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[(ele)-8.6(men)-7.6(ts)-250.2(and)-248.8(acce)-15.9(ssib)-8.2(le)-245.1(for)-250.9(tra)-8.8(nscr)-8(ipt)-7.8(ion)-249.7(facto)-12.1(rs)-243.7(whe)-8(re)-250(the)-251.5(a)-8.2(nking)-251.3(nu)-7.2(cleo)-9.4(som)-7(es)-249.2(are)-252.5(marked)-258.3(by)-246.2(H3K)-10.2(4me)-7.6(3.)]TJ 0 -1.195 TD [(In)-259.6(cont)-7.6(rast)-10.8(,)-256.5(mos)-7(t)-253.9(enhanc)-15.6(ers)-257.6(are)-258.2(les)-8(s)-258(conse)-8.6(rved)-262.9(and)-260.2(mar)-9.6(ked)-260.2(by)-257.6(H3K4)-10.9(me1)-7.6(.)-250.8(E)0(n)-7(ric)-8.8(hmen)-8.4(t)-253.9(o)0(f)-259.6(H3K27)-11.7(ac)-255.5(is)-255.9(fo)-9.2(und)]TJ 0 -1.2007 TD [(at)-415.8(act)-8.6(ive)-416.6(p)-6.5(romo)-8.6(ters)-414.8(an)-9(d)-410.5(enha)-12.3(ncer)-8.6(s,)-412.1(whe)-8(reas)-419.5(H3K)-10.2(27me)-8.4(3)-416.2(i)0(s)-409.5(k)-6.5(nown)-416.7(to)-414(b)-6.5(e)-412.3(a)-412.3(repr)-8.8(essi)-10(ve)-413(mar)-9.6(k)-410.5(o)-6.5(bser)-8(ved)-413.8(at)]TJ T* [(b)-6.5(ivalen)-13.7(t)-299.4(prom)-8.6(oter)-9.6(s)-303.6(and)-305.7(pois)-7(ed)-304.9(enh)-9.8(ancer)-11.1(s)-303.6(\(Bars)-9.8(ki)-305.9(et)-302(al.,)-308.4(20)-7.2(07;)-306.7(Heint)-9.4(zma)-9.4(n)-302.4(e)0(t)-302(al.,)-308.4(20)-7.2(07;)-306.7(Calo)-308.2(and)-305.7(Wys)-11.7(ocka,)]TJ T* [(2)-6.5(013;)-335.9(Hei)-10.8(nz)-339.1(et)-336.1(al.,)-342.6(2015\).)]TJ 1.0015 -1.2007 TD [(Most)-367.5(com)-7.6(mon)-364.3(segm)-9.6(entation)-370.8(methods)-373.1(are)-366.3(instanc)-9.9(es)-368.7(of)-362(hidde)-8.4(n)-365(Markov)-368.8(mode)-8.4(ls)-364(\(H)-7.4(MMs\))-368.6(where)-371.8(the)-365.3(ob-)]TJ -1.0015 -1.2007 TD [(serv)-8(ed)-248(data)-248.4(are)-252.5(assumed)-253.8(to)-249(be)-248(caused)-250.1(by)-251.9(an)-248(unobse)-7.6(rved)-245.8(seque)-8.6(nce)-250.6(of)-248.2(hidden)-248.1(sta)-8(tes)-247(with)-251.5(Markov)-249.3(depend)-8.1(ency)]TJ T* [(str)-8.2(ucture.)-331.9(A)-334.8(frequently)-339.3(used)-330.4(imple)-9(mentati)-9.3(on)-331.6(of)-327.9(this)-334.1(type)-332(is)-329.8(Chrom)-8.3(HMM)-334.5(\(Erns)-8.8(t)-327.9(and)-334.1(Kellis,)-333.1(2012\),)-336.2(which,)]TJ T* [(ho)-7.2(wever,)-429.1(relie)-9.2(s)-423.1(o)0(n)-422.6(bina)-7.6(rized)-427.5(data)-9.4(.)-421.5(A)-425.8(mor)-7.8(e)-423.7(advanc)-9.9(ed)-424.4(HM)-7.4(M-based)-429.4(method)-433.8(is)-426.6(EpiCSeg)-429(\()-88.1(Mamm)-8.2(ana)-427(and)]TJ 0 -1.195 TD [(Ch)16.5(un)15.5(g,)-342.6(20)21.2(15)15.5(\))-349.9(t)0(h)18.5(a)0(t)-341.8(a)0(d)13.8(d)0(r)19.3(e)0(s)18.3(s)0(e)18.3(s)-354.8(t)13.5(h)0(i)18.5(s)-354.8(sh)20(or)19.3(tc)16.7(om)17.7(in)18.5(g)-353.6(b)0(y)-343(u)0(s)20(i)0(n)18.5(g)-353.6(ne)19.4(ga)19.4(ti)15.7(ve)-344.8(m)12.8(u)0(l)18.5(t)0(i)15.7(n)0(o)21.2(m)0(i)14.9(a)0(l)-341.8(d)0(i)18.5(s)0(t)17.3(r)0(i)16.5(b)0(u)21.2(t)0(i)15.7(o)0(n)21.2(s)-354.8(to)-340(mo)17.7(de)13.8(l)-350.7(o)0(b)21.2(s)0(e)18.3(r)0(-)]TJ 0 -1.2007 TD [(v)-6.5(ations)-13.1(.)-256.5(The)-260(hand)-10.5(ling)-259(of)-259.6(bo)-7.2(th)-254.7(met)-10.4(hods)-260.3(is)-261.6(seem)-11.3(ingly)-259.7(ea)-10.8(sy.)-259.2(Param)-12.1(ete)-8.6(rs)-255.1(are)-263.9(est)-8(imat)-8.2(ed)-259.4(uns)-9.2(uperv)-7.6(ise)-8(dly)-261.1(witho)-7.6(ut)]TJ T* [(the)-354(ne)-9(ed)-350.4(for)-347.7(a)-349.7(tra)-8.8(ini)-7.8(ng)-348.7(set)-355.2(usin)-7(g)-347.9(a)-349.7(max)-7.6(imum)-354.3(lik)-7.8(elihoo)-11.9(d)-347.9(appro)-7.6(ach)-11.6(.)-347.5(After)-10.6(ward)-10.7(,)-347.5(b)0(y)-348.7(insp)-7(ect)-8.6(ion)-352.2(of)-350.6(est)-8(imat)-8.2(ed)]TJ T* [(p)-6.5(aramet)-12.5(ers)-240.6(each)-247.4(hidde)-8.4(n)-239.8(state)-241.7(is)-238.8(iden)-7.6(ti)-7.1(ed)-242.3(with)-240.1(o)-6.5(n)0(e)-236.6(o)0(r)-236.8(mor)-7.8(e)-235.9(c)0(h)-9(roma)-10.3(tin)-235.4(sta)-8(tes)-8(.)-233.7(A)0(l)-8.2(thoug)-6.6(h)-239.8(this)-243.1(appro)-7.6(ach)-244.9(is)-238.8(ve)19.4(ry)]TJ T* [(ea)12(sy)-275.9(to)-300.2(appl)-7.6(y,)-302.7(it)-297.3(als)-8(o)-296.7(bear)-8.6(s)-297.9(sever)-10.6(al)-302(ris)-8.2(ks.)-299(Th)-7(e)-298.5(speci)-11.3(c)-298.4(com)-7.6(bina)-7.6(ti)-7.1(on)-297.4(of)-299.4(feat)-11.4(ures)-303.9(kn)-7.2(own)-302.1(to)-300.2(mark)-300.6(a)-304.2(chrom)-11.1(atin)]TJ T* [(sta)-8(te)-336.1(an)-9(d)-330.8(thei)-10.4(r)-332.8(s)0(p)-8.4(atial)-340(d)-6.5(istri)-9.6(butio)-9.3(n)-330.8(i)0(s)-341.2(often)-340.4(no)-7.2(t)-333.6(well)-338.7(re)-11(ected)-342(by)-337.3(the)-342.6(mode)-8.4(l.)]TJ 1.0015 -1.2007 TD [(Hen)-8(ce,)-386.7(supervis)-9.3(ed)-384.6(methods)-390.2(sp)20(ec)12(i)13.5(a)0(l)16.7(i)0(z)16.7(e)0(d)-367.5(i)0(n)-362.8(t)0(h)18.5(e)-378.1(de)19.4(te)16.7(ct)16.7(io)18.5(n)-376.3(o)0(f)-362(r)0(e)17.5(g)0(u)15.5(l)0(a)16.7(t)13.5(or)13.6(y)-370.7(e)0(l)16.7(e)0(m)15.9(e)0(n)19.4(t)0(s)-369.7(t)13.5(yp)15.5(ic)16.7(al)16.7(l)13.5(y)-376.3(pe)19.4(rf)17.3(or)13.6(m)-374.2(m)0(u)17.7(c)0(h)]TJ -1.0015 -1.2007 TD [(be)13.8(tt)21.4(er)17.5(.)