o)-15.1(f)-217.8(sup)-15.1(e)10(r-rea)-15.1(d)10(s,)]TJ
/F7 1 Tf
37.5975 0 TD
0 Tc
(j)Tj
/F5 1 Tf
.2675 0 TD
(S)Tj
6.9738 0 0 6.9738 489.8267 260.4472 Tm
(i)Tj
/F1 1 Tf
0 -.9105 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F7 1 Tf
9.9626 0 0 9.9626 507.5148 256.8755 Tm
(j)Tj
/F1 1 Tf
.2731 0 TD
.2109 Tc
[(,v)227.2(a)225.4(r)210.9(i)238.8(e)210.9(s)]TJ
-40.4143 -1.4966 TD
0 Tc
[(for)-188.3(each)]TJ
/F7 1 Tf
3.3859 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(f)Tj
6.9738 0 0 6.9738 150.5763 245.5937 Tm
(i)Tj
/F1 1 Tf
-.2114 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 166.7905 241.9653 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(i)Tj
/F6 1 Tf
.4496 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
/F7 1 Tf
1.1666 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 221.9527 240.4913 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F7 1 Tf
9.9626 0 0 9.9626 239.6409 241.9653 Tm
(jg)Tj
/F1 1 Tf
.7739 0 TD
[(.)-182.5(For)]TJ
/F5 1 Tf
2.0031 0 TD
(f)Tj
6.9738 0 0 6.9738 271.559 245.5937 Tm
(i)Tj
/F1 1 Tf
-.2032 -.9186 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 287.7732 241.9653 Tm
[(,)-188.2(which)-188.7(has)-187.4(no)-189.3(matche)-10.5(d)-182.9(super)-8.8(-reads,)-190.1(that)-186.8(is,)]TJ
/F7 1 Tf
17.2367 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(S)Tj
6.9738 0 0 6.9738 467.2062 245.5937 Tm
(i)Tj
/F1 1 Tf
0 -.9186 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(i)Tj
/F6 1 Tf
.4471 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F7 1 Tf
9.9626 0 0 9.9626 484.7243 241.9653 Tm
(j)Tj
/F6 1 Tf
.4382 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
[(0,)-188.9(we)-189.3(keep)]TJ
-39.0087 -1.3031 TD
[(all)-186(of)]TJ
/F7 1 Tf
2.2136 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(B)Tj
6.9738 0 0 6.9738 138.5007 227.4519 Tm
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 141.1086 228.9826 Tm
(j)Tj
/F1 1 Tf
.4552 0 TD
[(possibl)-7.6(e)-184.7(extensi)-9.9(ons)-185.6(of)]TJ
/F5 1 Tf
8.9114 0 TD
(f)Tj
6.9738 0 0 6.9738 238.6771 232.5543 Tm
(i)Tj
/F6 1 Tf
.4471 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
-1.3739 -.9105 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 250.8094 228.9826 Tm
[(.)-182.5(B)0(y)-188.3(collec)-9.8(ting)-185(proba)-7.6(ble)-183.3(exte)-9.4(nsions)-186.1(for)-188.3(each)]TJ
/F5 1 Tf
17.4529 0 TD
(f)Tj
6.9738 0 0 6.9738 428.9384 232.5543 Tm
(i)Tj
/F1 1 Tf
-.2114 -.9105 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F7 1 Tf
9.9626 0 0 9.9626 447.9306 228.9826 Tm
(2)Tj
/F5 1 Tf
.9332 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 463.3511 227.4519 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 481.0392 228.9826 Tm
[(,)-182.5(w)0(e)-189.3(obtain)-188.3(the)]TJ
-37.4837 -1.2292 TD
[(set)-298.2(of)-293.7(partial)-298(strai)-8.6(ns)-292.9(stret)-8.6(ching)-298.6(over)-297(the)-297.1(rst)]TJ
/F5 1 Tf
18.0334 0 TD
(t)Tj
/F1 1 Tf
.5747 0 TD
[(SNV)-293.9(sites,)]TJ
/F5 1 Tf
4.615 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 345.0897 215.2062 Tm
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 368.3338 216.7369 Tm
[(.)-296.3(This)-297(procedure)-300.7(is)-295.7(formal)-10.9(ized)-293.9(as)-300.4(function)]TJ
/F5 1 Tf
-26.1708 -1.2007 TD
[(ExtendF)-11.3(rag)]TJ
/F1 1 Tf
5.0475 0 TD
[(in)-254.7(Append)-10.3(ix)-249(A.)]TJ
/F5 1 Tf
10.959 0 0 10.959 117.5811 175.8614 Tm
[(2.2.2.)-497(Inferring)-242.1(likely)-242.2(sets)-245.4(of)-243.3(K)-244.5(partial)-241.4(strains.)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 331.8235 175.8614 Tm
-.0149 Tc
[(Hav)-14.9(i)9.3(ng)-237.6(gen)-14.9(e)10.2(rated)-237.6(t)-1.4(h)-14.9(e)-223.1(p)-14.9(r)10(oba)-14.9(b)10.2(l)-1.4(e)-239.4(p)1.4(artial)-234.7(s)-14.9(t)8.1(r)-.6(ain,)]TJ
/F5 1 Tf
17.4927 0 TD
0 Tc
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 512.2203 174.3874 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
1.0081 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 535.4645 175.8614 Tm
(,)Tj
-42.9466 -1.2007 TD
[(w)12.4(e)-423.7(de)25.1(n)16.3(o)0(t)24.2(e)-423.7(t)13.5(h)16.3(e)-429.3(s)15.1(e)14.5(t)-424.6(of)-413.2(a)14.5(l)13.5(l)-424.6(i)13.5(t)13.5(s)-423.1(po)26.9(s)15.1(s)15.1(i)13.5(bl)24.2(e)-423.7(s)15.1(ub)26.9(s)15.1(e)0(t)28.1(s)-428.7(o)16.3(f)]TJ
/F5 1 Tf
19.8145 0 TD
(K)Tj
/F1 1 Tf
1.0926 0 TD
-.0149 Tc
[(s)-14.9(t)8.1(rains)-443.6(\()-.6(i)4.3(.)-14.9(e)10.6(.)1.8(,)-442.1(t)-1.4(he)-444.2(qu)-14.9(a)10.2(s).2(ispe)-14.9(c)8.4(i)-1.4(es)-438(p)-14.9(o)12(p)-14.9(u)12(lation)-442.5(can)-14.9(d)12(i)-1.4(d)-14.9(a)10.2(tes\))-438.8(a)-14.9(s)]TJ
/F7 1 Tf
-20.9071 -1.8893 TD
0 Tc
(Q)Tj
/F1 1 Tf
6.9738 0 0 6.9738 115.7102 143.4897 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F6 1 Tf
9.9626 0 0 9.9626 140.6551 145.0771 Tm
(=)Tj
/F5 1 Tf
1.3031 0 TD
(Q)Tj
6.9738 0 0 6.9738 160.7811 148.7055 Tm
(i)Tj
/F1 1 Tf
0 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 184.0818 145.0771 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(i)Tj
/F6 1 Tf
.4439 0 TD
(=)Tj
/F1 1 Tf
.7227 0 TD
(1)Tj
/F7 1 Tf
1.1666 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F7 1 Tf
1.2292 .5975 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 246.5007 149.5559 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 269.8015 151.0298 Tm
(j)Tj
/F5 1 Tf
-1.8437 -1.2007 TD
(K)Tj
/F9 1 Tf
-2.2762 2.0145 TD
3.8291 Tc
()Tj
-8.2911 0 TD
12.6626 Tc
()Tj
/F1 1 Tf
14.8353 -1.4113 TD
-.0124 Tc
[(wh)-12.4(e)12.7(r)1.9(e)]TJ
/F5 1 Tf
3.0558 0 TD
0 Tc
(Q)Tj
6.9738 0 0 6.9738 331.54 148.7055 Tm
(i)Tj
/F1 1 Tf
0 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F6 1 Tf
9.9626 0 0 9.9626 356.4849 145.0771 Tm
(=)Tj
/F7 1 Tf
.717 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(q)Tj
6.9738 0 0 6.9738 373.6062 148.7055 Tm
(i)Tj
0 -.9186 TD
-.0161 Tc
(kn)Tj
/F1 1 Tf
9.9626 0 0 9.9626 380.5794 145.0771 Tm
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(k)Tj
/F6 1 Tf
.6373 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
/F7 1 Tf
1.1723 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(K)Tj
/F1 1 Tf
.7284 0 TD
()Tj
/F5 1 Tf
.5008 0 TD
(n)Tj
/F6 1 Tf
.6658 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
/F7 1 Tf
1.1723 0 TD
.1682 Tc
()Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F5 1 Tf
.5008 0 TD
(t)Tj
/F7 1 Tf
.3016 0 TD
(g)Tj
/F1 1 Tf
1.1723 0 TD
-.0145 Tc
[(an)-14.5(d)]TJ
/F5 1 Tf
2.0827 0 TD
0 Tc
(q)Tj
6.9738 0 0 6.9738 525.033 148.7055 Tm
(i)Tj
0 -.9186 TD
-.0243 Tc
(kn)Tj
/F7 1 Tf
9.9626 0 0 9.9626 533.0833 145.0771 Tm
0 Tc
(2)Tj
/F5 1 Tf
-42.7076 -1.9575 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 113.726 124.1007 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 136.97 125.5748 Tm
-.0149 Tc
[(.)-334(T)-4.1(he)-336.1(log)-14.9(-)10(likeliho)-14.9(o)12(d)-14.9(s)-319.2(o)-14.9(f)]TJ
/F5 1 Tf
9.7536 0 TD
0 Tc
(Q)Tj
6.9738 0 0 6.9738 241.3417 129.2031 Tm
(i)Tj
/F1 1 Tf
0 -.9186 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 267.9306 125.5748 Tm
-.0147 Tc
[(can)-334.1(be)-335.9(ex)-14.7(p)12.2(r)-.4(es)-14.7(s)9.8(e)-.2(d)-334.1(a)-.2(s)-335.3(f)-.4(ollo)-14.7(w)8.3(s).4(:)]TJ
-2.3274 -3.1924 TD
0 Tc
(ln)Tj
/F5 1 Tf
.7853 0 TD
(P)Tj
/F1 1 Tf
.6146 0 TD
(\()Tj
/F2 1 Tf
.3357 0 TD
(S)Tj
/F7 1 Tf
.552 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(Q)Tj
6.9738 0 0 6.9738 277.3983 97.8519 Tm
(i)Tj
/F1 1 Tf
0 -.9837 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
1.008 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 300.6424 93.7701 Tm
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
/F9 1 Tf
.9105 .9446 TD
(X)Tj
/F5 1 Tf
6.9738 0 0 6.9738 318.7841 105.222 Tm
(M)Tj
-.6178 -3.1867 TD
(m)Tj
/F6 1 Tf
.8861 0 TD
(=)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 330.8597 93.7701 Tm
(ln)Tj
/F5 1 Tf
.7796 0 TD
(P)Tj
/F1 1 Tf
.6203 0 TD
(\()Tj
/F5 1 Tf
.3301 0 TD
(s)Tj
6.9738 0 0 6.9738 351.9495 92.2961 Tm
(m)Tj
/F7 1 Tf
.7235 0 TD
()Tj
9.9626 0 0 9.9626 359.3763 93.7701 Tm
(j)Tj
/F5 1 Tf
.2731 0 TD
(Q)Tj
6.9738 0 0 6.9738 369.2408 97.8519 Tm
(i)Tj
/F1 1 Tf
0 -.9837 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 392.4849 93.7701 Tm
(\))Tj
/F2 1 Tf
-28.595 64.6048 TD
[(A)-334.8(BAYE)-9(SIAN)-341.4(METHOD)-340.5(FOR)-339.6(QUA)-8(SISP)-8.2(ECIES)-336.3(REC)-9.2(ONST)-8.7(RUCTI)-10.1(ON)-10587.7(641)]TJ
ET
endstream
endobj
68 0 obj
<>stream
/GS1 gs
BT
/F5 1 Tf
9.9626 0 0 9.9626 198.1417 702.0848 Tm
0 0 0 rg
0 Tc
0 Tw
(P)Tj
/F1 1 Tf
.6146 0 TD
(\()Tj
/F5 1 Tf
.3301 0 TD
(s)Tj
6.9738 0 0 6.9738 211.4078 700.6108 Tm
(m)Tj
/F7 1 Tf
.7235 0 TD
()Tj
9.9626 0 0 9.9626 218.8346 702.0848 Tm
(j)Tj
/F5 1 Tf
.2731 0 TD
(Q)Tj
6.9738 0 0 6.9738 228.6991 706.2234 Tm
(i)Tj
/F1 1 Tf
0 -.9918 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
1.008 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 251.9999 702.0848 Tm
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
ET
265.776 704.409 7.2567 .39691 re
f
BT
/F1 1 Tf
9.9626 0 0 9.9626 266.9102 708.888 Tm
(1)Tj
/F5 1 Tf
-.1138 -1.3657 TD
(K)Tj
/F9 1 Tf
1.6787 1.6332 TD
(X)Tj
/F5 1 Tf
6.9738 0 0 6.9738 287.1495 713.5368 Tm
(K)Tj
-.5691 -3.1949 TD
(k)Tj
/F6 1 Tf
.6422 0 TD
(=)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F9 1 Tf
9.9626 0 0 9.9626 304.8944 711.5526 Tm
(Y)Tj
/F5 1 Tf
6.9738 0 0 6.9738 310.1668 713.5368 Tm
(t)Tj
-.7967 -3.1867 TD
(n)Tj
/F6 1 Tf
.6747 0 TD
(=)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
9.9626 0 0 9.9626 319.4645 702.0848 Tm
(P)Tj
/F1 1 Tf
.6146 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(s)Tj
6.9738 0 0 6.9738 332.7873 700.6108 Tm
(mn)Tj
/F7 1 Tf
9.9626 0 0 9.9626 341.8015 702.0848 Tm
(j)Tj
/F5 1 Tf
.2675 0 TD
(q)Tj
6.9738 0 0 6.9738 349.455 706.2234 Tm
(i)Tj
0 -.9918 TD
(kn)Tj
/F1 1 Tf
9.9626 0 0 9.9626 356.5983 702.0848 Tm
(\))Tj
/F9 1 Tf
-5.9978 1.7129 TD
5.5526 Tc
( !)Tj
-2.2193 0 TD
8.5515 Tc
( !)Tj
/F1 1 Tf
10.1178 -1.7129 TD
0 Tc
()Tj
-30.2566 -2.8908 TD
[(whe)-8(re)]TJ
/F5 1 Tf
2.7884 0 TD
(s)Tj
6.9738 0 0 6.9738 105.7322 671.7542 Tm
(m)Tj
/F7 1 Tf
.7154 0 TD
()Tj
/F1 1 Tf
9.9626 0 0 9.9626 116.4472 673.2849 Tm
[(denot)-8.4(es)-334.6(the)]TJ
/F5 1 Tf
4.9678 0 TD
(m)Tj
6.9738 0 0 6.9738 173.0834 676.8565 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 182.381 673.2849 Tm
[(row)-338.3(vector)-337.2(of)-333.6(the)-336.9(matri)-10.9(x)-330.8(o)0(f)-333.6(super)-8.8(-reads)]TJ
/F2 1 Tf
16.5538 0 TD
(S)Tj
/F1 1 Tf
.8877 0 TD
(and)Tj
/F5 1 Tf
-17.7033 -2.6859 TD
(P)Tj
/F1 1 Tf
.6146 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(s)Tj
6.9738 0 0 6.9738 193.096 645.0518 Tm
(mn)Tj
/F7 1 Tf
9.9626 0 0 9.9626 202.1102 646.5258 Tm
(j)Tj
/F5 1 Tf
.2675 0 TD
(q)Tj
6.9738 0 0 6.9738 209.7637 650.6644 Tm
(i)Tj
0 -.9918 TD
(kn)Tj
/F1 1 Tf
9.9626 0 0 9.9626 216.907 646.5258 Tm
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
/F1 1 Tf
1.6389 .6999 TD
(1)Tj
/F6 1 Tf
.6658 0 TD
(-)Tj
/F10 1 Tf
.7227 0 TD
(e)Tj
/F5 1 Tf
6.9738 0 0 6.9738 255.8551 651.9683 Tm
(mn)Tj
/F1 1 Tf
9.9626 0 0 9.9626 264.8692 653.499 Tm
1.1693 Tc
[(i)1169.3(f)]TJ
/F5 1 Tf
2.5038 0 TD
0 Tc
(q)Tj
6.9738 0 0 6.9738 294.8031 657.1274 Tm
(i)Tj
0 -.9186 TD
(kn)Tj
/F6 1 Tf
9.9626 0 0 9.9626 303.5905 653.499 Tm
(=)Tj
/F5 1 Tf
.717 0 TD
(s)Tj
6.9738 0 0 6.9738 314.5889 651.9683 Tm
(mn)Tj
/F1 1 Tf
9.9626 0 0 9.9626 323.6031 653.499 Tm
()Tj
ET
238.224 643.805 11.055 .39685 re
f
BT
/F10 1 Tf
6.9738 0 0 6.9738 239.1306 645.6754 Tm
(e)Tj
/F5 1 Tf
4.9813 0 0 4.9813 241.7952 644.5983 Tm
(mn)Tj
/F7 1 Tf
6.9738 0 0 6.9738 238.2235 638.1353 Tm
(j)Tj
/F5 1 Tf
.2683 0 TD
(B)Tj
4.9813 0 0 4.9813 244.4031 637.0581 Tm
(n)Tj
/F7 1 Tf
6.9738 0 0 6.9738 247.4078 638.1353 Tm
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 250.9228 641.5369 Tm
2.5692 Tc
[(i)2569.2(f)]TJ
/F5 1 Tf
3.9037 0 TD
0 Tc
(q)Tj
6.9738 0 0 6.9738 294.8031 645.1652 Tm
(i)Tj
0 -.9186 TD
(kn)Tj
/F7 1 Tf
9.9626 0 0 9.9626 304.6676 641.5369 Tm
(6)Tj
0 0 TD
()Tj
/F5 1 Tf
1.0527 0 TD
(s)Tj
6.9738 0 0 6.9738 319.0109 640.0061 Tm
(mn)Tj
/F1 1 Tf
9.9626 0 0 9.9626 337.9464 641.5369 Tm
(for)Tj
/F5 1 Tf
2.1738 0 TD
(s)Tj
6.9738 0 0 6.9738 363.4015 640.0061 Tm
(mn)Tj
/F7 1 Tf
9.9626 0 0 9.9626 375.1936 641.5369 Tm
(6)Tj
T*
()Tj
/F6 1 Tf
1.2178 0 TD
(-)Tj
/F11 1 Tf
.7227 0 TD
(:)Tj
/F9 1 Tf
-16.6107 1.912 TD
()Tj
/F1 1 Tf
-14.5507 -4.0687 TD
.013 Tc
(Let)Tj
/F5 1 Tf
1.6673 0 TD
0 Tc
(Q)Tj
6.9738 0 0 6.9738 107.8299 623.6219 Tm
.0211 Tc
(max)Tj
/F1 1 Tf
0 -.9105 TD
0 Tc
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
9.9626 0 0 9.9626 121.8897 620.0502 Tm
(=)Tj
/F1 1 Tf
2.2876 0 TD
.0148 Tc
(max)Tj
/F5 1 Tf
6.9738 0 0 6.9738 129.033 612.7368 Tm
0 Tc
(Q)Tj
4.9813 0 0 4.9813 134.0787 615.1179 Tm
(i)Tj
/F1 1 Tf
0 -.9788 TD
(1)Tj
/F8 1 Tf
.5008 0 TD
(:)Tj
/F5 1 Tf
.2731 0 TD
(t)Tj
/F6 1 Tf
.4666 0 TD
(-)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
/F5 1 Tf
1.0015 0 TD
(t)Tj
/F7 1 Tf
6.9738 0 0 6.9738 150.8598 612.7368 Tm
(2Q)Tj
/F1 1 Tf
4.9813 0 0 4.9813 161.1212 611.603 Tm
(1)Tj
/F8 1 Tf
.5008 0 TD
(:)Tj
/F5 1 Tf
.2618 0 TD
(t)Tj
/F6 1 Tf
.478 0 TD
(-)Tj
/F1 1 Tf
.717 0 TD
(1)Tj
/F5 1 Tf
1.0015 0 TD
(t)Tj
9.9626 0 0 9.9626 179.4897 620.0502 Tm
(P)Tj
/F1 1 Tf
.6203 0 TD
(\()Tj
/F2 1 Tf
.3301 0 TD
(S)Tj
/F7 1 Tf
.5577 0 TD
(j)Tj
/F5 1 Tf
.2675 0 TD
(Q)Tj
6.9738 0 0 6.9738 204.3779 623.6219 Tm
(i)Tj
/F1 1 Tf
0 -.9105 TD
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 227.622 620.0502 Tm
.0115 Tc
[(\))11.5(.)-287.5(Among)-285.2(th)-6.3(e)]TJ
/F7 1 Tf
6.675 .5975 TD
0 Tc
(j)Tj
/F5 1 Tf
.2731 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 302.9668 624.5289 Tm
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 326.2109 626.003 Tm
(j)Tj
/F5 1 Tf
-1.838 -1.2007 TD
(K)Tj
/F9 1 Tf
-2.2819 2.0088 TD
3.8291 Tc
()Tj
/F1 1 Tf
5.571 -1.4056 TD
.0145 Tc
[(sets)-277.7(in)]TJ
/F7 1 Tf
2.9249 0 TD
0 Tc
(Q)Tj
/F1 1 Tf
6.9738 0 0 6.9738 377.9149 618.4061 Tm
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 401.1589 620.0502 Tm
.0131 Tc
[(,)-283.2(w)2.7(e)-285.4(k)1(eep)-283.6(only)-277.9(t)-1.8(hose)-285.4(t)3.9(h)-4.7(a)4.9(t)]TJ
-32.8288 -1.9006 TD
.0141 Tc
[(satisf)5.7(y)]TJ
/F5 1 Tf
2.9875 0 TD
0 Tc
(P)Tj
/F1 1 Tf
.6146 0 TD
(\()Tj
/F2 1 Tf
.3357 0 TD
(S)Tj
/F7 1 Tf
.552 0 TD
(j)Tj
/F5 1 Tf
.2731 0 TD
(Q)Tj
6.9738 0 0 6.9738 128.6929 604.6865 Tm
(i)Tj
/F1 1 Tf
0 -.9105 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 151.9937 601.1148 Tm
(\))Tj
/F11 1 Tf
.6089 0 TD
(>)Tj
/F10 1 Tf
1.0528 0 TD
(d)Tj
/F1 1 Tf
6.9738 0 0 6.9738 173.537 599.5841 Tm
(1)Tj
/F7 1 Tf
9.9626 0 0 9.9626 179.7165 601.1148 Tm
()Tj
/F5 1 Tf
.4951 0 TD
(Q)Tj
6.9738 0 0 6.9738 191.7921 604.6865 Tm
.0211 Tc
(max)Tj
/F1 1 Tf
0 -.9105 TD
0 Tc
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 204.2078 601.1148 Tm
.0133 Tc
[(,)-283(w)2.9(hile)-279.5(the)-279.5(o)1.2(thers)-278.9(a)-.6(re)-285.2(dis)5.7(carded;)-286.1(let)-280.4(u)1.2(s)-284.6(d)1.2(enote)-279.5(t)-1.6(he)-285.2(collection)-283.4(o)1.2(f)-285.4(c)-.6(a)5.1(n)-4.5(dida)5.1(te)]TJ
-13.0598 -1.2007 TD
.0138 Tc
[(sets)-420.6(that)-416.5(pass)-420.6(this)-420.6(t)4.6(e)-.1(st)-422.2(as)]TJ
/F7 1 Tf
11.2161 0 TD
0 Tc
(Q)Tj
/F1 1 Tf
6.9738 0 0 6.9738 193.9464 587.5652 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 201.9401 589.1526 Tm
.0131 Tc
[(.)-419.8(F)1.7(or)-422.1(practical)-422.9(feasibility)-420.2(of)-422.1(the)-421.9(s)-.2(cheme,)-419.8(the)-421.9(c)-.8(ollec)4.9(tion)-420.2(o)1(f)-422.1(p)1(artially)-420.2(re-)]TJ
-12.8322 -1.2007 TD
[(co)-4.8(nstructed)-266.6(s)-.3(trains)]TJ
/F5 1 Tf
8.0123 0 TD
0 Tc
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 160.0441 575.7164 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 186.0094 577.1904 Tm
.2828 Tc
[(i)273.6(s)-3.7(t)273.6(r)268.7(i)267.9(m)267.1(m)272.8(e)268.9(db)270.7(ye)268.9(x)265(c)268.9(l)273.6(u)270.7(d)270.6(i)267.9(n)270.6(g)-2.5(f)268.7(r)274.4(o)270.7(m)-6(i)273.6(t).4(a)268.9(l)267.9(lt)267.9(h)270.7(e)1.4(s)269.5(t)267.9(r)274.4(a)268.9(i)267.9(n)270.7(st)273.6(h)270.7(a)268.9(ta)268.9(r)268.7(e)-4.3(n)270.6(o)270.7(tp)270.7(a)268.9(r)268.7(to)270.7(fa)268.9(tl)267.9(e)268.9(a)268.9(s)269.5(to)270.7(n)270.7(e)]TJ
