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[(n)16.3(di)18.5(ng)-348.7(a)-349.7(p)0(a)13.8(t)0(h)-345.7(t)13.5(hr)13.6(ou)21.2(gh)-348.7(t)13.5(h)0(e)-344.7(r)0(e)11.8(a)0(d)-344.7(s)0(e)18.3(t)0(.)-345.3(A)-351.8(cr)17.5(uc)13.8(i)13.5(a)0(l)-347.5(r)0(e)17.5(q)0(u)15.5(i)0(r)22.2(e)0(m)15.9(e)0(n)13.8(t)-350.6(fo)13.6(r)-349.9(t)0(h)18.5(e)0(s)18.3(e)-355.4(al)16.7(go)15.5(ri)16.5(t)13.5(h)0(m)17.7(s)0()-346.1(s)0(u)14.4(c)0(c)17.7(e)0(s)18.3(s)-354.8(is)-346.9(su)20(mm)14.2(ar)17.5(i)13.5(z)0(e)12(d)-353.6(by)]TJ
T*
[(Ch)16.5(ai)16.7(ss)18.9(on)-234.8(et)-233.7(al)16.7(.)-239.4(\()0(2)13.6(0)0(0)21.2(9)0(\))19.3(:)-242.5()88.3()14.3([t)16.5(hi)18.5(s])-232.3(ap)13.8(pr)19.3(oa)19.4(ch)-236.6(wo)17.3(rk)19.3(s)-241(b)0(e)13.8(s)0(t)-233.1(f)0(o)19.3(r)-241.7(er)17.5(ro)19.3(r-)17.3(fr)17.3(ee)-232.7(re)11.8(ad)19.5(s)-241(a)0(n)13.8(d)-239.8(qu)15.5(i)13.5(c)0(k)13.8(l)13.5(y)-245.5(d)0(e)19.4(t)0(e)16.7(r)0(i)16.5(o)0(r)19.3(a)0(t)16.7(e)0(s)-232.1(a)0(s)-237.8(s)0(o)20(o)0(n)-234.8(a)0(s)-232.1(t)0(h)18.5(e)]TJ
T*
[(re)17.5(ad)13.8(s)-332(h)0(a)19.4(v)0(e)-322(e)0(v)13.8(e)0(n)-322(a)-326.9(sm)16.5(al)16.7(l)-333.6(n)0(u)21.2(m)0(b)17.7(e)0(r)-324(o)0(f)-322.2(b)0(a)19.4(s)0(e)12.6(-)14.3(ca)12(l)13.5(l)0(i)15.7(n)0(g)-320.2(e)0(r)17.5(r)0(o)13.6(r)14.3(s.)14.7()94()-332.8(T)10.8(o)-330.8(sa)18.3(ti)15.7(sf)18.1(y)-330.8(t)0(h)18.5(i)0(s)-324.2(r)14.3(eq)13.8(ui)18.5(re)17.5(me)15.9(nt)18.5(,)-330.4(a)-332.6(l)13.5(a)0(r)17.5(g)0(e)-327.7(c)0(o)19.4(m)0(p)17.7(u)0(t)18.5(a)0(t)16.7(i)0(o)18.5(n)0(a)19.4(l)]TJ
T*
[(ef)17.5(fo)13.6(rt)-262.3(i)13.5(s)-275.1(de)19.4(vo)21.2(te)16.7(d)-273.9(t)0(o)-260.4(d)0(e)19.4(t)0(e)16.7(c)0(t)-262.1(a)0(n)13.8(d)-268.2(co)19.4(rr)17.3(ec)17.7(t)-271(r)0(e)17.5(a)0(d)-265.1(e)0(r)17.5(r)0(o)19.3(r)0(s)-260.8(b)0(e)13.8(f)0(o)19.3(r)0(e)-261.4(a)0(n)19.4(y)-273.9(as)18.3(se)18.3(mb)17.7(ly)-266.1(i)13.5(s)-275.1(ev)19.4(en)-259.4(at)16.7(te)16.7(mp)17.7(te)16.7(d.)-262.9(T)10.8(h)0(i)18.5(s)-275.1(be)19.4(co)19.4(me)15.9(s)-275.1(e)0(v)19.4(e)0(n)]TJ
T*
[(ha)13.8(rd)19.3(er)-221.5(in)-226.2(45)21.2(4,)-223.1(as)-220.7(th)18.5(e)-235.9(a)0(v)19.4(e)0(r)17.5(a)0(g)13.8(e)-230.2(re)17.5(ad)-225.2(l)13.5(e)0(n)13.8(g)0(t)18.5(h)-228.4(is)-221.7(ab)13.8(ov)21.2(e)-235.9(1)0(0)21.2(0)-234.1(\(a)17.5(nd)-217.8(ca)12(n)-228.4(r)0(e)17.5(a)0(c)17.7(h)-234.1(40)15.5(0b)21.2(\))-230.4(a)0(n)13.8(d)-228.4(th)18.5(e)-230.2(e)0(r)11.8(r)14.3(or)-225.4(ra)17.5(te)-222.3(is)-221.7(0.)15.9(4%)-220.5(pe)13.8(r)-230.4(b)0(a)19.4(s)0(e)]TJ
T*
[(\(Q)15.3(ui)18.5(nl)18.5(an)-287.8(et)-284.9(al)16.7(.,)-285.3(20)15.5(08)21.2(\),)-287.6(so)-287.2(t)13.5(h)0(a)13.8(t)-293.7(a)-292.8(l)0(a)16.7(r)0(g)13.6(e)-292.8(po)15.5(rt)22.2(io)18.5(n)-296.7(o)0(f)-288(t)13.5(he)-287.8(re)17.5(ad)13.8(s)-292.2(h)0(a)13.8(v)0(e)-282.2(a)0(n)-287.8(e)0(r)17.5(r)0(o)19.3(r)0(.)-287.7(T)10.8(hi)18.5(s)-297.9(l)0(e)16.7(a)0(d)19.4(s)-297.9(to)-283.1(re)17.5(mo)17.7(va)13.8(l)-293.7(o)0(f)-282.3(i)0(n)12.8(f)14.3(re)11.8(qu)21.2(en)19.4(t)]TJ
0 -1.195 TD
[(re)17.5(ad)13.8(s)-275.1(w)0(h)17.3(i)0(c)16.7(h)-279.6(co)19.4(rr)17.3(es)18.3(po)15.5(nd)-263.3(to)-271.7(po)21.2(or)19.3(ly)-271.7(se)18.3(qu)21.2(en)13.8(ce)17.7(d)-273.9(r)0(e)17.5(a)0(d)13.8(s)-275.1(or)-265.3(a)-281.4(r)0(e)17.5(a)0(d)-265.1(f)0(r)17.3(o)0(m)-266.8(a)-281.4(l)13.5(o)0(w)-272.9(f)0(r)17.3(e)0(q)19.4(u)0(e)19.4(n)0(c)13.8(y)-273.9(sp)14.3(ec)17.7(ie)16.7(s.)-264.1(In)-271(t)13.5(h)0(e)-270.8(l)0(a)16.7(t)0(t)21.4(e)0(r)-272.7(c)0(a)17.7(s)0(e)18.3(,)]TJ