-279.2(T)10.8(o)-279.6(o)0(b)15.5(t)13.5(ai)16.7(n)-279.6(g)0(o)15.5(o)0(d)-263.3(c)0(l)16.7(a)0(s)12.6(s)0(i)23()0(c)14.5(a)0(t)16.7(i)0(o)18.5(n)-273.9(pe)13.8(rf)17.3(or)19.3(ma)15.9(nc)19.4(es)-272(of)-265.3(un)15.5(su)20(pe)13.8(rv)19.3(is)17.3(ed)-270.8(H)12.4(M)0(M)11.6(s)-275.1(th)18.5(e)-281.4(n)0(u)21.2(m)0(b)17.7(e)0(r)-272.7(o)0(f)-265.3(h)0(i)18.5(d)0(d)15.5(e)0(n)-270.8(s)0(t)23(a)0(t)16.7(e)0(s)-272(o)0(f)19.3(t)0(e)16.7(n)]TJ 0 -1.195 TD [(ex)13.8(ce)17.7(ed)19.4(s)-337.7(t)13.5(he)-327.7(ac)17.7(tu)18.5(al)-324.7(ob)15.5(se)18.3(rv)19.3(ed)-322(nu)15.5(mb)17.7(er)-324(of)-322.2(ch)13.8(ro)19.3(ma)15.9(ti)21.4(n)-336.5(s)0(t)17.3(a)0(t)16.7(e)0(s)18.3(.)-330.4(Th)15.7(is)-324.2(le)16.7(ad)19.4(s)-332(t)0(o)-323(h)0(i)18.5(g)0(h)15.5(l)0(y)-323(f)0(r)17.3(a)0(g)19.4(m)0(e)15.9(n)0(t)18.5(e)0(d)-327.7(g)0(e)19.4(n)0(o)15.5(m)12.8(e)-338.3(s)0(e)18.3(g)0(m)17.7(e)0(n)19.5(-)]TJ 0 -1.2007 TD [(ta)16.7(ti)15.7(on)21.2(s)-229.6(w)0(h)17.3(e)0(r)17.5(e)-230.2(si)17.3(ng)15.5(l)13.5(e)-230.2(ch)13.8(r)14.3(o)0(m)12(a)0(t)22.4(i)0(n)-220.5(sta)-8(tes)-241.3(are)-246.8(repr)-8.8(esent)-11.3(ed)-242.3(by)-240.5(mul)-8.6(tiple)-247.2(sta)-8(tes)-241.3(of)-242.5(the)-240.2(HM)-7.4(M.)-242.1(Figu)-10.7(re)-238.6(1)-239.8(i)0(l)-7.1(lustra)-9.4(tes)-247(this)]TJ T* [(p)-6.5(robl)-7.8(em)-445(on)-445.4(a)-446.4(prom)-8.6(oter)-447.7(o)-6.5(f)-440.9(a)-446.4(tran)-9.6(scribed)-453(g)-6.5(ene.)-450.1(An)-443.6(o)-6.5(ptima)-9(l)-441.7(seg)-11(men)-7.6(tati)-7.4(on)-445.4(woul)-9.7(d)-438.9(d)-6.5(etect)-452.9(the)-445(reg)-11.7(ion)-443.2(as)-448.4(a)]TJ T* [(sing)-12.7(le)-341.8(ac)-10.8(tive)-346.1(pro)-10(moter)-349.6(wi)-8.2(th)-345.7(a)-344(t)0(r)16.5(a)0(n)19.4(s)0(c)18.3(r)0(i)16.5(b)0(e)19.4(d)-336.5(re)17.5(gi)18.5(on)-320.2(to)-328.7(t)13.5(h)0(e)-327.7(l)0(e)16.7(f)0(t)22.2(.)-336.1(Ho)17.3(we)15.5(ve)19.4(r,)-321.8(ty)12.8(pi)18.5(ca)17.7(l)-333.6(s)0(e)18.3(g)0(m)17.7(e)0(n)19.5(t)0(a)16.7(t)0(i)15.7(o)0(n)21.2(s)-337.7(ob)21.2(ta)16.7(in)18.5(ed)-327.7(w)12.4(i)0(t)15.7(h)]TJ T* [(Ch)16.5(ro)13.6(m)12.8(H)0(M)15.3(M)-406.8(or)-396.2(Ep)15.7(iC)19.4(Se)14.5(g)-404.8(i)0(n)18.5(s)0(t)17.3(e)0(a)17.7(d)-404.8(sho)-9.2(w)-414.4(a)-418(highl)-9.3(y)-416.2(fra)-8(gme)-7.6(nted)-423(prom)-8.6(oter)-419.3(regi)-9.6(on.)-417.3(Ano)-11.9(ther)-419.3(draw)-10.8(back)-422(of)-418.9(the)]TJ T* [(u)-6.5(nsuper)-9.5(vise)-8.8(d)-273.9(HMM)-277.6(appro)-7.6(ach)-279(is)-272.9(the)-274.3(low)-276.4(ex)-9(ibili)-9.2(ty)-271.7(of)-271(the)-274.3(mod)-11.5(el)-273.5(offe)-8.8(ring)-275.2(no)-274.7(glarin)-8.2(g)-273.9(way)-275.5(to)-271.7(im)-7.8(prove)-275(a)-275.7(poor)]TJ T* [(se)-10.2(gmen)-8.4(tati)-7.4(on.)-332(Chr)-9(omH)-9.7(MM)-335.5(and)-334.1(Ep)-7(iCSeg)-336.7(h)-6.5(ave)-335.9(only)-335.9(tw)-8.2(o)-330.8(para)-8.6(meter)-10(s,)-332.4(n)-6.5(amely)-338(the)-336.9(numb)-6.6(er)-335.3(of)-333.6(hidde)-14.1(n)-330.8(states)]TJ T* [(an)-9(d)-262.5(the)-268.6(genom)-9.1(ic)-267.8(bin)-266.8(siz)-8(e,)-264.7(whos)-8.2(e)-264.3(eff)-8(ect)-264.7(o)-6.5(n)-262.5(the)-268.6(resu)-8(lting)-268.2(segm)-9.6(enta)-9.4(tio)-7.8(n)-262.5(i)0(s)-261.6(h)-6.5(ighly)-271.1(unpre)-7.6(dict)-10.4(able)-9.4(.)-262.2(Furt)-7(herm)-10.3(ore,)]TJ 0 -1.195 TD [(to)-288.8(dete)-9.4(rmine)-287(the)-291.4(optim)-7.2(al)-284.9(set)-286.9(of)-288(para)-8.6(meter)-10(s)-280.8(i)0(t)-285.9(i)0(s)-284.3(nece)-14.1(ssary)-288.8(to)-283.1(lea)-8.6(rn)-282.3(an)-9(d)-279.6(eval)-9.4(uate)-288.2(a)-287.1(large)-291(numb)-6.6(er)-284.1(o)-6.5(f)-281.6(differ)-9.4(ent)]TJ 0 -1.2007 TD [(mod)-11.5(els,)-338.5(eff)-8(ect)-8.6(ively)-341.2(negat)-10.1(ing)-340.8(the)-336.9(pres)-8(u)-6.5(med)-337.7(sim)-9.8(plici)-8.2(ty.)]TJ 1.0015 -1.2007 TD [(ChroMo)-7.5(dule)-263.7(\(Won)-269.3(et)-262.1(al.,)-262.9(2013\))-261.9(is)-261.6(a)-264.3(supervis)-9.3(ed)-259.4(alter)-9.2(native)-264.1(that)-266.4(models)-264.2(the)-262.9(spat)-8.8(ial)-260(distribut)-9.7(ion)-261.1(of)-265.3(features)]TJ -1.0015 -1.2007 TD [(at)-358.9(chromat)-11.5(in)-351.4(sta)-8(tes)-355.2(with)-359.6(leftrig)-8.7(ht)-357.1(structure)-9.7(d)-353.6(H)0(M)-7.4(M)0(s)-357.5(that)-357.5(are)-355(com)-7.6(monly)-357.2(used)-358.8(in)-357.1(speec)-10.4(h)-353.6(recogniti)-9.3(on)-354.3(\(Ra-)]TJ T* [(bine)-7.6(r,)-304.7(1989\).)-313.5(Howeve)-10.3(r,)-304.7(the)-308.4(construc)-9.9(tion)-310.2(of)-305.1(a)-309.8(model)-307.8(require)-9.9(s)-303.6(a)-309.8(training)-314.1(set)-309.6(for)-307.8(each)-310(chromat)-11.5(in)-305.9(state.)-310.4(As)-308.2(an)]TJ T* [(alter)-9.2(native)-355.1(to)-351.4(the)-348.3(HM)-7.4(M-based)-355.5(methods)-8.9(,)-353.2(Segway)-352.7(\(H)-7.4(offman)-355.3(et)-347.5(al.,)-354(2012a,b)-6.7(\))-349.9(allow)-9.4(s)-349.1(t)0(o)-345.7(com)-7.6(pute)-354.7(segmenta-)]TJ T* [(tio)-7.8(ns)-298.6(based)-304.5(on)-297.4(arbitrar)-9.7(y)-296.7(hidden)-305(processe)-10.1(s,)-298.2(as)-300.4(long)-301.7(as)-300.4(the)-297.1(mode)-8.4(l)-299.4(can)-301.8(be)-299.2(represe)-10.2(nted)-297.8(as)-300.4(a)-298.5(d)0(y)-7.2(namic)-303.9(Bayesian)]TJ T* [(networ)-9.3(k.)