-11.2331 -1.2007 TD
.0157 Tc
[(of)-294.3(th)3.6(e)-294.1(s)2.4(ets)-293.5(i).8(n)]TJ
/F7 1 Tf
5.6849 0 TD
0 Tc
(Q)Tj
/F1 1 Tf
6.9738 0 0 6.9738 138.8409 563.6408 Tm
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 146.8346 565.2282 Tm
.013 Tc
[(;)-297.8(w)-3.1(e)-296.8(d).9(enote)-302.5(t)3.8(he)-302.5(resulting)-300.7(c)-.9(ollection)-300.7(o).9(f)-302.7(p).9(ar)4.6(tial)-297.8(s)-.3(trains)-301.9(by)]TJ
/F5 1 Tf
23.4678 0 TD
0 Tc
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 386.8156 563.7542 Tm
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 397.5306 565.2282 Tm
(2)Tj
/F5 1 Tf
.9389 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 413.0078 563.7542 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 439.2566 565.2282 Tm
.0138 Tc
[(and)-300(u)1.7(se)-296(it)-297(when)]TJ
-36.6528 -1.2007 TD
.0132 Tc
[(ext)4(e)-.7(nding)-533.9(t)-1.7(he)-535.6(st)4(rains)-535.1(o)1.1(nt)4(o)-533.9(t)-1.7(he)]TJ
/F5 1 Tf
13.8167 0 TD
0 Tc
(t)Tj
/F6 1 Tf
.4666 0 TD
(+)Tj
/F1 1 Tf
.7227 0 TD
.0132 Tc
[(1)-522.5(S)1.8(NV)-532.1(site.)-533.5(T)-4.5(he)-530(d)-4.6(e)-.7(scribed)-533.9(p)1.1(rocedure)-535.6(i)4(s)-535.1(f)-.9(ormalized)-533.9(as)-529.4(fun)-4.6(c)-.7(tion)]TJ
/F5 1 Tf
-15.006 -1.2007 TD
.0135 Tc
(InferQuasi)Tj
/F1 1 Tf
4.7971 0 TD
.0132 Tc
[(in)-329(Appendix)-334.7(A.)]TJ
/F5 1 Tf
10.959 0 0 10.959 84.0755 517.3794 Tm
0 Tc
[(2.2.3.)-497(Determining)-404.9(the)-406.7(number)-405.7(of)-403.7(strains)]TJ
/F1 1 Tf
17.6095 0 TD
(K)Tj
/F5 1 Tf
1.1226 0 TD
[(in)-408.8(a)-405.3(quasispecies.)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 380.4094 517.3794 Tm
[(In)-418.9(this)-413.8(ste)-8(p,)-410.9(we)-422.7(assess)-422.6(appro-)]TJ
-30.746 -1.195 TD
[(pri)-7(ateness)-249.2(of)]TJ
/F5 1 Tf
5.332 0 TD
(K)Tj
/F1 1 Tf
.9105 0 TD
[(used)-239.3(in)-243.3(the)-240.2(infere)-9.2(nce)-244.9(of)]TJ
/F7 1 Tf
9.6227 0 TD
(Q)Tj
/F1 1 Tf
6.9738 0 0 6.9738 240.2645 503.8865 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 250.6393 505.4739 Tm
[(and)-243.1(updat)-8.4(e)-235.9(i)0(t)-240.4(i)0(f)-245.3(necessary.)-246.4(To)-246(this)-243.1(end,)-237.8(we)-246.3(rely)-242.9(on)-240.5(the)-240.2(minimum)]TJ
-17.7204 -1.2007 TD
[(err)-8(or)-430.3(correctio)-10.3(n)-433.3(\()-82.4(MEC\))-438.3(score,)-437.7(which)-433.4(has)-437.7(previous)-8.1(ly)-431.1(been)-433.4(broad)-7.6(ly)-431.1(used)-432.8(as)-431.3(a)-435(criteri)-9.8(on)-428.3(in)-431.1(the)-433.6(desi)-8.8(gn)-428.3(of)]TJ
T*
[(methods)-407.2(for)-404.6(haplotyp)-7.7(e)-400.9(assembly)-405.3(\(Lanc)-9.2(ia)-398.7(et)-398.7(al.,)-405.2(2001;)-399.2(Lippe)-8.2(rt)-398.9(et)-398.7(al.,)-405.2(2002\).)-404.5(In)-396.2(the)-405.2(context)-401.4(o)-6.5(f)-395.4(polyp)-6.6(loid)]TJ
T*
[(hapl)-7.6(otype)-423.8(asse)-9(mbly,)-425.1(the)-422.2(MEC)-424.2(scor)-8(e)-418(i)0(s)-426.6(dened)-428.5(as)-419.9(the)-422.2(sma)-8.8(llest)-424.8(number)-427.3(of)-418.9(nucl)-7.6(eotides)-425.3(that)-425.8(needs)-429.7(to)-419.7(be)]TJ
T*
[(change)-9.9(d)-336.5(i)0(n)-340(data)-339.4(\(i.e.,)-340(in)-334.3(obser)-8.8(ved)-339.8(reads\))-343.3(so)-332.8(that)-340.4(the)-342.6(corrected)-345.1(read)-8.6(s)-332(are)-343.6(consistent)-346.2(with)-336.9(havi)-7.6(ng)-337.3(originate)-9.3(d)]TJ
T*
(from)Tj
/F5 1 Tf
2.2478 0 TD
(K)Tj
/F1 1 Tf
.9674 0 TD
[(haplotyp)-7.7(es.)-300.8(Let)]TJ
/F5 1 Tf
6.5384 0 TD
(HD)Tj
6.9738 0 0 6.9738 185.6125 444.1889 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 188.2204 445.6629 Tm
(\()Tj
/F7 1 Tf
.5577 0 TD
()Tj
/F1 1 Tf
.4951 0 TD
()Tj
/F7 1 Tf
.552 0 TD
()Tj
/F1 1 Tf
.4951 0 TD
[(\))-298.7(denote)-301.1(the)-302.7(Hammin)-8.7(g)-296.7(distanc)-9.9(e)-292.8(betwee)-10.9(n)-296.7(two)-299.2(seque)-8.6(nces)-303.7(counted)-301.9(over)-302.7(the)]TJ
-13.5549 -1.2007 TD
[(ob)-7.2(served)-341.4(nucl)-7.6(eotides)-340(in)-340(the)-342.6(rst)]TJ
/F5 1 Tf
13.4581 0 TD
(t)Tj
/F1 1 Tf
.6203 0 TD
[(SNV)-345.1(positions.*)-343(Th)-7(en,)-339.4(the)-336.9(ME)-9(C)-335.5(scor)-8(e)-338.3(o)0(f)-339.2(the)-336.9(mos)-7(t)-339.3(likely)-339(set)]TJ
/F5 1 Tf
25.3457 0 TD
(Q)Tj
6.9738 0 0 6.9738 474.0093 437.329 Tm
[(ma)-9.6(x)]TJ
/F1 1 Tf
0 -.9105 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 486.1983 433.7007 Tm
(of)Tj
/F5 1 Tf
1.1666 0 TD
(K)Tj
/F1 1 Tf
-42.5312 -1.2007 TD
[(vir)-7(al)-336.1(strains)-335.7(eval)-9.4(uated)-340.2(on)-331.6(the)-336.9(rst)]TJ
/F5 1 Tf
14.1183 0 TD
(t)Tj
/F1 1 Tf
.6146 0 TD
[(SNVs)-341.4(is)]TJ
-2.134 -3.016 TD
(MEC)Tj
/F5 1 Tf
6.9738 0 0 6.9738 221.2157 390.1605 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 223.8235 391.6912 Tm
(\()Tj
/F5 1 Tf
.3357 0 TD
(K)Tj
/F1 1 Tf
.7284 0 TD
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
/F9 1 Tf
.9048 .9446 TD
(X)Tj
/F5 1 Tf
6.9738 0 0 6.9738 252.5669 403.0865 Tm
(M)Tj
-.6178 -3.1786 TD
(m)Tj
/F6 1 Tf
.8861 0 TD
(=)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 274.8472 391.6912 Tm
(min)Tj
/F5 1 Tf
6.9738 0 0 6.9738 264.5858 384.7747 Tm
(k)Tj
/F7 1 Tf
.4715 0 TD
(2f)Tj
/F1 1 Tf
1.1544 0 TD
(1)Tj
/F7 1 Tf
1.0081 0 TD
()Tj
/F1 1 Tf
.8129 0 TD
()Tj
/F5 1 Tf
.4959 0 TD
(K)Tj
/F7 1 Tf
.7316 0 TD
(g)Tj
/F9 1 Tf
9.9626 0 0 9.9626 302.3432 401.1022 Tm
(X)Tj
/F7 1 Tf
6.9738 0 0 6.9738 303.2503 403.8802 Tm
(j)Tj
/F5 1 Tf
.2683 0 TD
(C)Tj
4.9813 0 0 4.9813 309.77 402.8597 Tm
(m)Tj
/F7 1 Tf
6.9738 0 0 6.9738 313.8519 403.8802 Tm
(j)Tj
/F5 1 Tf
-1.4552 -3.2924 TD
(j)Tj
/F6 1 Tf
.4471 0 TD
(=)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
/F5 1 Tf
9.9626 0 0 9.9626 318.3306 391.6912 Tm
(HD)Tj
6.9738 0 0 6.9738 332.6739 390.1605 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 335.2818 391.6912 Tm
(\()Tj
/F5 1 Tf
.3301 0 TD
(c)Tj
6.9738 0 0 6.9738 343.0487 395.7731 Tm
(j)Tj
0 -.9837 TD
(m)Tj
/F1 1 Tf
9.9626 0 0 9.9626 348.6046 391.6912 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(q)Tj
6.9738 0 0 6.9738 358.5826 395.7731 Tm
(max)Tj
0 -.9837 TD
(k)Tj
/F7 1 Tf
.4634 0 TD
()Tj
/F1 1 Tf
9.9626 0 0 9.9626 370.7149 391.6912 Tm
(\))Tj
-29.773 -2.9705 TD
[(whe)-8(re)]TJ
/F5 1 Tf
2.777 0 TD
(q)Tj
6.9738 0 0 6.9738 106.7527 365.7259 Tm
[(ma)-9.6(x)]TJ
0 -.9186 TD
(k)Tj
/F7 1 Tf
.4715 0 TD
()Tj
/F1 1 Tf
9.9626 0 0 9.9626 122.1732 362.0976 Tm
[(is)-324.2(the)]TJ
/F5 1 Tf
2.5437 0 TD
(k)Tj
6.9738 0 0 6.9738 152.2204 365.7259 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 161.4047 362.0976 Tm
[(row)-326.9(vector)-331.6(of)]TJ
/F5 1 Tf
5.8783 0 TD
(Q)Tj
6.9738 0 0 6.9738 227.1118 365.7259 Tm
(max)Tj
/F1 1 Tf
0 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 239.244 362.0976 Tm
[(.)-324.7(Let)]TJ
/F5 1 Tf
2.2478 0 TD
(N)Tj
7.4718 0 0 6.641 268.2708 360.3968 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 273.5999 362.0976 Tm
[(be)-327.7(the)-331.2(total)-326.9(numb)-6.6(er)-324(of)-327.9(nucleot)-8.7(ides)-327.5(observed)-331.5(in)-328.7(the)-325.5(rst)]TJ
/F5 1 Tf
22.8931 0 TD
(t)Tj
/F1 1 Tf
-42.9181 -1.2007 TD
[(SNV)-248.4(posi)-7(tions)-243.8(of)-248.2(all)-242.9(the)-245.8(read)-8.6(s)-241(o)0(f)-242.5(the)-245.8(data)-248.4(set.)-247.4(Note)-244.8(that)-249.4(the)-245.8(smaller)-248.7(the)-245.8(MEC)-247.8(scor)-8(es,)-243.9(the)-245.8(highe)-8.4(r)-241.7(the)-245.8(accuracy)]TJ
T*
[(of)-276.7(a)-281.4(clusteri)-9.7(ng.)-275.1(If)-278.6(MEC)]TJ
/F5 1 Tf
6.9738 0 0 6.9738 168.1511 336.6991 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 170.759 338.1731 Tm
(\()Tj
/F5 1 Tf
.3357 0 TD
(K)Tj
/F1 1 Tf
.7284 0 TD
(\))Tj
/F11 1 Tf
.3357 0 TD
(=)Tj
/F5 1 Tf
.5008 0 TD
(N)Tj
6.9738 0 0 6.9738 196.3275 336.6991 Tm
(t)Tj
/F11 1 Tf
9.9626 0 0 9.9626 201.7133 338.1731 Tm
(<)Tj
/F1 1 Tf
1.0471 0 TD
(2)Tj
/F11 1 Tf
.5008 0 TD
()Tj
/F1 1 Tf
.3983 0 TD
[(,)-273.5(w)0(e)-280.4(use)-278.4(the)-280(same)-278.8(valu)-7.6(e)]TJ
/F5 1 Tf
9.8845 0 TD
(K)Tj
/F1 1 Tf
.9446 0 TD
[(in)-277.4(the)-274.3(next)-280.8(step)-281.9(where)-280.8(the)-280(likely)-282.1(set)-275.5(of)-276.7(vir)-7(al)]TJ
-25.5847 -1.2007 TD
[(str)-8.2(ains)-338.8(stretching)-341.3(over)-342.6(the)-336.9(rst)]TJ
/F5 1 Tf
12.8322 0 TD
(t)Tj
/F6 1 Tf
.4666 0 TD
(+)Tj
/F1 1 Tf
.717 0 TD
[(1)-336.5(SNV)-339.4(posi)-7(tions)-334.9(is)-341.2(inferred.)-343.1(Otherwise,)-346(we)-337.3(increas)-10.9(e)]TJ
/F5 1 Tf
21.7322 0 TD
(K)Tj
/F1 1 Tf
1.0015 0 TD
[(by)-337.3(1,)-336.9(repeat)-339(the)]TJ
-36.7496 -1.2007 TD
[(est)-8(imation)-337.6(of)]TJ
/F7 1 Tf
5.6962 0 TD
(Q)Tj
/F1 1 Tf
6.9738 0 0 6.9738 139.011 312.6613 Tm
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 146.948 314.2487 Tm
[(,)-336.1(and)-334.1(eval)-9.4(uate)-339.4(the)-331.2(im)-7.8(proveme)-8.7(nt)-334.3(rate)-335.7(of)-333.6(MEC)-338.8(scor)-8(e)-332.6(a)0(s)-334.6(fol)-7(lows:)]TJ
/F5 1 Tf
5.8613 -2.5152 TD
(MECimpr)Tj
/F1 1 Tf
4.0403 0 TD
(\()Tj
/F5 1 Tf
.3301 0 TD
(K)Tj
/F1 1 Tf
.7284 0 TD
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
ET
269.972 291.458 98.929 .39685 re
f
BT
/F1 1 Tf
9.9626 0 0 9.9626 269.9716 295.9936 Tm
(MEC)Tj
/F5 1 Tf
6.9738 0 0 6.9738 291.6283 294.4629 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 294.2361 295.9936 Tm
(\()Tj
/F5 1 Tf
.33 0 TD
(K)Tj
/F1 1 Tf
.7284 0 TD
(\))Tj
/F6 1 Tf
.5008 0 TD
(-)Tj
/F1 1 Tf
.7227 0 TD
(MEC)Tj
/F5 1 Tf
6.9738 0 0 6.9738 338.57 294.4629 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 341.1779 295.9936 Tm
(\()Tj
/F5 1 Tf
.3357 0 TD
(K)Tj
/F6 1 Tf
.8934 0 TD
(+)Tj
/F1 1 Tf
.7227 0 TD
(1\))Tj
-6.0491 -1.3714 TD
(MEC)Tj
/F5 1 Tf
6.9738 0 0 6.9738 322.0157 280.8566 Tm
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 324.6235 282.3307 Tm
(\()Tj
/F5 1 Tf
.3301 0 TD
(K)Tj
/F1 1 Tf
.7341 0 TD
(\))Tj
/F11 1 Tf
3.5509 .6886 TD
(:)Tj
/F1 1 Tf
-28.76 -2.5038 TD
.0089 Tc
[(The)-369.2(r)-5.2(ea)-5(s)-4.4(o)2.4(n)-373.1(f)-5.2(or)-375.1(se)-5(le)-5(ct)-6(ing)]TJ
/F5 1 Tf
10.6186 0 TD
0 Tc
(K)Tj
/F1 1 Tf
1.0471 0 TD
.0122 Tc
[(based)-369.8(o)5.7(n)-369.8(t)3(he)-365.9(MEC)-368.9(i)3(mp)5.7(rov)5.7(e)-1.7(ment)-366.9(rate)-371.6(\()]TJ
/F5 1 Tf
16.4059 0 TD
.012 Tc
[(MECi)2.8(mpr)]TJ
/F1 1 Tf
4.0801 0 TD
.0113 Tc
[(\))-367(i)2.1(s)-371.9(t)2.1(hat)-367.8(t)-3.6(he)-366.8(MEC)-369.8(s)3.7(core)]TJ
-33.1531 -1.2007 TD
[(dro)4.9(p)-.7(s)-400.3(s)3.8(ignicantly)-393.4(o)-.7(nce)]TJ
/F5 1 Tf
10.4934 0 TD
0 Tc
(K)Tj
/F1 1 Tf
1.0755 0 TD
.0116 Tc
[(matches)-394.4(t)2.4(he)-395(actual)-396(number)-395.2(o)5.1(f)-400.9(c)3.4(lusters;)]TJ
16.9009 0 TD
.0093 Tc
[(our)-397.5(s)-4(c)-4.6(h)-2.8(eme)-403(a)1.1(t)-5.6(t).1(e)-4.6(m)-.7(pts)-396.7(t).1(o)-401.2(d)-2.8(et)-5.6(ec)-4.6(t)-398.3(t).1(hat)]TJ
-28.4698 -1.2007 TD
.0107 Tc
[(change)-469.9(to)-473.8(infer)-470.1(p)4.2(opulation)-468.1(s)-2.6(ize.)-473.4(If)]TJ
/F5 1 Tf
15.4328 0 TD
.011 Tc
[(MEC)-5.9(i)1.8(mpr)]TJ
/F1 1 Tf
4.0972 0 TD
0 Tc
(\()Tj
/F5 1 Tf
.3357 0 TD
(K)Tj
/F1 1 Tf
.7284 0 TD
(\))Tj
/F11 1 Tf
.6089 0 TD
(>)Tj
/F10 1 Tf
1.0527 0 TD
(g)Tj
/F1 1 Tf
.5008 0 TD
.4784 Tc
[(,w)468(h)466.3(e)464.5(r)470(e)]TJ
/F10 1 Tf
3.6989 0 TD
0 Tc
(g)Tj
/F1 1 Tf
.9731 0 TD
.0115 Tc
[(denotes)-468.5(a)-469.1(p)-.6(respecied)-467.3(th)5(reshold,)-466.9(the)]TJ
-27.4284 -1.195 TD
0 Tc
[(n)-12.1(u)-12.2(m)-10(b)-12.2(e)-13.9(r)-361.2(o)-12.1(f)-361.2(s)-13.3(p)-12.2(e)-8.2(c)-13.9(i)-9.2(e)-13.9(s)-360.5(i)0(s)-358.3(updated)-358.8(as)]TJ
/F5 1 Tf
13.7597 0 TD
(K)Tj
/F12 1 Tf
.7284 0 TD
(\))Tj
/F1 1 Tf
1.3657 0 TD
(min)Tj
/F7 1 Tf
1.5649 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(K)Tj
/F6 1 Tf
.8934 0 TD
(+)Tj
/F5 1 Tf
.7227 0 TD
(n)Tj
/F1 1 Tf
.5008 0 TD
()Tj
/F7 1 Tf
.5008 0 TD
(j)Tj
/F5 1 Tf
.2675 0 TD
(F)Tj
/F1 1 Tf
6.9738 0 0 6.9738 287.4897 226.885 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F6 1 Tf
.4715 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
.9999 0 TD
(t)Tj
/F7 1 Tf
9.9626 0 0 9.9626 310.7904 228.4157 Tm
(jg)Tj
/F1 1 Tf
1.121 0 TD
[(whe)-8(re)]TJ
/F5 1 Tf
2.8054 0 TD
(n)Tj
/F1 1 Tf
.8536 0 TD
[(is)-358.3(the)-354(smallest)-365.3(integer)-357.8(numb)-6.6(er)-352.4(such)]TJ
-28.5381 -1.2007 TD
(that)Tj
/F5 1 Tf
1.8722 0 TD
[(MEC)-9.6(impr)]TJ
/F1 1 Tf
4.0403 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(K)Tj
/F6 1 Tf
.8934 0 TD
(+)Tj
/F5 1 Tf
.717 0 TD
(n)Tj
/F1 1 Tf
.5008 0 TD
(\))Tj
/F11 1 Tf
.6146 0 TD
(<)Tj
/F10 1 Tf
1.0471 0 TD
(g)Tj
/F1 1 Tf
.5065 0 TD
.3532 Tc
[(.I)353.2(f)]TJ
/F5 1 Tf
1.6332 0 TD
0 Tc
(MECimpr)Tj
/F1 1 Tf
4.0346 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(K)Tj
/F1 1 Tf
.7284 0 TD
(\))Tj
/F11 1 Tf
.6146 0 TD
(<)Tj
/F10 1 Tf
1.0471 0 TD
(g)Tj
/F1 1 Tf
.5008 0 TD
[(,)-358.9(w)0(e)-360.1(updat)-8.4(e)-355.4(the)-365.3(number)-364.7(of)-356.3(speci)-11.3(es)-357.3(as)]TJ
/F5 1 Tf
15.8368 0 TD
(K)Tj
/F12 1 Tf
.7284 0 TD
(\))Tj
/F1 1 Tf
1.3657 0 TD
(max)Tj
/F7 1 Tf
1.7299 0 TD
(f)Tj
/F5 1 Tf
.5008 0 TD
(K)Tj
/F6 1 Tf
.8934 0 TD
(-)Tj
/F5 1 Tf
.7227 0 TD
(n)Tj
/F1 1 Tf
.5008 0 TD
.1678 Tc
(2)Tj
/F7 1 Tf
1.0015 0 TD
0 Tc
(g)Tj
/F1 1 Tf
-42.7019 -1.2007 TD
[(whe)-8(re)]TJ
/F5 1 Tf
2.7941 0 TD
(n)Tj
/F1 1 Tf
.8422 0 TD
[(is)-341.2(the)-342.6(sma)-8.8(llest)-345.1(integer)-346.5(such)-341.8(that)]TJ
/F5 1 Tf
13.3842 0 TD
[(MECimp)-12.8(r)]TJ
/F1 1 Tf
4.0403 0 TD
(\()Tj
/F5 1 Tf
.3301 0 TD
(K)Tj
/F6 1 Tf
.8991 0 TD
(-)Tj
/F5 1 Tf
.717 0 TD
(n)Tj
/F1 1 Tf
.5008 0 TD
(\))Tj
/F7 1 Tf
.6146 0 TD
()Tj
/F10 1 Tf
1.0471 0 TD
(g)Tj
/F1 1 Tf
.5008 0 TD
[(.)-341.8(The)-345.3(choice)-348.4(of)-339.2(thr)-7(eshold)]TJ
/F10 1 Tf
10.721 0 TD
(g)Tj
/F1 1 Tf
.8422 0 TD
[(is)-341.2(discusse)-10.3(d)-336.5(i)0(n)]TJ
-37.2333 -1.2007 TD
[(Appe)-8.8(ndix)-279(B.)-284.7(The)-277(u)-6.5(pdated)-284.1(value)-283.3(of)]TJ
/F5 1 Tf
14.306 0 TD
(K)Tj
/F1 1 Tf
.9503 0 TD
[(is)-278.6(used)-279.2(for)-285.1(the)-280(infere)-9.2(nce)-279(of)]TJ
/F7 1 Tf
11.1535 0 TD
(Q)Tj
/F1 1 Tf
6.9738 0 0 6.9738 345.3164 190.9417 Tm
(1)Tj
/F8 1 Tf
.4959 0 TD
(:)Tj
/F5 1 Tf
.2764 0 TD
(t)Tj
/F6 1 Tf
.4634 0 TD
(+)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
9.9626 0 0 9.9626 362.9479 192.5291 Tm
[(.)-279.2(Note)-284.7(that)-283.5(the)-280(proba)-7.6(ble)-280(set)-281.2(of)-276.7(vir)-7(al)]TJ
-28.9934 -1.2007 TD
[(str)-8.2(ains,)]TJ
/F7 1 Tf
3.2038 0 TD
(Q)Tj
/F1 1 Tf
6.9738 0 0 6.9738 114.1228 178.9795 Tm
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(t)Tj
/F1 1 Tf
9.9626 0 0 9.9626 122.1165 180.5669 Tm
[(,)-336.1(i)0(s)-335.5(stored)-336.7(for)-336.3(each)]TJ
/F5 1 Tf
8.0521 0 TD
(K)Tj
/F1 1 Tf
1.0015 0 TD
[(to)-334.3(avoi)-7.6(d)-330.8(perf)-8.8(orming)-337.2(redun)-7.6(dant)]TJ
/F5 1 Tf
12.8891 0 TD
(MECimpr)Tj
/F1 1 Tf
4.0346 0 TD
(\()Tj
/F7 1 Tf
.5577 0 TD
()Tj
/F1 1 Tf
.4951 0 TD
[(\))-332.8(calcul)-9.8(ations.)]TJ
-30.8485 -1.2007 TD
[(Onc)-8(e)-423.7(w)0(e)-428.3(obta)-7.6(in)-425.4(the)-427.9(mos)-7(t)-424.6(likely)-430.1(set)-429.1(of)]TJ
/F5 1 Tf
16.6335 0 TD
(K)Tj
/F1 1 Tf
1.0983 0 TD
[(viral)-428.5(seque)-8.6(nces)-428.9(covering)]TJ
/F5 1 Tf
10.7096 0 TD
(N)Tj
/F1 1 Tf
1.0926 0 TD
(SNVs,)Tj
/F5 1 Tf
3.0558 0 TD
(Q)Tj
6.9738 0 0 6.9738 415.8991 172.233 Tm
(max)Tj
/F1 1 Tf
0 -.9186 TD
(1)Tj
/F8 1 Tf
.504 0 TD
(:)Tj
/F5 1 Tf
.2683 0 TD
(N)Tj
/F1 1 Tf
9.9626 0 0 9.9626 428.0314 168.6047 Tm
[(,)-427.2(the)-427.9(ful)-7(l-length)]TJ
/F5 1 Tf
7.0108 0 TD
(K)Tj
/F1 1 Tf
-42.5369 -1.2007 TD
[(qu)-7.2(asispecies)-359.6(strains)-352.7(are)-355(reconstruct)-13(ed)-350.4(by)-348.7(inserting)-355.8(the)-348.3(conse)-8.6(nsus)-352.6(nucleot)-8.7(ides)-350.2(obser)-8.8(ved)-351.2(in)]TJ
/F5 1 Tf
36.9089 0 TD
(R)Tj
/F1 1 Tf
.9617 0 TD
[(int)-7.8(o)-347.9(the)-348.3(non-)]TJ
-37.8706 -1.2007 TD
[(SNV)-299.6(sites.)-292.7(We)-296.1(estimate)-297.6(relative)-300.6(frequenc)-9.7(ies)]TJ
/F5 1 Tf
18.187 0 TD
(p)Tj
7.4718 0 0 6.641 260.2771 143.0362 Tm
(k)Tj
/F1 1 Tf
9.9626 0 0 9.9626 263.622 144.6803 Tm
.2906 Tc
(,1)Tj
/F7 1 Tf
1.3202 0 TD
0 Tc
()Tj
/F5 1 Tf
1.0471 0 TD
(k)Tj
/F7 1 Tf
.7455 0 TD
()Tj
/F5 1 Tf
1.0528 0 TD
(K)Tj
/F1 1 Tf
.7284 0 TD
[(,)-290.6(o)0(f)-288(quasispe)-9.1(cie)-8.6(s)-286.5(strai)-8.6(ns)-287.2(based)-298.8(on)-291.7(the)-291.4(Hammin)-8.7(g)]TJ
-23.9174 -1.195 TD