0 -1.2007 TD
[(th)18.5(e)-326.9(a)0(s)18.3(s)0(e)12.6(m)12.8(bl)18.5(er)17.5(s)-317.7(ab)19.4(il)15.7(it)21.4(y)-325.1(t)0(o)-317.3(r)0(e)17.5(c)0(o)19.4(n)0(s)14.4(t)13.5(ru)13.6(ct)-313.4(a)-326.9(l)13.5(ow)-318.4(fr)17.3(eq)19.4(ue)13.8(nc)19.4(y)-325.1(s)0(p)20(e)0(c)17.7(i)0(e)16.7(s)-326.3(is)-312.8(ad)13.8(ve)19.4(rs)18.1(el)16.7(y)-325.1(a)0(f)17.5(f)0(e)17.5(c)0(t)16.7(e)0(d)19.4(.)]TJ
1.0015 -1.2007 TD
[(Our)-372.4(approach)-377.6(to)-362.8(the)-371(problem)-373.9(is)-369.7(different)-10.5(.)-364.6(Firs)-8.2(t,)-362.4(we)-371.4(introdu)-7.2(ce)-369.3(a)-366.8(proba)-7.6(bilistic)-375.7(model)-370.4(of)-367.7(a)-366.8(read)-372.8(set.)-372.6(Our)]TJ
-1.0015 -1.2007 TD
[(mode)-8.4(l)-299.4(associa)-10.1(tes)-303.9(a)-298.5(proba)-7.6(bility)-300.2(to)-305.9(each)-304.3(possibl)-7.6(e)-298.5(list)-302.7(of)-299.4(seque)-8.6(nces)-303.7(that)-306.3(could)-304.3(have)-302.5(give)-7.6(n)-296.7(rise)-306.7(to)-300.2(this)-300(read)-8.6(set.)]TJ
T*
[(Th)-7(e)-270(formulat)-9.5(ion)-266.8(of)-271(the)-274.3(model)-273.6(takes)-273.1(the)-274.3(form)-272.3(of)-271(a)-270(gener)-9.4(ative)-269(p)-6.5(rocess)-274.3(that)-272.1(construc)-9.9(ts)-267.2(a)-270(n)-6.5(umber)-272.9(of)-271(sequences)]TJ
T*
[(and)-425.2(sam)-8.8(ples)-424.2(read)-8.6(s)-417.4(from)-425.9(thes)-8.8(e)-423.7(sequences)-10.7(.)-421.5(Such)-425.2(an)-424.4(asse)-9(mbly)-424.7(of)-424.6(sequences)-431.8(can)-427(be)-424.4(seen)-428.9(as)-419.9(a)-423.7(reas)-9.8(onable)]TJ
T*
[(sum)-7(mary)-334.7(of)-327.9(the)-331.2(read)-338.7(set.)-332.8(We)-330.2(do)-331.6(not)-329.4(a)-332.6(priori)-332.7(assume)-338.4(the)-331.2(numb)-6.6(er)-329.7(of)-333.6(sequences)-340.8(or)-327.9(their)-331.8(leng)-7.6(th.)-329(The)-333.9(model)]TJ
T*
[(do)-7.2(es,)-431.7(however)-9.1(,)-427.2(favor)-436.3(compact)-438.1(assembli)-9.7(es.)-431.7(Second,)-434.5(we)-434(descr)-10.6(ibe)-427.9(an)-435.8(algorithm)-437.8(that)-431.5(reconst)-9.1(ructs)-432.6(a)-429.3(lik)-7.8(ely)]TJ
0 -1.195 TD
[(asse)-9(mbly)-339.4(from)-340.6(a)-338.3(read)-344.3(set.)-338.5(The)-339.6(algori)-8.2(thm)-338.6(accompl)-11.3(ishes)-340.8(this)-339.8(by)-337.3(seeking)-342.9(the)-342.6(most)-340.6(probable)-344.5(assembly)-342.7(in)-340(an)]TJ
0 -1.2007 TD
[(itera)-9.2(tive)-243.7(fashion,)-246.7(moving)-244.2(between)-245(increas)-10.9(ingly)-242.7(likely)-242.3(asse)-9(mblies)-244.2(via)-240.2(a)-241.6(set)-241.3(of)-236.8(move)-8.4(s)-241(designed)-246.9(to)-237.6(increas)-10.9(e)-241.6(the)]TJ
T*
[(proba)-7.6(bility)-300.2(of)-299.4(the)-297.1(assembl)-11.9(y.)-291.4(Int)-7(uitively,)-303.8(a)-292.8(move)-304.3(rearranges)-306.4(read)-8.6(s)-292.2(into)-298.8(a)-298.5(more)-300.6(compact)-307.2(assembli)-9.7(es)-294.7(that)-300.6(still)]TJ
T*
[(accur)-11.1(ately)-365.7(repr)-8.8(esent)-364.2(the)-365.3(whol)-9.7(e)-361.1(read)-367.1(set.)-366.9(For)-367.7(exampl)-8.7(e,)-361.4(a)-366.8(prototy)-7.1(pical)-365.7(move)-366.9(is)-364(one)-368.3(that)-363.2(b)-6.5(rings)-362.6(a)-366.8(read)-367.1(that)]TJ
T*
[(ov)-7.2(erlaps)-327.1(wi)-8.2(th)-323(a)-326.9(seque)-8.6(nce)-330.2(into)-327.2(that)-329(seque)-8.6(nce.)-330.6(Crucially,)-333.1(the)-331.2(moves)-329(are)-332.2(not)-323.7(all)-328.3(gree)-8.6(dy,)-326.3(thus)-331.4(allowing)-333.1(some)]TJ