-359.7(It)-364.8(operate)-9.7(s)-360.5(o)0(n)-360(a)-366.7(single)-365.9(base-pair)-367.2(reso)-8(lution)-365.7(and)-362.6(with)-365.3(its)-361.8(defa)-8.6(ult)-360.6(model)-364.7(com)-7.6(putes)-362.4(segm)-9.6(entations)]TJ 0 -1.195 TD [(that)-306.3(are)-309.4(even)-308.2(more)-306.2(ne-grai)-9.9(ned)-300(than)-309.2(those)-305.5(of)-305.1(Chrom)-8.3(HMM)-306(and)-305.7(EpiCSeg)-309.5(\(Hoff)-8(man)-303.5(et)-302(al.,)-308.4(2012a\).)-304.6(Se)-8.2(gway)]TJ 0 -1.2007 TD [(mode)-8.4(ls)-290(are)-286.7(typi)-8.6(cally)-291.7(trained)-295.3(on)-286.1(a)-287.1(small)-294.7(fraction)-292.3(of)-288(the)-291.4(avai)-9.4(lable)-291.8(data,)-288.6(due)-294.3(to)-288.8(the)-285.7(com)-7.6(putational)-295.4(comp)-8.4(lexity)]TJ T* [(of)-339.2(the)-336.9(inference)-345.1(algorithm)-341.1(and)-334.1(the)-336.9(high)-335.9(data)-339.4(reso)-8(lution.)]TJ 1.0015 -1.2007 TD [(A)-266.5(different)-272.3(appro)-7.6(ach)-267.6(is)-261.6(imple)-9(mented)-270.5(in)-260.4(Stat)-9.6(eHub-Stat)-9.7(ePaintR)-268.8(\(C)-8.2(oetzee)-270.6(et)-262.2(al.,)-268.6(2018\).)-267.9(Instead)-270.9(of)-265.3(inferring)]TJ -1.0015 -1.2007 TD [(chrom)-11.1(atin)-323.3(states)-329(de)-322(novo)-321.7(ever)-8.6(y)-319.4(time)-326.9(a)-321.2(segment)-10.7(ation)-324.1(is)-324.2(compute)-9.5(d,)-319.8(the)-325.5(method)-325.6(imple)-9(ments)-326.1(a)-321.2(model)-324.9(of)-322.2(our)]TJ T* [(cu)13.8(rr)17.3(en)19.4(t)-282.4(u)0(n)15.5(d)0(e)19.4(r)0(s)18.1(t)0(a)16.7(n)0(d)15.5(i)0(n)18.5(g)-285.3(of)-271(ch)13.8(ro)19.3(ma)15.9(ti)21.4(n)-285.3(s)0(t)17.3(a)0(t)16.7(e)-287.1(ch)19.4(ar)17.5(ac)17.7(te)16.7(ri)16.5(st)17.3(i)13.5(c)0(s)12.6(.)-279.2(In)-276.7(pa)13.8(r)14.3(t)0(i)15.7(c)0(u)19.4(l)0(a)16.7(r)0(,)-276.3(t)0(h)18.5(e)-287.1(m)12.8(o)0(d)15.5(e)0(l)-273.5(e)0(n)13.8(c)0(o)19.4(d)0(e)13.8(s)-280.8(fo)19.3(r)-287.3(e)0(a)17.7(c)0(h)-276.5(c)0(h)19.4(r)0(o)13.6(m)12.8(at)16.7(in)]TJ T* [(st)17.3(at)16.7(e)-292.8(t)0(h)18.5(e)-292.8(se)12.6(t)-288.1(o)0(f)-288(f)0(e)17.5(a)0(t)16.7(u)0(r)19.3(e)0(s)-283.3(t)0(h)18.5(a)0(t)-284.9(a)0(r)17.5(e)-292.8(po)15.5(si)23(ti)15.7(ve)19.4(ly)-283.1(or)-288(ne)19.4(ga)19.4(ti)15.7(ve)19.4(ly)-283.1(as)12.6(so)20(ci)16.7(at)16.7(ed)-282.2(wi)14.5(t)13.5(h)-296.7(th)18.5(at)-284.9(st)17.3(at)22.4(e.)-287.5(T)10.8(h)0(e)-287.8(m)12.8(et)16.7(ho)15.5(d)-291(i)0(s)-284.3(c)0(e)17.7(r)0(t)16.5(a)0(i)16.7(n)0(l)18.5(y)-291(a)]TJ T* [(st)17.3(ep)-236.6(to)18.5(wa)15.5(rd)-236.8(th)18.5(e)-241.6(r)0(i)16.5(g)0(h)15.5(t)-242.5(di)18.5(re)17.5(ct)16.7(io)18.5(n,)-234.5(bu)21.2(t)-248.2(i)13.5(t)-248.2(a)0(l)16.7(s)0(o)-230.3(d)0(o)15.5(e)0(s)-237.8(n)0(o)21.2(t)-242.5(mo)17.7(de)13.8(l)-242.5(t)0(h)18.5(e)-247.2(sp)20(at)16.7(ia)16.7(l)-242.5(d)0(i)18.5(s)0(t)17.3(r)0(i)16.5(b)0(u)21.2(t)0(i)15.7(o)0(n)-234.8(o)0(f)-231.1(f)0(e)11.8(a)0(t)22.4(u)0(r)13.6(e)0(s)-232.1(a)0(r)17.5(o)0(u)15.5(n)0(d)-234.8(c)0(h)19.4(r)0(o)13.6(m)12.8(at)16.7(in)]TJ 0 -1.195 TD [(st)17.3(at)16.7(es)-317.5(an)19.4(d,)-314.1(th)18.5(er)17.5(ef)17.5(or)13.6(e,)-315.9(pr)19.3(od)21.2(uc)13.8(es)-311.8(hi)12.8(gh)21.2(ly)-317.3(fr)17.3(ag)19.4(me)15.9(nt)18.5(ed)-316.3(se)18.3(gm)17.7(en)19.4(ta)16.7(ti)15.7(on)21.2(s,)-315.3(si)17.3(mi)14.9(la)16.7(r)-321.4(t)0(o)-317.3(t)13.5(ho)15.5(se)-317.5(of)-310.8(un)15.5(su)20(pe)13.8(rv)19.3(is)17.3(ed)-316.3(HM)15.3(Ms)18.1(.)]TJ ET q 1 i 139.351 206.702 m 439.2 206.702 l 439.2 107.83 l 139.351 107.83 l W n q 300.089 0 0 98.872 139.351 107.83 cm /Im1 Do Q Q BT /F2 1 Tf 8.9663 0 0 8.9663 74.0976 91.8425 Tm [(FIG.)-410.7(1.)]TJ /F1 1 Tf 4.1921 0 TD [(Genome)-407.1(segmentations.)-413.8(Typical)-407.6(genome)-410.1(segmentation)-410.2(\(s1\))-409.1(where)-413(the)-403.3(promoter)-409.6(is)-408.9(fragmented)-413.5(into)-404.4(many)]TJ -4.1921 -1.2266 TD [(different)-269.2(segments.)-266.7(In)-267.2(this)-266.5(example,)-267.2(the)-264.2(optimal)-267.5(segmentation)-264.8(\(s2\))-263.7(shows)-268.8(a)-267.5(single)-261.6(active)-271.6(promoter)-264.2(segment)-263.1(\(PA\))-270.7(with)-262.3(a)]TJ 0 -1.2203 TD [(transcribed)-338.8(region)-334.9(to)-331.8(the)-333.8(left)-339.9(and)-329.7(no)-334.1(signal)-337.5(to)-331.8(the)-333.8(right.)]TJ /F2 1 Tf 9.9626 0 0 9.9626 74.0976 737.4045 Tm [(2)-30877.7(BEN)-10(NER)-339.2(AND)-338.4(VINGR)-8.9(ON)]TJ ET endstream endobj 56 0 obj <>stream Adobed       q  s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& 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WS~,ן'V=:8CmyEn>W2G$V(H@9@m/ӿߝ{wd@дk_vaA8\O#]^$"@7M57>lU2yHLU Ȗ,D4+_va~lͨ,z1C{9z~,ן'P:mcQoi;M&РObw8yٹV;9T⨯~,ן'RSϩ7@+Qv^j+dK*H{(U~,ן'RCn"OH?jiveVӊPy!D+eU<@_/Os9-?iXW,U8o+oxOsi?*8 ZO./)op2q&q_B)\U8yHLUlrӒ6smyEn㧹b]n/n$2G ;ߵ WSo~,ן'TA[lAP USutZ(~MMϰS?~,ן'Pڇmm̉irZ(&k1U+ͳ0ywbB?!z~,ן'PZmma3잼m }*~UvHXy+9S"8/_5#I1T̾dn-N4i t]؊ B8|Ig5^2ٸ]v*UثWb]v*U?Z_.hgN:Ps ޭF7^m̍'ζ:/!4Y.{c AڳHY]To8/)hV4{uMy13TU-P#eiMUlUDu([bTPV:-̓Z+B%xZאNTv*h!6dY#mqT6iUHCK"׍qTf*wgkw %#1UvȲ,_?<1TN*loYW#p|UWڥ[]sb-GFӵ ]IY҉# Bsɍ*OsP{"$f; $(KqT~*U/BӤPt ӳفS Uت= N_[mE#SAUʬXSpF*,,VxQחAbUl4mF20*Ӵ=8Ni@hԏSk튣qU+K[L71,7TpqU-;M0[T.