[(distanc)-9.9(e)-378.1(betwee)-10.9(n)-370.7(super)-8.8(-reads)-383.2(and)-374(the)-382.4(reconstruct)-13(ed)-373.2(seque)-8.6(nces.)-378.1(In)-379.1(particula)-11.1(r,)-373(for)-381.8(each)-378.3(super)-8.8(-read)]TJ
/F5 1 Tf
40.3915 0 TD
(sr)Tj
6.9738 0 0 6.9738 484.1573 131.244 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 486.6519 132.7748 Tm
.376 Tc
[(,w)376(e)]TJ
-41.4101 -1.2007 TD
0 Tc
[(dete)-9.4(rmine)-463.4(the)-456.4(near)-8.6(est)-457.6(assembled)-464.7(str)-8.2(ain)]TJ
/F5 1 Tf
16.8099 0 TD
(q)Tj
7.4718 0 0 6.641 246.5574 119.1118 Tm
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 253.1905 120.8126 Tm
[(whe)-8(re)]TJ
/F5 1 Tf
2.9136 0 TD
(j)Tj
/F6 1 Tf
.4439 0 TD
(=)Tj
/F1 1 Tf
.8877 0 TD
[(arg)-1201.1(min)]TJ
/F5 1 Tf
6.9738 0 0 6.9738 309.9401 113.896 Tm
(k)Tj
/F7 1 Tf
.4715 0 TD
(2f)Tj
/F1 1 Tf
1.1544 0 TD
(1)Tj
/F7 1 Tf
.9999 0 TD
()Tj
/F1 1 Tf
.8129 0 TD
()Tj
/F5 1 Tf
.504 0 TD
(K)Tj
/F7 1 Tf
.7316 0 TD
(g)Tj
/F5 1 Tf
9.9626 0 0 9.9626 347.6975 120.8126 Tm
(HD)Tj
/F1 1 Tf
1.4397 0 TD
(\()Tj
/F5 1 Tf
.3301 0 TD
(sr)Tj
6.9738 0 0 6.9738 373.0393 119.2819 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 375.5338 120.8126 Tm
()Tj
/F5 1 Tf
.5008 0 TD
(q)Tj
6.9738 0 0 6.9738 385.5117 119.2819 Tm
(k)Tj
/F1 1 Tf
9.9626 0 0 9.9626 389.2534 120.8126 Tm
[(\),)-458.4(and)-459.3(the)-456.4(numb)-6.6(er)-460.5(of)-458.7(reads)]TJ
ET
q
1 i
74.098 94.054 m
504.51 94.054 l
504.51 69.902 l
74.098 69.902 l
W n
0 0 0 RG
1 J 1 j .454 w 10 M []0 d
q 1 0 0 1 74.098 94.054 cm 0 0 m
490.677 0 l
S
Q
Q
BT
8.9663 0 0 8.9663 84.0755 79.8803 Tm
[(*If)-408.4(either)-410.9(of)-406.3(the)-403.3(two)-410.5(sequences)-412.3(has)-406.8(a)-406.6(gap)-405.6()54.8()]TJ
/F6 1 Tf
18.583 0 TD
(-)Tj
/F1 1 Tf
.5501 0 TD
[()54.8()-406.8(in)-407.7(a)-406.6(position,)-404.3(that)-406.9(position)-407.7(is)-408.9(ignored)-410.3(in)-407.7(the)-403.3(computation)-407.1(of)-412.6(the)]TJ
-20.246 -1.1128 TD
[(aforementioned)-342.1(Hamming)-335.9(distance.)]TJ
/F2 1 Tf
9.9626 0 0 9.9626 74.0976 737.4045 Tm
[(64)-7.2(2)]TJ
34.0921 0 TD
[(AHN)-338(AND)-344.1(VIKALO)]TJ
ET
endstream
endobj
73 0 obj
<>stream
0 0 0 rg
/GS1 gs
107.603 686.154 430.356 .51025 re
f
107.603 375.364 430.356 .51022 re
f
107.603 667.729 430.356 .51025 re
f
BT
/F1 1 Tf
9.9626 0 0 9.9626 107.6031 715.4644 Tm
0 Tc
0 Tw
[(involved)-480(in)-470.9(construc)-9.9(ting)-475.2(the)-473.5(super-r)-8.6(ead)]TJ
/F5 1 Tf
17.0887 0 TD
(sr)Tj
6.9738 0 0 6.9738 285.5621 713.9904 Tm
(i)Tj
/F1 1 Tf
9.9626 0 0 9.9626 292.7054 715.4644 Tm
[(is)-472.1(counted)-478.3(towar)-8.6(d)]TJ
/F5 1 Tf
8.0464 0 TD
(p)Tj
7.4718 0 0 6.641 377.8582 713.8203 Tm
(j)Tj
/F1 1 Tf
9.9626 0 0 9.9626 380.0125 715.4644 Tm
[(.)-467(The)-476.2(entire)-476.6(scheme)-481.3(propos)-7.7(ed)-469.9(in)-470.9(thi)-7.8(s)]TJ
-27.3431 -1.195 TD
[(subse)-8(ction)-335.5(is)-335.5(summa)-8.1(rized)-336.5(as)-340.2(Algorithm)-343.3(2.)]TJ
/F2 1 Tf
8.9663 0 0 8.9663 107.6031 674.192 Tm
[(Algorithm)-335.1(2:)]TJ
/F1 1 Tf
5.9435 0 TD
[(Sequential)-341.8(Bayesian)-335.7(inference)-337(for)-332.5(quasispecies)-337.9(reconstruction)]TJ
/F2 1 Tf
-5.9435 -2.0802 TD
(Input:)Tj
/F1 1 Tf
3.0413 0 TD
[(Set)-332.3(of)-336.7(super-reads)-334.5(and)-336.1(the)-333.8(corresponding)-331.4(condence)-339(scores)]TJ
/F2 1 Tf
-3.0413 -1.2203 TD
(Output:)Tj
/F1 1 Tf
3.7685 0 TD
[(Set)-332.3(of)]TJ
/F5 1 Tf
2.7821 0 TD
(K)Tj
/F1 1 Tf
.999 0 TD
[(strains)-334.5(of)-336.7(a)-330.7(viral)-339.4(quasispecies)]TJ
-7.5496 -1.2203 TD
(Initial)Tj
/F5 1 Tf
2.7378 0 TD
(K)Tj
/F12 1 Tf
.7271 0 TD
(\))Tj
/F1 1 Tf
1.195 0 TD
(2,)Tj
/F5 1 Tf
1.0875 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 164.6362 632.2959 Tm
(1)Tj
/F8 1 Tf
.4968 0 TD
(:)Tj
/F1 1 Tf
.271 0 TD
(1)Tj
/F12 1 Tf
8.9663 0 0 8.9663 173.0834 633.6565 Tm
(\))Tj
/F5 1 Tf
1.2014 0 TD
(B)Tj
/F1 1 Tf
6.2762 0 0 6.2762 189.3543 632.2959 Tm
(1)Tj
/F2 1 Tf
8.9663 0 0 8.9663 107.6031 622.6581 Tm
(for)Tj
/F1 1 Tf
1.6123 0 TD
(t)Tj
/F7 1 Tf
.6133 0 TD
.2798 Tc
(2f)Tj
/F1 1 Tf
1.4353 0 TD
0 Tc
(2)Tj
/F7 1 Tf
1.1697 0 TD
.1663 Tc
()Tj
/F1 1 Tf
1.3088 0 TD
0 Tc
()Tj
/F5 1 Tf
.4995 0 TD
(N)Tj
/F7 1 Tf
.7271 0 TD
(g)Tj
/F2 1 Tf
.8346 0 TD
(do)Tj
/F5 1 Tf
-7.2018 -1.2203 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 122.0598 610.3557 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
.4607 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(1)Tj
/F5 1 Tf
1.0027 0 TD
(t)Tj
/F6 1 Tf
8.9663 0 0 8.9663 144.5102 611.7164 Tm
(=)Tj
/F13 1 Tf
.7208 0 TD
(ExtendFrag)Tj
/F1 1 Tf
4.9951 0 TD
(\()Tj
/F5 1 Tf
.3351 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 204.2645 610.3557 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
.4607 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(1)Tj
8.9663 0 0 8.9663 220.1952 611.7164 Tm
()Tj
/F5 1 Tf
.4995 0 TD
(t)Tj
/F1 1 Tf
.3035 0 TD
()Tj
/F10 1 Tf
.4995 0 TD
(d)Tj
/F1 1 Tf
6.2762 0 0 6.2762 236.3527 610.3557 Tm
(0)Tj
8.9663 0 0 8.9663 239.981 611.7164 Tm
(\))Tj
/F7 1 Tf
-13.765 -1.2203 TD
(Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 123.8173 599.3573 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
8.9663 0 0 8.9663 132.548 600.7747 Tm
(=)Tj
/F13 1 Tf
.7208 0 TD
(InferQuasi)Tj
/F1 1 Tf
4.5399 0 TD
(\()Tj
/F5 1 Tf
.3351 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 188.2204 599.414 Tm
(1)Tj
/F8 1 Tf
.4968 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
.4697 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(1)Tj
/F5 1 Tf
.9936 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 209.1968 600.7747 Tm
()Tj
/F5 1 Tf
.4995 0 TD
(K)Tj
/F1 1 Tf
.7271 0 TD
()Tj
/F10 1 Tf
.4995 0 TD
(d)Tj
/F1 1 Tf
6.2762 0 0 6.2762 229.1527 599.414 Tm
(1)Tj
8.9663 0 0 8.9663 232.781 600.7747 Tm
(\))Tj
/F5 1 Tf
-12.962 -1.2203 TD
(K)Tj
/F7 1 Tf
6.2762 0 0 6.2762 123.0803 593.0644 Tm
()Tj
/F12 1 Tf
8.9663 0 0 8.9663 126.7086 589.8329 Tm
(\))Tj
/F5 1 Tf
1.195 0 TD
(K)Tj
/F1 1 Tf
.7335 0 TD
(,)Tj
/F7 1 Tf
.5817 0 TD
(Q)Tj
6.2762 0 0 6.2762 156.4724 593.6313 Tm
()Tj
/F1 1 Tf
0 -1.0027 TD
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F12 1 Tf
8.9663 0 0 8.9663 163.7291 589.8329 Tm
(\))Tj
/F7 1 Tf
1.195 0 TD
(Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 181.7007 588.3589 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F2 1 Tf
8.9663 0 0 8.9663 116.5606 578.8345 Tm
(if)Tj
/F1 1 Tf
.9484 0 TD
(MEC)Tj
/F5 1 Tf
6.2762 0 0 6.2762 144.5102 577.5306 Tm
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 146.8913 578.8345 Tm
(\()Tj
/F5 1 Tf
.3288 0 TD
(K)Tj
/F1 1 Tf
.7335 0 TD
(\))Tj
/F11 1 Tf
.3288 0 TD
(=)Tj
/F5 1 Tf
.4995 0 TD
(N)Tj
6.2762 0 0 6.2762 169.8519 577.5306 Tm
(t)Tj
/F7 1 Tf
8.9663 0 0 8.9663 174.7275 578.8345 Tm
()Tj
/F1 1 Tf
1.0496 0 TD
(2)Tj
/F11 1 Tf
.4995 0 TD
()Tj
/F1 1 Tf
.7271 0 TD
(and)Tj
/F5 1 Tf
1.7831 0 TD
(K)Tj
/F11 1 Tf
1.0053 0 TD
(<)Tj
/F7 1 Tf
1.0496 0 TD
(j)Tj
/F5 1 Tf
.2656 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 237.4865 577.5306 Tm
(1)Tj
/F8 1 Tf
.4968 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
.4697 0 TD
(-)Tj
/F1 1 Tf
.7136 0 TD
(1)Tj
/F5 1 Tf
1.0027 0 TD
(t)Tj
/F7 1 Tf
8.9663 0 0 8.9663 258.4062 578.8345 Tm
(j)Tj
/F2 1 Tf
.607 0 TD
(do)Tj
/F7 1 Tf
-14.4289 -1.2203 TD
(Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 141.7889 566.4755 Tm
(1)Tj
/F8 1 Tf
.4968 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
8.9663 0 0 8.9663 150.5196 567.8928 Tm
(=)Tj
/F13 1 Tf
.7145 0 TD
(InferQuasi)Tj
/F1 1 Tf
4.5399 0 TD
(\()Tj
/F5 1 Tf
.3351 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 206.1354 566.5321 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
.4607 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(1)Tj
/F5 1 Tf
1.0027 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 227.1118 567.8928 Tm
()Tj
/F5 1 Tf
.4995 0 TD
(K)Tj
/F6 1 Tf
.8915 0 TD
(+)Tj
/F1 1 Tf
.7208 0 TD
(1)Tj
/F10 1 Tf
.999 0 TD
(d)Tj
/F1 1 Tf
6.2762 0 0 6.2762 259.4834 566.5321 Tm
(1)Tj
8.9663 0 0 8.9663 263.1118 567.8928 Tm
(\))Tj
/F2 1 Tf
-14.3467 -1.2203 TD
(if)Tj
/F5 1 Tf
.9484 0 TD
(MECimpr)Tj
/F1 1 Tf
4.034 0 TD
(\()Tj
/F5 1 Tf
.3288 0 TD
(K)Tj
/F1 1 Tf
.7271 0 TD
(\))Tj
/F11 1 Tf
.6133 0 TD
(<)Tj
/F10 1 Tf
1.0496 0 TD
(g)Tj
/F2 1 Tf
.8346 0 TD
(do)Tj
-6.5316 -1.2266 TD
(while)Tj
/F5 1 Tf
2.6114 0 TD
[(M)-317.8(ECimpr)]TJ
/F1 1 Tf
4.3502 0 TD
(\()Tj
/F5 1 Tf
.3288 0 TD
(K)Tj
/F1 1 Tf
.7335 0 TD
(\))Tj
/F11 1 Tf
.607 0 TD
(<)Tj
/F10 1 Tf
1.0496 0 TD
(g)Tj
/F1 1 Tf
.8346 0 TD
(and)Tj
/F5 1 Tf
1.7767 0 TD
(K)Tj
/F11 1 Tf
1.0053 0 TD
(>)Tj
/F1 1 Tf
1.0496 0 TD
(2)Tj
/F7 1 Tf
-12.3486 -1.2203 TD
(Q)Tj
6.2762 0 0 6.2762 177.6189 538.866 Tm
()Tj
/F1 1 Tf
0 -1.0117 TD
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F12 1 Tf
8.9663 0 0 8.9663 184.8755 535.0109 Tm
(\))Tj
/F7 1 Tf
1.195 0 TD
(Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 202.8472 533.5936 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 210.1039 535.0109 Tm
(,)Tj
/F5 1 Tf
.5817 0 TD
(K)Tj
/F7 1 Tf
6.2762 0 0 6.2762 221.8393 538.2424 Tm
()Tj
/F12 1 Tf
8.9663 0 0 8.9663 225.4677 535.0109 Tm
(\))Tj
/F5 1 Tf
1.2014 0 TD
(K)Tj
/F1 1 Tf
.7271 0 TD
(,)Tj
/F5 1 Tf
.5817 0 TD
(K)Tj
/F12 1 Tf
.7271 0 TD
(\))Tj
/F5 1 Tf
1.195 0 TD
(K)Tj
/F6 1 Tf
.8979 0 TD
(-)Tj
/F1 1 Tf
.7145 0 TD
(1)Tj
/F7 1 Tf
-12.1906 -1.2203 TD
(Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 177.6189 522.5951 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
8.9663 0 0 8.9663 186.3495 524.0692 Tm
(=)Tj
/F13 1 Tf
.7208 0 TD
(InferQuasi)Tj
/F1 1 Tf
4.5398 0 TD
(\()Tj
/F5 1 Tf
.3351 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 242.022 522.7086 Tm
(1)Tj
/F8 1 Tf
.4968 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
.4697 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(1)Tj
/F5 1 Tf
.9936 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 262.9417 524.0692 Tm
()Tj
/F5 1 Tf
.4995 0 TD
(K)Tj
/F1 1 Tf
.7335 0 TD
()Tj
/F10 1 Tf
.4995 0 TD
(d)Tj
/F1 1 Tf
6.2762 0 0 6.2762 282.9543 522.7086 Tm
(1)Tj
8.9663 0 0 8.9663 286.5826 524.0692 Tm
(\))Tj
/F2 1 Tf
-14.96 -1.2266 TD
[(end)-333.2(while)]TJ
-2.0044 -1.2203 TD
[(else)-336.9(do)]TJ
2.0044 -1.2203 TD
(while)Tj
/F5 1 Tf
2.6114 0 TD
[(M)-317.8(ECimpr)]TJ
/F1 1 Tf
4.3502 0 TD
(\()Tj
/F5 1 Tf
.3288 0 TD
(K)Tj
/F1 1 Tf
.7335 0 TD
(\))Tj
/F7 1 Tf
.607 0 TD
()Tj
/F10 1 Tf
1.0496 0 TD
(g)Tj
/F1 1 Tf
.8346 0 TD
(and)Tj
/F5 1 Tf
1.7767 0 TD
(K)Tj
/F11 1 Tf
1.0053 0 TD
(<)Tj
/F7 1 Tf
1.0496 0 TD
(j)Tj
/F5 1 Tf
.2719 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 289.0204 489.8266 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
.4607 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(1)Tj
/F5 1 Tf
1.0027 0 TD
(t)Tj
/F7 1 Tf
8.9663 0 0 8.9663 309.9968 491.1873 Tm
(j)Tj
-15.5733 -1.2266 TD
(Q)Tj
6.2762 0 0 6.2762 177.6189 484.0439 Tm
()Tj
/F1 1 Tf
0 -1.0027 TD
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F12 1 Tf
8.9663 0 0 8.9663 184.8755 480.1888 Tm
(\))Tj
/F7 1 Tf
1.195 0 TD
(Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 202.8472 478.7715 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 210.1039 480.1888 Tm
(,)Tj
/F5 1 Tf
.5817 0 TD
(K)Tj
/F7 1 Tf
6.2762 0 0 6.2762 221.8393 483.477 Tm
()Tj
/F12 1 Tf
8.9663 0 0 8.9663 225.4677 480.1888 Tm
(\))Tj
/F5 1 Tf
1.2014 0 TD
(K)Tj
/F7 1 Tf
-7.3472 -1.2203 TD
(Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 177.6189 467.8298 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
8.9663 0 0 8.9663 186.3495 469.2471 Tm
(=)Tj
/F13 1 Tf
.7208 0 TD
(InferQuasi)Tj
/F1 1 Tf
4.5398 0 TD
(\()Tj
/F5 1 Tf
.3351 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 242.022 467.8865 Tm
(1)Tj
/F8 1 Tf
.4968 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
.4697 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(1)Tj
/F5 1 Tf
.9936 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 262.9417 469.2471 Tm
()Tj
/F5 1 Tf
.4995 0 TD
(K)Tj
/F6 1 Tf
.8979 0 TD
(+)Tj
/F1 1 Tf
.7208 0 TD
(1)Tj
/F10 1 Tf
.999 0 TD
(d)Tj
/F1 1 Tf
6.2762 0 0 6.2762 295.37 467.8865 Tm
(1)Tj
8.9663 0 0 8.9663 298.9984 469.2471 Tm
(\))Tj
/F2 1 Tf
-16.3447 -1.2203 TD
[(end)-333.2(while)]TJ
-2.0044 -1.2203 TD
[(end)-333.2(if)]TJ
-1.998 -1.2266 TD
[(end)-333.2(if)]TJ
/F5 1 Tf
0 -1.2203 TD
(K)Tj
/F12 1 Tf
.7271 0 TD
(\))Tj
/F5 1 Tf
1.195 0 TD
(K)Tj
/F7 1 Tf
6.2762 0 0 6.2762 140.3149 428.655 Tm
()Tj
/F1 1 Tf
8.9663 0 0 8.9663 144 425.4235 Tm
(,)Tj
/F7 1 Tf
.5817 0 TD
(Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 156.4724 424.0062 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F12 1 Tf
8.9663 0 0 8.9663 163.7291 425.4235 Tm
(\))Tj
/F7 1 Tf
1.195 0 TD
(Q)Tj
6.2762 0 0 6.2762 181.7007 429.2219 Tm
()Tj
/F1 1 Tf
0 -1.0027 TD
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 116.5606 414.4818 Tm
(Get)Tj
/F5 1 Tf
1.7831 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 138.0472 413.1211 Tm
(1)Tj
/F8 1 Tf
.4968 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 148.2519 414.4818 Tm
[(by)-334.1(pruning)]TJ
/F5 1 Tf
4.7801 0 TD
(F)Tj
/F1 1 Tf
6.2762 0 0 6.2762 196.611 413.1211 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F6 1 Tf
.4607 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(1)Tj
/F5 1 Tf
1.0027 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 220.5921 414.4818 Tm
[(based)-332.4(on)]TJ
/F7 1 Tf
3.9455 0 TD
(Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 263.2251 413.0078 Tm
(1)Tj
/F8 1 Tf
.5058 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F2 1 Tf
8.9663 0 0 8.9663 107.6031 403.4833 Tm
[(end)-333.2(for)]TJ
/F1 1 Tf
0 -1.2203 TD
[(Reconstruct)-334.6(full-length)-334.5(quasispecies)]TJ
/F5 1 Tf
15.0359 0 TD
(Q)Tj
/F1 1 Tf
1.0559 0 TD
(from)Tj
/F5 1 Tf
2.2762 0 TD
(Q)Tj
6.2762 0 0 6.2762 278.759 395.7731 Tm
(max)Tj
/F1 1 Tf
0 -.9123 TD
(1)Tj
/F8 1 Tf
.4968 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(N)Tj
/F7 1 Tf
8.9663 0 0 8.9663 292.1952 392.5416 Tm
.2798 Tc
(2Q)Tj
/F1 1 Tf
6.2762 0 0 6.2762 307.8424 391.1243 Tm
0 Tc
(1)Tj
/F8 1 Tf
.5059 0 TD
(:)Tj
/F5 1 Tf
.271 0 TD
(t)Tj
/F1 1 Tf
8.9663 0 0 8.9663 318.1039 392.5416 Tm
(and)Tj
/F5 1 Tf
1.7767 0 TD
(R)Tj
/F1 1 Tf
-25.2537 -1.2203 TD
[(Estimate)-333.7(frequencies)-337.2(of)-336.7(each)-334.1(strain)]TJ
/F5 1 Tf
14.7134 0 TD
(q)Tj
6.2762 0 0 6.2762 244.0062 380.2393 Tm
(k)Tj
/F7 1 Tf
8.9663 0 0 8.9663 249.959 381.5999 Tm
(2)Tj
/F5 1 Tf
.9358 0 TD
(Q)Tj
/F1 1 Tf
1.0496 0 TD
[(based)-332.4(on)]TJ
/F5 1 Tf
3.9455 0 TD
(HD)Tj
/F1 1 Tf
1.4416 0 TD
(\()Tj
/F5 1 Tf
.3288 0 TD
(sr)Tj
6.2762 0 0 6.2762 325.9275 380.2393 Tm
(i)Tj
/F1 1 Tf
8.9663 0 0 8.9663 328.1952 381.5999 Tm
()Tj
/F5 1 Tf
.4995 0 TD
(q)Tj
6.2762 0 0 6.2762 337.1526 380.2393 Tm
(k)Tj
/F1 1 Tf
8.9663 0 0 8.9663 340.6109 381.5999 Tm
[(\))-330.9(and)]TJ
/F7 1 Tf
2.447 0 TD
(j)Tj
/F5 1 Tf
.2719 0 TD
(C)Tj
6.2762 0 0 6.2762 370.9416 380.2393 Tm
(i)Tj
/F7 1 Tf
8.9663 0 0 8.9663 373.2094 381.5999 Tm
(j)Tj
/F2 1 Tf
10.959 0 0 10.959 242.3621 334.4881 Tm
[(3.)-496.7(RESULTS)-330(AND)-334.3(DISCUSSION)]TJ
/F5 1 Tf
-12.2966 -1.6347 TD
[(3.1.)-496.9(Performance)-332.1(comparison)-327.9(on)-334.7(simulated)-328.4(data)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 298.6582 Tm
[(To)-263.1(evaluate)-269.1(perf)-8.8(ormance)-266.6(of)-265.3(the)-262.9(propos)-7.7(ed)-265.1(method)-268.7(for)-262.3(quasispe)-9.1(cies)-266.7(reco)-8.6(nstructio)-8.7(n,)-262.9(we)-263.3(use)-267(metrics)]TJ
/F5 1 Tf
39.3672 0 TD
[(Recal)-10(l)]TJ
/F1 1 Tf
2.5778 0 TD
(,)Tj
/F5 1 Tf
-42.9466 -1.2007 TD
[(Precisi)-10.9(on)]TJ
/F1 1 Tf
3.8525 0 TD
(,)Tj
/F5 1 Tf
.5634 0 TD
[(Pr)-8.2(edicted)-323.5(Proport)-10.3(ion)]TJ
/F1 1 Tf
8.6895 0 TD
[(,)-319.1(and)]TJ
/F5 1 Tf
2.3388 0 TD
[(Recons)-9.1(truction)-324.6(Rate)]TJ
/F1 1 Tf
8.2456 0 TD
(.)Tj
/F5 1 Tf
.5691 0 TD
[(Recal)-10(l)]TJ
/F1 1 Tf
2.8965 0 TD
[(is)-318.5(dened)-326(as)-317.5(the)-325.5(ratio)-320.4(of)-322.2(the)-319.8(number)-324.8(of)]TJ
-27.1553 -1.2007 TD
[(correctly)-266.4(reco)-8.6(nstructed)-269.5(strains)-261.7(to)-260.4(the)-262.9(total)-264.3(numb)-6.6(er)-261.4(of)-259.6(true)-260(strai)-8.6(ns)-258.8(in)-260.4(the)-262.9(quasispe)-9.1(cies,)-261.3(that)-260.7(is,)]TJ