T*
[(un)-7.2(doing)-279.7(of)-282.3(potential)-288.9(erroneous)-288.7(moves.)-283.8(Con)-7(vergence)-288.4(is)-284.3(achieved)-289.2(when)-281.9(no)-280.4(reaso)-10.6(nable)-283.3(move)-281.5(is)-284.3(available)-10.9(.)-279.2(A)0(t)]TJ
T*
[(thi)-7.8(s)-343.4(point,)-351.1(we)-354.4(report)-354.5(the)-348.3(assembl)-11.9(y)-342.2(w)0(i)-8.2(t)0(h)-345.7(the)-348.3(best)-355.9(probability.)-353.6(Th)-7(is)-346.9(is)-346.9(the)-354(assembly)-354.1(that)-351.8(best)-350.2(trad)-9.6(es)-345.9(off)-353.4(the)]TJ
T*
[(com)-7.6(pactness)-255.6(and)-254.5(read)-253.3(set)-252.7(representa)-11.3(tion)-247.6(from)-255.2(among)-253.8(the)-251.5(assembli)-9.7(es)-249.2(that)-255.1(the)-251.5(algorithm)-255.8(explored)-8.7(,)-250.8(thus)-251.7(being)]TJ
0 -1.195 TD
[(a)-338.3(likely)-339(candidat)-11.3(e)-332.6(for)-336.3(the)-336.9(true)-333.9(set)-338.1(of)-333.6(seque)-8.6(nces)-337.9(that)-340.4(generat)-9.7(ed)-333.4(the)-336.9(reads.)]TJ
1.0015 -1.2007 TD
[(Unlik)-7.6(e)-395.2(the)-399.5(othe)-7.6(r)-395.4(methods)-8.9(,)-393(our)-402.6(method)-399.6(does)-398.7(not)-397.7(thr)-7(ow)-398.1(away)-403.2(reads)-397.5(and)-402.4(hence)-401.8(is)-398.1(able)-402(to)-396.9(extract)-405.1(more)]TJ
-1.0015 -1.2007 TD
[(inf)-7(ormation)-275(from)-266.6(the)-274.3(data,)-271.5(which)-274.1(contribute)-10.1(s)-263.7(t)0(o)-271.7(the)-268.6(discover)-9.9(y)-268.2(o)0(f)-265.3(more)-272.1(low-a)-8.6(bundanc)-8.9(e)-264.3(seque)-8.6(nces.)-270(Th)-7(e)-264.3(joint)]TJ
T*
[(denoi)-8.4(sing)-320(and)-317.1(asse)-9(mbly)-322.3(of)-316.5(the)-319.8(reads)-323.5(enables)-327.6(us)-315.7(to)-317.3(post)-7(pone)-317.8(the)-319.8(decisi)-9.2(on)-314.5(about)-327(which)-319.6(bases)-322.8(are)-320.8(nois)-7(e)-315.5(and)]TJ
T*
[(mak)-7.6(e)-309.8(those)-316.8(decisions)-314.2(based)-315.9(on)-314.5(an)-310.6(assembly)-319.9(rather)-316.5(than)-309.2(in)-311.6(a)-309.8(preproce)-9.7(ssing)-316.2(step,)-310.8(thus)-314.3(in)-311.6(principle)-316.6(enablin)-8.7(g)]TJ
T*
[(better)-374.2(asse)-9(mbly,)-373.9(albeit)-374.9(at)-364.6(a)-372.4(higher)-375.3(computa)-9.5(tional)-373.1(cost.)-367.7(Th)-7(e)-366.7(asse)-9(mbly)-367.8(returne)-9.9(d)-370.7(b)0(y)-365.7(our)-368.5(algo)-7.6(rithm)-373.4(is)-369.7(a)-366.8(full)]TJ
T*
[(descr)-10.6(iption)-268.9(of)-265.3(the)-268.6(origina)-8.9(l)-259.6(D)0(N)-9.4(A)-266.5(sequences)-272.5(and)-271.5(how)-268(each)-270.2(read)-270.4(maps)-265.6(to)-266.1(them.)-273.3(Hence,)-269.6(Gen)-8(ovo)-264.1(does)-267.8(not)-266.8(only)]TJ
T*
[(provi)-8.5(de)-475.6(a)-474.9(recon)-9.4(struction)-481(of)-475.8(the)-479.2(originating)-484.1(sequences)-10.7(,)-472.7(but)-477.4(also)-481.1(performs)-479.5(read)-480.9(denoisi)-8.1(ng)-473.8(and)-476.4(multip)-10.7(le)]TJ
0 -1.195 TD
[(alignm)-9.7(ent)-336.9(that)-334.7(scales)-345.1(up)-331.6(to)-334.3(the)-336.9(order)-339.6(of)-333.6(3)]TJ
/F7 1 Tf
17.2481 0 TD
()Tj
/F1 1 Tf
.4382 0 TD
(10)Tj
7.4718 0 0 6.641 260.2771 134.1354 Tm
(5)Tj
9.9626 0 0 9.9626 267.307 129.7133 Tm
[(read)-8.6(s.)]TJ
-18.3919 -1.2007 TD
[(The)-294.1(accurat)-11.5(e)-287.1(and)-294.3(sensitive)-294.2(reco)-8.6(nstructio)-8.7(n)-291(o)0(f)-288(popul)-6.6(ations)-291.9(has)-289.8(been)-296.8(tackled)-295.1(in)-288.8(restrict)-11.7(ed)-287.8(doma)-8.4(ins,)-291.1(such)-290.6(as)]TJ