튢T=cw ̝ 1Vl㳵Kh#V 9UTi;/ؔ|2)W#D!83(w<ӻTMK1uG@ZxP5w 7QoZ1P~?hQTt-:; IQOتaX` =P&gxVBDD^^ٯGd9ch@̌{4NyMx㖄ȘԎ׽1Tn*skos Cq}pqU 7LӢx,ܖ7vpʴت/I(?<a8z),w7Y7ثWb]v*UثWb]/̟(kg u|^G{m}5e叒Cδ5lU\o[ y+{ KII%ԬZ;睊YorAo튾ҢK^] kqv @g oWLWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbR_89yO8$D?毲~{ܽo~m\7b]v*UثWb]v*U($FO|Uax|zI2-!Ϭ"N}}?m&48n(#I=6i?dޝTV*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*Uت_.P z %)J=}T Zk[˛  SïEWfN/ds[Wb]v*UثWb]v* endstream endobj 62 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 117.5811 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(We)-330.2(develop)-330.3(in)-328.7(this)-328.4(stud)-7(y)-325.1(a)-326.9(new)-332.4(modu)-6.6(lar)-327.5(segment)-10.7(ation)-329.8(method)-331.3(based)-332.9(on)-331.6(HMMs)-330.7(calle)-9(d)-325.1(ModHMM)-338.7(that)]TJ -1.0015 -1.195 TD [(addresse)-10.1(s)-292.2(some)-294.1(of)-293.7(these)-295.9(shortcomi)-9.5(ngs)-293.7(in)-288.8(the)-291.4(fol)-7(lowing)-292.9(way)-8(.)-290.6(First)-290.6(of)-293.7(all,)-294.5(we)-291.8(reco)-8.6(gnize)-294.7(that)-294.9(jointly)-295.2(learning)]TJ 0 -1.2007 TD [(all)-237.2(p)-6.5(arameters)-247.4(of)-236.8(an)-242.3(HMM)-243.4(in)-237.6(an)-242.3(unsupe)-7.6(rvised)-239.9(way)-247(is)-238.8(overly)-244.4(ambitiou)-8.3(s)-235.3(and)-243.1(leads)-244.7(to)-237.6(poor)-238.3(resu)-8(lts.)-237(Inst)-9(ead,)-239.6(we)]TJ T* [(assemble)-372.9(the)-365.3(segment)-10.7(ation)-363.9(method)-371.2(piece)-364.7(by)-365.7(piece)-370.4(allowing)-367.2(us)-366.9(to)-362.8(guide)-366.9(the)-365.3(learning)-370(process)-366.1(as)-368.7(much)-366.9(as)]TJ T* [(possibl)-7.6(e.)-327.3(Second,)-326.4(ou)-7.2(r)-321.4(obje)-7.6(ctive)-325.9(is)-324.2(to)-328.7(construc)-9.9(t)-322.2(a)-326.9(method)-331.3(that)-329(may)-326.3(benet)-328.8(from)-329.2(the)-331.2(ample)-326.7(variet)-10(y)-325.1(o)0(f)-322.2(well)-8.6(-)]TJ T* [(pe)19.4(rf)17.3(or)19.3(mi)14.9(ng)-246.2(cl)16.7(as)18.3(si)17.3()11.4(e)0(r)17.5(s)-252.3(th)18.5(at)-245.1(ha)13.8(ve)-242.3(be)13.8(en)-242.3(de)13.8(ve)19.4(lo)18.5(pe)13.8(d)-251.2(f)0(o)19.3(r)-253.1(mo)17.7(st)-244.5(re)17.5(gu)15.5(la)16.7(to)18.5(ry)-242.5(el)16.7(em)15.9(en)19.4(ts)17.3(.)-256.5(I)0(n)19.3(s)0(p)20(i)0(r)16.5(e)0(d)-248(b)0(y)-240.5(t)0(h)18.5(e)-258.6(su)20(pr)19.3(a-)17.5(Ba)14.7(ye)19.4(si)17.3(an)]TJ T* [(appro)-7.6(ac)-10.8(h)-268.2(\(Lin)-7.6(dley)-275.1(et)-267.8(al.,)-274.3(19)-7.2(79;)-272.5(Lindl)-9.1(ey,)-271.1(19)-7.2(82,)-269.4(198)-8(5;)-266.1(Gen)-8(est)-275.5(and)-271.5(Zid)-10.6(ek,)-271.1(198)-8(6;)-266.1(Gel)-10.8(fand)-274.3(et)-273.5(al.,)-268.6(1)-6.5(995;)-273.3(Jacob)-8.6(s,)]TJ T* [(199)-8(5\),)-453.4(we)-451.1(con)-9.8(struct)-458.9(an)-452.9(HM)-7.4(M)-452.3(that)-454.2(act)-8.6(s)-451.5(a)0(s)-454.1(a)-446.4(d)-6.5(ecisio)-9.2(n)-450.3(mak)-7.6(er)-454.8(who)-455.8(int)-7.8(egra)-8.6(tes)-451.9(asse)-14.7(ssmen)-11.5(ts)-449.3(from)-460.1(sever)-10.6(al)]TJ T* [(exper)-9.4(ts.)-381.4(Each)-382(exper)-9.4(t)-379.1(o)0(r)-373.4(cla)-8.6(ssi)-7.4(er)-375.2(is)-381.1(speci)-11.3(alize)-9(d)-376.3(i)0(n)-374.2(the)-382.4(dete)-9.4(ctio)-10.4(n)-370.7(o)0(f)-379.1(a)-372.4(sing)-12.7(le)-376(chrom)-11.1(atin)-380.2(sta)-8(te,)-376.3(p)-6.5(ossib)-9(ly)-374.2(by)]TJ 0 -1.195 TD [(consi)-9.6(deri)-9.6(ng)-240.5(o)-6.5(nly)-244.1(a)-241.6(subse)-8(t)-242.5(o)0(f)-242.5(the)-245.8(avai)-9.4(lable)-251.9(featur)-9.2(es.)-243.9(Th)-7(e)-241.6(cla)-8.6(ssi)-7.4(ers)-246.2(may)-246.6(als)-8(o)-239.8(mode)-8.4(l)-242.5(the)-245.8(spat)-8.8(ial)-242.9(dist)-9.8(rib)-7(ution)-248.3(of)]TJ 0 -1.2007 TD [(feat)-11.4(ures)-338.1(near)-344.3(funct)-10.3(iona)-7.6(l)-333.6(ele)-8.6(men)-7.6(ts)-335.5(to)-340(improv)-12.8(e)-332.6(predi)-10.3(cti)-9.6(on)-337.3(accur)-11.1(acy.)]TJ 1.0015 -1.2007 TD [(Hence,)-269.6(our)-266(segmentat)-11.1(ion)-261.1(method)-268.7(consi)-9.6(sts)-263.5(of)-265.3(an)-265.1(HMM)-266.2(comb)-8.4(ined)-263.7(with)-268.6(a)-264.3(set)-264.1(of)-265.3(chromati)-9.3(n)-262.5(state)-264.5(cla)-8.6(ssiers.)]TJ -1.0015 -1.2007 TD [(As)-370.8(oppose)-7.6(d)-370.7(t)0(o)-368.5(traditi)-8.8(onal)-371.8(segment)-10.7(ation)-369.6(methods)-8.9(,)-370.3(our)-368.5(HM)-7.4(M)-366.9(d)-6.5(oes)-369.5(not)-369.3(take)-373.6(featur)-9.2(e)-372.4(tracks)-372.6(\(i.e.,)-374.2(ChIP-s)-8(eq/)]TJ T* [(ATAC)-9.7(-seq)-286.8(tracks\))-295.7(as)-289(input)-9.3(,)-284.9(but)-289.6(instea)-9.2(d)-285.3(rega)-8.6(rds)-290(the)-285.7(genom)-9.1(e-wid)-8.6(e)-287.1(probabil)-9.7(ity)-286.7(assessm)-11.5(ents)-287.6(of)-293.7(the)-285.7(chrom)-11.1(atin)]TJ T* [(state)-355.5(classi)-10.3(ers)-348.7(as)-357.3(observation)-9.3(s.)-349.5(We)-353(const)-9.6(ructed)-354.3(the)-354(method)-354.1(in)-351.4(a)-355.4(highly)-351.5(modu)-6.6(lar)-350.2(way)-8(,)-347.5(allow)-9.4(ing)-352.2(to)-351.4(easily)]TJ T* [(improv)-7.2(e)-252.9(segm)-9.6(entations)-258.9(by)-257.6(replacing)-264.4(sing)-7(le)-256.5(classiers)-11.9(.)