/F5 1 Tf
37.1024 0 TD
[(Recal)-10(l)]TJ
/F6 1 Tf
2.7485 0 TD
(=)Tj
ET
511.767 277.001 23.698 .39685 re
f
BT
/F5 1 Tf
6.9738 0 0 6.9738 519.5338 278.3621 Tm
(TP)Tj
-1.1137 -1.008 TD
(TP)Tj
/F6 1 Tf
1.3332 0 TD
(+)Tj
/F5 1 Tf
.7235 0 TD
(FN)Tj
/F1 1 Tf
9.9626 0 0 9.9626 535.4645 274.7338 Tm
(,)Tj
-42.9466 -1.2007 TD
(while)Tj
/F5 1 Tf
2.7087 0 TD
[(Preci)-11.1(sion)]TJ
/F1 1 Tf
4.3305 0 TD
[(is)-477.8(dened)-485.4(as)-482.5(the)-479.2(fraction)-485.8(of)-481.5(correctly)-488.3(reconstruct)-13(ed)-475.6(strai)-8.6(ns)-475(amo)-7.6(ng)-479.5(all)-481.9(the)-479.2(assembled)]TJ
-7.0392 -1.2007 TD
[(seque)-8.6(nces,)-270(that)-272.1(is,)]TJ
/F5 1 Tf
7.5514 0 TD
(Precision)Tj
/F6 1 Tf
4.0175 0 TD
(=)Tj
ET
230.003 253.134 22.961 .39685 re
f
BT
/F5 1 Tf
6.9738 0 0 6.9738 237.4299 254.4377 Tm
(TP)Tj
-1.065 -1.0081 TD
(TP)Tj
/F6 1 Tf
1.3414 0 TD
(+)Tj
/F5 1 Tf
.7154 0 TD
(FP)Tj
/F1 1 Tf
9.9626 0 0 9.9626 252.9637 250.8094 Tm
[(.)-262.1(Not)-9(ing)-266.8(that)]TJ
/F5 1 Tf
5.3491 0 TD
(Precision)Tj
/F1 1 Tf
4.1143 0 TD
[(usually)-275.6(reports)-271.1(high)-267.6(scor)-8(es)-266.3(whe)-8(n)-268.2(the)-268.6(number)-273.6(of)]TJ
-24.054 -1.2007 TD
[(strains)-358.4(is)-352.6(underest)-9.9(imated)-358.6(while)-356.5(penalizing)-362.7(overest)-9.1(imation)-354.7(of)-350.6(the)-354(p)-6.5(opulation)-358.4(size,)-352.4(we)-354.4(als)-8(o)-347.9(repor)-9.6(t)-350.7(the)-354(ratio)]TJ
0 -1.195 TD
[(of)-390.5(the)-393.8(numb)-6.6(er)-392.2(of)-390.5(reco)-8.6(nstructed)-400.4(sequences)-397.7(to)-391.2(the)-393.8(tru)-7(e)-389.5(popul)-6.6(ation)-392.4(size,)]TJ
/F5 1 Tf
29.4429 0 TD
[(Predict)-9.7(ed)-390.3(Proport)-10.3(ion)]TJ
/F1 1 Tf
8.7578 0 TD
[(.)-393(The)-396.5(closer)]TJ
-38.2007 -1.2007 TD
(the)Tj
/F5 1 Tf
1.5365 0 TD
[(Predict)-9.7(ed)-304.9(Proporti)-8.1(on)]TJ
/F1 1 Tf
8.974 0 TD
[(to)-305.9(1,)-308.4(the)-302.7(mor)-7.8(e)-304.1(accurate)-315.7(the)-302.7(numb)-6.6(er)-306.9(of)-305.1(recon)-9.4(structed)-308.6(strai)-8.6(ns.)-304.7(Moreover)-9.9(,)-302(t)0(o)-305.9(asse)-9(ss)]TJ
-10.5104 -1.5934 TD
[(the)-285.7(degre)-9.4(e)-281.4(o)0(f)-288(reconst)-9.1(ructio)-8.2(n)-279.6(accur)-11.1(acy,)-285.1(we)-291.8(dene)]TJ
/F5 1 Tf
19.9397 0 TD
[(Reconstru)-9.7(ction)-335.5(Ra)-7(te)]TJ
/F6 1 Tf
8.4277 0 TD
(=)Tj
ET
397.417 201.43 5.0457 .39685 re
f
BT
/F1 1 Tf
6.9738 0 0 6.9738 398.2109 202.7338 Tm
(1)Tj
/F5 1 Tf
-.1138 -1.008 TD
(K)Tj
/F9 1 Tf
9.9626 0 0 9.9626 404.1637 206.5889 Tm
(P)Tj
/F5 1 Tf
6.9738 0 0 6.9738 414.6519 203.8676 Tm
(K)Tj
0 -1.0893 TD
(k)Tj
/F6 1 Tf
.6341 0 TD
(=)Tj
/F1 1 Tf
.7154 0 TD
(1)Tj
9.9626 0 0 9.9626 433.9841 199.1054 Tm
(1)Tj
/F6 1 Tf
.6715 0 TD
(-)Tj
ET
449.461 201.43 30.841 .39685 re
f
BT
/F5 1 Tf
6.9738 0 0 6.9738 449.4613 203.811 Tm
(HD)Tj
/F1 1 Tf
1.4389 0 TD
(\()Tj
/F5 1 Tf
.3414 0 TD
(q)Tj
4.9813 0 0 4.9813 465.3353 202.7905 Tm
(k)Tj
/F1 1 Tf
6.9738 0 0 6.9738 468.17 203.811 Tm
()Tj
/F8 1 Tf
.5447 .0081 TD
(^)Tj
/F5 1 Tf
-.0406 -.0081 TD
(q)Tj
4.9813 0 0 4.9813 475.1432 202.2236 Tm
(k)Tj
/F1 1 Tf
6.9738 0 0 6.9738 477.9778 203.811 Tm
(\))Tj
/F5 1 Tf
-2.2356 -1.1625 TD
(G)Tj
/F9 1 Tf
9.9626 0 0 9.9626 428.0881 210.1606 Tm
4.648 Tc
()Tj
/F1 1 Tf
5.8385 -1.1097 TD
0 Tc
[()-452.3(where)]TJ
/F5 1 Tf
3.5225 0 TD
(G)Tj
/F1 1 Tf
1.0015 0 TD
(is)Tj
-42.5312 -1.6787 TD
[(the)-262.9(leng)-7.6(th)-260.4(of)-265.3(a)-264.3(genome,)]TJ
/F5 1 Tf
9.7707 0 TD
(K)Tj
/F1 1 Tf
.9276 0 TD
[(is)-261.6(the)-268.6(number)-267.9(of)-259.6(str)-8.2(ains)-264.9(in)-260.4(a)-264.3(quasispe)-9.1(cies,)-267(and)]TJ
/F5 1 Tf
18.7276 0 TD
(q)Tj
7.4718 0 0 6.641 405.7511 180.7369 Tm
(k)Tj
/F1 1 Tf
9.9626 0 0 9.9626 411.7038 182.381 Tm
(and)Tj
/F8 1 Tf
1.7584 .0114 TD
(^)Tj
/F5 1 Tf
-.0455 -.0114 TD
(q)Tj
6.9738 0 0 6.9738 433.7574 180.907 Tm
(k)Tj
/F1 1 Tf
9.9626 0 0 9.9626 440.107 182.381 Tm
[(denot)-8.4(e)-258.6(the)]TJ
/F5 1 Tf
4.4386 0 TD
(k)Tj
6.9738 0 0 6.9738 488.9763 186.0094 Tm
(th)Tj
/F1 1 Tf
9.9626 0 0 9.9626 497.5369 182.381 Tm
[(true)-265.7(strain)]TJ
-39.1396 -1.195 TD
[(and)-368.3(its)-373.2(nearest)-375.1(sequence)-378.6(among)-373.3(the)]TJ
/F5 1 Tf
15.1027 0 TD
(K)Tj
/F1 1 Tf
1.03 0 TD
[(est)-8(imated)-370(ones,)-376.3(respective)-12.1(ly.)-368.9(To)-371.2(assess)-371.4(the)-371(accuracy)-381.2(of)-367.7(estimated)]TJ
-16.1327 -1.2007 TD
[(frequenc)-9.7(ies,)-355.5(we)-354.4(use)-352.4(the)-354(Jense)-9.8(nShanno)-7.1(n)-353.6(divergen)-8.7(ce)-352.2(\()-127.9(JSD\),)-356.9(which)-353.7(quant)-8.4(ies)-355.1(similar)-10.7(ity)-349.3(betwee)-10.9(n)-353.6(two)-350.4(dis-)]TJ
T*
[(tributio)-7.7(ns.)-418.5(Given)-422(a)-412.3(tru)-7(e)-412.3(d)-6.5(istribution)]TJ
/F5 1 Tf
15.2791 0 TD
(P)Tj
/F1 1 Tf
1.03 0 TD
[(and)-419.5(its)-418.7(approximat)-10.8(ion)]TJ
/F5 1 Tf
9.5089 0 TD
(Q)Tj
/F1 1 Tf
.7227 0 TD
[(,)-415.8(the)-416.6(Kullb)-7.6(ackLe)-9.7(ibler)-417.1(\(K)-7.4(L\))-418.7(divergen)-8.7(ce)]TJ
/F5 1 Tf
-26.5407 -1.8096 TD
(D)Tj
/F1 1 Tf
.717 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(P)Tj
/F7 1 Tf
.6146 0 TD
(jj)Tj
/F5 1 Tf
.5463 0 TD
(Q)Tj
/F1 1 Tf
.717 0 TD
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
/F9 1 Tf
.9446 .7511 TD
(P)Tj
/F5 1 Tf
6.9738 0 0 6.9738 154.7149 137.9905 Tm
(n)Tj
-.5853 -2.6177 TD
(i)Tj
/F6 1 Tf
.4471 0 TD
(=)Tj
/F1 1 Tf
.7235 0 TD
(1)Tj
/F5 1 Tf
9.9626 0 0 9.9626 163.9559 128.5228 Tm
(P)Tj
/F1 1 Tf
.6146 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(i)Tj
/F1 1 Tf
.2788 0 TD
(\)log)Tj
ET
194.003 130.847 11.622 .39685 re
f
BT
/F5 1 Tf
6.9738 0 0 6.9738 194.3432 132.7748 Tm
(P)Tj
/F1 1 Tf
.6178 0 TD
(\()Tj
/F5 1 Tf
.3333 0 TD
(i)Tj
/F1 1 Tf
.2845 0 TD
(\))Tj
/F5 1 Tf
-1.2844 -1.0893 TD
(Q)Tj
/F1 1 Tf
.7154 0 TD
(\()Tj
/F5 1 Tf
.3333 0 TD
(i)Tj
/F1 1 Tf
.2845 0 TD
(\))Tj
9.9626 0 0 9.9626 208.6866 128.5228 Tm
[(is)-307.1(unden)-11.3(ed)-304.9(whe)-8(n)]TJ
/F5 1 Tf
7.7164 0 TD
(Q)Tj
/F1 1 Tf
.717 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(i)Tj
/F1 1 Tf
.2845 0 TD
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
/F1 1 Tf
.717 0 TD
[(0.)-308.4(JSD,)-314.3(a)-304.1(sym)-7(metrize)-10.3(d)-308.1(and)-311.4(smoothe)-8.9(d)-308.1(version)-314.7(of)-305.1(the)-314.1(KL)]TJ
-20.4177 -2.0088 TD
[(di)24.2(ve)19.4(rg)24.9(en)19.4(ce)17.7(,)-233.7(c)0(i)16.7(r)14.3(cu)19.4(m)12.8(v)0(e)19.4(n)0(t)24.2(s)-241(t)13.5(h)0(i)18.5(s)-235.3(pr)19.3(ob)21.2(l)13.5(e)0(m)-228.8(b)0(y)-229.2(d)0(e)25.1()0(n)16.3(i)13.5(ng)-229.1(s)15.1(i)0(m)20.6(i)0(l)21.4(a)0(r)23.2(i)0(t)21.4(y)-239.8(of)]TJ
/F5 1 Tf
24.7141 0 TD
(P)Tj
/F1 1 Tf
.8536 0 TD
[(an)19.4(d)]TJ
/F5 1 Tf
1.6673 0 TD
(Q)Tj
/F1 1 Tf
.956 0 TD
(as)Tj
/F5 1 Tf
1.0584 0 TD
[(JS)19.4(D)]TJ
/F1 1 Tf
1.6503 0 TD
(\()Tj
/F5 1 Tf
.3301 0 TD
(P)Tj
/F7 1 Tf
.6203 0 TD
(jj)Tj
/F5 1 Tf
.5406 0 TD
(Q)Tj
/F1 1 Tf
.717 0 TD
(\))Tj
/F6 1 Tf
.5008 0 TD
(=)Tj
ET
449.631 110.778 3.515 .39685 re
f
BT
/F1 1 Tf
6.9738 0 0 6.9738 449.6313 112.1385 Tm
(1)Tj
0 -1.008 TD
(2)Tj
/F5 1 Tf
9.9626 0 0 9.9626 453.1464 108.5102 Tm
(D)Tj
/F1 1 Tf
.717 0 TD
(\()Tj
/F5 1 Tf
.3357 0 TD
(P)Tj
/F7 1 Tf
.6146 0 TD
(jj)Tj
/F5 1 Tf
.5406 0 TD
(M)Tj
/F1 1 Tf
.8763 0 TD
(\))Tj
/F6 1 Tf
.5008 0 TD
(+)Tj
ET
496.063 110.778 3.4583 .39685 re
f
BT
/F1 1 Tf
6.9738 0 0 6.9738 496.0628 112.1385 Tm
(1)Tj
0 -1.008 TD
(2)Tj
/F5 1 Tf
9.9626 0 0 9.9626 499.5211 108.5102 Tm
(D)Tj
/F1 1 Tf
.7227 0 TD
(\()Tj
/F5 1 Tf
.3301 0 TD
(Q)Tj
/F7 1 Tf
.7227 0 TD
(jj)Tj
/F5 1 Tf
.5406 0 TD
(M)Tj
/F1 1 Tf
.8763 0 TD
(\))Tj
-42.5312 -1.3714 TD
-.0124 Tc
[(wh)-12.4(e)7(r)-12.4(e)]TJ
/F5 1 Tf
2.7258 0 TD
0 Tc
(M)Tj
/F1 1 Tf
1.1552 0 TD
-.0131 Tc
[(is)-339.4(d)-13.1(e)12(n)-13.1(e)6.3(d)-338.2(as)]TJ
/F5 1 Tf
5.3377 0 TD
0 Tc
(M)Tj
/F6 1 Tf
1.0414 0 TD
(=)Tj
ET
216.964 97.115 3.515 .39685 re
f
BT
/F1 1 Tf
6.9738 0 0 6.9738 216.9637 98.4755 Tm
(1)Tj
0 -1.008 TD
(2)Tj
9.9626 0 0 9.9626 220.4787 94.8472 Tm
(\()Tj
/F5 1 Tf
.3301 0 TD
(P)Tj
/F6 1 Tf
.7853 0 TD
(+)Tj
/F5 1 Tf
.717 0 TD
(Q)Tj
/F1 1 Tf
.7227 0 TD
(\))Tj
/F11 1 Tf
.3357 0 TD
(:)Tj
/F1 1 Tf
-13.2191 -1.2918 TD
[(We)-529.4(com)-7.6(pare)-532.1(our)-527.8(algo)-7.6(rithm)-532.7(with)-530.3(publicly)-534(availa)-9.8(ble)-530.4(ShoRAH)-534.2(\(Zagor)-10.1(di)-527.8(et)-529.6(al.,)-530.4(2011\),)-535.4(PredictHa)-11.5(plo)]TJ
-1.0015 -1.2007 TD
[(\(Prabhaka)-9.7(ran)-358.9(et)-364.6(al.,)-359.7(2014\),)-359(and)-362.6(ViQu)-8(aS)-355.3(\()-127.9(Jayas)-9.8(undara)-362.9(et)-358.9(al.,)-359.7(2014\).)-364.7(Since)-362.2(ViQu)-8(aS)-355.3(is)-358.3(an)-361.8(extensi)-9.9(on)-360(of)-356.3(the)]TJ
/F2 1 Tf
0 66.9892 TD
[(A)-334.8(BAYE)-9(SIAN)-341.4(METHOD)-340.5(FOR)-339.6(QUA)-8(SISP)-8.2(ECIES)-336.3(REC)-9.2(ONST)-8.7(RUCTI)-10.1(ON)-10587.7(643)]TJ
ET
endstream
endobj
78 0 obj
<>stream
/GS1 gs
BT
/F1 1 Tf
9.9626 0 0 9.9626 74.0976 715.4644 Tm
0 0 0 rg
0 Tc
0 Tw
[(algo)-7.6(rithm)-458.7(in)-453.8(Prosperi)-458.9(et)-455.6(al.)-456(\(2011\))-458.1(and)-453.6(Prospe)-8.7(ri)-450.1(and)-459.3(Salemi)-460.3(\(2012\),)-458.5(and)-453.6(was)-458.8(shown)-458.5(to)-453.8(have)-456.2(super)-8.8(ior)]TJ
0 -1.195 TD
[(perf)-8.8(ormance)-249.5(compare)-10.5(d)-239.8(t)0(o)-243.3(its)-242.3(prede)-9.4(cessor,)-246.2(we)-246.2(omit)-245.4(the)-245.8(comparison)-254(with)-240.1(the)-245.8(softw)-8(are)-246.8(QuRe)-246.8(in)-243.3(Prosperi)-248.3(et)-245.1(al.)]TJ
0 -1.2007 TD
[(\(2011\))-338.6(and)-339.8(Prospe)-8.7(ri)-330.6(and)-339.8(Salemi)-340.8(\(2012\).)-339(It)-336.3(is)-329.8(wor)-8.2(th)-334.3(pointing)-338.8(out)-335.1(that)-340.4(for)-330.6(the)-336.9(synt)-7(hetic)-337.3(data)-339.4(sets)-340(we)-331.6(stud)-7(y,)]TJ
T*
[(Sh)-6.4(oRAH)-271.7(coul)-7.6(d)-268.2(not)-266.8(recon)-9.4(struct)-271.1(strains)-273.1(in)-271.7(the)-268.6(regions)-274.8(where)-275.1(the)-268.6(simul)-8.4(ated)-271.2(seque)-8.6(ncing)-270.1(cover)-9.4(age)-267.6(is)-272.9(relatively)]TJ
T*
[(low)-316.3(com)-7.6(pared)-316.7(to)-311.6(the)-314.1(average,)-322.1(resulting)-316(in)-317.3(reconstruct)-13(ion)-312.3(of)-310.8(strai)-8.6(ns)-310(that)-317.6(are)-315.1(shorter)-316.6(than)-314.9(the)-314.1(true)-316.9(length)]TJ
/F5 1 Tf
42.2296 0 TD
(G)Tj
/F1 1 Tf
.7227 0 TD
(.)Tj
-42.9523 -1.2007 TD
[(To)-285.9(facil)-9.2(itate)-288.8(a)-287.1(fair)-284.7(com)-7.6(parison)-291.9(with)-285.7(ShoR)-7(AH,)-282.9(we)-291.8(aligned)-287.6(its)-287.8(recon)-9.4(structed)-291.5(strains)-290.2(to)-283.1(the)-285.7(ref)-8(erence)-292.5(genome)]TJ
T*
[(and)-328.4(comple)-8.7(ted)-325.5(missing)-329.7(sites)-326.5(with)-325.5(b)-6.5(ases)-327.7(from)-323.5(the)-325.5(refere)-10.2(nce.)-324.9(ViQu)-8(aS,)-327.3(on)-320.2(the)-325.5(cont)-7.6(rary,)-327.8(tends)-328.2(to)-323(reconst)-9.1(ruct)]TJ
T*
[(man)-7.6(y)-382(more)-385.9(strains)-386.9(than)-383.2(act)-8.6(ually)-386.7(present;)-388.2(thus,)-383(we)-388.5(followed)-389.2(ViQuaSs)-390.8(authors)-385.7(reco)-8.6(mmenda)-9.5(tion)-384.2(and)-385.3(re-)]TJ
T*
[(tained)-366.5(on)-7.2(ly)-357.1(thos)-7(e)-361.1(having)-361.9(fre)-8(quencies)-368.2(greater)-370.2(than)]TJ
/F5 1 Tf
20.7819 0 TD
(f)Tj
6.9738 0 0 6.9738 283.9747 618.3494 Tm
(min)Tj
/F1 1 Tf
9.9626 0 0 9.9626 298.4881 619.8235 Tm
[(whe)-8(n)-359.3(calcul)-9.8(ating)]TJ
/F5 1 Tf
7.318 0 TD
[(Precisi)-10.9(on)]TJ
/F1 1 Tf
3.8525 0 TD
[(.)-358.9(Finall)-8.2(y,)-359.6(not)-363.6(all)-362.4(of)-356.3(the)]TJ
-33.6937 -1.195 TD
[(synt)-7(hetic)-308.8(data)-311(sets)-311.6(could)-310(be)-304.9(p)-6.5(rocessed)-311.7(with)-308.4(Predi)-9.6(ctHaplo,)-314.6(preventing)-314.6(us)-310(from)-306.4(reporting)-314(its)-310.6(performanc)-11.1(e)-304.2(i)0(n)]TJ
0 -1.2007 TD
[(som)-7(e)-332.6(o)0(f)-339.2(the)-331.2(scena)-10.4(rios.)]TJ
1.0015 -1.2007 TD
[(We)-375.7(generated)-377.3(synth)-7.8(etic)-370.7(data)-373.6(sets)-374.2(by)-365.7(emu)-7.6(lating)-373.2(high-th)-7.1(roughp)-6.6(ut)-368.5(seque)-8.6(ncing)-372.6(of)-367.7(a)-372.4(viral)-371.6(popul)-6.6(ation)-369.6(con-)]TJ
-1.0015 -1.2007 TD
[(sis)-7.4(ting)-344.3(of)-339.2(a)-344(numb)-6.6(er)-341(o)-6.5(f)-338.5(closel)-9.2(y)-342.2(related)-348.2(viral)-348.8(genomes)-349.4(having)-344.9(leng)-7.6(th)-340(of)-344.9(1300)-173.8(bp;)-340.8(this)-345.5(partic)-10(ular)-345.3(length)-347.6(was)]TJ
T*
[(chose)-8.6(n)-313.7(t)0(o)-317.3(coincide)-318.6(with)-319.8(the)-314.1(longe)-8.4(st)-312.8(region)-318.4(of)-316.5(the)-314.1(HIV)]TJ
/F5 1 Tf
22.4378 0 TD
(pol)Tj
/F1 1 Tf
1.5934 0 TD
[(gene.)-320(Quasis)-9.7(pecies)-321.2(sequences)-323.7(are)-315.1(gener)-9.4(ated)-316.7(by)]TJ
-24.0312 -1.2007 TD
[(int)-7.8(roducing)-251.6(inde)-7.6(pendent)-250.7(mutat)-9(ions)-251.7(at)-245.1(unif)-7.8(ormly)-251.1(random)-250.9(loca)-9.4(tions)-249.5(along)-253.1(the)-245.8(leng)-7.6(th)-249(of)-248.2(a)-247.3(rando)-7.6(mly)-247.6(gener)-9.4(ated)]TJ
T*
[(ref)-8(erence)-446.2(genome)-444.2(so)-440.9(as)-442.7(to)-442.5(obtain)-444.4(a)-440.7(predened)-445.9(leve)-9.4(l)-436(o)0(f)-441.7(diversity)-446.9(\()]TJ
/F5 1 Tf
28.1113 0 TD
(div)Tj
/F1 1 Tf
1.2292 0 TD
[(%\),)-444.8(that)-442.8(is,)-438.3(a)-440.7(prede)-9.4(ned)-442.2(average)]TJ
-29.3405 -1.2007 TD
[(Hamm)-10.1(ing)-244.1(distance)-245.8(betwee)-10.9(n)-239.8(quasispe)-9.1(cies)-243.9(strai)-8.6(ns.)-242.1(Simulating)-250.8(Illuminas)-248.3(MiSeq)-248.5(data,)-243.1(2)]TJ
/F6 1 Tf
34.5303 0 TD
()Tj
/F1 1 Tf
.7227 0 TD
[(250)-241.3(bp-long)-243.4(paired-)]TJ
-35.253 -1.195 TD
[(end)-265.8(read)-8.6(s)-263.7(are)-263.9(sample)-9.9(d)-262.5(uniforml)-7.7(y)-262.5(from)-266.6(each)-264.5(vir)-7(al)-262.1(strain)-265.4(wi)-8.2(th)-260.4(a)-264.3(mean)-266.2(cover)-9.4(age)-261.9(o)-6.5(f)]TJ
/F5 1 Tf
32.5955 0 TD
(cov)Tj
/F6 1 Tf
1.5649 0 TD
()Tj
/F1 1 Tf
.9845 0 TD
[(per)-262.1(strai)-8.6(n.)-262.9(Inserts)-266.6(of)]TJ
-35.1448 -1.2007 TD
[(the)-302.7(paired-)-9.9(end)-300(reads)-300.8(are)-303.7(on)-297.4(aver)-8.6(age)-301.8(150)-167.3(bp)-297.4(long)-301.7(with)-302.7(standar)-9.1(d)-296.7(deviation)-308.9(of)-299.4(30.)-297.8(In)-299.4(our)-300.2(benchmar)-11.3(king)-296(tes)-8(ts,)]TJ
T*
[(we)-337.3(focus)-338.8(on)-337.3(explori)-8.9(ng)-331.6(the)-336.9(effect)-11(s)-332(o)0(f)-333.6(dive)-7.6(rsity)-336.9(\()]TJ
/F5 1 Tf
19.4617 0 TD
(div)Tj
/F1 1 Tf
1.2292 0 TD
[(%\))-336.3(on)-331.6(the)-336.9(accur)-11.1(acy)-335.9(of)-333.6(the)-336.9(quasi)-9.6(species)-340.2(reconst)-9.2(ruction.)]TJ
-19.6893 -1.2007 TD
[(Two)-364.5(sets)-368.5(of)-362(viral)-360.2(po)-7.2(pulations)-365.2(are)-366.3(consider)-9.9(ed:)-359.6(\(1\))-364.7(a)-361.1(mix)-367.1(of)-362(5)-359.3(viral)-365.9(strains)-364.1(with)-365.3(abunda)-8.1(nce)-364.4(levels)-367.7(50%,)]TJ
-1.0015 -1.2007 TD
[(30)-7.2(%,)-254.3(15%,)-255.8(4%,)-260.7(and)-254.5(1%;)-258.2(and)-260.2(\(2\))-256.6(a)-252.9(mix)-259(of)-253.9(10)-257.6(strains)-261.7(with)-257.2(abunda)-8.1(nce)-256.2(levels)-259.6(36%,)-261.5(24%,)-255.8(16%,)-255.8(8%,)-260.7(5.5%,)-256.2(4%,)]TJ
T*
[(3%,)-380.2(2%,)-374.5(1%,)-374.5(and)-374(0)]TJ
/F11 1 Tf
8.2001 0 TD
(:)Tj
/F1 1 Tf
.2731 0 TD
(5)Tj
/F5 1 Tf
.5008 0 TD
(%)Tj
/F1 1 Tf
.8365 0 TD
[(.)-370.3(Note)-381.4(that)-374.6(the)-376.7(abunda)-8.1(nces)-377.7(are)-377.7(chosen)-379.2(to)-374.2(appro)-7.6(ximately)-380(follow)-380.2(geomet)-8.7(ric)-373(distri-)]TJ
-9.8105 -1.2007 TD
[(bu)-7.2(tion)-281.7(and)-277.2(that)-283.5(the)-280(p)-6.5(opulations)-286.3(include)-287.6(low-abundan)-9.2(t)-282.4(strains.)-284.8(For)-282.3(each)-281.6(com)-7.6(bination)-283.6(of)-282.3(the)-280(para)-8.6(meters,)-285.4(100)]TJ
T*
[(data)-271.2(sets)-266.1(were)-268.6(gener)-9.4(ated)-265.5(and)-271.5(the)-262.9(repor)-9.6(ted)-262.9(resu)-8(lts)-265.1(were)-268.6(obtaine)-8.7(d)-262.5(b)0(y)-263.3(aver)-8.6(aging)-270.1(over)-262.9(thos)-7(e)-264.3(data)-265.5(instanc)-9.9(es.)-266.6(For)]TJ
0 -1.195 TD
[(Predi)-9.6(ctHaplo,)-263.4(which)-268.4(did)-255.4(not)-261.1(produc)-8.3(e)-258.6(results)-261.7(in)-260.4(each)-264.5(instanc)-9.9(e,)-259(the)-257.2(aver)-8.6(aged)-262.7(results)-261.7(are)-263.9(reporte)-9.9(d)-256.8(i)0(f)-256.7(more)-266.4(than)]TJ
0 -1.2007 TD
[(50)-337.3(instanc)-9.9(es)-334.6(were)-336.9(succe)-10.4(ssfully)-339.6(processe)-10.1(d.)]TJ
1.0015 -1.2007 TD