-1.0015 -1.2007 TD
[(HI)-7.4(V)-260.8(seque)-8.6(ncin)-7.6(g,)-262.9(both)-267.6(experiment)-12.6(ally)-266.4(\(Wan)-9.4(g)-262.5(e)0(t)-262.2(al.,)-268.6(2007\))-267.6(and)-265.8(com)-7.6(putational)-10.9(ly)-266.1(\()-122.2(Jojic)-268.4(et)-267.8(al.,)-268.6(2008;)-268.3(Eriksson)]TJ
T*
[(et)-284.9(al.,)-285.7(2008;)-279.7(Zago)-10.3(rdi)-280.2(et)-279.2(al.,)-285.7(2009\).)-285(A)-283.5(probabilis)-9.5(tic)-282.7(model,)-285.4(partly)-287(similar)-289.6(to)-277.4(ours,)-285.4(was)-288(also)-281.9(used)-284.9(in)-283.1(the)-280(recen)-11.1(t)]TJ
T*
[(wor)-8.2(k)-273.9(o)0(f)-271(Zagord)-8.1(i)-271(e)0(t)-273.5(al.)-279.6(\(2009\).)-276.4(Howeve)-10.3(r,)-270.6(their)-280.6(appro)-7.6(ach)-273.3(is)-272.9(appl)-7.6(icable)-277.2(only)-279(to)-271.8(a)-275.7(very)-274.3(small-s)-9.1(cale)-278.6(\(10)]TJ
7.4718 0 0 6.641 472.592 86.2866 Tm
(3)Tj
9.9626 0 0 9.9626 476.3337 81.8646 Tm
[(\))-270.2(set)-275.5(of)]TJ
-40.3744 -1.2007 TD
[(read)-8.6(s)-332(already)-345.5(aligned)-338.8(to)-334.3(a)-332.6(short)-339.8(refere)-10.2(nce)-335.9(seque)-8.6(nce.)]TJ
/F3 1 Tf
0 67.0005 TD
[(43)-7.2(0)]TJ
34.1774 0 TD
[(LASER)-8.9(SON)-339(ET)-335.3(AL.)]TJ
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[(We)-301.8(com)-7.6(pare)-304.5(the)-302.7(perf)-8.8(ormance)-312.1(of)-299.4(our)-305.9(algorithm)-307(to)-305.9(three)-308(state)-304.3(of)-305.1(the)-302.7(art)-304.7(short)-305.6(read)-310.2(assembly)-308.6(progr)-7.8(ams)-304.7(in)]TJ
-1.0015 -1.195 TD
[(terms)-288.2(of)-282.3(the)-285.7(number)-285(of)-288(GenBank)-290.7(bases)-288.6(covered,)-291.9(the)-280(numb)-6.6(er)-284.1(of)-282.3(amino)-290.7(acids)-284.5(reco)-8.6(gnized)-284.1(b)-6.5(y)-279.6(PFAM)-286.2(prol)-7.8(es,)]TJ
0 -1.2007 TD
[(and)-396.7(usin)-7(g)-399.1(a)-395.2(score)-403.2(we)-399.9(developed)-9.3(,)-398.7(which)-399.3(qu)-7.2(anties)-401.8(the)-399.5(qualit)-9(y)-393.4(o)0(f)-396.1(a)]TJ
/F2 1 Tf
28.1625 0 TD
[(de)-396(no)-7.2(vo)]TJ
/F1 1 Tf
3.6932 0 TD
[(assembl)-11.9(y)-393.4(usin)-7(g)-393.4(n)0(o)-399.9(externa)-9.7(l)]TJ
-31.8557 -1.2007 TD
[(informat)-9.5(ion.)-272.9(The)-271.3(comp)-8.4(arison)-274.1(is)-267.2(conduc)-8.1(ted)-274.3(on)-269(9)-273.9(metagenom)-10.7(ic)-273.5(datasets)-275.4(\(Qu)-275.6(et)-267.8(al.,)-274.3(2008;)-274(Biddle)-272.7(et)-273.5(al.,)-274.3(2008;)]TJ
T*
[(Breitba)-9.7(rt)-347.7(et)-347.5(al.,)-354(2009;)-348(Cox)-7(-Foster)-350(et)-353.2(al.,)-348.3(2007;)-353.7(Vega)-352(Thurbe)-8.2(r)-349.9(e)0(t)-347.5(al.,)-348.3(2008;)-353.7(Dinsda)-8.6(le)-347.5(et)-347.5(al.,)-354(2008\))-352.9(and)-345.5(one)]TJ
T*
[(single)-360.2(sequence)-361.6(assembl)-11.9(y)-353.6(dataset.)-359.2(Genov)-9.5(os)-352.6(recon)-9.4(struction)-8.7(s)-349.1(show)-361(better)-357.1(perfo)-9.6(rmance)-356.9(acro)-8.6(ss)-351(a)-355.4(variet)-10(y)-353.6(o)0(f)]TJ
T*
[(datasets.)-440.8(In)-430.3(additi)-9(on,)-428.7(synt)-7(hetic)-434(tests)-434.6(show)-435(that)-431.5(the)-433.6(our)-436.7(method)-433.8(consist)-9.3(ently)-432.2(outpe)-8.4(rforms)-436.3(other)-431.4(method)-12.6(s)]TJ
T*
[(across)-399.5(a)-395.2(range)-402(of)-396.2(seque)-8.6(nce)-398.5(abunda)-8.1(nces)-394.8(and)-402.4(thus)-394(is)-398.1(robus)-7(t)-390.5(t)0(o)-396.9(dimin)-7.2(ishing)-398.3(coverage.)-402.6(Gen)-8(ovo)-394.9(is)-398.1(publicly)]TJ