-250.8(T)0(o)-257.4(facil)-9.2(itate)-260.4(the)-257.2(usage)-259(of)-253.9(ModH)-8.9(MM,)-256.2(we)-257.6(construc)-9.9(ted)]TJ T* [(a)-247.2(default)-249.7(set)-247(of)-248.2(chromati)-9.3(n)-245.5(state)-247.4(classi)-10.4(ers.)-246.6(The)-248.6(para)-8.6(meters)-250.9(of)-242.5(super)-8.8(vised)-248.6(classi)-10.4(ers)-246.2(are)-246.8(com)-7.6(monly)-249.1(estimat)-10.5(ed)]TJ 0 -1.195 TD [(on)-325.9(som)-7(e)-326.9(training)-331.1(set.)-332.8(However,)-332.1(const)-9.6(ructing)-333.3(a)-326.9(training)-331.1(set)-332.4(for)-324.9(each)-332.8(classi)-10.3(er)-324(woul)-9.7(d)-325.1(not)-329.4(only)-324.5(be)-327.7(a)-332.6(tedious)]TJ 0 -1.2007 TD [(task,)-259.6(but)-255.4(it)-251.7(would)-255.2(als)-8(o)-251.2(shift)-257.2(cont)-7.6(rol)-251.7(over)-257.2(the)-257.2(resulting)-259.1(segm)-9.6(entation)-257(to)-254.7(the)-257.2(com)-7.6(position)-260.3(of)-253.9(such)-256.4(training)-257.2(set)-8(s.)]TJ T* [(Instead)-9.2(,)-245.1(w)0(e)-246.2(d)0(o)-251.9(not)-244.1(rely)-254.3(on)-246.2(a)-247.2(training)-251.5(set)-247(b)-6.5(u)0(t)-243.3(engi)-7.6(neer)-247.6(each)-253.1(classi)-10.3(er)-244.3(by)-251.9(translating)-253.8(cont)-7.6(emporary)-256.1(knowled)-8.1(ge)]TJ T* [(of)-248.2(chromati)-9.3(n)-245.5(states)-255.1(into)-247.6(a)-247.2(probab)-8.3(ilistic)-249.8(model.)-251.3(This)-251.5(makes)-251.1(ModH)-8.9(MM)-250.1(easily)-248.2(appl)-7.6(icable)-254.5(to)-243.3(new)-252.7(data)-248.4(set)-8(s)-246.7(and)]TJ T* [(ensures)-343.3(that)-334.7(the)-336.9(interp)-8.2(retation)-338.6(of)-333.6(h)-6.5(idden)-338.4(states)-340.4(is)-329.8(consi)-9.6(stent)-336.7(across)-342.6(samples.)]TJ 1.0015 -1.2007 TD [(We)-324.5(evaluat)-10.5(e)-321.2(ModH)-8.9(MM)-324.1(equi)-7.6(pped)-323.5(with)-325.5(its)-327.7(default)-329.4(chromat)-11.5(in)-323(state)-327.1(classi)-10.4(ers)-325.9(on)-325.9(promoter)-331.1(and)-322.8(enhanc)-9.9(er)]TJ -1.0015 -1.2007 TD [(test)-301.8(sets)-300.2(and)-305.7(show)-298.4(that)-306.3(it)-297.3(outperf)-8.2(orms)-300(traditi)-8.8(onal)-303.5(segmentat)-11.1(ion)-301(methods)-304.8(not)-301(only)-301.7(in)-300.2(classicatio)-11.9(n)-296.7(accur)-11.1(acy)]TJ T* [(but)-386.3(also)-384.4(in)-379.9(qual)-7.6(itative)-389.8(aspects)-10.1(,)-381.7(meanin)-8.7(g)-382(that)-385.9(ModHMM)-389.9(segment)-10.7(ations)-388.7(are)-383.4(less)-385.6(fragme)-9.9(nted.)-383.6(To)-388.3(improve)]TJ 0 -1.195 TD [(segment)-10.7(ation)-346.9(resu)-8(lts,)-345.1(classi)-10.4(ers)-348.7(from)-346.3(the)-348.3(defa)-8.6(ult)-343.6(set)-349.5(can)-347.3(be)-350.4(easily)-350.6(replace)-11.5(d)-342.2(b)0(y)-348.7(more)-351.8(powerfu)-9.3(l)-345(supervised)]TJ 0 -1.2007 TD [(alternat)-10.3(ives,)-259.6(allowing)-259.1(to)-260.4(incorpor)-8.9(ate)-253.3(p)-6.5(rediction)-9.3(s)-252.3(from)-260.9(state-of-)-11.7(the-art)-257.4(methods)-8.9(.)-256.5(Inspire)-9.3(d)-251.1(b)0(y)-257.6(the)-257.2(DFilter)-265.2(peak)]TJ T* [(calling)-387.1(method)-388.2(\(Kuma)-9.3(r)-378.3(e)0(t)-381.7(al.,)-388.1(2013\),)-381.7(we)-388.5(develop)-387.3(a)-383.8(classier)-391.2(that)-380.2(mode)-8.4(ls)-381.1(the)-382.4(spat)-8.8(ial)-385.2(distributio)-8.3(n)-382(o)0(f)-379.1(fea-)]TJ T* [(tures)-313.1(around)-309.9(chromat)-11.5(in)-305.9(states)-10.4(.)-302(W)0(e)-313.2(train)-309(this)-311.4(classi)-10.3(er)-306.9(on)-308.8(a)-309.8(set)-309.6(of)-305.1(active)-317.1(enhancers)-313.1(and)-311.4(show)-309.8(that)-312(it)-308.7(can)-313.1(be)]TJ T* [(effective)-12.1(ly)-334.3(integr)-8.2(ated)-333.7(into)-338.6(our)-334.3(genom)-9.1(e)-332.6(segment)-10.7(ation)-335.5(method.)]TJ /F2 1 Tf 10.959 0 0 10.959 287.9432 332.9007 Tm [(2.)-501.9(METHODS)]TJ /F1 1 Tf 9.9626 0 0 9.9626 117.5811 309.033 Tm [(We)-409.9(consider)-413.9(chromat)-11.5(in)-402.6(sta)-8(tes)-406.4(that)-414.4(are)-406.2(mos)-7(t)-407.6(relevant)-411.6(for)-410.3(the)-410.9(analysi)-9.9(s)-406(o)0(f)-407.5(gene)-410.7(regulatio)-9.3(n)-404.8(and)-413.8(that)-408.7(are)]TJ -1.0015 -1.2007 TD [(typicall)-9.3(y)-268.2(found)-278.9(in)-271.7(genome)-273.4(annot)-8.4(ation)-272.9(stud)-7(ies)-275.5(\(Hoffma)-9.1(n)-268.2(e)0(t)-273.5(al.,)-274.3(2012b;)-274.8(Ernst)-277(and)-271.5(Kell)-8.6(is,)-273.3(2017;)-274(Gorkin)-275(et)-273.5(al.,)]TJ T* [(2017\).)-285(This)-280(include)-8.7(s)-280.8(act)-8.6(ive)-280(promot)-7.1(ers)-280.4(\(PA)-7.4(\))-281.6(and)-282.9(enhancers)-290.3(\(EA\),)-284.3(prime)-8.2(d)-279.6(\(PR\))-284.1(and)-282.9(bivalen)-8.7(t)-276.7(\(BI\))-286.8(regions,)-286.6(as)]TJ T* [(well)-321.6(as)-317.5(regions)-320.3(of)-316.5(act)-8.6(ive)-319.8(\(TR\))-318.8(and)-317.1(low)-322(transcrip)-9.7(tion)-315.9(\(TL)-9.6(\).)-316.1(In)-316.5(addition,)-323.8(we)-320.2(model)-319.2(heteroc)-9.7(hromat)-8.9(ic)-313.4(regi)-9.6(ons)]TJ T* [(marked)-286.8(b)-6.5(y)-279.6(H3K27m)-10.3(e3)-282.2(\(R1\))-290.6(or)-282.3(H3K9m)-9.5(e3)-282.1(\(R2\))-284.9(and)-288.6(regions)-286.2(whe)-8(re)-284.1(either)-288.8(no)-286.1(signal)-286.2(\(NS\))-289(or)-282.3(a)-281.4(cont)-7.6(rol)-285.9(signal)]TJ T* [(\(CL\))-415.6(is)-409.5(observed.)