[(In)-401.8(all)-396.6(of)-401.8(the)-399.5(followi)-8.1(ng)-399.9(experiment)-12.6(s,)-395(pote)-7.6(ntial)-400.8(SNVs)-404(are)-400.5(called)-402.4(if)-398.9(their)-405.7(abundance)-406.7(is)-398.1(highe)-8.4(r)-395.4(than)-400.2(1%,)]TJ
-1.0015 -1.2007 TD
[(whi)-9(ch)-356.1(is)-364(set)-360.8(relat)-9.2(ively)-363.9(high)-358.6(to)-362.8(avoid)-361.2(false)-366.1(posi)-7(tives)-359.4(\(FP)-8.4(s\);)-361(FPs)-360.4(prevent)-366.5(reads)-363.4(to)-362.8(be)-361.8(merged)-366.5(with)-365.3(existing)]TJ
T*
[(clus)-8.8(ters)-420.5(in)-425.4(Section)-423.4(2.1.)-423.4(We)-427(execute)-425(the)-422.2(funct)-10.3(ion)]TJ
/F13 1 Tf
20.7876 0 TD
[(ExtendFr)-9.1(ag)]TJ
/F1 1 Tf
5.4288 0 TD
[(with)-422.2(para)-8.6(meter)]TJ
/F10 1 Tf
6.6522 0 TD
(d)Tj
/F1 1 Tf
6.9738 0 0 6.9738 406.5448 367.3133 Tm
(0)Tj
/F6 1 Tf
9.9626 0 0 9.9626 412.2141 368.7873 Tm
(=)Tj
/F1 1 Tf
.717 0 TD
(0)Tj
/F11 1 Tf
.5008 0 TD
(:)Tj
/F1 1 Tf
.2731 0 TD
[(1.)-416.6(Pa)-8.2(rameter)]TJ
/F10 1 Tf
5.6678 0 TD
(d)Tj
/F1 1 Tf
6.9738 0 0 6.9738 488.5227 367.3133 Tm
(1)Tj
9.9626 0 0 9.9626 496.6865 368.7873 Tm
(in)Tj
-42.4174 -1.2007 TD
[(funct)-10.3(ion)]TJ
/F13 1 Tf
3.7501 0 TD
[(InferQua)-8.9(si)]TJ
/F1 1 Tf
4.9451 0 TD
[(is)-392.4(initial)-9.6(ly)-396.9(set)-395(to)-396.9(0.001,)-402.2(but)-397.7(adaptively)-402.5(increas)-10.9(es)-397.2(if)-398.9(the)-393.8(numb)-6.6(er)-397.9(of)-396.2(combina)-9.5(tions)-397.5(of)]TJ
-8.6952 -1.2007 TD
[(part)-9.6(ially)-343.9(reco)-8.6(nstructed)-349.2(strai)-8.6(ns)-344.2(exceeds)-349.4(10,000;)-349.1(this)-345.5(is)-346.9(done)-346.3(to)-345.7(limit)-342.7(the)-348.3(numb)-6.6(er)-341(of)-344.9(likel)-8.2(ihood)-342.3(cal)-8.6(culations)]TJ
T*
[(perf)-8.8(ormed)-363.9(in)-357.1(each)-361.2(run)-362.8(of)]TJ
/F13 1 Tf
10.7722 0 TD
[(Infer)-9.2(Quasi)]TJ
/F1 1 Tf
4.5524 0 TD
[(.)-358.9(The)-356.7(reco)-8.6(mmende)-9.5(d)-359.3(value)-363(of)]TJ
/F10 1 Tf
12.3143 0 TD
(g)Tj
/F1 1 Tf
.5008 0 TD
[(,)-358.9(a)-355.4(thr)-7(eshold)-363.1(used)-358.8(to)-357.1(dete)-9.4(rmine)-361(pop-)]TJ
-28.1398 -1.195 TD
[(ulati)-8.2(on)-331.6(siz)-8(e)]TJ
/F5 1 Tf
5.0304 0 TD
(K)Tj
/F1 1 Tf
1.0015 0 TD
[(based)-338.6(on)]TJ
/F5 1 Tf
3.9549 0 TD
[(MECimpr)-9.1(\()]TJ
/F7 1 Tf
4.3419 0 TD
()Tj
/F5 1 Tf
.2675 0 TD
(\))Tj
/F1 1 Tf
.3357 0 TD
[(,)-336.1(i)0(s)-335.5(discussed)-341.1(in)-334.3(Appe)-8.8(ndix)-335.9(B.)]TJ
-13.9305 -1.2007 TD
[(We)-438.3(com)-7.6(pare)-435.4(perform)-10.9(ances)-437.2(of)-436(aB)-8(ayesQR,)-439.5(Sho)-7.2(RAH,)-436.3(ViQu)-8(aS,)-435.4(and)-436.6(Predi)-9.6(ctHaplo)-439.5(whe)-8(n)-433.3(applied)-441.2(to)-431.1(the)]TJ
-1.0015 -1.2007 TD
[(reco)-8.6(nstructio)-8.7(n)-575.5(o)0(f)-572.6(a)-577.3(quasispe)-9.1(cies)-579.6(spectru)-9.1(m)-573.4(with)-575.9(dive)-7.6(rsity)-575.9(levels)-583.9(varying)-580.9(between)-580.8(1%)-579(and)-573.1(5%)-579(\(i.e.,)]TJ
/F5 1 Tf
T*
(div)Tj
/F7 1 Tf
1.5137 0 TD
.2772 Tc
(2f)Tj
/F1 1 Tf
1.434 0 TD
0 Tc
(1)Tj
/F5 1 Tf
.5008 0 TD
(%)Tj
/F1 1 Tf
.8365 0 TD
.1678 Tc
(2)Tj
/F5 1 Tf
1.0015 0 TD
0 Tc
(%)Tj
/F1 1 Tf
.8365 0 TD
.1678 Tc
(3)Tj
/F5 1 Tf
1.0015 0 TD
0 Tc
(%)Tj
/F1 1 Tf
.8308 0 TD
.1678 Tc
(4)Tj
/F5 1 Tf
1.0015 0 TD
0 Tc
(%)Tj
/F1 1 Tf
.8365 0 TD
.1678 Tc
(5)Tj
/F5 1 Tf
1.0015 0 TD
0 Tc
(%)Tj
/F7 1 Tf
.8365 0 TD
(g)Tj
/F1 1 Tf
.5008 0 TD
[(\).)-242.1(To)-246(test)-244.9(the)-245.8(ability)-245.8(o)-6.5(f)-241.7(different)-249.5(methods)-253.6(to)-243.3(reconstruct)-252(quasispe)-9.1(cies)-249.6(with)-245.8(low)]TJ
-12.1323 -1.2007 TD
[(dive)-7.6(rsity,)-360(we)-360.1(assume)-366.9(low-s)-8(equencing)-367.8(error)-358.7(rate)-364.2(of)]TJ
/F5 1 Tf
21.0436 0 TD
(err)Tj
/F6 1 Tf
1.417 0 TD
(=)Tj
/F1 1 Tf
.7227 0 TD
(0)Tj
/F11 1 Tf
.5008 0 TD
(:)Tj
/F1 1 Tf
.2731 0 TD
(1)Tj
/F5 1 Tf
.5008 0 TD
(%)Tj
/F1 1 Tf
1.1893 0 TD
[([medi)-8.2(an)-356.1(mism)-8.4(atch)-362.2(error)-358.7(rates)-366.1(for)-359.1(454)-360.8(Life)]TJ
-25.6473 -1.2007 TD
[(Sc)-8.2(iences)-389.5(and)-385.3(Illumin)-7.7(a)-383.8(platfo)-8.2(rms)-384.6(are)-389.1(0.1%)-386.7(and)-385.3(0.12%)-6.2(,)-381.7(respective)-12.1(ly)-385.6(\(Archer)-388.6(et)-387.3(al.,)-388.1(2012\)].)-384.5(Cov)-7(erage)-386.7(per)]TJ
T*
[(str)-8.2(ain)]TJ
/F5 1 Tf
2.5778 0 TD
(cov)Tj
/F6 1 Tf
1.5706 0 TD
()Tj
/F1 1 Tf
1.0641 0 TD
[(is)-346.9(set)-343.8(to)-345.7(5)-6.5(0)0(0)]TJ
/F6 1 Tf
5.2694 0 TD
()Tj
/F1 1 Tf
.717 0 TD
[(,)-347.5(imply)-7.2(ing)-346.5(total)-349.6(coverage)-356.7(of)-344.9(2500)]TJ
/F6 1 Tf
14.0386 0 TD
()Tj
/F1 1 Tf
1.0641 0 TD
[(and)-351.2(5000)]TJ
/F6 1 Tf
3.9663 0 TD
()Tj
/F1 1 Tf
1.0641 0 TD
[(for)-347.7(the)-348.3(5-stra)-8.6(in)-345.7(and)-351.2(10-strain)]TJ
-31.3322 -1.2007 TD
[(po)-7.2(pulation,)-386.4(resp)-8(ectively;)-393.2(strains)-386.9(havi)-7.6(ng)-382.8(frequenc)-9.7(ies)-389.3(0.23%)-387.4(or)-384.8(higher)-386.7(in)-385.6(the)-382.4(5-st)-9(rain)-385.2(case)-390.9(and)-385.3(those)-385.1(with)]TJ
0 -1.195 TD
[(fre)-8(quencies)-288.6(0.46%)-285(o)-6.5(r)-281.6(higher)-284.2(in)-283.1(the)-285.7(10-stra)-9.3(in)-283.1(case)-288.4(are)-281(cover)-9.4(ed)-282.2(with)-285.6(proba)-7.6(bility)-288.8(0.99)-281.5(\(Erikss)-8.6(on)-286.1(et)-279.2(al.,)-285.7(2008\).)]TJ
1.0015 -1.2007 TD
[(Table)-300.2(1)-296.7(dem)-7.6(onstrates)-304.8(that)-300.6(the)-297.1(propos)-7.7(ed)-293.5(aB)-8(ayesQR)-302.5(algori)-8.2(thm)-298.8(outperform)-10.2(s)-292.2(exis)-8.8(ting)-298.8(schemes)-10.9(.)-290.6(I)0(n)-299.4(terms)-299.6(of)]TJ
/F5 1 Tf
-1.0015 -1.2007 TD
[(Re)-8.8(call)]TJ
/F1 1 Tf
2.8225 0 TD
(and)Tj
/F5 1 Tf
1.6958 0 TD
[(Precisi)-10.9(on)]TJ
/F1 1 Tf
3.8525 0 TD
[(,)-245.1(aBayes)-10.1(QR)-249.2(exhibits)-250.7(exceptio)-11.3(nally)-244.4(good)-247.7(perf)-8.8(ormance)-249.5(com)-7.6(pared)-248.4(to)-249(compet)-8.7(ing)-244.1(methods)]TJ
-8.3708 -1.2007 TD
[(whe)-8(n)-251.2(reco)-8.6(nstructin)-8.7(g)-256.8(quasispe)-9.1(cies)-255.3(strai)-8.6(ns)-253.1(with)-257.2(dive)-7.6(rsity)]TJ
/F5 1 Tf
22.3866 0 TD
(div)Tj
/F11 1 Tf
1.508 0 TD
(<)Tj
/F1 1 Tf
1.0528 0 TD
(4)Tj
/F5 1 Tf
.5008 0 TD
(%)Tj
/F1 1 Tf
.8308 0 TD
[(.)-256.5(The)-254.3(p)-6.5(erformanc)-10.3(e)-252.9(o)0(f)-253.9(V)0(i)-8.2(QuaS)-258.4(deteriora)-10.3(tes)]TJ
-26.279 -1.2007 TD
[(at)-319.1(low)-316.3(d)-6.5(iversities)-322.5(in)-317.3(terms)-322.3(of)-316.5(most)-317.8(of)-316.5(the)-319.8(criteria)-319.6(\(i.)-6.6(e.,)]TJ
/F5 1 Tf
22.3752 0 TD
(Recall)Tj
/F1 1 Tf
2.5778 0 TD
(,)Tj
/F5 1 Tf
.5634 0 TD
[(Precisi)-10.9(on)]TJ
/F1 1 Tf
3.8525 0 TD
(,)Tj
/F5 1 Tf
.5634 0 TD
[(Predi)-9.4(cted)-316.7(Proport)-10.3(ion)]TJ
/F1 1 Tf
8.6838 0 TD
[(,)-319.1(and)]TJ
/F5 1 Tf
2.3331 0 TD
(JSD)Tj
/F1 1 Tf
1.6673 0 TD
(\).)Tj
-42.6165 -1.2007 TD
[(Predi)-9.6(ctHaplo)-246(coul)-7.6(d)-239.8(not)-238.4(perform)-249.9(reconst)-9.1(ruction)-242.2(in)-243.3(most)-243.8(of)-236.8(the)-245.8(low)-242.3(diversity)-247.7(instanc)-9.9(es,)-238.2(yet)-245.8(it)-240.4(overall)-244(achieves)]TJ
T*
[(the)-422.2(highest)]TJ
/F5 1 Tf
4.9622 0 TD
[(Preci)-11.1(sion)]TJ
/F1 1 Tf
4.2679 0 TD
[(because)-423.4(it)-416.8(typically)-419.8(under)-7.6(estimat)-10.5(es)-414.2(the)-416.6(numb)-6.6(er)-415(of)-418.9(strains)-421(as)-414.2(show)-8.2(n)-410.5(b)0(y)]TJ
/F5 1 Tf
30.0575 0 TD
[(Predi)-9.4(cted)]TJ
-39.2876 -1.2007 TD
[(Pr)-8.2(oportion)]TJ
/F1 1 Tf
4.7004 0 TD
[(\(e.g.,)-246.2(est)-8(imating)-246.6(only)-250.5(23)-241.3(out)-249.7(of)-242.5(10)-246.2(strains\),)-247.7(which)-251.3(is)-244.5(in)-243.3(agreem)-9.7(ent)-245.8(with)-245.8(the)-245.8(resu)-8(lts)-242.3(reporte)-9.9(d)-239.8(b)0(y)-246.2(a)]TJ
-4.7004 -1.195 TD
[(previ)-10.3(ous)-333.5(study)-337.8(\(Schirm)-10.9(er)-335.3(et)-336.1(al.,)-331.2(2)-6.5(012\).)]TJ
1.0015 -1.2007 TD
[(Among)-261.7(all)-260(methods)-8.9(,)-250.8(Sho)-7.2(RAH)-259.6(has)-255.7(the)-257.2(lowest)-261.7(perfo)-9.6(rmance)-260.1(in)-254.7(terms)-259.7(o)-6.5(f)]TJ
/F5 1 Tf
28.2536 0 TD
(Recall)Tj
/F1 1 Tf
2.8339 0 TD
(and)Tj
/F5 1 Tf
1.7015 0 TD
[(Precisi)-10.9(on)]TJ
/F1 1 Tf
3.8525 0 TD
[(.)-256.5(A)0(s)-257(indicated)]TJ
-37.643 -1.2007 TD
(by)Tj
/F5 1 Tf
1.2633 0 TD
[(Predi)-9.4(cted)-265.5(Proport)-10.3(ion)]TJ
/F1 1 Tf
8.6326 0 TD
[(,)-262.1(aBayes)-10.1(QR)-266.2(is)-261.6(the)-262.9(mos)-7(t)-259.6(accurat)-11.5(e)-264.3(method)-268.7(in)-260.4(terms)-265.4(of)-265.3(estimat)-10.5(ing)-261.1(the)-262.9(popu)-8.7(lation)-265(size)]TJ
-9.8959 -1.2007 TD
[(although)-263.8(it)-257.4(often)-260.7(misse)-8.6(s)-252.3(a)-258.6(strain)-259.7(with)-257.2(the)-257.2(low)-9(est)-258.4(frequenc)-9.7(y)-251.1(whe)-8(n)-256.8(applied)-259.1(to)-254.7(reco)-8.6(nstructio)-8.7(n)-256.8(o)0(f)-253.9(a)-258.6(quasispe)-9.1(cies)]TJ
T*
[(consi)-9.6(sting)-352(of)-350.6(10)-354.3(strains.)-358.8(ViQuaS)-357.6(and)-351.2(Sh)-6.4(oRAH)-357.1(typically)-357.2(overest)-9.2(imate)-357.9(the)-348.3(n)-6.5(umber)-352.5(of)-350.6(strai)-8.6(ns)-349.8(espec)-10.4(ially)-355.3(at)]TJ
T*
[(low)-259.4(diversity)-259.1(levels)-9.2(.)-250.8(aBayes)-10.1(QR)-254.9(is)-255.9(the)-251.5(best)-259.2(method)-257.3(in)-254.7(terms)-259.7(of)]TJ
/F5 1 Tf
25.0669 0 TD
[(Recons)-9.1(truction)-256.4(Ra)-7(te)]TJ
/F1 1 Tf
8.4334 0 TD
[(at)-256.5(all)-254.3(levels)-259.6(of)-253.9(diversity)-8.7(.)]TJ
/F2 1 Tf
-33.5003 67.0005 TD
[(64)-7.2(4)]TJ
34.0921 0 TD
[(AHN)-338(AND)-344.1(VIKALO)]TJ
ET
endstream
endobj
82 0 obj
<>stream
/GS1 gs
BT
/F1 1 Tf
9.9626 0 0 9.9626 107.6031 291.1747 Tm
0 0 0 rg
0 Tc
0 Tw
[(In)-458.8(terms)-458.9(of)-458.7(frequenc)-9.7(y)-456(estimat)-10.5(ion,)-455(aB)-8(ayesQR)-461.8(overa)-9.4(ll)-456.6(outperf)-8.1(orms)-459.3(all)-459.2(the)-456.4(othe)-7.6(r)-452.3(methods)-8.9(,)-455.6(whe)-8(reas)-459.4(Pre-)]TJ
0 -1.2007 TD
[(dictHapl)-10.5(o)-313.8(show)-8.2(s)-314.9(the)-319.8(highe)-8.4(st)]TJ
/F5 1 Tf
11.8591 0 TD
(JSD)Tj
/F1 1 Tf
1.986 0 TD
[(due)-322.7(to)-317.3(its)-316.3(drawbac)-10.9(k)-319.4(o)0(f)-316.5(under)-7.6(estimat)-10.5(ing)-318(the)-319.8(number)-324.8(of)-316.5(strains.)-324.7(Note)-324.5(that)]TJ
-13.8451 -1.2007 TD
[(both)-352.9(ViQuaS)-357.6(and)-351.2(ShoR)-7(AH)-350.8(exhibit)-356.8(signica)-9.9(ntly)-350(increas)-10.9(ed)-350.4(\(i.e.,)-351.4(deteri)-10(orated\))]TJ
/F5 1 Tf
31.7874 0 TD
(JSD)Tj
/F1 1 Tf
2.0145 0 TD
[(at)-353.2(low)-350.4(dive)-7.6(rsity)-353.9(levels.)]TJ
-33.8019 -1.2007 TD
[(This)-280(fact,)-279.2(along)-281.5(with)-280(the)-274.3(low)]TJ
/F5 1 Tf
11.9502 0 TD
(Recall)Tj
/F1 1 Tf
2.851 0 TD
(and)Tj
/F5 1 Tf
1.7242 0 TD
[(Precisi)-10.9(on)]TJ
/F1 1 Tf
4.1256 0 TD
[(scores)-280(they)-280.8(have)-279.8(in)-277.4(low)-276.4(dive)-7.6(rsity)-280(settings,)-280.7(indicat)-11.5(es)-272(that)]TJ
-20.651 -1.2007 TD
[(state-of-)-11.7(the-art)-320(methods)-316.2(exper)-9.4(ience)-319.2(major)-315.5(difcul)-8.1(ties)-313.2(whe)-8(n)-308.1(attem)-10.7(pting)-316.6(to)-311.6(reconst)-9.2(ruct)-316.9(viral)-314.7(quasispe)-9.1(cies)-317.9(in)]TJ
T*
[(those)-379.4(settings,)-383.1(as)-380.1(also)-378.7(obser)-8.8(ved)-379.7(in)-374.2(Eriksson)-382.9(et)-381.7(al.)-376.3(\(2008\),)-378.8(Schir)-9.6(mer)-379.5(et)-376(al.)-376.3(\(2012\))-8.5(,)-376(and)-379.7(Jayasundar)-11.7(a)-378.1(e)0(t)-376(al.)]TJ
T*
(\(2014\).)Tj
1.0015 -1.195 TD
[(We)-244.9(further)-243.4(stud)-7(y)-239.8(the)-240.2(eff)-8(ects)-243.9(that)-243.7(seque)-8.6(ncing)-241.7(error)-244.8(rate)-244.7(\()]TJ
/F5 1 Tf
22.2045 0 TD
(err%)Tj
/F1 1 Tf
2.0543 0 TD
[(\))-241.7(and)-243.1(cover)-9.4(age)-244.9(per)-239.4(strai)-8.6(n)-239.8(\()]TJ
/F5 1 Tf
10.4706 0 TD
(cov)Tj
/F6 1 Tf
1.5649 0 TD
()Tj
/F1 1 Tf
.717 0 TD
[(\))-241.8(have)-245.6(on)-240.5(the)]TJ
-38.0129 -1.2007 TD
[(performanc)-11.1(e)-270(o)0(f)-271(the)-268.6(algorithm)-11.1(s.)-264.1(Th)-7(ose)-267(resu)-8(lts)-265.1(are)-275.3(reported)-272.5(in)-271.8(Suppleme)-9.5(ntary)-272.1(Tables)-273.7(S2)-268.2(and)-271.5(S3)-268.2(in)-266.1(Appe)-8.8(ndix)]TJ
T*
[(C,)-261.9(dem)-7.6(onstratin)-8.7(g)-262.5(super)-8.8(iority)-265.2(of)-265.3(aBayes)-10.1(QR)-266.2(compare)-10.5(d)-262.5(t)0(o)-266.1(the)-262.9(com)-7.6(peting)-268(methods)-8.9(.)-262.2(The)-265.7(runtim)-9.9(es)-260.6(of)-265.3(the)-268.6(tested)]TJ
T*
[(algori)-8.2(thms)-334.9(are)-337.9(shown)-339(in)-334.3(Supple)-8.3(mentary)-341.5(Table)-340(S4)-336.5(in)-334.3(Appendi)-8.1(x)-330.8(C)0(.)]TJ
/F5 1 Tf
10.959 0 0 10.959 107.6031 147.685 Tm
[(3.2.)-496.9(Performance)-332.1(comparison)-327.9(on)-334.7(real)-332.1(HIV)-331.9(data)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 129.7701 Tm
[(To)-234.7(further)-243.4(test)-239.2(the)-240.2(perfo)-9.6(rmance)-243.1(of)-236.8(our)-237.6(propos)-7.7(ed)-236.6(method,)-246.3(we)-234.9(use)-244.3(it)-234.7(for)-239.6(the)-240.2(analysis)-245.2(of)-236.8(the)-240.2(HIV)-239.7(5-virus)-7.6(-mix)]TJ
-1.0015 -1.2007 TD
[(data)-276.8(set)-275.5(p)-6.5(ublished)-276.4(in)-277.4(Di)-275.7(Gial)-8.6(lonardo)-279.3(et)-273.5(al.)-279.6(\(2014\).)-276.4(Speci)-9.4(cally,)-280.7(we)-274.7(appl)-7.6(y)-273.9(our)-277.4(algorithm)-278.5(to)-277.4(reconst)-9.1(ruct)-277(an)-276.5(in)]TJ
T*
[(vitro)-426.7(generat)-9.7(ed)-424.4(quasispe)-9.1(cies)-426(popul)-6.6(ation)-426.5(consist)-9.3(ing)-426.2(of)-424.6(ve)-424.4(know)-7(n)-421.9(HIV-1)-431(strains:)-430.3(HIV-1)]TJ
/F5 1 Tf
6.9738 0 0 6.9738 472.3085 104.3716 Tm
(HXB)Tj
/F1 1 Tf
1.9511 0 TD
(2)Tj
9.9626 0 0 9.9626 489.94 105.8456 Tm
[(,)-421.5(HIV-1)]TJ
6.9738 0 0 6.9738 522.5952 104.3716 Tm
(89)Tj
/F11 1 Tf
1.008 0 TD
(:)Tj
/F1 1 Tf
.2683 0 TD
(6)Tj
9.9626 0 0 9.9626 535.4645 105.8456 Tm
(,)Tj
-42.9466 -1.2007 TD
(HIV-1)Tj
/F5 1 Tf
6.9738 0 0 6.9738 133.5685 92.4094 Tm
(JR)Tj
/F6 1 Tf
1.2357 0 TD
(-)Tj
/F5 1 Tf
.7154 0 TD
(CSF)Tj
/F1 1 Tf
9.9626 0 0 9.9626 160.4409 93.8834 Tm
[(,)-307.7(HIV-)-9.2(1)]TJ
/F5 1 Tf
6.9738 0 0 6.9738 192.0188 92.4094 Tm
(NL)Tj
/F1 1 Tf
1.2194 0 TD
(4)Tj
/F6 1 Tf
.6666 0 TD
(-)Tj
/F1 1 Tf
.7235 0 TD
(3)Tj
9.9626 0 0 9.9626 214.1858 93.8834 Tm
[(,)-313.4(and)-311.4(HIV-)-9.2(1)]TJ
/F5 1 Tf
6.9738 0 0 6.9738 263.3385 92.4094 Tm
(YU)Tj
/F1 1 Tf
1.317 0 TD
(2)Tj
9.9626 0 0 9.9626 276.5479 93.8834 Tm
[(.)-307.7(Compa)-8.2(red)-313.3(to)-317.3(the)-308.4(simul)-8.4(ated)-316.7(data)-316.7(set,)-310(rel)-8.8(ative)-314.5(frequenc)-9.7(ies)-315.3(of)-310.8(the)]TJ
-16.9578 -1.2007 TD
[(ve)-435.8(HIV-1)-436.7(strai)-8.6(ns)-429.5(are)-434.6(mor)-7.8(e)-429.3(evenl)-10.1(y)-433.3(distributed)-439.8(\(abou)-7.6(t)-430.3(1)0(0)]TJ
/F5 1 Tf
24.0312 0 TD
(%)Tj
/F6 1 Tf
1.0015 0 TD
(-)Tj
/F1 1 Tf
.7227 0 TD
(30)Tj
/F5 1 Tf
1.0015 0 TD
(%)Tj
/F1 1 Tf
.8308 0 TD
[(\))-435.2(and)-436.6(the)-433.6(pairwise)-437.7(distanc)-9.9(es)-437(between)]TJ
-27.5878 -1.195 TD
[(strains)-369.8(are)-360.7(highe)-8.4(r)-361.2(\()0(2)]TJ
/F11 1 Tf
8.3367 0 TD
(:)Tj
/F1 1 Tf
.2675 0 TD
(61)Tj
/F5 1 Tf
1.0015 0 TD
(%)Tj
/F6 1 Tf
1.0015 0 TD
(-)Tj
/F1 1 Tf
.7227 0 TD
(8)Tj
/F11 1 Tf
.5008 0 TD
(:)Tj
/F1 1 Tf
.2675 0 TD
.0065 Tc
(45)Tj
/F5 1 Tf
1.0072 0 TD
0 Tc
(%)Tj
/F1 1 Tf
.8308 0 TD
[(\))-361.2(\()0(D)-7.4(i)-356.3(Gial)-8.6(lonardo)-364.7(et)-364.6(al.,)-365.3(2014\).)-364.7(We)-364.4(use)-363.8(the)-365.3(2)]TJ
/F6 1 Tf
18.8983 0 TD
()Tj
/F1 1 Tf
.7227 0 TD
[(250)-360.8(bp-long)-368.6(paired-end)]TJ
ET
107.603 709.965 430.356 .51019 re
f
107.603 379.332 430.356 .51022 re
f
176.768 691.597 174.217 .28345 re
f
363.742 691.597 174.217 .28345 re
f
107.603 672.661 430.356 .51025 re
f
BT
/F3 1 Tf
8.9663 0 0 8.9663 113.3858 716.1447 Tm
(Table)Tj
/F1 1 Tf
3.0034 0 TD
(1.)Tj
/F3 1 Tf
1.2519 0 TD
-.0183 Tc
[(Performanc)-5.2(e)-334(C)2.8(omparis)-18.3(o)14.5(n)-333.8(o)-3.7(f)-330(D)-2.1(ifferen)]TJ
16.5534 0 TD
-.018 Tc
[(t)-333.7(M).8(ethods)-334.8(f)-1(or)-333.7(Varied)-332.2(Diversities)]TJ
/F1 1 Tf
15.137 0 TD
0 Tc
(\()Tj
/F5 1 Tf
.3161 0 TD
-.0175 Tc
(div)Tj
/F1 1 Tf
1.1761 0 TD
0 Tc
(\))Tj
/F3 1 Tf
.6449 0 TD
-.0208 Tc
[(o)-6.2(n)-336.3(Si)-5.4(mu)-7.5(lat)-7.7(e)-1.3(d)-335(D)-4.6(at)-7.7(a)]TJ
/F1 1 Tf
-38.7278 -4.1289 TD
0 Tc
(div\(%\))Tj
/F5 1 Tf
15.6492 2.1119 TD
[(5)-334.6(strains)-17054.8(10)-334.1(strains)]TJ
-6.8161 -2.1119 TD
3.6731 Tc
[(123)6.3(451)6.3(234)6.3(5)]TJ
/F1 1 Tf
-8.8331 -2.0739 TD
0 Tc
(Recall)Tj
.999 -1.2203 TD
(aBayesQR)Tj
/F2 1 Tf
6.7149 0 TD