T*
[(availa)-9.8(ble)-331.2(o)-6.5(nline)-335.5(at)-336.1(http://)-7.8(cs.stanford)-9.3(.edu/)-8(genovo.)]TJ
/F3 1 Tf
10.959 0 0 10.959 291.118 586.9416 Tm
[(2.)-496.7(RESULTS)]TJ
/F2 1 Tf
-16.7456 -1.6347 TD
[(2.1.)-496.9(Algorithm)-332.1(overview)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 551.1117 Tm
[(Each)-325.1(environment)-11.6(al)-319.1(sample)-328.6(origina)-8.9(tes)-321(from)-323.5(an)-322(unknown)-322.3(pop)-8(ulation)-322.7(of)-322.2(sequences)-10.7(.)-319.1(The)-322.6(numb)-6.6(er,)-318.7(leng)-7.6(th,)]TJ
-1.0015 -1.2007 TD
[(and)-465(cont)-7.6(ent)-462.1(of)-464.4(thes)-8.8(e)-463.5(sequences)-471.6(are)-468.8(uncer)-9.4(tain.)-466(In)-464.4(order)-464.8(to)-465.2(cope)-467.6(with)-467.8(this)-465(un)-7.2(certainty,)-472.4(we)-462.5(formul)-9.1(ate)-469.6(a)]TJ
T*
[(proba)-7.6(bilistic)-318.8(mode)-8.4(l)-316.5(that)-317.6(represe)-10.1(nts)-313.5(a)-321.2(potentially)-321.7(unbou)-9.5(nded)-317.8(set)-315.3(of)-316.5(DNA)-321.4(seque)-8.6(nces,)-321.2(also)-321.8(called)-322.8(contigs,)-321.5(of)]TJ
T*
[(unknow)-8.5(n)-291(leng)-7.6(th.)-294.9(In)-293.7(addi)-7.6(tion,)-293.5(we)-303.2(model)-296.4(the)-297.1(read)-8.6(s)-292.2(obta)-7.6(ined)-297.8(from)-295.1(the)-297.1(envi)-7.6(ronment)-9.7(al)-296.3(sample)-300.2(as)-294.7(nois)-7(y)-291(copi)-7.6(es)]TJ
T*
[(of)-276.7(cont)-7.6(iguous)-276(p)-6.5(arts)-278.2(of)-276.6(these)-284.5(contigs)-8.1(.)-273.5(Thus,)-283.3(different)-283.6(compon)-9.9(ents)-276.2(of)-276.6(our)-283.1(probabilis)-9.5(tic)-277.1(mode)-8.4(l)-276.7(account)-280.9(for)-279.4(the)]TJ
T*
[(generat)-9.7(ion)-352.2(of)-350.6(contigs)-8.1(,)-347.5(the)-354(locations)-361.3(from)-352(which)-353.7(the)-354(read)-8.6(s)-349.1(are)-355(copied,)-358.4(and)-351.2(the)-354(errors)-354.9(in)-351.4(the)-354(copy)-352(proce)-9.4(ss.)]TJ
0 -1.195 TD
[(The)-282.7(detailed)-287.2(proba)-7.6(bilistic)-284.7(mode)-8.4(l)-276.7(that)-283.5(capture)-9.7(s)-280.8(this)-282.9(precisely)-288.4(is)-278.6(give)-7.6(n)-279.6(i)0(n)-277.4(the)-285.7(Methods)-286.2(section)-9.9(.)-279.2(This)-280(mode)-8.4(l)-276.7(i)0(s)]TJ
0 -1.2007 TD
[(the)-388.1(basis)-386.3(for)-387.5(our)-385.5(metage)-10.5(nomic)-387.5(seque)-8.6(ncing)-389.6(method,)-388.6(as)-385.8(well)-389.9(as)-385.8(the)-388.1(score)-386.1(we)-388.5(propos)-7.7(e)-383.8(for)]TJ
/F2 1 Tf
36.9658 0 TD
[(de)-384.6(novo)]TJ
/F1 1 Tf
3.6647 0 TD
[(reco)-8.6(n-)]TJ
-40.6305 -1.2007 TD
[(struction)-8.7(s.)]TJ
1.0015 -1.2007 TD
[(The)-248.6(data)-9.4(set)-247(of)-248.2(read)-8.6(s)-246.7(obta)-7.6(ined)-252.3(from)-249.5(an)-253.7(environment)-11.6(al)-250.8(sample)-254.6(serves)-251.5(as)-254.9(an)-248(input)-254(to)-249(our)-249(seque)-8.6(nce)-250.6(assembly)]TJ
-1.0015 -1.2007 TD
[(algori)-8.2(thm.)-259.3(Our)-258.6(mode)-8.4(l-based)-265.2(appro)-7.6(ach)-261.9(uses)-257.6(thi)-7.8(s)-258(data)-259.8(to)-260.4(infer)-262.7(the)-262.9(number)-262.2(and)-260.2(the)-262.9(content)-264.8(of)-259.6(the)-262.9(contigs)-264.2(used)]TJ
T*
[(to)-271.7()82.6(generate)73.3()-270.2(the)-274.3(reads,)-278.4(as)-272(well)-270.4(as)-277.7(the)-268.6(read)-8.6(s)-272.2(location.)-274.4(We)-273.3(cal)-8.6(l)-265.3(the)-274.3(outpu)-6.6(t)-271(o)0(f)-271(such)-273.5(infere)-9.2(nce)-273.3(an)]TJ
/F2 1 Tf
38.4226 0 TD
[(assembl)-10.5(y)]TJ
/F1 1 Tf