-417.2(Enhance)-10.5(rs)-408.7(and)-413.8(promot)-7.1(ers)-411.3(are)-411.9(dete)-9.4(cted)-413.4(based)-412.6(on)-411.2(ATAC)-9.7(-seq)-412(\(Buenr)-9.3(ostro)-413.8(et)-410.1(al.,)-410.9(2013,)]TJ T* [(2015\))-250.5(data)-248.4(measur)-9.1(ing)-244.1(chrom)-11.1(atin)-249.4(accessibili)-11.9(ty)-243.3(in)-249(combina)-9.5(tion)-247.6(with)-245.8(h)-6.5(istone)-246.4(marks)-251.3(H3K4m)-9.5(e1)-248(and)-248.8(H3K4m)-9.5(e3.)]TJ 0 -1.195 TD [(To)-416.8(mea)-9.4(sure)-417.7(the)-422.2(activit)-8.6(y)-416.2(o)0(f)-418.9(prom)-8.6(oters)-421.2(and)-419.5(enhanc)-9.9(ers)-417(we)-422.7(use)-420.7(histone)-423.6(mark)-425.8(H3K27a)-8.5(c)-418(\(Creyghto)-8.7(n)-416.2(e)0(t)-421.5(al.,)]TJ 0 -1.2007 TD [(2010\).)-370.4(Although)-368.4(active)-374(promot)-7.1(ers)-365.7(and)-362.6(enhanc)-9.9(ers)-365.7(can)-370.1(be)-367.5(accuratel)-11.9(y)-365(discriminat)-12.6(ed)-361.8(by)-365.7(the)-371(ratio)-365.9(of)-367.7(histone)]TJ T* [(marks)-427.7(H3K4m)-9.5(e1)-424.4(and)-425.2(H3K4me3,)-428.6(we)-428.3(observed)-428.3(that)-425.8(the)-427.9(predictio)-9.3(n)-421.9(accuracy)-432.4(is)-420.9(muc)-7.6(h)-421.9(lower)-429.7(for)-421.7(bivalen)-8.7(t)]TJ T* [(promot)-7.1(ers)-337.3(and)-334.1(pois)-7(ed)-333.4(enhanc)-9.9(ers)-337.3(\(Section)-340.7(3.3\).)]TJ 1.0015 -1.2007 TD [(Therefor)-9.7(e,)-293.1(we)-303.2(decided)-303.7(to)-294.5(merge)-303.1(both)-301.7(chromati)-9.3(n)-296.7(states)-300.6(into)-298.8(a)-298.5(single)-297.6(biva)-7.6(lent)-294.9(sta)-8(te)-296.3(\(BI\),)-298.6(which)-302.5(is)-295.7(mark)-10.3(ed)]TJ -1.0015 -1.2007 TD [(by)-297.4(H3K)-10.2(27me3)-299.3(and)-305.7(H3K4m)-9.5(e1)-299.2(or)-299.4(H3K4m)-9.5(e3.)-299.6(Similar)-8.7(ly,)-300.6(we)-303.2(dene)-302.5(pri)-7(med)-297.8(sta)-8(tes)-298.2(\(PR)-8.2(\))-298.7(a)0(s)-300.4(accessi)-11.9(ble)-297.1(regi)-9.6(ons)]TJ T* [(marked)-446.1(by)-445.4(H3K4m)-9.5(e1)-441.5(or)-441.7(H3K4m)-9.5(e3)-441.5(but)-443.2(show)-8.2(ing)-443.2(no)-439.7(H3K27a)-8.5(c)-446.4(and)-442.2(H3K27m)-10.3(e3)-441.5(sign)-7(al.)-438.9(We)-449.7(also)-441.3(mode)-8.4(l)]TJ T* [(regions)-314.7(solely)-314.7(marked)-315.3(by)-308.8(either)-317.2(H3K27me3)-315.2(\(R1\))-313.3(or)-310.8(H3K9m)-9.5(e3)-310.6(\(R2\).)-313.7(Histone)-313.7(mark)-311.9(H3K27m)-10.3(e3,)-311(catal)-9(yzed)]TJ 0 -1.195 TD [(by)-434(the)-439.3(po)-7.2(lycomb)-439.4(repress)-9.6(ive)-439.3(comple)-8.7(x)-433.3(2)0(,)-439.3(i)0(s)-438(involved)-440.2(in)-442.5(gene)-439.1(silenc)-9.2(ing)-437.5(and)-436.6(assoc)-9.8(iated)-439.7(with)-439.3(constitut)-9.5(ive)]TJ 0 -1.2007 TD [(heteroc)-9.7(hromatin)-485.5(\(Kuzmic)-9.7(hev)-482.1(et)-478.4(al.,)-479.2(2002;)-478.9(Mar)-8(guero)-7.6(n)-473.1(and)-482.1(Reinbe)-9.9(rg,)-476.2(2011\).)-484.2(In)-475.8(cont)-7.6(rast,)-483.5(histone)-480.5(mark)]TJ T* [(H3K9m)-9.5(e3)-367.5(is)-364(associa)-10.1(ted)-365.3(with)-371(constitut)-9.5(ive)-365.3(hete)-9.4(rochrom)-8.9(atin,)-369.2(predominant)-11.6(ly)-362.8(formed)-372.3(in)-368.5(gene-em)-10.5(pty)-363.6(regio)-10.3(ns)]TJ T* [(\(Saks)-8(ouk)-349.4(et)-353.2(al.,)-348.3(2015\).)-353.3(Trans)-8.6(cribed)-354.3(regions)-360.2(are)-349.3(typical)-11.5(ly)-345.7(marked)-360.8(by)-348.7(H3K36m)-10.3(e3)-350.4(\(Wagner)-356.8(and)-351.2(Ca)-8(rpenter,)]TJ T* [(2012\);)-362.1(however)-9.1(,)-353.2(w)0(e)-360.1(d)-6.5(ecided)-359.8(to)-357.1(use)-363.8(polyA)-363.3(RNA-seq)-364.3(data)-362.2(instea)-9.2(d)-353.6(since)-364.2(it)-359.9(is)-352.6(a)-361.1(more)-363.2(direct)-362.8(and)-356.9(less)-362.8(noisy)]TJ T* [(measur)-9.1(ement.)-503.4(Our)-497.6(model)-501.3(also)-498.2(accou)-9.2(nts)-495.6(for)-501.3(low)-498.4(levels)-504.3(of)-492.9(transcr)-11.1(iption)-496.6(\(TL)-9.6(\))-492.1(that)-499.7(freq)-8.8(uently)-501.3(occur)-498.8(at)]TJ /F2 1 Tf 0 67.0005 TD (M)Tj 7.1731 0 0 7.1731 117.0708 737.4045 Tm (OD)Tj 9.9626 0 0 9.9626 127.8425 737.4045 Tm [(HMM:)-338(SUPR)-9.9(A-BAY)-10.9(ESIAN)-341.2(GENOM)-10.7(E)-335.5(SEGMEN)-11.8(TATION)-14981.3(3)]TJ ET endstream endobj 66 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 [(repr)-8.8(essed)-339.8(genes)-344.3(or)-333.6(in)-340(interg)-8.2(enic)-339.4(regions,)-343.5(for)-336.3(instanc)-9.9(e)-338.3(near)-338.6(certai)-11.7(n)-330.8(type)-7.6(s)-337.7(o)0(f)-333.6(enhanc)-9.9(ers)-343(that)-334.7(gener)-9.4(ate)-338.7(unidi-)]TJ 0 -1.195 TD [(recti)-9.2(onal)-337.7(polyA)]TJ /F5 1 Tf 6.3677 0 TD (+)Tj /F1 1 Tf .8877 0 TD [(eRNAs)-338(\(K)-7.4(och)-334.1(et)-336.1(al.,)-336.9(2011\).)]TJ -6.2539 -1.2007 TD [(ModH)-8.9(MM)-284.3(is)-278.6(a)-281.4(highly)-288.9(modular)-288.5(genome)-284.8(segment)-10.7(ation)-284.3(method)-285.8(that)-283.5(inco)-7.6(rporates)-285(p)-6.5(rediction)-9.3(s)-280.8(from)-283.7(a)-281.4(set)-281.2(of)]TJ -1.0015 -1.2007 TD [(cla)-8.6(ssiers)-9(.)