[(0.7080)-1416.8(0.7120)-1423.1(0.6840)]TJ
/F1 1 Tf
12.513 0 TD
[(0.6560)-1416.8(0.6320)]TJ
/F2 1 Tf
8.3399 0 TD
[(0.5810)-1423.1(0.6380)-1416.8(0.6080)-1423.1(0.5860)-1423.1(0.5550)]TJ
/F1 1 Tf
-27.5679 -1.2266 TD
[(ShoRAH)-3060.9(0.1920)-1416.8(0.1600)-1423.1(0.1300)-1423.1(0.1060)-1416.8(0.0780)-1423.1(0.0150)-1423.1(0.0380)-1416.8(0.0740)-1423.1(0.0640)-1423.1(0.0930)]TJ
0 -1.2203 TD
[(ViQuaS)-3498.9(0.3700)-1416.8(0.5240)-1423.1(0.6040)-1423.1(0.6360)-1416.8(0.5960)-1423.1(0.0980)-1423.1(0.1700)-1416.8(0.3730)-1423.1(0.4720)-1423.1(0.5050)]TJ
T*
[(PredictHaplo)-2300.5()-3173.1()-3166.8()]TJ
/F2 1 Tf
19.228 0 TD
[(0.6918)-1416.8(0.6808)]TJ
/F1 1 Tf
9.2125 0 TD
[()-3173.1()-2294.2(0.1021)-1423.1(0.1550)-1423.1(0.2010)]TJ
-29.4395 -1.5554 TD
(Precision)Tj
.999 -1.2266 TD
(aBayesQR)Tj
/F2 1 Tf
6.7149 0 TD
[(0.7113)-1416.8(0.7130)-1423.1(0.6826)]TJ
/F1 1 Tf
12.513 0 TD
[(0.6447)-1416.8(0.6319)]TJ
/F2 1 Tf
8.3399 0 TD
[(0.6210)-1423.1(0.6881)-1416.8(0.6610)-1423.1(0.6373)]TJ
/F1 1 Tf
16.6862 0 TD
(0.6140)Tj
-44.2541 -1.2203 TD
[(ShoRAH)-3060.9(0.1062)-1416.8(0.1418)-1423.1(0.1240)-1423.1(0.1078)-1416.8(0.0790)-1423.1(0.0050)-1423.1(0.0170)-1416.8(0.0498)-1423.1(0.0506)-1423.1(0.0824)]TJ
T*
[(ViQuaS)-3498.9(0.1960)-1416.8(0.3206)-1423.1(0.4559)-1423.1(0.4982)-1416.8(0.5298)-1423.1(0.0485)-1423.1(0.1079)-1416.8(0.2973)-1423.1(0.4690)-1423.1(0.5596)]TJ
0 -1.2266 TD
[(PredictHaplo)-2300.5()-3173.1()-3166.8()]TJ
/F2 1 Tf
19.228 0 TD
[(0.9373)-1416.8(0.8822)]TJ
/F1 1 Tf
9.2125 0 TD
[()-3173.1()-2294.2(0.4509)-1423.1(0.6000)]TJ
/F2 1 Tf
15.8136 0 TD
(0.6833)Tj
/F1 1 Tf
-45.2531 -1.5554 TD
(PredProp)Tj
.999 -1.2203 TD
(aBayesQR)Tj
/F2 1 Tf
6.7149 0 TD
[(1.0180)-1416.8(1.0120)-1423.1(1.0120)-1423.1(1.0360)-1416.8(1.0140)-1423.1(0.9680)-1423.1(0.9440)-1416.8(0.9240)-1423.1(0.9240)-1423.1(0.9100)]TJ
/F1 1 Tf
-6.7149 -1.2203 TD
[(ShoRAH)-3060.9(1.9660)-1416.8(1.2200)-1423.1(1.0780)-1423.1(1.0000)-1416.8(1.0180)-1423.1(3.2000)-1423.1(2.9100)-1416.8(1.6710)-1423.1(1.3520)-1423.1(1.1860)]TJ
0 -1.2266 TD
[(ViQuaS)-3498.9(2.1100)-1416.8(1.7220)-1423.1(1.4080)-1423.1(1.3340)-1416.8(1.2180)-1423.1(2.0860)-1423.1(1.8580)-1416.8(1.5450)-1423.1(1.2320)-1423.1(1.0730)]TJ
0 -1.2203 TD
[(PredictHaplo)-2300.5()-3173.1()-3166.8()-2300.6(0.7388)-1416.8(0.7737)-2295.7()-3173.1()-2294.2(0.1947)-1423.1(0.2430)-1423.1(0.2890)]TJ
-.999 -1.5554 TD
(ReconRate)Tj
.999 -1.2203 TD
(aBayesQR)Tj
/F2 1 Tf
6.7149 0 TD
[(0.9990)-1416.8(0.9982)-1423.1(0.9971)-1423.1(0.9961)-1416.8(0.9953)-1423.1(0.9975)-1423.1(0.9967)-1416.8(0.9952)-1423.1(0.9942)-1423.1(0.9924)]TJ
/F1 1 Tf
-6.7149 -1.2203 TD
[(ShoRAH)-3060.9(0.9948)-1416.8(0.9903)-1423.1(0.9891)-1423.1(0.9851)-1416.8(0.9827)-1423.1(0.9941)-1423.1(0.9900)-1416.8(0.9899)-1423.1(0.9897)-1423.1(0.9911)]TJ
0 -1.2266 TD
[(ViQuaS)-3498.9(0.9963)-1416.8(0.9949)-1423.1(0.9917)-1423.1(0.9936)-1416.8(0.9897)-1423.1(0.9944)-1423.1(0.9910)-1416.8(0.9899)-1423.1(0.9881)-1423.1(0.9858)]TJ
0 -1.2203 TD
[(PredictHaplo)-2300.5()-3173.1()-3166.8()-2300.6(0.9906)-1416.8(0.9896)-2295.7()-3173.1()-2294.2(0.9850)-1423.1(0.9797)-1423.1(0.9747)]TJ
-.999 -1.5554 TD
(JSD)Tj
.999 -1.2203 TD
(aBayesQR)Tj
/F2 1 Tf
6.7149 0 TD
[(0.0022)-1416.8(0.0008)-1423.1(0.0008)]TJ
/F1 1 Tf
12.513 0 TD
(0.0014)Tj
/F2 1 Tf
4.1668 0 TD
[(0.0008)-1423.1(0.0043)-1423.1(0.0026)-1416.8(0.0023)-1423.1(0.0023)-1423.1(0.0025)]TJ
/F1 1 Tf
-23.3948 -1.2266 TD
[(ShoRAH)-3060.9(0.0762)-1416.8(0.0174)-1423.1(0.0047)]TJ
/F2 1 Tf
19.228 0 TD
(0.0009)Tj
/F1 1 Tf
4.1668 0 TD
[(0.0012)-1423.1(0.1390)-1423.1(0.1110)-1416.8(0.0422)-1423.1(0.0238)-1423.1(0.0109)]TJ
-23.3948 -1.2203 TD
[(ViQuaS)-3498.9(0.0651)-1416.8(0.0255)-1423.1(0.0222)-1423.1(0.0097)-1416.8(0.0180)-1423.1(0.0993)-1423.1(0.0747)-1416.8(0.0495)-1423.1(0.0469)-1423.1(0.0454)]TJ
T*
[(PredictHaplo)-2300.5()-3173.1()-3166.8()-2300.6(0.1020)-1416.8(0.1036)-2295.7()-3173.1()-2294.2(0.1971)-1423.1(0.1636)-1423.1(0.1312)]TJ
7.9702 0 0 7.9702 115.5401 368.3905 Tm
[(Performance)-335.8(compariso)12.8(n)-339.4(o)0(f)-333.6(aBayesQR,)-332.3(ShoRAH,)-328.3(ViQuaS,)-332.4(and)-338.4(PredictHap)10.5(lo)-335.8(in)-335.8(terms)-333.7(of)]TJ
/F5 1 Tf
36.7607 0 TD
(Recall)Tj
/F1 1 Tf
2.5607 0 TD
(,)Tj
/F5 1 Tf
.5904 0 TD
(Precision)Tj
/F1 1 Tf
3.834 0 TD
(,)Tj
/F5 1 Tf
.5904 0 TD
[(Predicted)-330.3(Proportio)12.4(n)]TJ
/F1 1 Tf
-45.332 -1.2519 TD
(\()Tj
/F5 1 Tf
.3343 0 TD
(PredProp)Tj
/F1 1 Tf
3.9336 0 TD
(\),)Tj
/F5 1 Tf
.8465 0 TD
[(Reconstru)11.6(ction)-260.1(Rate)]TJ
/F1 1 Tf
8.422 0 TD
(\()Tj
/F5 1 Tf
.3343 0 TD
[(ReconRat)12.1(e)]TJ
/F1 1 Tf
4.339 0 TD
[(\))-264.5(and)]TJ
/F5 1 Tf
2.3047 0 TD
(JSD)Tj
/F1 1 Tf
1.9277 0 TD
[(on)-259(the)-265.8(simulated)-251.1(data)-259.8(with)]TJ
/F5 1 Tf
10.8831 0 TD
(err)Tj
/F6 1 Tf
1.4155 0 TD
(=)Tj
/F1 1 Tf
.7184 0 TD
(0)Tj
/F11 1 Tf
.4979 0 TD
(:)Tj
/F1 1 Tf
.2703 0 TD
(1)Tj
/F5 1 Tf
.4979 0 TD
(%)Tj
/F1 1 Tf
1.0954 0 TD
(and)Tj
/F5 1 Tf
1.7072 0 TD
(cov)Tj
/F6 1 Tf
1.5578 0 TD
(=)Tj
/F1 1 Tf
.7184 0 TD
(500)Tj
/F6 1 Tf
1.6645 0 TD
()Tj
/F1 1 Tf
.9745 0 TD
(versus)Tj
/F5 1 Tf
2.8097 0 TD
(div)Tj
/F1 1 Tf
1.4938 0 TD
[(for)-256.6(a)-264.3(mixture)]TJ
-48.7463 -1.2519 TD
[(of)-269.5(5)-268.2(and)-267.3(10)-273.3(viral)-263.5(strains.)-267.8(Averaged)-262.1(PredictHap)10.5(lo)-271.7(results)-268.8(are)-266.8(reported)-265.4(if)-268(they)-270.8(provide)-260.9(answers)-270.5(for)-270.9(more)-265(than)-263.7(50%)-272.5(of)-269.5(data)-266.9(sets.)-265(Boldface)]TJ
T*
[(values)-327.9(indicate)-329.9(the)-329.8(best)-328.9(performanc)11.7(e)-335.4(for)-327.8(each)]TJ
/F5 1 Tf
18.9636 0 TD
(div)Tj
/F1 1 Tf
1.2235 0 TD
(\()Tj
/F5 1 Tf
.3343 0 TD
(%)Tj
/F1 1 Tf
.8322 0 TD
(\).)Tj
-20.3578 -1.2448 TD
[(JSD,)-335.6(Jensen)12.9(Shannon)-327.9(divergence.)]TJ
/F2 1 Tf
9.9626 0 0 9.9626 107.6031 737.4045 Tm
[(A)-334.8(BAYE)-9(SIAN)-341.4(METHOD)-340.5(FOR)-339.6(QUA)-8(SISP)-8.2(ECIES)-336.3(REC)-9.2(ONST)-8.7(RUCTI)-10.1(ON)-10587.7(645)]TJ
ET
endstream
endobj
87 0 obj
<>stream
/GS1 gs
BT
/F1 1 Tf
9.9626 0 0 9.9626 74.0976 715.4644 Tm
0 0 0 rg
0 Tc
0 Tw
[(read)-8.6(s)-241(provi)-8.6(ded)-243.1(by)-246.2(Illumin)-7.7(as)-246.2(MiSe)-8.8(q)-239.8(B)0(e)-8(nchtop)-248.1(Sequenc)-9.9(er.)-244.7(The)-248.6(reads)-249.6(are)-246.8(aligned)-247.7(to)-249(the)-245.8(HIV-1)]TJ
/F5 1 Tf
6.9738 0 0 6.9738 447.1369 713.9904 Tm
(HXB)Tj
/F1 1 Tf
1.9511 0 TD
(2)Tj
9.9626 0 0 9.9626 467.2062 715.4644 Tm
(reference)Tj
-39.4583 -1.195 TD
[(genom)-9.1(e;)-250.8(the)-257.2(reads)-255.2(shorter)-259.7(than)-252.3(150)-8(nt)-249(and)-254.5(thos)-7(e)-247.2(havi)-7.6(ng)-251.9(bases)-260.1(with)-251.5(qual)-7.6(ity)-252.5(scores)-257.2(less)-254.7(than)-258(a)-252.9(Phred)-251.5(thr)-7(eshold)]TJ
0 -1.2007 TD
[(of)-492.9(60)-490.9(are)-491.5(discard)-9.2(ed.)-487.4(We)-495.3(compare)-494.2(the)-490.5(perf)-8.8(ormance)-494.2(of)-492.9(our)-488(method)-496.3(applied)-498.1(to)-488(gene-wise)-500.1(quasispe)-9.1(cies)]TJ
T*
[(reco)-8.6(nstructio)-8.7(n)-347.9(o)0(f)-350.6(the)-348.3(above)-354.5(described)-353.9(HI)-7.4(V)-346.1(data)-350.8(with)-353.9(that)-351.8(of)-344.9(the)-354(competing)-355.2(techniq)-8.7(ues.)-347.1(Since)-356.5(the)-348.3(current)]TJ
T*
[(vers)-8(ion)-437.5(of)-430.3(Vi)-8.2(QuaS)-434.8(softw)-8(are)-440.3(does)-432.8(no)-7.2(t)-430.3(suppor)-7.7(t)-436(specifying)-441(genom)-9.1(ic)-432.9(regions,)-440.2(we)-439.7(could)-435.2(n)-6.5(o)0(t)-431.1(use)-437.8(it)-433.8(in)-436.8(this)]TJ
T*
[(exper)-9.4(iment.)-373.5(When)-371.6(running)-374.3(aBayes)-10.1(QR,)-369.1(we)-371.4(set)-366.5(the)-371(parame)-9.7(ter)]TJ
/F10 1 Tf
25.3173 0 TD
(g)Tj
/F1 1 Tf
.8707 0 TD
[(to)-362.8(0.)-6.8(09)-365.7(\(the)-368.1(set)-8(ting)-367.1(recomm)-11.5(ended)-371.6(in)-368.5(Ap-)]TJ
-26.1879 -1.2007 TD
[(pendi)-8.4(x)-330.8(B)0(\))-8.2(.)-330.4(Other)-338.6(para)-8.6(meters)-342(are)-337.9(set)-332.4(to)-334.3(the)-336.9(sam)-8.8(e)-332.6(values)-342.2(as)-334.6(the)-336.9(ones)-336.1(used)-336.1(in)-334.3(Se)-8.2(ction)-335.5(3.1.)]TJ
1.0015 -1.2007 TD
[(We)-438.3(eval)-9.4(uate)-436.2(and)-436.6(repor)-9.6(t)-430.3(the)]TJ
/F5 1 Tf
12.0128 0 TD
[(Predi)-9.4(cted)-436.2(Proport)-10.3(ion)]TJ
/F1 1 Tf
9.2414 0 TD
[(\(i.e.,)-436.7(the)-439.3(fraction)-440.3(of)-436(corr)-8.8(ectly)-439.7(estimated)-446.3(strains)-438.1(as)]TJ
-22.2557 -1.2007 TD
[(de)-9(ned)-356.9(in)-351.4(Sect)-8.6(ion)-352.2(3.1\))-357.5(and)]TJ
/F5 1 Tf
11.5575 0 TD
[(Recons)-9.1(truction)-358.8(Ra)-7(te)]TJ
/F1 1 Tf
8.6383 0 TD
[(in)-357.1(Table)-357.1(2.)-354(On)-358.3(this)-356.9(real)-358.5(HIV-)-9.2(1)-353.6(data)-356.5(set)-355.2(that)-357.5(\(as)-360.1(pointed)]TJ
-20.1958 -1.195 TD
[(above\))-334.5(has)-323.9(differ)-9.4(ent)-325.5(prope)-7.6(rties)-327.3(than)-326.3(the)-325.5(simul)-8.4(ated)-328.1(data)-328.1(set)-326.7(in)-323(Sect)-8.6(ion)-323.7(3.1,)-326.6(aBayes)-10.2(QR)-323.2(is)-329.8(the)-325.5(most)-323.5(accur)-11.1(ate)]TJ
0 -1.2007 TD
[(amo)-7.6(ng)-343(the)-348.3(considered)-349(methods)-350.3(in)-345.7(terms)-350.8(of)]TJ
/F5 1 Tf
17.9651 0 TD
[(Pr)-8.2(edicted)-346.3(Propo)-10.5(rtion)]TJ
/F1 1 Tf
8.7122 0 TD
[(.)-347.5(PredictHa)-11.5(plo)-340.8(und)-8(erestimate)-12.7(s)-343.4(the)-342.6(popu-)]TJ
-26.6773 -1.2007 TD
[(lati)-7.4(on)-354.3(size)-357.7(and)-351.2(reco)-8.6(nstructs)-359.2(three)-359.3(or)-350.6(four)-359.8(strains)-358.4(in)-351.4(the)-354(8)-353.6(consid)-10.3(ered)-355.7(genes,)-356.1(and)-356.9(ShoR)-7(AH)-356.5(greatly)-357.8(overes-)]TJ
T*
[(tima)-8.2(tes)-258.4(the)-251.5(pop)-8(ulation)-254.4(siz)-8(e)-252.9(for)-256.6(all)-254.3(13)-257.6(genes)-259(of)-253.9(the)-257.2(HIV-1)-260.3(data)-254.1(set)-258.4(\(e.g.,)-257.6(it)-257.4(reconstruct)-13(s)-252.3(119)-252.7(strai)-8.6(ns)-253.1(in)-254.7(gp120\))-6.6(,)]TJ
T*
[(whi)-9(ch)-464.3(is)-472.1(consist)-9.3(ent)-467.8(with)-473.4(our)-465.2(simul)-8.4(ation)-472.1(results)-472.3(as)-471.1(well)-469.5(as)-471.1(with)-473.4(the)-467.8(resu)-8(lts)-469.9(in)-465.2(Schirm)-8.2(er)-471.9(et)-467(al.)-467.4(\(2012\))-8.5(.)]TJ
T*
[(aB)-8(ayesQR)-478.9(and)-482.1(PredictHa)-11.5(plo)-477.4(are)-474.5(tied)-477(for)-478.6(the)-479.2(number)-478.5(of)-475.8(genes)-480.9(whe)-8(re)-471.9(all)-476.2(the)-479.2(strai)-8.6(ns)-475(are)-474.5(perf)-8.8(ectly)-479.5(re-)]TJ
T*
[(const)-9.6(ructed)-485.2(\(ve)-478.3(each\))-11.1(;)-475.8(for)-484.2(the)-479.2(remai)-10(ning)-478.1(genes)-8.6(,)-478.4(PredictHa)-11.5(plo)-477.4(provi)-8.6(des)-477.6(a)-480.6(larger)-487.2(numb)-6.6(er)-477.6(of)-481.5(perfectly)]TJ
T*
[(reco)-8.6(nstructed)-383.3(strains.)-375.9(How)-10.2(ever,)-373.2(it)-376.9(is)-369.7(wor)-8.2(th)-374.2(pointing)-378.6(out)-374.9(that)-374.6(Predict)-9.9(Haplo,)-376.9(designed)-383.5(for)-370.4(iden)-7.6(tication)-379.2(of)]TJ
0 -1.195 TD
[(HI)-7.4(V)-425.8(haplotyp)-7.7(es,)-431.7(missed)-430.4(at)-427.2(least)-435.2(one)-425.2(strai)-8.6(n)-421.9(i)0(n)-431.1(each)-429.5(of)-430.3(the)-427.9(remainin)-9.3(g)-427.6(eight)-426.5(genes)-8.6(,)-427.2(while)-430.5(aBayes)-10.2(QR)-431.3(re-)]TJ
0 -1.2007 TD
[(const)-9.6(ructed)-246.2(mos)-7(t)-242.5(o)0(f)-242.5(the)-245.8(strains)-244.6(on)-246.2(all)-242.9(but)-244.1(two)-248(genes,)-248(gp120)-242.8(and)-248.8(gp41.)-242.4(Sh)-6.4(oRAH)-243.3(d)-6.5(i)0(d)-237.6(n)-6.5(ot)-237.6(p)-6.5(erfectly)-248.6(reconst)-9.1(ruct)]TJ
T*
[(any)-300(of)-293.7(the)-297.1(13)-291.7(genes)-8.6(,)-290.6(which)-302.5(is)-290(consi)-9.6(stent)-296.8(with)-297(the)-297.1(simulation)-298.3(resu)-8(lts.)-293.9(More)-8.8(over,)-297.4(overest)-9.1(imating)-297.8(the)-297.1(number)]TJ
T*
[(of)-424.6(strai)-8.6(ns)-418.1(negat)-10.1(ively)-426.5(affects)-428.3(the)-422.2(accuracy)-432.4(of)-424.6(ShoRAH)-10.7(s)-420.1(frequenc)-9.7(y)-421.9(estimat)-10.5(ion;)-424(for)-421.6(instanc)-9.9(e,)-424(the)-422.2(sum)-422.4(of)]TJ
T*
[(fre)-8(quencies)-288.6(correspo)-9.1(nding)-285.4(to)-283.1(the)-285.7(most)-283.7(abunda)-8.1(nt)-283.1(ve)-282.1(strai)-8.6(ns)-281.6(does)-284.9(not)-283.9(excee)-11(d)-279.6(50%)-283.9(in)-283.1(9)-279.6(o)0(f)-282.3(1)0(3)-286.1(genes)-287.4(\(71%)-286.6(is)]TJ
T*
[(the)-336.9(largest)-342(such)-341.8(sum,)-337.4(on)]TJ
/F5 1 Tf
10.3397 0 TD
(vpu)Tj
/F1 1 Tf
1.4511 0 TD
[(\))-332.8(\(see)-339.8(Supple)-8.3(mentary)-341.5(Table)-340(S5)-336.5(in)-334.3(Appendi)-8.1(x)-330.8(C\).)]TJ
-10.7893 -1.2007 TD
[(To)-280.2(comple)-8.7(ment)-278.6(the)-280(gene-)-9.4(wise)-280.2(quasi)-9.6(species)-283.3(reco)-8.6(nstructio)-8.7(n)-273.9(stud)-7(y)-273.9(with)-285.7(that)-277.8(of)-276.6(a)-281.4(global)-279.3(reco)-8.6(nstructio)-8.7(n,)-280(we)]TJ
-1.0015 -1.2007 TD
[(consi)-9.6(der)-296.3(the)-297.1(HI)-7.4(V-1)]TJ
/F5 1 Tf
8.1318 0 TD
[(gap-po)-6.6(l)]TJ
/F1 1 Tf
3.4143 0 TD
[(region)-301.3(spanning)-302.1(4307)-173.8(bp.)-292.1(To)-302.9(efcientl)-10.3(y)-291(proce)-9.4(ss)-294.1(35)-7.2(5,241)-293.7(p)-6.5(aired-end)-303.5(reads)-300.8(that)]TJ
-11.5461 -1.195 TD
[(rem)-9.6(ain)-297.1(after)-304.3(applying)-303.6(a)-298.5(qual)-7.6(ity)-298(lter,)-302.9(we)-297.5(organ)-7.6(ize)-298.8(the)-302.7(region)-301.3(into)-298.8(a)-298.5(seque)-8.6(nce)-301.8(of)-299.4(windows)-301.7(o)-6.5(f)-293(leng)-7.6(th)-294.5(4)-6.5(0)0(0)-166.6(b)0(p)]TJ
ET
74.098 372.699 430.413 .51022 re
f
74.098 110.778 430.413 .45352 re
f
74.098 354.274 430.413 .51022 re
f
BT
/F3 1 Tf
8.9663 0 0 8.9663 136.0063 378.8786 Tm
(Table)Tj
/F1 1 Tf
2.9971 0 TD
(2.)Tj
/F3 1 Tf
1.2519 0 TD
[(Performance)-332.5(Comparisons)-337.2(on)-332.5(a)-333.2(Real)]TJ
/F1 1 Tf
17.0908 0 TD
[(HIV-1)-331.8(5-)]TJ
/F3 1 Tf
3.7685 0 TD
[(Virus-Mix)-332.3(Data)-333.6(Set)]TJ
/F5 1 Tf
-25.6457 -2.017 TD
[(p17)-1661.5(p24)-1282.1(p2p6)-1420.2(PR)-1958.8(RT)-1451.7(RNase)-1504.2(int)-2118.4(vif)-1988.1(vpr)-2019.1(vpu)-1562.7(gp120)-1028.2(gp41)-1793.8(nef)]TJ
/F1 1 Tf
-6.3672 -2.0802 TD
(aBayesQR)Tj
1.0053 -1.2203 TD
(PredProp)Tj
/F2 1 Tf
5.9878 0 TD
(1)Tj
/F1 1 Tf
3.1615 0 TD
(1)Tj
/F2 1 Tf
3.2816 0 TD
2.7816 Tc
(11)Tj
/F1 1 Tf
6.443 0 TD
0 Tc
(1)Tj
/F2 1 Tf
3.3385 0 TD
(1)Tj
/F1 1 Tf
3.3385 0 TD
2.6551 Tc
(11)Tj
/F2 1 Tf
5.8171 0 TD
0 Tc
(12)Tj
/F1 1 Tf
3.6546 0 TD
[(1)-3287.4(0.8)-2031.6(0.8)-1905.1(1.2)]TJ
-35.0226 -1.2266 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 318.8976 Tm
(HXB2)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 320.2015 Tm
(100)Tj
/F1 1 Tf
3.661 0 TD
(99.4)Tj
/F2 1 Tf
2.7821 0 TD
[(100)-1781.6(100)]TJ
/F1 1 Tf
6.9362 0 TD
(98.5)Tj
/F2 1 Tf
2.8453 0 TD
(100)Tj
/F1 1 Tf
3.838 0 TD
[(99.9)-905.6(100)]TJ
/F2 1 Tf
5.8171 0 TD
(100)Tj
/F1 1 Tf
3.6546 0 TD
[(99.6)-2037.4(98)-2781.1(0)-2155.6(95.8)]TJ
-34.5231 -1.2203 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 307.8991 Tm
(89)Tj
/F11 1 Tf
1.0027 0 TD
(:)Tj
/F1 1 Tf
.271 0 TD
(6)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 309.2598 Tm
(100)Tj
/F1 1 Tf
3.661 0 TD
(98.7)Tj
/F2 1 Tf
2.7821 0 TD
[(100)-1781.6(100)]TJ
/F1 1 Tf
6.9362 0 TD
(98.6)Tj
/F2 1 Tf
2.8453 0 TD
(100)Tj
/F1 1 Tf
3.3385 0 TD
[(100)-1655.1(100)]TJ
/F2 1 Tf
6.3166 0 TD
(100)Tj
/F1 1 Tf
3.6546 0 TD
[(92)-2787.4(96.5)-1531.6(98.9)-1405.1(95.5)]TJ
-34.5231 -1.2203 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 296.9574 Tm
(JR)Tj
/F6 1 Tf
1.2195 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(CSF)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 298.318 Tm
(100)Tj
/F1 1 Tf
3.661 0 TD
(99.6)Tj
/F2 1 Tf
2.7821 0 TD
[(100)-1781.6(100)]TJ
/F1 1 Tf
6.9362 0 TD
(99)Tj
/F2 1 Tf
2.8453 0 TD
(100)Tj
/F1 1 Tf
3.3385 0 TD
[(100)-1655.1(100)]TJ
/F2 1 Tf
6.3166 0 TD
(100)Tj
/F1 1 Tf
3.6546 0 TD
[(98.8)-2037.4(97.7)-1531.6(99.1)-1405.1(98.2)]TJ
-34.5231 -1.2266 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 286.0157 Tm
(NL4)Tj
/F6 1 Tf
2.0053 0 TD
(-)Tj
/F1 1 Tf
.7136 0 TD
(3)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 287.3196 Tm
(100)Tj
/F1 1 Tf
3.1615 0 TD
(100)Tj
/F2 1 Tf
3.2816 0 TD
[(100)-1781.6(100)]TJ
/F1 1 Tf
6.9362 0 TD
(98.9)Tj
/F2 1 Tf
2.8453 0 TD
(100)Tj
/F1 1 Tf
3.3385 0 TD
[(100)-2154.6(99.8)]TJ
/F2 1 Tf
6.3166 0 TD
(100)Tj
/F1 1 Tf
3.1551 0 TD
[(100)-2786.9(96.3)-1531.6(98.8)-905.6(100)]TJ