3.9436 0 TD
(of)Tj
-42.3661 -1.2007 TD
[(the)-336.9(reads)-340.6(\(Fig.)-337.4(1A\).)]TJ
1.0015 -1.2007 TD
[(Our)-361(algori)-8.2(thm)-361.4(is)-358.3(an)-361.8(instanc)-9.9(e)-361.1(o)0(f)-362(the)-359.7(itera)-9.2(ted)-359.7(condi)-8.4(tional)-361.8(mode)-8.4(s)-354.8(\(ICM)-8(\))-361.2(algori)-8.2(thm)-361.4(\(Besag,)-363.5(1)-6.5(986\),)-358.2(whi)-9(ch)]TJ
-1.0015 -1.195 TD
[(maximiz)-10.1(es)-306.1(or)-310.8(samples)-313.5(local)-314.5(conditional)-313.2(proba)-7.6(biliti)-7(es)-306.1(seque)-8.6(ntially,)-308.8(in)-311.6(order)-311.2(to)-305.9(reach)-312.8(the)-308.4(asse)-9(mbly)-310.9(with)-308.4(the)]TJ
0 -1.2007 TD
[(maximum)-253.8(proba)-7.6(bility.)-255(Starting)-250.7(from)-255.2(an)-248(initial)-254.2(rando)-7.6(m)-249(assembly,)-257.7(Genovo)-249.3(p)-6.5(erforms)-251.1(a)-252.9(random)-250.9(walk)-256.2(on)-246.2(states)]TJ
T*
[(correspo)-9.1(nding)-461.8(to)-465.2(different)-471.4(assembli)-9.7(es.)-460.1(Th)-7(e)-457.8(step)-8.8(s)-457.2(are)-463.1(desi)-8.8(gned)-465.8(to)-459.5(guide)-463.6(the)-467.8(walk)-461.1(into)-463.8(regions)-468.3(of)-464.4(high)]TJ
T*
[(proba)-7.6(bility.)-272.1(The)-271.3(availa)-9.8(ble)-268.6(arse)-9.8(nal)-268.6(of)-271(steps)-272.5(include)-8.7(s)-269.4(dete)-9.4(rministic)-276.8(hill-clim)-10.9(bing)-267.6(ste)-8(ps)-270.2(\(that)-269.2(are)-275.3(guarante)-10.5(ed)-270.8(to)]TJ
T*
[(increas)-10.9(e)-275.7(the)-285.7(probabilit)-11.1(y\))-276.7(and)-282.9(stochast)-11.9(ic)-279.2(steps)-283.9(\(where)-289.2(the)-280(next)-280.7(asse)-9(mbly)-282.5(is)-278.6(sam)-8.8(pled)-280.7(from)-283.7(a)-281.4(distributio)-8.3(n)-279.6(over)]TJ
T*
[(candidat)-11.3(e)-292.8(assembl)-11.9(ies,)-292.9(som)-7(e)-292.8(o)0(f)-293.7(them)-301.3(with)-297(lower)-298.8(proba)-7.6(bility\),)-297.6(which)-302.5(are)-298.1(necessary)-302.9(in)-294.5(order)-299.8(to)-294.5(avoid)-298.6(getting)]TJ
T*
[(stuck)-413.6(in)-408.3(a)-412.3(local)-411.2(max)-7.6(imum.)-411.6(We)-409.9(run)-414(our)-408.3(algo)-7.6(rithm)-413.2(until)-410.4(converg)-10.9(ence)-412.4(\(2003)-6.6(00)-405.6(itera)-9.2(tions\))-7.6(,)-404.4(and)-413.8(then)-411.6(we)]TJ
T*
[(outpu)-6.6(t)-345(the)-348.3(asse)-9(mbly)-345.1(that)-351.8(achi)-9.4(eved)-348.1(the)-348.3(highe)-8.4(st)-346.9(proba)-7.6(bility)-351.4(thus)-348.4(far.)-349.8(Running)-354.3(the)-348.3(algo)-7.6(rithm)-350.6(multiple)-352.5(times)]TJ
0 -1.195 TD
[(with)-314.1(differ)-9.4(ent)-314.1(random)-319.2(seeds)-317.1(showed)-318.8(no)-314.5(signicant)-321.5(inuence)-320.7(on)-308.8(the)-314.1(resu)-8(lting)-313.7(asse)-9(mbly.)-317(This)-314.1(suggests)-321.5(that)]TJ
0 -1.2007 TD
[(while)-339.4(our)-334.3(algo)-7.6(rithm)-333.5(has)-341(some)-339.6(stochasti)-9.7(c)-332.6(eleme)-9.8(nts,)-336.7(the)-336.9(variabilit)-9.9(y)-330.8(o)0(f)-333.6(the)-336.9(outpu)-6.6(t)-333.6(i)0(s)-335.5(low.)]TJ
1.0015 -1.2007 TD
[(In)-265.3(Figure)-266.4(1B)-7(E,)-262.7(we)-269(illustrate)-272.9(the)-262.9(four)-268.8(types)-265.6(of)-265.3(step)-8.8(s)-263.7(w)0(e)-263.3(use)-267(to)-266.1(enable)-268.8(an)-265.1(efcient)-274.3(and)-265.8(correct)-273.5(traver)-9.2(sal)-264.1(in)]TJ
-1.0015 -1.2007 TD
[(the)-393.8(assembly)-399.6(space.)-397.7(One)-395(step)-395.8(type,)-394.9(illustrated)-398.8(in)-391.2(Figure)-397.3(1B,)-393.6(samples)-398.8(a)-389.5(lett)-7.4(er)-392.2(for)-393.2(a)-389.5(position)-396.8(in)-391.3(a)-389.5(cont)-7.6(ig.)]TJ