-364.6(I)0(n)-367.7(cont)-7.6(rast)-369.3(to)-374.2(unsupervi)-8.9(sed)-369.5(methods)-8.9(,)-370.3(w)0(e)-371.4(manually)-377.2(construct)-377.6(most)-369(parts)-375.7(of)-367.7(the)-371(model.)-376.5(It)-364.8(con-)]TJ T* [(sis)-7.4(ts)-329.8(of)-333.6(two)-333.3(component)-11(s,)-326.7(the)-336.9(HMM)-334.5(and)-334.1(the)-331.2(set)-332.4(of)-333.6(chromati)-9.3(n)-330.8(state)-332.8(cla)-8.6(ssiers,)-333.7(both)-335.9(will)-333.9(be)-333.4(outlined)-334.8(in)-334.3(the)]TJ T* [(fol)-7(lowing.)-270.5(Fo)-6.4(r)-264.5(the)-274.3(chromati)-9.3(n)-268.2(state)-275.9(classiers)-279.3(we)-269(consi)-9.5(der)-267.8(a)-270(defa)-8.6(ult)-269.6(set)-269.8(of)-271(engineer)-10.5(ed)-270.8(classi)-10.3(ers)-269(as)-272(well)-270.4(as)-272(a)]TJ T* [(super)-8.8(vised)-339.6(alternat)-10.3(ive.)]TJ /F6 1 Tf 10.959 0 0 10.959 74.0976 619.8235 Tm [(2.1.)-502(Hidden)-328.7(Markov)-333.4(model)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 601.9085 Tm [(ModH)-8.9(MM)-278.6(imple)-9(ments)-286.2(a)-275.7(H)0(M)-7.4(M)0(,)-281.9(which)-285.4(consists)-284.4(of)-282.3(an)-282.2(unobserved)-287.5(Markov)-283.4(proce)-9.4(ss)-282.7(generating)-287.9(a)-281.4(series)-282.7(of)]TJ -1.0015 -1.2007 TD [(hidde)-8.4(n)-325.1(sta)-8(tes,)-332.8(each)-332.8(emitting)-335.4(a)-326.9(sing)-7(le)-330.4(observation)-339.3(\(Cappe)]TJ 22.7736 .0455 TD ()Tj .7113 -.0455 TD [(et)-330.4(al.,)-331.2(2005\).)-330.5(To)-331.4(dene)-331(the)-331.2(HM)-7.4(M,)-327.5(we)-331.6(rst)-332.6(must)]TJ -23.4849 -1.2007 TD [(assi)-10(gn)-399.9(each)-412.4(chromati)-9.3(n)-399.1(sta)-8(te)-404.4(to)-402.6(one)-408.1(or)-401.8(more)-408.7(hidden)-407.5(states)-408.7(of)-407.5(the)-405.2(HMM)-408.5(and)-402.4(deci)-9.4(de)-401.7(on)-405.6(a)-400.9(set)-406.4(of)-407.5(feasible)]TJ T* [(tra)-8.8(nsitions)-375.3(of)-373.4(the)-376.7(unobse)-7.6(rved)-371(Mar)-8(kov)-372.2(proce)-9.4(ss.)-374.2(Finally,)-373.5(we)-377.1(pres)-8(ent)-371(the)-376.7(emission)-377.8(mode)-8.4(l)-367.7(for)-376.1(inco)-7.6(rporating)]TJ 0 -1.195 TD [(genom)-9.1(e-wid)-8.6(e)-383.8(p)-6.5(rediction)-9.3(s)-383.2(o)-6.5(f)-384(the)-393.8(classiers)-398.8(and)-391(show)-389.4(that)-391.6(transi)-9.4(tion)-389.8(rates)-394.6(must)-391.8(be)-390.3(further)-391.4(constra)-9.1(ined)-388.9(to)]TJ 0 -1.2007 TD [(const)-9.6(ruct)-333.9(a)-338.3(well-fu)-9.2(nctioning)-341.3(model.)]TJ /F6 1 Tf 10.959 0 0 10.959 84.0755 518.2298 Tm [(2.1.1.)-497(Hidden)-318.3(states)-312.8(and)-321(feasible)-313(transitions.)]TJ /F1 1 Tf 9.9626 0 0 9.9626 295.5401 518.2298 Tm [(Unsuper)-8.5(vised)-322.5(HMM-b)-7.9(ased)-320.8(segment)-10.7(ations)-320.4(methods)-8.9(,)]TJ -22.2273 -1.2007 TD [(includi)-9.7(ng)-434(Chr)-9(omHMM)-442(and)-436.6(Ep)-7(iCSeg,)-439.5(learn)-438.9(tra)-8.8(nsition)-441.6(rates)-440.1(using)-440.3(a)-435(maxim)-9.7(um)-437.5(likelihoo)-8.3(d)-433.2(appro)-7.6(ach)-438.3(and)]TJ T* [(ini)-7.8(tially)-427.1(allow)-430.5(transi)-9.4(tions)-425.9(betwee)-10.9(n)-421.9(any)-430.9(two)-424.4(sta)-8(tes.)-423.8(To)-428.1(guide)-429.5(the)-427.9(learni)-10(ng)-422.6(proce)-9.4(ss,)-425.4(it)-428.2(is)-420.9(oft)-7(en)-424.4(help)-7.6(ful)-422.4(to)]TJ T* [(enfor)-9.6(ce)-369.3(a)-366.7(prede)-9.4(ned)-368.3(structu)-10.1(re)-363.8(on)-371.4(the)-371(transition)-370.7(matri)-10.9(x)-365(\(Galassi)-376.3(et)-370.3(al.,)-371(2007\).)-370.4(In)-367.7(genetic)-10.5(s)-366.2(such)-370.2(structure)-9.7(d)]TJ T* [(HM)-7.4(Ms)-312(have)-319.6(been)-313.9(utilize)-8.6(d)-308.1(befor)-9.6(e,)-310.2(for)-313.5(instanc)-9.9(e,)-310.2(for)-313.5(the)-314.1(predict)-10.7(ion)-312.3(of)-310.8(gene)-313.9(str)-8.2(uctures)-316.4(from)-312.1(DN)-9.4(A)-312(sequences)]TJ 0 -1.195 TD [(\(B)-8.2(urge)-268.6(and)-271.5(Karlin,)-274.2(1997\).)-267.9(In)-271(our)-271.7(case,)-271.7(the)-268.6(struct)-9.4(ure)-267.8(of)-271(the)-268.6(HMM)-271.9(shoul)-7.8(d)-268.2(encode)-271.7(any)-271.5(prior)-272.3(knowled)-8.1(ge)-270.8(about)]TJ 0 -1.2007 TD [(the)-291.4(context)-287.6(in)-288.8(which)-285.4(chromat)-11.5(in)-283.1(states)-289.2(appea)-9.2(r)-281.6(i)0(n)-288.8(the)-285.7(genome)-290.5(and)-288.6(may,)-286.8(for)-285.1(instanc)-9.9(e,)-281.8(be)-287.8(used)-290.6(to)-283.1(impleme)-10.1(nt)-283.1(a)]TJ T* [(mode)-8.4(l)-310.8(for)-319.2(active)-9.8(ly)-311.6(transcr)-11.1(ibed)-314.9(genes)-8.6(.)-313.4(Howeve)-10.3(r,)-316.1(one)-317.1(has)-312.6(to)-317.3(be)-316.3(cautiou)-8.7(s)-314.9(not)-312.3(to)-317.3(enforce)-321.9(an)-316.3(overly)-318.4(simpl)-8.4(istic)]TJ T* [(mode)-8.4(l.)-237.2(Fo)-6.4(r)-236.1(instanc)-9.9(e,)-241.9(an)-242.3(HMM)-243.4(that)-243.7(require)-9.9(s)-241(each)-241.7(gene)-245.6(to)-243.3(have)-239.9(exact)-11.9(ly)-237.6(one)-243.1(promot)-7.1(er)-238.6(and)-243.1(a)-241.6(sing)-7(le)-239.4(transcr)-11.1(ibed)]TJ T* [(regi)-9.6(on)-360(would)-369(not)-363.6(be)-367.5(realistic)-373.6(and)-362.6(resu)-8(lt)-359.9(in)-368.5(wrong)-368.2(predictio)-9.3(ns.)