-34.0236 -1.2203 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 275.0173 Tm
(YU2)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 276.3779 Tm
(100)Tj
/F1 1 Tf
3.661 0 TD
(99.7)Tj
/F2 1 Tf
2.7821 0 TD
[(100)-1781.6(100)]TJ
/F1 1 Tf
6.9362 0 TD
(99.2)Tj
/F2 1 Tf
2.8453 0 TD
(100)Tj
/F1 1 Tf
3.838 0 TD
[(99.5)-1405.1(99.7)]TJ
/F2 1 Tf
5.8171 0 TD
(100)Tj
/F1 1 Tf
3.1551 0 TD
[(100)-3286.5(0)-2282.1(98.6)-1405.1(99.2)]TJ
-35.0289 -1.5554 TD
(ShoRAH)Tj
1.0053 -1.2203 TD
[(PredProp)-1771.3(13)-2161.5(16.4)-1531.6(13.8)-2031.1(8.8)-1405.6(21.8)-1594.8(11.8)-1588.5(13.6)-1405.1(12.8)-1911(7.8)-1905.1(4)-2787.9(23.8)-1531.6(19.8)-1405.1(17.4)]TJ
T*
(RR)Tj
6.2762 0 0 6.2762 95.0173 239.1873 Tm
(HXB2)Tj
8.9663 0 0 8.9663 127.8425 240.548 Tm
[(100)-2161(96.7)-1032.1(100)-1781.6(100)-2154.6(98.2)-1095.3(100)-2338(97.5)-905.6(100)-1661.5(100)-1655.1(100)-2786.9(97.7)-1531.6(98.4)-1405.1(98.2)]TJ
-4.9888 -1.2267 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 228.1889 Tm
(89)Tj
/F11 1 Tf
1.0027 0 TD
(:)Tj
/F1 1 Tf
.271 0 TD
(6)Tj
8.9663 0 0 8.9663 127.8425 229.5495 Tm
[(100)-2161(99.7)-1032.1(100)-1781.6(100)-2154.6(98.6)-1095.3(100)-2338(98.9)-1405.1(99.8)-912(100)-2154.6(93.6)-2037.4(96.1)-1531.6(98.6)-1405.1(98.9)]TJ
-4.9888 -1.2203 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 217.2472 Tm
(JR)Tj
/F6 1 Tf
1.2195 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(CSF)Tj
8.9663 0 0 8.9663 127.8425 218.6078 Tm
[(100)-1661.5(100)-1781.6(100)-1781.6(100)-2154.6(99.8)-1594.8(96.4)-1588.5(99)-1655.6(100)-1661.5(100)-2154.6(98)-2787.4(96.9)-1531.6(96.3)-1405.1(94.7)]TJ
-4.9888 -1.2203 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 206.3054 Tm
(NL4)Tj
/F6 1 Tf
2.0053 0 TD
(-)Tj
/F1 1 Tf
.7136 0 TD
(3)Tj
8.9663 0 0 8.9663 127.8425 207.6661 Tm
[(100)-2161(99.1)-1531.6(97.3)-1032.1(100)-2154.6(98.9)-1594.8(99.2)-1588.5(99.3)-1405.1(99.3)-912(100)-1655.1(100)-2786.9(96.1)-1531.6(98.5)-1405.1(98.6)]TJ
-4.9888 -1.2266 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 195.3637 Tm
(YU2)Tj
8.9663 0 0 8.9663 132.3212 196.6676 Tm
[(94.2)-1411.5(99)-1782.1(100)-2281.1(98.3)-1405.1(98)-2344.8(94.5)-1588.5(98.6)-1405.1(95)-2161.5(93.2)-1405.1(90.8)-2037.4(97)-2281.6(95.4)-1405.1(97.9)]TJ
-6.4936 -1.5554 TD
(PredictHaplo)Tj
1.0053 -1.2203 TD
(PredProp)Tj
/F2 1 Tf
5.9878 0 TD
(1)Tj
/F1 1 Tf
3.1615 0 TD
(0.6)Tj
/F2 1 Tf
3.2816 0 TD
2.7816 Tc
[(11)120.1(1)]TJ
/F1 1 Tf
9.7815 0 TD
0 Tc
[(0.8)-2088.5(0.8)-1905.1(0.8)]TJ
/F2 1 Tf
9.6551 0 TD
(1)Tj
/F1 1 Tf
3.1551 0 TD
[(0.8)-2537.4(0.8)-2031.6(0.8)-1905.1(0.8)]TJ
-35.0226 -1.2203 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 159.4771 Tm
(HXB2)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 160.8377 Tm
(100)Tj
/F1 1 Tf
4.1605 0 TD
(0)Tj
/F2 1 Tf
2.2826 0 TD
[(100)-1781.6(100)-1655.1(100)]TJ
/F1 1 Tf
10.2811 0 TD
[(98.9)-1089(100)-1655.1(100)]TJ
/F2 1 Tf
9.1556 0 TD
(100)Tj
/F1 1 Tf
3.6546 0 TD
[(93.17)-2036.9(0)-2781.6(0)-2655.1(0)]TJ
-34.5231 -1.2266 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 148.5354 Tm
(89)Tj
/F11 1 Tf
1.0027 0 TD
(:)Tj
/F1 1 Tf
.271 0 TD
(6)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 149.8393 Tm
(100)Tj
/F1 1 Tf
3.1615 0 TD
(100)Tj
/F2 1 Tf
3.2816 0 TD
[(100)-1781.6(100)-1655.1(100)]TJ
/F1 1 Tf
9.7815 0 TD
[(100)-2338(99.8)-905.6(100)]TJ
/F2 1 Tf
9.6551 0 TD
(100)Tj
/F1 1 Tf
4.1541 0 TD
[(0)-2787.9(97.8)-1032.1(100)-2154.6(98.87)]TJ
-35.0226 -1.2203 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 137.5369 Tm
(JR)Tj
/F6 1 Tf
1.2195 0 TD
(-)Tj
/F1 1 Tf
.7226 0 TD
(CSF)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 138.8976 Tm
(100)Tj
/F1 1 Tf
3.1615 0 TD
(100)Tj
/F2 1 Tf
3.2816 0 TD
[(100)-1781.6(100)-1655.1(100)]TJ
/F1 1 Tf
9.7815 0 TD
[(100)-1838.5(100)-1655.1(100)]TJ
/F2 1 Tf
9.6551 0 TD
(100)Tj
/F1 1 Tf
3.1551 0 TD
[(100)-2786.9(99.7)-1032.1(100)-1655.1(100)]TJ
-34.0236 -1.2203 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 126.5952 Tm
(NL4)Tj
/F6 1 Tf
2.0053 0 TD
(-)Tj
/F1 1 Tf
.7136 0 TD
(3)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 127.9559 Tm
(100)Tj
/F1 1 Tf
3.661 0 TD
(99.1)Tj
/F2 1 Tf
2.7821 0 TD
[(100)-1781.6(100)-1655.1(100)]TJ
/F1 1 Tf
9.7815 0 TD
[(100)-1838.5(100)-1655.1(100)]TJ
/F2 1 Tf
9.6551 0 TD
(100)Tj
/F1 1 Tf
3.1551 0 TD
[(100)-2281.1(100)-1787.9(100)-1655.1(100)]TJ
-34.0236 -1.2266 TD
(RR)Tj
6.2762 0 0 6.2762 95.0173 115.6535 Tm
(YU2)Tj
/F2 1 Tf
8.9663 0 0 8.9663 127.8425 116.9575 Tm
(100)Tj
/F1 1 Tf
4.1605 0 TD
(0)Tj
/F2 1 Tf
2.2826 0 TD
[(100)-1781.6(100)-1655.1(100)]TJ
/F1 1 Tf
10.7806 0 TD
2.8385 Tc
[(00)183.4(0)]TJ
/F2 1 Tf
8.6561 0 TD
0 Tc
(100)Tj
/F1 1 Tf
3.1551 0 TD
[(100)-2786.9(98.6)-1032.1(100)-1655.1(100)]TJ
/F5 1 Tf
7.9702 0 0 7.9702 82.0913 99.7795 Tm
[(Predicted)-273.4(Proport)13.9(ion)]TJ
/F1 1 Tf
8.8843 0 TD
[(\(PredProp\))-269(and)-274.4(reconstru)12.9(ction)-274.3(rate)-277.4(\(RR\))-271.1(for)-278(aBayesQR,)-268.3(ShoRAH,)-271.4(and)-267.3(PredictHaplo)-268.4(applied)-273.4(to)-271.7(reconstruction)]TJ
-9.8873 -1.2448 TD
[(of)-312.2(HIV-1)]TJ
5.5789 0 0 5.5789 103.9181 88.611 Tm
(HXB2)Tj
7.9702 0 0 7.9702 119.7354 89.8583 Tm
[(,)-311.9(HIV-1)]TJ
5.5789 0 0 5.5789 144.907 88.611 Tm
(89)Tj
/F11 1 Tf
.9959 0 TD
(:)Tj
/F1 1 Tf
.2744 0 TD
(6)Tj
7.9702 0 0 7.9702 156.0755 89.8583 Tm
[(,)-311.9(HIV-1)]TJ
5.5789 0 0 5.5789 181.2472 88.611 Tm
(JR)Tj
/F6 1 Tf
1.2093 0 TD
(-)Tj
/F1 1 Tf
.7215 0 TD
(CSF)Tj
7.9702 0 0 7.9702 203.1873 89.8583 Tm
[(,)-311.9(HIV-1)]TJ
5.5789 0 0 5.5789 228.359 88.611 Tm
(NL4)Tj
/F6 1 Tf
1.9918 0 TD
(-)Tj
/F1 1 Tf
.7215 0 TD
(3)Tj
7.9702 0 0 7.9702 247.5779 89.8583 Tm
[(,)-311.9(and)-310(HIV-1)]TJ
5.5789 0 0 5.5789 286.7527 88.611 Tm
(YU2)Tj
7.9702 0 0 7.9702 301.3228 89.8583 Tm
[(for)-313.5(all)-306.9(13)-315.9(genes)-310.2(of)-305.1(the)-315.6(HIV-1)-307.3(data)-309.6(set.)-315.7(\(Note:)-306.6(RR)-311.1(expressed)-302.6(in)]TJ
-28.5094 -1.2519 TD
[(percentages.\))-288.2(Boldface)-284.1(values)-285.3(indicate)-287.2(the)-294.2(genes)-288.9(where)-286.5(all)-292.7(the)-287.1(strains)-290.2(are)-288.1(perfectly)-286.3(reconstructed)9.2(.)-290.6(The)-295.5(inferred)-283(frequencie)9.8(s)-297.9(are)-288.1(shown)]TJ
T*
[(in)-335.8(Supplemen)12.5(tary)-331.1(Table)-328.6(S5)-328(in)-335.8(Appendix)-321.9(C.)]TJ
/F2 1 Tf
9.9626 0 0 9.9626 74.0976 737.4045 Tm
[(64)-7.2(6)]TJ
34.0921 0 TD
[(AHN)-338(AND)-344.1(VIKALO)]TJ
ET
endstream
endobj
91 0 obj
<>stream
/GS1 gs
BT
/F1 1 Tf
9.9626 0 0 9.9626 107.6031 715.4644 Tm
0 0 0 rg
0 Tc
0 Tw
[(where)-275.1(the)-268.6(consecut)-9.7(ive)-268.6(windows)-273.2(overlap)-269.7(b)-6.5(y)-262.5(150)-173(bp)-263.3(and)-271.5(run)-266(aBayes)-10.1(QR)-271.9(on)-263.3(thos)-7(e)-264.3(window)-9.5(s.)-264.1(Th)-7(e)-264.3(entire)-271.7(region)]TJ
0 -1.195 TD
[(is)-250.2(asse)-9(mbled)-256.6(by)-251.9(connec)-9.9(ting)-253.3(strai)-8.6(ns)-253.1(in)-254.7(the)-251.5(conse)-8.6(cutive)-258.4(window)-9.5(s)-252.3(while)-254.1(tes)-8(ting)-253.3(consistency)-260.7(in)-254.7(the)-257.2(overlapp)-8.7(ing)]TJ
0 -1.2007 TD
[(interv)-8.2(als.)-292.9(Th)-7(e)-292.8(numb)-6.6(er)-295.5(of)-293.7(strains)-301.5(retrieved)-300.5(in)-294.5(the)-297.1(globa)-8.4(l)-293.7(reconst)-9.2(ruction)-299.2(is)-295.7(decided)-298(by)-297.4(major)-8.2(ity)-292.3(voting)-300.3(of)-293.7(the)]TJ
T*
[(numb)-6.6(er)-346.7(of)-350.6(strains)-352.7(obta)-7.6(ined)-349(in)-351.4(each)-349.8(wi)-8.2(ndow.)-348.8(Th)-7(e)-344(fre)-8(quencies)-356.8(are)-349.3(estim)-10.2(ated)-350.8(by)-348.7(counting)-354.8(read)-8.6(s)-343.4(near)-8.6(est)-349.5(\(in)]TJ
T*
[(terms)-259.7(of)-259.6(Hamm)-10.1(ing)-255.4(distanc)-9.9(e\))-255.7(to)-260.4(each)-258.8(of)-259.6(the)-257.2(reco)-8.6(nstructed)-263.8(strai)-8.6(ns.)-259.2(Follow)-7.6(ing)-255.4(this)-260.2(procedu)-10.9(re,)-256.1(both)-261.9(aBayes)-10.1(QR)]TJ
T*
[(and)-282.9(Predi)-9.5(ctHaplo)-291.5(could)-287.2(reconst)-9.1(ruct)-288.4(all)-282.7(ve)-287.8(HIV-1)-288.8(strai)-8.6(ns)-281.6(in)-283.1(the)]TJ
/F5 1 Tf
26.0343 0 TD
[(gap)-8(-pol)]TJ
/F1 1 Tf
3.4029 0 TD
[(regi)-9.6(on)-280.4(corr)-8.8(ectly,)-286.4(that)-289.2(is,)-284.7(they)-286.4(both)]TJ
-29.4372 -1.2007 TD
(achieved)Tj
/F5 1 Tf
3.9436 0 TD
[(Recons)-9.1(truction)-370.2(Rate)]TJ
/F1 1 Tf
8.6553 0 TD
[(of)-362(1)-6.5(0)0(0)-360(for)-364.7(all)-368.1(ve)-367.5(strains)-369.8(and)]TJ
/F5 1 Tf
12.633 0 TD
[(Predict)-9.7(ed)-361.8(Proport)-10.3(ion)]TJ
/F1 1 Tf
9.0935 0 TD
[(of)-362(1)-6.5(.)-358.9(The)-368.1(frequenc)-9.7(ies)]TJ
-34.3254 -1.2007 TD
[(estimat)-10.5(ed)-418.7(by)-422.6(aBayes)-10.1(QR)-419.9(are)-423.3(15)-7.2(.21%,)-421.2(19.34%)-6.9(,)-421.5(25.56%,)-422.7(27.61%)-6.9(,)-421.5(and)-419.5(12.27%)-6.9(,)-421.5(while)-424.8(those)-425(estimat)-10.5(ed)-418.7(by)]TJ
T*
[(Predict)-9.9(Haplo)-496(are)-497.2(13.21%)-6.9(,)-489.8(13.56%)-6.9(,)-489.8(25.6)-8.4(7%,)-494(19.69%)-6.9(,)-489.8(and)-493.5(27.86%)-6.9(.)-495.5(ShoRAH)-500.1(highly)-493.8(overe)-9.4(stimate)-10.5(d)-490.2(the)]TJ
0 -1.195 TD
[(numb)-6.6(er)-324(of)-322.2(strai)-8.6(ns)-321.4(and)-328.4(reported)]TJ
/F5 1 Tf
12.9346 0 TD
[(Predi)-9.4(cted)-322.4(Pr)-8.2(oportion)]TJ
/F1 1 Tf
9.0138 0 TD
[(of)-327.9(41.8;)-324.9(its)-322(v)-6.4(e)-321.2(mos)-7(t)-322.2(abunda)-8.1(nt)-323(strains)-330(estimated)-332.5(are)]TJ
-21.9485 -1.2007 TD
[(reporte)-9.9(d)-330.8(t)0(o)-334.3(have)-342.4(frequenc)-9.7(ies)-332.4(8.51%)-6.2(,)-336.1(5.04%)-6.2(,)-330.4(3.41%)-6.2(,)-336.1(3.24%,)-336.6(and)-334.1(3.09%)-6.2(.)]TJ
/F2 1 Tf
10.959 0 0 10.959 275.9243 560.0692 Tm
[(4.)-496.7(CONCLUSIONS)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 536.1447 Tm
-.0186 Tc
[(In)-207.2(this)-208.3(article,)-206.8(w)-.5(e)-208.9(p)-2.3(resented)-212.9(a)-208.9(n)3.4(ovel)-209.9(m)-.1(aximum-likelihood-)]TJ
22.0679 0 TD
-.0188 Tc
[(based)-213(a)1.4(pproximate)-209.1(algorith)]TJ
10.3909 0 TD
-.0208 Tc
[(m)-212.9(f)-.8(or)-211.3(r)-6.5(eco)-4.5(ns)-5.7(tr)]TJ
5.3662 0 TD
-.019 Tc
[(ucting)-213.2(v)3(iral)]TJ
-38.8266 -1.2007 TD
-.0177 Tc
[(q)4.3(u)-1.4(asispecies)-378.2(from)-374.8(h)-1.4(ig)4.3(h-thro)4.3(ug)4.3(hp)4.3(ut)-379.7(sequ)4.3(en)4.3(cin)4.3(g)-382.7(d)4.3(a)2.5(ta.)-376.6(a)]TJ
21.3509 0 TD
-.0204 Tc
[(Ba)-5.9(yes)-5.3(Q)-2.3(R)-378.7(a)-5.9(ss)-5.3(emble)-5.9(s)-380.9(pa)-5.9(ired)-4.1(-en)-4.1(d)-379.7(s)-5.3(h)1.6(o)-4.1(r)-.4(t)-376.7(r)-6.1(ead)-4.1(s)-380.9(i)-1.2(n)-4.1(t)-1.2(o)-379.7(l)-1.2(on)-4.1(ge)-5.9(r)]TJ
-21.3509 -1.195 TD
-.0194 Tc
[(fragments)-374.2(based)-373(o)2.6(n)-373(s)-4.3(imilarity)-373(of)-375(the)-374.8(r).6(ead)-373(o)2.6(verlaps)-374.2(a).8(nd)-373(th)]TJ
22.9841 0 TD
[(e)-369.1(u)-3.1(ncertainty)-373(level)-370.1(o)-3.1(f)-369.3(n)-3.1(on)]TJ
10.3227 0 TD
-.0185 Tc
[(overlapping)-372.1(r)1.5(egions.)-366(T)-2(he)]TJ
-33.3068 -1.2007 TD
-.0191 Tc
[(probable)-209.4(sets)-214.5(of)-215.3(partially)-213.3(reconstructe)]TJ
14.2833 0 TD
-.0161 Tc
[(d)-204.7(s)-1(tr)3.9(a)4.1(i)3.1(ns)-205.8(ar)3.9(e)-212.1(i)3.1(n)5.9(d).2(u)5.9(c)4.1(tiv)5.9(e)4.1(ly)-210.3(se)4.1(a)4.1(r)3.9(ch)5.9(ed)-204.7(an)5.9(d)-210.3(a)]TJ
15.1027 0 TD
-.0184 Tc
[(subset)-209.7(of)-208.9(those)-208.7(s)-3.3(trains)-208.1(is)-213.8(extended)-207(to)]TJ
-29.386 -1.2007 TD
-.0186 Tc
[(efciently)-195.8(deduce)-191.9(the)-191.9(m)-.1(ost)-192.8(likely)-195.8(s)2.2(et)-187.2(of)]TJ
15.0287 0 TD
-.0196 Tc
[(stra)-5.1(ins)-192.3(i)-.4(n)-196.8(a)-192.9(quas)-4.5(ispecie)-5.1(s)1.2(.)-190.7(D)-1.5(e)-5.1(t)-.4(ection)-191.1(o)]TJ
13.8394 0 TD
-.0205 Tc
[(f)-194(t)-1.3(he)-199.5(po)-4.2(pu)-4.2(latio)-4.2(n)-192(s).3(iz)-6(e)-193.8(i)-1.3(s)-193.2(e)-.3(mb)-4.2(ed)-4.2(de)-6(d)-192(i)-1.3(nto)]TJ
-28.8682 -1.2007 TD
-.0189 Tc
[(the)-192.2(a)-4.4(lgorithm)-193.9(a)1.3(nd)-190.4(is)-191.6(empirically)-190.4(shown)-190.4(t).3(o)-190.4(b)-2.6(e)-192.2(v)3.1(ery)-190.4(a)1.3(ccurate;)]TJ
22.5346 0 TD
-.0183 Tc
[(th)3.7(e)-191.6(n)-2(u)3.7(m).2(ber)-191.8(o)3.7(f)-191.8(s)2.5(trains)-185.3(is)-191(dy)3.7(namically)-189.8(adjusted)-189.8(based)-189.8(o)3.7(n)]TJ
-22.5346 -1.2007 TD
-.019 Tc
[(the)-180.9(r)1(eliability)-179.1(of)-181.1(the)-175.2(p)-2.7(artially)]TJ
10.9202 0 TD
-.0185 Tc
[(assembled)-178.6(q)-2.2(uasispecies)-179.8(i).7(n)-178.6(e)1.7(ach)-178.6(e)1.7(xtension)]TJ
15.8652 0 TD
-.0189 Tc
[(step.)-178.6(P)-1.8(erformance)-180.8(of)-175.3(the)-180.8(d)3.1(eveloped)-179(method)]TJ
-26.7854 -1.2007 TD
-.0186 Tc
[(is)-299.4(tested)-298.2(on)-298.2(both)-298.2(synthetic)-300(data)-300(sets)-299.4(and)-298.2(a)-300(real)-295.3(HIV-1)-298.2(d)-2.3(at)]TJ
22.2273 0 TD
-.0192 Tc
[(a)-300.6(s)1.6(et.)-298.4(I).8(n)-298.8(b)-2.9(oth)-298.8(s)-4.1(ettings,)-304.1(t)0(he)-300.6(new)-302.7(a)1(lgorithm)-296.6(outperform)-6.4(s)]TJ
-22.2273 -1.2007 TD
-.0205 Tc
[(ex)-4.2(istin)-4.2(g)-345.6(t)-1.3(e)-6(c)-.3(h)-4.2(n)1.5(iq)-4.2(ue)-6(s)-346.8(i)-1.3(n)-351.3(t)-1.3(erms)-352.5(of)-353.3(acc)-6(ura)-6(c)-.3(y)-351.3(o)1.5(f)-353.3(t)-1.3(he)-353.1(qu)-4.2(as)-5.4(ispe)-6(ci)]TJ
22.95 0 TD
-.0189 Tc
[(es)-350.9(size)-345.8(estimation,)-349.3(perfect)-346.8(re)]TJ
11.3014 0 TD
-.0191 Tc
[(construction)-349.9(o)2.9(f)-351.9(s)1.7(trains,)]TJ
-34.2514 -1.2007 TD
-.0204 Tc
[(pr)-6.1(op)-4.1(ortio)-4.1(n)-248.8(o)-4.1(f)-250.8(c)-.2(o)-4.1(rre)-5.9(ct)-251.5(ba)-5.9(ses)-255.7(i)-1.2(n)-248.8(e)-5.9(ach)-254.5(rec)-5.9(o)1.6(n)-4.1(s).4(tru)-4.1(c)-.2(ted)-254.5(s).4(tra)-5.9(i)-1.2(n,)-254.1(an)-4.1(d)-248.8(t)-1.2(h)-4.1(e)-250.6(es)-5.3(timatio)-4.1(n)-248.8(o)-4.1(f)-250.8(t)-1.2(he)-5.9(ir)-250.8(ab)-4.1(un)-4.1(da)-5.9(nce)-5.9(.)]TJ
1.0015 -1.195 TD
0 Tc
[(A)-232.3(partic)-10(ularly)-241.5(high)-239.1(accuracy)-244.6(is)-233.1(obser)-8.8(ved)-237.4(in)-237.6(estimating)-243.2(the)-240.2(popul)-6.6(ation)-238.7(size)-238.2(\(i.e.,)-237.6(the)-240.2(numb)-6.6(er)-232.9(of)-236.8(strai)-8.6(ns\))-238.8(and)]TJ
-1.0015 -1.2007 TD
[(the)-245.8(relat)-9.2(ive)-245.8(abunda)-8.1(nce.)-245.2(Test)-8.6(s)-241(o)0(n)-246.2(synthet)-8.2(ic)-245.1(data)-248.4(sets)-249(demonst)-8.9(rate)-244.7(that)-249.4(aBayes)-10.2(QR)-249.2(is)-244.5(capable)-248.6(of)-248.2(reconst)-9.2(ructing)]TJ
T*
[(quasispe)-9.1(cies)-317.9(at)-307.7(low)-316.3(diversity)-8.7(,)-307.7(show)-8.2(ing)-312.3(superior)-317.4(perform)-10.9(ance)-315.7(in)-311.6(those)-311.2(set)-8(tings)-312.1(com)-7.6(pared)-316.7(to)-311.6(state-of-th)-10.3(e-art)]TJ
T*
[(algori)-8.2(thms.)-420.6(Furt)-7(hermor)-8.1(e,)-418.3(the)-422.2(stud)-7(y)-416.2(o)0(n)-422.6(a)-418(real)-426.8(HIV-)-9.2(1)-416.2(data)-424.8(set)-423.4(demo)-8.4(nstrates)-423.6(that)-425.8(our)-419.7(propos)-7.7(ed)-424.4(algorithm)]TJ
T*
[(outperf)-8.1(orms)-317(or)-322.2(has)-318.2(performanc)-11.1(e)-321.2(compara)-10.5(ble)-314.1(to)-317.3(that)-323.3(of)-316.5(the)-319.8(existing)-324.6(methods)-321.9(in)-317.3(the)-319.8(gener)-9.4(al)-319.1(setting)-323.9(of)-316.5(viral)]TJ
T*
[(quasispe)-9.1(cies)-340.6(reconstruct)-13(ion.)]TJ
1.0015 -1.2007 TD
[(aBayesQR)-304.8(can)-296.1(be)-293.5(extended)-298.7(and)-294.3(appl)-7.6(ied)-291.4(to)-294.5(the)-291.4(p)-6.5(roblem)-293.5(of)-293.7(est)-8(imating)-297.8(the)-291.4(popul)-6.6(ation)-295.7(size)-295.1(and)-300(the)-291.4(degre)-9.4(e)]TJ
-1.0015 -1.2007 TD
[(of)-390.5(variation)-396.3(amo)-7.6(ng)-388.5(the)-393.8(constitu)-11.7(ent)-388.1(species)-402.8(in)-385.6(rel)-8.8(ated)-390.7(elds)-395.7(such)-393(as)-391.5(immu)-7.2(nogene)-8.1(tics.)-393.2(On)-392.4(a)-389.5(relat)-9.2(ed)-390.3(note,)]TJ
0 -1.195 TD
[(bacterial)-502.3(pop)-8(ulations)-501.1(are)-497.2(charact)-11.5(erized)-498.4(by)-496.6(havi)-7.6(ng)-490.9(rel)-8.8(atively)-500.9(lower)-498(mutat)-9(ion)-494.4(rates)-502.7(than)-497(viral)-496.8(and)-499.2(thus)]TJ
0 -1.2007 TD
[(typicall)-9.3(y)-427.6(have)-433.4(few)-10(er)-432.1(segregatin)-10.3(g)-427.6(sites)-434.6(on)-434(the)-433.6(sequen)-9.3(ces)-433.8(in)-431.1(a)-429.3(popul)-6.6(ation.)-432.6(The)-436.4(ability)-433.6(of)-430.3(our)-431.1(method)-439.4(to)]TJ
T*
[(perform)-340.9(highly)-340.2(accurate)-344.1(reconst)-9.1(ructions)-340.9(in)-334.3(such)-336.1(settings)-342.9(should)-338.6(be)-333.4(further)-340.2(inve)-7.6(stigated.)]TJ