T*
[(Another)-294.6(type)-292.1(of)-288(step)-287.6(\(Fig.)-291.9(1C\),)-288.2(move)-8.4(s)-286.5(a)-287.1(single)-291.9(read)-293.1(either)-288.8(to)-288.8(an)-287.8(already)-294.3(exis)-8.8(ting)-287.4(contig)-290.7(or)-288(to)-288.8(a)-287.1(new)-292.5(one.)-289(A)]TJ
T*
[(single)-320.4(read)-321.6(move)-315.7(invol)-9.3(ves)-318.2(local)-320.2(alignment)-10.9(,)-313.4(which)-319.6(eff)-8(ectively)-321.3(denoi)-8.4(ses)-313.7(the)-319.8(read)-8.6(.)-313.4(A)-317.7(third)-318.6(type)-314.9(of)-316.5(ste)-8(p)-313.7(\(Fig.)]TJ
T*
[(1D\))-281.3(takes)-278.8(even)-285.5(larger)-282.3(steps)-283.9(in)-277.4(the)-280(probability)-285(space)-283.5(by)-274.7(mer)-9.6(ging)-279(entire)-283.1(contigs)-8.1(.)-273.5(A)-277.8(four)-7(th)-277.4(step)-281.9(type)-280.8(\(Fig.)-274.8(1)-6.5(E)0(\))]TJ
T*
[(is)-335.5(used)-336.1(to)-334.3(x)-336.5(indels)-337.4(based)-338.6(on)-337.3(the)-336.9(conse)-8.6(nsus)-335.5(of)-333.6(the)-336.9(read)-8.6(s.)]TJ
/F2 1 Tf
10.959 0 0 10.959 107.6031 183.4582 Tm
[(2.2.)-496.9(Methods)-330.5(compared)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 165.5433 Tm
[(While)-377.9(many)-378.2(seque)-8.6(ncing)-378.3(technologie)-10.6(s)-371.8(are)-377.7(gain)-7.6(ing)-374.9(popularity)-8.3(,)-370.3(mos)-7(t)-373.4(o)0(f)-373.4(the)-376.7(short-read)-385.3(metagenom)-10.7(ic)-376(da-)]TJ
-1.0015 -1.2007 TD
[(tasets)-317.7(curr)-8.8(ently)-312.7(avai)-9.4(lable)-314.5(h)-6.5(ave)-313.2(been)-319.6(seque)-8.6(nced)-313.9(usin)-7(g)-313.7(454)-315.3(sequencer)-11.5(s)-314.9(\(probably)-317(du)-7.2(e)-309.8(t)0(o)-317.3(their)-314.7(longe)-8.4(r)-310(read)-8.6(s\),)]TJ
T*
[(hence)-458.7(we)-456.8(focus)-452.6(on)-456.8(this)-453.6(technol)-8.7(ogy.)-452.2(Through)-7.1(out)-454.6(this)-453.6(man)-7.6(uscript,)-460.1(we)-451.1(com)-7.6(pare)-452.5(the)-456.4(perform)-10.9(ance)-458(of)-453.1(our)]TJ
0 -1.195 TD
[(algori)-8.2(thm)-401.2(to)-408.3(three)-404.8(othe)-7.6(r)-401.1(tools:)-406.7(Velvet)-410.2(\(Zer)-8.6(bino)-404.2(and)-408.1(Birney,)-408.8(2008\),)-410.2(EULER-SR)-412.7(\(Chai)-9.4(sson)-403.8(and)-408.1(Pevzne)-9.2(r,)]TJ
0 -1.2007 TD
[(2008\),)-273.6(and)-277.2(Newbler)-10.1(,)-273.5(the)-274.3(454)-269.7(Life)-276.8(Scie)-8.6(nce)]TJ
/F2 1 Tf
17.1855 0 TD
[(de)-276.5(novo)]TJ
/F1 1 Tf
3.4428 0 TD
[(asse)-9(mbler.)-276(We)-273.3(chose)-276(Velvet)-279.4(and)-277.2(Euler)-277.6(due)-271.5(to)-277.4(their)-274.9(high)]TJ
-20.6282 -1.2007 TD
[(popul)-6.6(arity)-400.1(and)-402.4(as)-402.8(represe)-10.1(ntatives)-406.1(of)-401.8(the)-399.5(sta)-8(te)-398.7(of)-401.8(the)-399.5(art.)-401.8(Both)-403.2(thes)-8.8(e)-395.2(tool)-8.6(s)-394.6(wer)-10(e)-395.2(d)-6.5(esigned)-405.5(for)-398.9(the)-405.2(shorter)]TJ
T*
[(Illumin)-7.7(a)-326.9(reads,)-329.6(but)-323.7(suppor)-7.7(t)-322.2(454)-326.7(read)-8.6(s)-320.6(a)0(s)-328.9(well)-327.3(and)-328.4(are)-332.2(freely)-327.8(availa)-9.8(ble.)-325.9(Newbl)-10.5(er)-324(was)-327.9(speci)-11.3(cally)-325.9(desig)-9.6(ned)]TJ
T*
[(for)-313.5(454)-315.3(reads,)-318.2(is)-312.8(extremel)-11.1(y)-308.1(p)0(o)-7.2(pular,)-312.3(and)-317.1(is)-312.8(provided)-319.9(with)-314.1(the)-314.1(454)-315.3(machin)-8.7(e.)-315.9(As)-313.9(far)-315.3(as)-311.8(we)-314.5(know)-7(,)-307.7(this)-317.1(is)-312.8(the)]TJ
T*