1.0015 -1.2007 TD
[(A)-255.1(s)15.1(of)19.3(t)13.5(w)0(a)15.5(r)14.3(e)-258.6(a)14.5(Ba)20.4(ye)19.4(sQ)21.8(R)-255.9(i)0(s)-244.5(a)0(v)19.4(a)14.5(il)21.4(ab)19.4(l)13.5(e)-258.6(at)-245.1(ht)24.2(t)13.5(p)0(s)20(:)0(/)21.4(/)13.5(gi)18.5(t)13.5(h)0(u)21.2(b)0(.)21.6(c)0(o)25.1(m)0(/)20.6(S)11.4(oy)21.2(eo)19.4(nA)23(/a)16.7(B)11.6(a)0(y)19.4(e)14.5(sQ)21.8(R.)-244.9(An)-244.5(ap)19.4(pe)19.4(nd)21.2(i)13.5(x)-256.8(c)14.5(a)0(n)-248(b)0(e)-242.3(f)0(o)19.3(u)16.3(nd)-246.2(i)13.5(n)]TJ
-1.0015 -1.2007 TD
[(a)-321.2(b)0(i)18.5(o)16.3(Rx)16.5(i)13.5(v)-325.1(v)16.3(e)0(r)17.5(s)0(i)23(o)0(n)-308.8(o)0(f)-310.8(t)0(h)18.5(i)13.5(s)-320.6(a)0(r)17.5(t)13.5(ic)22.4(le)22.4(,)-324.7(w)12.4(hi)18.5(c)14.5(h)-325.1(i)13.5(s)-326.3(a)14.5(v)0(a)19.4(i)13.5(la)16.7(bl)24.2(e)-321.2(a)0(t)-313.4(h)0(t)24.2(t)0(p)18.5(:)13.5(/)13.5(/)0(b)18.5(i)13.5(or)19.3(xi)24.2(v.)21.6(or)24.9(g/)18.5(co)25.1(nt)18.5(en)19.4(t)13.5(/)13.5(e)0(a)17.7(r)14.3(ly)18.5(/)13.5(2)0(0)21.2(1)0(7)21.2(/)13.5(02)21.2(/0)18.5(6)16.3(/)0(1)18.5(0)0(3)21.2(6)0(3)21.2(0)16.3(.)]TJ
/F2 1 Tf
10.959 0 0 10.959 265.0393 237.2598 Tm
-.0003 Tc
(ACKNOWLEDGMENT)Tj
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 213.3921 Tm
0 Tc
[(T)10.8(h)0(i)24.2(s)-280.8(w)12.4(o)0(r)19.3(k)-279.6(w)12.4(a)0(s)-272(f)14.3(un)21.2(de)19.4(d)-279.6(b)0(y)-269(t)13.5(he)-270.8(N)12.4(a)0(t)16.7(i)13.5(on)21.2(al)-267.8(S)11.4(c)0(i)22.4(e)0(n)19.4(c)0(e)-266.9(F)0(o)16.3(u)16.3(n)0(d)21.2(a)0(t)22.4(i)0(o)18.5(n)-279.6(un)21.2(de)25.1(r)-281.6(g)0(r)24.9(a)0(n)19.4(t)0(s)-267.2(C)0(C)17.5(F)-278.8(15)21.2(07)21.2(99)21.2(8)-279.6(a)14.5(nd)-269(CC)17.5(F)-278.8(1)0(6)21.2(1)0(8)21.2(4)0(2)26.9(7)0(.)]TJ
/F2 1 Tf
10.959 0 0 10.959 225.3543 177.5054 Tm
[(AUTHOR)-330.8(DISCLOSURE)-328.8(STATEMENT)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 153.5811 Tm
[(No)-335.5(compet)-8.7(ing)-335.1(nancial)-340.6(intere)-10(sts)-331.8(exis)-8.8(t.)]TJ
/F2 1 Tf
10.959 0 0 10.959 286.0724 126.7086 Tm
(REFERENCES)Tj
/F1 1 Tf
8.9663 0 0 8.9663 107.6031 102.7842 Tm
[(Archer,)-335.8(J.,)-329(Baillie,)-335(G.,)-331.1(Watson,)-338.3(S.J.,)-330(et)-334.3(al.)-330.8(2012.)-336.1(Analysis)-334.7(of)-330.4(high-depth)-330.7(sequence)-335.7(data)-335.7(for)-332.5(studying)-334.1(viral)-333.1(diversity:)-333.6(A)]TJ
.999 -1.2203 TD
[(comparison)-333.8(of)-336.7(next)-333.3(generation)-335.5(sequencing)-336.4(platforms)-338.5(using)-331.6(segminator)-337.8(II.)]TJ
/F5 1 Tf
30.3689 0 TD
[(BMC)-334(Bioinformatics)]TJ
/F1 1 Tf
8.7383 0 TD
[(13,)-337.1(47.)]TJ
-40.1062 -1.2266 TD
[(Astrovskaya,)-299.2(I.,)-298.8(Tork,)-300.6(B.,)-294.6(Mangul,)-304.3(S.,)-294.8(et)-302.6(al.)-292.9(2011.)-298.1(Inferring)-303.3(viral)-301.5(quasispecies)-299.9(spectra)-302.5(from)-297.6(454)-295.7(pyrosequencing)-305.4(reads.)]TJ
/F5 1 Tf
.999 -1.2203 TD
[(BMC)-334(Bioinformatics)]TJ
/F1 1 Tf
8.7383 0 TD
[(12,)-330.7(1.)]TJ
/F2 1 Tf
9.9626 0 0 9.9626 107.6031 737.4045 Tm
[(A)-334.8(BAYE)-9(SIAN)-341.4(METHOD)-340.5(FOR)-339.6(QUA)-8(SISP)-8.2(ECIES)-336.3(REC)-9.2(ONST)-8.7(RUCTI)-10.1(ON)-10587.7(647)]TJ
ET
endstream
endobj
96 0 obj
<>stream
/GS1 gs
BT
/F1 1 Tf
8.9663 0 0 8.9663 74.0976 715.4644 Tm
0 0 0 rg
0 Tc
0 Tw
[(Di)-423.7(Giallonardo,)-418.7(F.,)-414.9(To)]TJ
9.0481 .0253 TD
()Tj
.4173 -.0253 TD
[(pfer,)-413.3(A.,)-419.6(Rey,)-419.6(M.,)-417(et)-422.8(al.)-419.4(2014.)-412(Full-length)-419(haplotype)-419.5(reconstruction)-423.5(to)-420.4(infer)-420.2(the)-416(structure)-419.5(of)]TJ
-8.4601 -1.2203 TD
[(heterogeneous)-333.6(virus)-334.2(populations.)]TJ
/F5 1 Tf
13.7144 0 TD
[(Nucleic)-339.1(Acids)-333.8(Res.)]TJ
/F1 1 Tf
7.9985 0 TD
[(42,)-330.7(e115e115.)]TJ
-22.7182 -1.2203 TD
[(Duarte,)-356.2(E.,)-352.9(Novella,)-357.1(I.,)-349.4(Weaver,)-359.5(S.,)-351.7(et)-353.2(al.)-349.8(1994.)-355.1(RNA)-351.3(virus)-353.1(quasispecies:)-360.4(Signicance)-350.9(for)-351.5(viral)-358.4(disease)-351.7(and)-355(epidemi-)]TJ
1.0053 -1.2203 TD
(ology.)Tj
/F5 1 Tf
2.8643 0 TD
[(Infect.)-331.6(Agents)-333.3(Dis.)]TJ
/F1 1 Tf
7.9036 0 TD
[(3,)-331.2(201214.)]TJ
-11.7733 -1.2266 TD
[(Er)17.5(i)15.4(k)13.1(ss)23.9(on)19.9(,)-262.2(N)0(.)25.9(,)-262.2(Pa)18.9(c)17(h)0(t)22.2(e)0(r)21.2(,)-262.2(L)13.3(.)0(,)-252.4(M)12.4(it)24.6(su)25.1(ya)17.5(,)-262.2(Y)16.2(.,)-252.4(et)-252.1(al)26.2(.)-262.2(2)0(0)19.9(0)13.1(8)13.1(.)-262.2(Vi)25.3(ra)21.2(l)-262.8(p)13.1(op)19.9(u)13.1(l)15.4(at)19.8(io)22.3(n)-258.7(e)0(s)22.7(t)0(i)24.6(m)0(a)20.3(t)0(i)24.6(o)13.1(n)-265.1(u)13.1(si)21.1(n)13.1(g)-258.7(py)19.9(ro)23.7(se)22.7(q)13.1(u)13.1(e)0(n)23.9(c)0(i)19.8(n)13.1(g)13.1(.)]TJ
/F5 1 Tf
40.1252 0 TD
[(P)13.3(L)0(o)21.4(S)-258.8(Co)21.5(mp)23(u)13.1(t)0(.)-253(B)13.3(io)22.2(l)15.4(.)]TJ
/F1 1 Tf
-39.1199 -1.2203 TD
-.0131 Tc
[(4,)-332.2(e)-13.1(1)10.8(00)-13.1(0)6.8(074.)]TJ
-1.0053 -1.2203 TD
0 Tc
[(Jayasundara,)-391.6(D.,)-381.7(Saeed,)-379.4(I.,)-381(Maheswararajah,)-391.7(S.,)-383.3(et)-378.5(al.)-387.8(2014.)-380.3(ViQuaS:)-385.3(An)-381.7(improved)-381.7(reconstruction)-385.6(pipeline)-379.7(for)-383.1(viral)]TJ
1.0053 -1.2266 TD
[(quasispecies)-337.9(spectra)-334.1(generated)-334.4(by)-334.1(next-generation)-335.8(sequencing.)]TJ
/F5 1 Tf
25.8164 0 TD
(Bioinformatics)Tj
/F1 1 Tf
5.9562 0 TD
[(,)-331.7(vol.)-334.3(31,)-337.1(btu754.)]TJ
-32.778 -1.2203 TD
[(Jung,)-387.8(S.Y.,)-389(and)-380.3(Kim,)-391.7(T.-S.)-384.7(2001.)-380.3(An)-388(agglomerative)-388.3(hierarchical)-390.2(clustering)-388.9(using)-388.5(partial)-382.8(maximum)-386.7(array)-387(and)-386.6(incre-)]TJ
1.0053 -1.2203 TD
[(mental)-234.8(similarity)-233.6(computation)-236.4(method,)-237.6(265272.)]TJ
/F5 1 Tf
19.7844 0 TD
[(In)-235.6(Data)-233(Mining,)-237.8(2001.)-228.6(ICDM)-238.4(2001,)-234.9(Proc.)-232(IEEE)-234(Int.)-235.7(Conf.)-237.3(on)]TJ
/F1 1 Tf
24.3053 0 TD
[(.)-230.5(IEEE,)]TJ
-44.0897 -1.2266 TD
[(San)-328.3(Jose,)-340.9(CA.)]TJ
-1.0053 -1.2203 TD
[(Lancia,)-264(G.,)-255.2(Bafna,)-259.2(V.,)-261.6(Istrail,)-260.6(S.,)-256.8(Lippert,)-259(R.,)-256.7(and)-253.9(Schwartz,)-261.4(R.)-260.1(2001.)-253.9(SNPs)-258.9(problems,)-259.4(complexity,)-258.7(and)-260.2(algorithms,)-260.1(182)]TJ
1.0053 -1.2203 TD
(193.)Tj
/F5 1 Tf
2.0802 0 TD
[(In)-336.7(AlgorithmsESA)-333.5(2001)]TJ
/F1 1 Tf
10.5593 0 TD
[(.)-331.7(ESA)-335.3(\(European)-340.6(Symposium)-328.9(on)-334.1(Algorithms\).)-339(Springer.)]TJ
-13.6448 -1.2203 TD
[(Lauring,)-267.6(A.S.,)-256.3(and)-266.5(Andino,)-260.2(R.)-260.1(2010.)-260.2(Quasispecies)-265.3(theory)-265.4(and)-260.2(the)-264.2(behavior)-260.5(of)-260.9(RNA)-262.8(viruses.)]TJ
/F5 1 Tf
36.9637 0 TD
[(PLoS)-262(Pathog.)]TJ
/F1 1 Tf
5.8297 0 TD
[(6,)-261.7(e1001005.)]TJ
-42.7935 -1.2266 TD
[(Le,)-554.3(T.,)-548.9(Chiarella,)-550(J.,)-550.3(Simen,)-546.5(B.B.,)-548.3(et)-549.2(al.)-552.1(2009.)-551.1(Low-abundance)-546.5(HIV)-551.5(drug-resistant)-551.4(viral)-554.4(variants)-550.2(in)-546.8(treatment-)]TJ
1.0053 -1.2203 TD
[(experienced)-335.8(persons)-332.8(correlate)-341(with)-331.9(historical)-336(antiretroviral)-338.2(use.)]TJ
/F5 1 Tf
26.1073 0 TD
[(PLoS)-331.6(One.)]TJ
/F1 1 Tf
4.7485 0 TD
[(4,)-331.2(e6079.)]TJ
-31.8612 -1.2203 TD
[(Lippert,)-455(R.,)-459(Schwartz,)-457.4(R.,)-452.7(Lancia,)-453.7(G.,)-451.3(et)-454.4(al.)-457.3(2002.)-449.9(Algorithmic)-458.9(strategies)-455.7(for)-452.7(the)-453.9(single)-457.6(nucleotide)-457(polymorphism)]TJ
1.0053 -1.2266 TD
[(haplotype)-331(assembly)-339.6(problem.)]TJ
/F5 1 Tf
12.2791 0 TD
[(Brief.)-334.4(Bioinform.)]TJ
/F1 1 Tf
7.2334 0 TD
[(3,)-337.5(2331.)]TJ
-20.5178 -1.2203 TD
[(Mangul,)-298(S.,)-294.8(Wu,)-294.7(N.C.,)-294(Mancuso,)-297.1(N.,)-299.5(et)-296.3(al.)-292.9(2014.)-298.1(Accurate)-293.9(viral)-301.5(population)-294.1(assembly)-295.4(from)-297.6(ultra-deep)-293.8(sequencing)-298.4(data.)]TJ
/F5 1 Tf
1.0053 -1.2203 TD
(Bioinformatics)Tj
/F1 1 Tf
6.285 0 TD
[(30,)-337.1(i329i337.)]TJ
-7.2903 -1.2266 TD
[(Posada-Cespedes,)-339.6(S.,)-326.4(Seifert,)-332.3(D.,)-331.1(and)-329.7(Beerenwinkel,)-335.2(N.)-328.2(2016.)-329.8(Recent)-335.5(advances)-335.7(in)-325.5(inferring)-336.3(viral)-326.8(diversity)-330(from)-335.6(high-)]TJ
1.0053 -1.2203 TD
[(throughput)-328.2(sequencing)-336.4(data.)]TJ
/F5 1 Tf
11.8302 0 TD
[(Virus)-332.6(Res)]TJ
/F1 1 Tf
3.9455 0 TD
[(.)-331.7(239,)-336.6(1432.)]TJ
-16.781 -1.2203 TD
[(Prabhakaran,)-422(S.,)-408.6(Rey,)-419.6(M.,)-410.7(Zagordi,)-413(O.,)-413.3(et)-416.4(al.)-413(2014.)-412(HIV)-418.7(haplotype)-413.2(inference)-419.2(using)-413.8(a)-412.9(propagating)-414.8(dirichlet)-417.5(process)]TJ
1.0053 -1.2266 TD
[(mixture)-329.3(model.)]TJ
/F5 1 Tf
6.5505 0 TD
[(IEEE/ACM)-331.3(Trans.)-336.6(Comput.)-334.5(Biol.)-331.3(Bioinform.)]TJ
/F1 1 Tf
18.4629 0 TD
[(11,)-330.7(182191.)]TJ
-26.0188 -1.2203 TD
[(Prosperi,)-415.1(M.C.,)-417.9(Prosperi,)-415.1(L.,)-416.1(Bruselles,)-413.1(A.,)-413.3(et)-416.4(al.)-413(2011.)-418.3(Combinatorial)-417.4(analysis)-416(and)-411.9(algorithms)-415.3(for)-414.7(quasispecies)-420.1(re-)]TJ
1.0053 -1.2203 TD
[(construction)-331(using)-337.9(next-generation)-335.8(sequencing.)]TJ
/F5 1 Tf
19.5125 0 TD
[(BMC)-334(Bioinformatics)]TJ
/F1 1 Tf
8.7383 0 TD
[(12,)-337.1(5.)]TJ
-29.2561 -1.2203 TD
[(Prosperi,)-465.7(M.C.,)-462.1(and)-462.5(Salemi,)-463.9(M.)-464.7(2012.)-462.5(QuRe:)-460.9(Software)-467.3(for)-465.3(viral)-459.5(quasispecies)-470.7(reconstruction)-461.5(from)-462(next-generation)]TJ
1.0053 -1.2266 TD
[(sequencing)-336.4(data.)]TJ
/F5 1 Tf
7.1006 0 TD
(Bioinformatics)Tj
/F1 1 Tf
6.2913 0 TD
[(28,)-330.7(132133.)]TJ
-14.3973 -1.2203 TD
[(Sasirekha,)-277.7(K.,)-267.9(and)-266.5(Baby,)-273.7(P.)-266.6(2013.)-272.9(Agglomerative)-275.3(hierarchical)-270.1(clustering)-275(algorithmA)-271(review.)]TJ
/F5 1 Tf
38.5255 0 TD
[(Int.)-267.3(J.)-270.4(Sci.)-267.1(Res.)-270.4(Publ.)]TJ
/F1 1 Tf
8.7256 0 TD
(3,)Tj
-46.2458 -1.2203 TD
(13.)Tj
-1.0053 -1.2266 TD
[(Schirmer,)-381.9(M.,)-379.1(Sloan,)-378.5(W.T.,)-382.6(and)-380.3(Quince,)-378.9(C.)-380.2(2012.)-374(Benchmarking)-383(of)-381(viral)-377.4(haplotype)-381.5(reconstruction)-385.6(programmes:)-377.4(An)]TJ
1.0053 -1.2203 TD
[(overview)-333.3(of)-330.4(the)-340.1(capacities)-336.6(and)-329.7(limitations)-335.7(of)-336.7(currently)-336.2(available)-333.5(programmes.)]TJ
/F5 1 Tf
32.1899 0 TD
[(Brief.)-334.4(Bioinform.)]TJ
/F1 1 Tf
7.2397 0 TD
[(Vol.)-331.2(15.)-337.1(bbs081.)]TJ
-40.435 -1.2203 TD
-.0137 Tc
[(S)-13.7(i)10(m)-13.7(e)6.6(n,)-351.7(B.)-13.7(B.,)-351.7(S).9(i)-13.7(m)11.3(o)-13.7(n)6.2(s)-13.7(,)-339.8(J)-13.7(.)14.3(F)-13.7(.)10.6(,)-351.7(H)-13.7(u)9.3(l)1.7(l)-13.7(s)7.4(i)-13.7(e)6.1(k,)-345.4(K)-13.7(.)5.9(H)-13.7(.)12.2(,)-351.7(e)-13.7(t)-341.6(a)3.3(l)-13.7(.)-342.6(2009.)-351.7(Lo)-13.7(w)9.3(-)-13.7(a)7.6(bun)-13.7(d)6.2(a)-13.7(n)10.2(c)-13.7(e)-340(d)-.6(r)-13.7(u)10(g-)-13.7(r)7.4(e)-13.7(s)9(i)1.7(s)-13.7(t)7.4(a)-13.7(n)10.2(t)-352.3(v)-.6(ir)-13.7(a)7.5(l)-352.3(va)-13.7(r)7.6(i)1.7(a)-13.7(n)10.1(t)-13.7(s)-340.4(i)-13.7(n)-339.2(c)-13.7(h)10.2(r)-13.7(o)10(ni)-13.7(c)6.1(a)-13.7(l)12.5(l)-13.7(y)-339.2(H)-13.7(I)13(V)-13.7(-)]TJ
1.0053 -1.2266 TD
0 Tc
[(i)15.4(n)13.1(fe)21.2(ct)19.8(ed)23.9(,)-319.1(a)0(n)23.9(t)15.4(ir)19.6(et)26.2(ro)23.7(v)13.1(i)0(r)19.6(a)0(l)-309(t)15.4(re)21.2(at)26.2(me)20.3(n)13.1(t)0()22.3(n)13.1(ai)19.8(v)13.1(e)-318.1(p)13.1(a)0(t)19.8(i)15.4(en)23.9(ts)-307.7(si)21.1(g)13.1(n)13.1(i)0()23.7(c)0(a)21.4(n)13.1(tl)24.5(y)-322(i)15.4(mp)22.7(ac)21.4(t)-319.7(t)15.4(re)21.3(at)19.8(m)15.9(e)0(n)23.8(t)-319.7(o)13.1(u)0(t)22.3(c)0(o)23.9(m)0(e)20.3(s)0(.)]TJ
/F5 1 Tf
35.5917 0 TD
[(J.)-308.3(I)16.9(n)0(f)22.2(e)0(c)21.4(t)0(.)-309.9(D)16.2(is)21.1(.)]TJ
/F1 1 Tf
5.7096 0 TD
-.0131 Tc
[(199,)-332.2(69)-13.1(3)6.8(701.)]TJ
-42.3066 -1.2203 TD
0 Tc
(To)Tj
.7018 .019 TD
()Tj
.4173 -.019 TD
[(pfer,)-305.8(A.,)-305.8(Marschall,)-315.5(T.,)-302.3(Bull,)-310.9(R.A.,)-306.7(et)-309(al.)-311.9(2014.)-304.5(Viral)-311.1(quasispecies)-312.6(assembly)-308(via)-308.5(maximal)-307.4(clique)-307.1(enumeration.)]TJ
/F5 1 Tf
44.7156 0 TD
(PLoS)Tj
-44.8294 -1.2203 TD
[(Comput.)-334.5(Biol.)]TJ
/F1 1 Tf
6.0068 0 TD
[(10,)-330.7(e1003515.)]TJ
-7.0121 -1.2203 TD
(To)Tj
.7018 .019 TD
()Tj
.4173 -.019 TD
[(pfer,)-369(A.,)-369.1(Zagordi,)-375.1(O.,)-369.1(Prabhakaran,)-371.4(S.,)-370.7(et)-372.2(al.)-375.1(2013.)-367.7(Probabilistic)-375(inference)-374.9(of)-368.4(viral)-371(quasispecies)-375.8(subject)-371.1(to)-369.8(recom-)]TJ
-.1138 -1.2266 TD
(bination.)Tj
/F5 1 Tf
3.8696 0 TD
[(J.)-333.6(Comput.)-334.5(Biol.)]TJ
/F1 1 Tf
7.0437 0 TD
[(20,)-330.7(113123.)]TJ
-11.9187 -1.2203 TD
[(Westbrooks,)-258(K.,)-255.2(Astrovskaya,)-261.3(I.,)-254.5(Campo,)-251.4(D.,)-255.2(et)-258.4(al.)-255(2008.)-253.9(HCV)-256.5(quasispecies)-255.7(assembly)-257.5(using)-255.7(network)-255.5(ows,)-257(159170.)]TJ
/F5 1 Tf
47.1689 0 TD
(In)Tj
-46.1636 -1.2203 TD
[(Bioinformatics)-331(Research)-340.7(and)-333.7(Applications)]TJ
/F1 1 Tf
17.2552 0 TD
[(.)-331.7(Bioinformatics)-338.6(Research)-336.7(and)-336.1(Applications,)-332.3(Atlanta,)-335.8(GA.)]TJ
-18.2606 -1.2267 TD
[(Zagordi,)-305.5(O.,)-299.5(Bhattacharya,)-302.7(A.,)-299.5(Eriksson,)-305(N.,)-299.5(et)-296.3(al.)-299.2(2011.)-304.5(ShoRAH:)-301.4(Estimating)-302.7(the)-295.8(genetic)-302.7(diversity)-304.7(of)-298.8(a)-299.1(mixed)-298.4(sample)]TJ
1.0053 -1.2203 TD
[(from)-329.3(next-generation)-342.1(sequencing)-330(data.)]TJ
/F5 1 Tf
16.0159 0 TD
[(BMC)-334(Bioinformatics)]TJ
/F1 1 Tf
8.7383 0 TD
[(12,)-330.7(119.)]TJ
-25.7595 -1.2203 TD
[(Zagordi,)-413(O.,)-407(Geyrhofer,)-412.8(L.,)-409.8(Roth,)-408(V.,)-407(et)-410.1(al.)-406.7(2010a.)-407.6(Deep)-410.8(sequencing)-412.2(of)-406.3(a)-412.9(genetically)-412.4(heterogeneous)-409.5(sample:)-412.5(Local)]TJ
1.0053 -1.2266 TD
[(haplotype)-331(reconstruction)-341.3(and)-329.7(read)-334.3(error)-336.6(correction.)]TJ
/F5 1 Tf
21.1375 0 TD
[(J.)-333.6(Comput.)-334.5(Biol)]TJ
/F1 1 Tf
6.462 0 TD
[(.)-331.7(17,)-330.7(417428.)]TJ
-28.6048 -1.2203 TD
[(Zagordi,)-406.7(O.,)-400.7(Klein,)-399.9(R.,)-402.1(Da)]TJ
10.6794 .019 TD
()Tj
.3857 -.019 TD
[(umer,)-401.5(M.,)-398.1(et)-403.8(al.)-400.4(2010b.)-398.8(Error)-403.5(correction)-407.6(of)-400(next-generation)-405.3(sequencing)-399.6(data)-405.2(and)-399.3(reliable)]TJ
-10.0598 -1.2203 TD
[(estimation)-330.6(of)-336.7(HIV)-336.5(quasispecies.)]TJ
/F5 1 Tf
13.3793 0 TD
[(Nucleic)-339.1(Acids)-333.8(Res.)]TJ
/F1 1 Tf
7.9985 0 TD
[(38,)-337.1(74007409.)]TJ
9.9626 0 0 9.9626 391.8046 198.6519 Tm
[(Address)-345.5(correspo)-9.1(ndence)-340(to:)]TJ
/F5 1 Tf
4.7687 -1.195 TD
[(Dr.)-337.1(Soyeon)-343.9(Ahn)]TJ
-15.1482 -1.2007 TD
[(Departme)-10.1(nt)-334.3(of)-334.3(Elec)-9.2(trical)-334.5(and)-338(Comput)-10.3(er)-334.6(Engine)-8.9(ering)]TJ
7.8643 -1.2007 TD
[(Th)-6.4(e)-332.6(Univer)-10.3(sity)-335.9(of)-334.3(Texas)-343.5(at)-334.3(Austin)]TJ
6.6693 -1.2007 TD
[(Austin,)-341.5(TX)-336.3(78712)]TJ
-5.9694 -2.4014 TD
(E-mail:)Tj
/F1 1 Tf
3.403 0 TD
[(soyeon.ahn@)-12.2(utexas.e)-9.3(du)]TJ
/F2 1 Tf
-33.4775 61.2758 TD
[(64)-7.2(8)]TJ
34.0921 0 TD
[(AHN)-338(AND)-344.1(VIKALO)]TJ
ET
endstream
endobj
99 0 obj
<>stream
8;X]O>EqN@%''O_@%e@?J;%+8(9e>X=MR6S?i^YgA3=].HDXF.R$lIL@"pJ+EP(%0
b]6ajmNZn*!='OQZeQ^Y*,=]?C.B+\Ulg9dhD*"iC[;*=3`oP1[!S^)?1)IZ4dup`
E1r!/,*0[*9.aFIR2&b-C#soRZ7Dl%MLY\.?d>Mn
6%Q2oYfNRF$$+ON<+]RUJmC0InDZ4OTs0S!saG>GGKUlQ*Q?45:CI&4J'_2j$XKrcYp0n+Xl_nU*O(
l[$6Nn+Z_Nq0]s7hs]`XX1nZ8&94a\~>
endstream
endobj
102 0 obj
<>stream
htXytSosR9e* "TL-JK@':1II:dNtVs4:w >酖.6o`v:B
o0"KX
YZq&E/I_&xޫZuUZc.TV6qF=7G4O(oHWz63{+4Hh
h*
/nתa LbsgF\nm:hZ6E0&9^
L
װȍ^%ES#
E};,erk7!A[2B
'1~1 zB)ܛTYUcHkNJFw9F1F6im$0^m`cÂ$u5~ڜ[*\ ]^X XYg"cMR=p0'ys0 9#=G[7n
+`j
řIfStziD$9z|x'UdN|Bm$(">"P 9%28 ~JGK7YP&3#'9=6@9zld=Ȍ"iaCXu!2Vk*ѥq6lkpBu?mBbLjXl{l>.%ƧoY
b6Ҩ8
!oTR=r@GtX09tZFwwBx-o(x _l.f[ؔ^vW?auۃKKc_{lh_0/;ӚiǸvw
dRۻVjE]R54
Bn
]U
>Vas>VXQ^:
a4uB>o(X儑'Or̗R3t8߃l?y~<ޒy,*u:KhO.X
ߡjSMRƸC"hNrBQ?smTTq<ޘ-`"ӨsE>[$A(
pN?NqYDH6D0h#xy%N1bc؋9m&+uR
հBQ:HGUUF}лVZq˞1j\-%\]xbbѶhϤ:5ADKuRL:-IyL5=Q@7@RWh,gxUs;H&}-Q%iϝJv4V^18@ȯПetaNUkCrxހ\+tEr<_J̄