[(only)-267.6(assembl)-11.9(er)-267.1(that)-266.4(was)-271(designed)-275.4(specica)-10.7(lly)-263.9(to)-266.1(meet)-269(the)-268.6(asse)-9(mbly)-265.4(n)-6.5(eeds)-269.6(of)-265.3(the)-268.6(454)-264.1(tec)-8.6(hnology.)-270.2(Howeve)-10.3(r,)]TJ
/F3 1 Tf
0 67.0005 TD
(GENOVO)Tj
41.6947 0 TD
(431)Tj
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9.9626 0 0 9.9626 74.0976 287.2062 Tm
0 0 0 1 k
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[(the)-240.2(source)-238.9(code)-234.2(for)-239.6(Newbler)-243.4(is)-233.1(unavail)-8.7(able.)-237.4(We)-233.5(als)-8(o)-234.1(tested)-236.8(SOAP)-9.3(denovo,)-234.4(as)-237.8(well)-236.2(as)-237.8(ABySS)-238.5(\(Simps)-7.6(on)-234.8(et)-233.7(al.,)]TJ
0 -1.2007 TD
[(20)-7.2(09\),)-311.9(two)-310.6(relat)-9.2(ively)-312.7(new)-315.3(asse)-9(mbly)-310.9(progr)-7.8(ams,)-310.8(b)-6.5(u)0(t)-311.6(w)0(e)-308.8(did)-312.3(n)-6.5(o)0(t)-311.6(include)-316(a)-309.8(deta)-9.4(iled)-312(comparison)-322.3(with)-314.1(them)-312.7(in)]TJ
T*
[(the)-336.9(paper)-339.4(becau)-9.2(se)-334.6(they)-337.7(did)-335.1(not)-335.1(wor)-8.2(k)-330.8(well)-338.6(on)-337.3(454)-332.3(read)-8.6(s.)]TJ
1.0015 -1.2007 TD
[(Run)-7(ning)-233.4(on)-234.8(a)-235.9(set)-241.3(of)-231.1(read)-8.6(s,)-235.6(each)-241.7(method)-240.3(outputs)-239.7(the)-234.5(list)-240.1(of)-236.8(contigs)-235.8(\(seq)-8(uence)-9.2(s\))-232.3(that)-238(it)-234.7(was)-242.5(able)-237(to)-237.6(assemble)]TJ
-1.0015 -1.2007 TD
[(from)-260.9(the)-257.2(reads.)-255.6(As)-257(done)-260.9(in)-254.7(previous)-258.5(stud)-7(ies)-252.7(\(Ch)-9(aisson)-256.2(and)-260.2(Pevzner,)-262.6(2008;)-257(Margulies)-260.1(et)-256.5(al.,)-257.2(2005;)-257(Qin)-259.4(et)-256.5(al.,)]TJ
T*
[(20)-7.2(10\),)-334.7(we)-337.3(evaluate)-343.1(only)-335.9(contigs)-338.2(longe)-8.4(r)-332.8(than)-337.7(500bp.)]TJ
/F2 1 Tf
10.959 0 0 10.959 74.0976 203.5275 Tm
[(2.3.)-502(A)-332.7(single)-332.3(sequence)-331.1(dataset)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 84.0755 185.5559 Tm
[(Befor)-8.6(e)-349.7(tes)-8(ting)-355.7(the)-354(methods)-356(on)-354.3(the)-354(metage)-10.5(nomic)-359(datasets,)-361.2(we)-354.4(benchm)-11.7(arked)-356.5(them)-358.3(on)-348.7(a)-355.4(single)-360.2(sequence)]TJ
-1.0015 -1.2007 TD
[(asse)-9(mbly)-254(tas)-8(k.)-251.5(We)-256.2(used)-256.4(run)-254.7([SRR)-8(:024126])-255.5(from)-260.9(NCBI)-257.4(short)-254.4(read)-259(arch)-8.6(ive,)-251.9(which)-262.7(contains)-261.1(110k)-253.4(read)-8.6(s)-252.3(taken)]TJ
T*
(from)Tj
/F2 1 Tf
2.2819 0 TD
[(E.)-331(coli)]TJ
/F1 1 Tf
3.0388 0 TD
[(\(length)-333.3(4.6Mb\))-8.1(,)-330.4(sequenced)-339.6(using)-332.1(454)-332.3(Titani)-8.8(um.)-329.8(Even)-334.7(though)-331.7(Gen)-8(ovo)-332.3(was)-333.6(not)-329.4(optim)-7.2(ized)-333.7(for)]TJ
-5.3207 -1.195 TD
[(the)-274.3(sing)-7(le)-273.5(sequence)-281.9(assembly)-280.1(task,)-270.9(it)-274.5(perform)-10.9(ed)-270.8(on)-269(p)-6.5(a)0(r)-272.7(with)-274.3(the)-274.3(other)-272.1(methods)-8.9(,)-273.5(a)0(s)-272(Table)-277.4(1)-268.2(show)-8.2(s)-269.4(\(New)-9(bler)]TJ
0 -1.2007 TD
[(achi)-9.4(eved)-348.1(a)-344(slight)-8.4(ly)-345.7(better)-351.4(cover)-9.4(age)-347.3(than)-349(Genovo\).)-354.8(Genovo)-351.7(and)-345.5(Newbl)-10.5(er)-346.7(report)-348.8(muc)-7.6(h)-342.2(longe)-8.4(r)-344.2(cont)-7.6(igs)-342(than)]TJ
T*
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