-361.6(The)-368.1(converse,)-373.5(a)-361.1(mode)-8.4(l)-362(that)-368.9(is)-364(excessivel)-11.3(y)]TJ T* [(co)13.8(mp)17.7(le)16.7(x)-325.1(w)12.4(ou)15.5(ld)-311.6(ha)13.8(ve)-316.3(eq)19.4(ua)13.8(l)13.5(l)0(y)-317.3(p)0(o)21.2(o)0(r)-316.5(p)0(r)19.3(e)0(d)13.8(i)0(c)16.7(t)13.5(iv)18.5(e)-326.9(p)0(e)19.5(r)0(f)17.3(o)0(r)13.6(m)12.8(an)13.8(ce)17.7(.)]TJ 1.0015 -1.2007 TD [(There)-9.2(fore,)-373.4(we)-371.4(decided)-377.7(on)-365.7(an)-373.2(HMM)-374.3(with)-371(minimal)-375.3(str)-8.2(uctu)-7.6(re,)-375.6(as)-368.7(dep)-9.8(icted)-377.1(in)-368.5(Fi)-9.2(gure)-371(2)-6.5(.)-364.6(So)-6.4(me)-371(ch)-9(romat)-8.2(in)]TJ -1.0015 -1.2007 TD [(sta)-8(tes)-423.4(a)-8.2(r)0(e)-420.7(repr)-8.8(esent)-11.3(ed)-424.4(by)-422.6(multi)-9.9(ple)-422.3(hidde)-8.4(n)-421.9(sta)-8(tes)-423.4(of)-424.6(the)-422.2(HM)-7.4(M.)-424.2(For)-424.6(instan)-13.1(ce,)-420.9(ac)-10.8(tive)-425.8(enhanc)-9.9(ers)-428.3(\(EA)-8(\))-418.1(are)]TJ 0 -1.195 TD [(rep)-11.7(rese)-9.8(nted)-343.3(by)-337.3(hidd)-11.5(en)-339.1(sta)-8(tes)-338.1(EA,)-347.1(EA)]TJ 6.9738 0 0 6.9738 225.8645 361.3038 Tm (1)Tj 9.9626 0 0 9.9626 229.8897 362.8345 Tm [(,)-336.1(and)-345.5(EA)]TJ 6.9738 0 0 6.9738 266.8535 361.3038 Tm (2)Tj 9.9626 0 0 9.9626 274.2235 362.8345 Tm [(to)-340(mode)-8.4(l)-339.3(differ)-9.4(ent)-342.6(con)-9.8(texts)-342.4(in)-340(whi)-9(ch)-339.1(en)-9(hance)-9.2(rs)-340.4(may)-343.3(ap-)]TJ -20.0876 -1.2007 TD [(p)-6.5(ear.)-412.2(The)-407.9(HM)-7.4(M)-406.8(str)-8.2(uctu)-7.6(re)-409.3(enfor)-9.6(ces)-411.1(that)-414.4(each)-412.4(tra)-8.8(nscr)-8(ibed)-411.6(regi)-9.6(on)-405.6(mus)-7(t)-407.6(b)0(e)-407.3()0(a)-8.2(nked)-408.9(b)-6.5(y)-404.8(at)-404.4(lea)-8.6(st)-409.5(one)-408.1(act)-8.6(ive)]TJ T* [(p)-6.5(romo)-8.6(ter)-276.3(a)-8.2(n)0(d)-274.7(each)-287.2(active)-288.6(prom)-8.6(oter)-282.7(mus)-7(t)-276.7(b)0(e)-276.5()0(a)-8.2(nked)-278(b)-6.5(y)-273.9(a)-275.7(tra)-8.8(nscr)-8(ibed)-280.7(reg)-11.7(ion.)-278.6(It)-279.4(als)-8(o)-273.9(forb)-7(ids)-279.4(that)-283.5(tra)-8.8(nscr)-8(ibed)]TJ T* [(reg)-11.7(ions)-365.5(are)-366.3(a)-8.2(nked)-363.3(b)-6.5(y)-359.3(act)-8.6(ive)-365.3(enh)-9.8(ancer)-11.1(s)-360.5(and)-368.3(pri)-7(med)-366.1(or)-362(biva)-7.6(lent)-368.9(regi)-9.6(ons.)-368.1(In)-362(add)-9.8(ition,)-371(transi)-9.4(tio)-7.8(ns)-361.2(betw)-11.5(een)]TJ T* [(ac)-10.8(tive)-340.4(prom)-8.6(oters)-11.5(,)-330.4(act)-8.6(ive)-336.9(e)-8.2(nhance)-9.9(rs,)-340.8(pri)-7(med)-7.6(,)-330.4(a)0(n)-9(d)-330.8(b)-6.5(ivalent)-347.2(states)-346.1(are)-337.9(forb)-7(idde)-7.6(n)-6.5(.)]TJ /F6 1 Tf 10.959 0 0 10.959 84.0755 291.0613 Tm [(2.1.2.)-497(Emissions.)]TJ /F1 1 Tf 9.9626 0 0 9.9626 171.2125 291.0613 Tm [(Th)-7(e)-344(ModH)-8.9(MM)-346.9(segm)-9.6(entation)-353.7(method)-354.1(is)-346.9(inspired)-352.3(by)-348.7(the)-348.3(supra)-8.8(-Bayesia)-10.7(n)-347.9(approach)]TJ -9.7479 -1.2007 TD [(that)-351.8(integr)-8.2(ates)-346.3(p)-6.5(rediction)-9.3(s)-343.4(o)0(f)-350.6(a)0(n)-344.7(exper)-9.4(t)-345(committee)-357.6(from)-346.3(which)-353.7(a)-349.7(decision)-352.1(maker)-354.3(reaches)-351.4(a)-349.7(nal)-348.2(decisi)-9.2(on.)]TJ 0 -1.195 TD [(Th)-7(e)-264.3(expert)-269(committee)-272.2(consists)-267.4(of)-265.3(a)-264.3(set)-264.1(of)-265.3(classi)-10.3(ers,)-263.7(each)-270.2(specialized)-271.5(in)-266.1(the)-262.9(dete)-9.4(ction)-261.5(o)-6.5(f)-258.8(a)-264.3(single)-269.2(chromati)-9.3(n)]TJ ET q 1 i 121.266 241.568 m 457.398 241.568 l 457.398 129.713 l 121.266 129.713 l W n q 336.132 0 0 111.855 121.266 129.713 cm /Im2 Do Q Q BT /F2 1 Tf 8.9663 0 0 8.9663 74.0976 113.7826 Tm [(FIG.)-398(2.)]TJ /F1 1 Tf 4.1794 0 TD [(ModHMM)-394.5(state)-397.3(diagram.)-400.2(Some)-394.6(chromatin)-400.3(states)-398(are)-398(represented)-400.4(by)-397.4(multiple)-397.5(hidden)-395.5(states.)-394.6(For)-398.1(instance,)]TJ -4.1794 -1.2266 TD [(active)-265.3(enhancers)-255.7(\(EA\))-259.3(are)-258.9(represented)-261.3(by)-258.3(hidden)-256.4(states)-265.2(EA,)-258(EA)]TJ 6.2762 0 0 6.2762 302.3432 101.4803 Tm (1)Tj 8.9663 0 0 8.9663 306.0283 102.7842 Tm [(,)-255.8(and)-253.9(EA)]TJ 6.2762 0 0 6.2762 337.7763 101.4803 Tm (2)Tj 8.9663 0 0 8.9663 341.4046 102.7842 Tm [(.)-255.8(I)0(f)-263.5(two)-252.5(states)-265.2(are)-258.9(connected)-255.9(by)-258.3(an)-260.7(undirected)]TJ -29.8125 -1.2203 TD [(edge,)-284(transitions)-283.7(in)-281.3(both)-286.6(directions)-281.4(are)-284.2(allowed.)-287.6(Self-transitions)-285.1(are)-284.2(in)-281.3(general)-282.3(allowed)-284.6(but)-280.8(omitted)-286.5(in)-281.2(the)-283.2(gure.)-282.3(A)-281(box)]TJ T* [(is)-276.1(used)-273.5(to)-274.9(group)-272(states)-277.9(that)-274.1(are)-277.9(fully)-273.8(connected.)-271.5(If)-276.1(an)-273.3(arrow)-274(points)-278.2(to)-268.6(the)-276.9(box,)-273.3(transitions)-277.4(to)-268.6(any)-279.2(of)-273.5(the)-270.5(states)-277.9(in)-274.9(that)-274.1(box)]TJ 0 -1.2266 TD [(are)-341.1(admissible.)-330.7(Crossing)-338.6(edges)-332.4(are)-334.8(connected)-338.1(if)-334.4(marked)-336.8(with)-331.9(a)-337(circle.)]TJ /F2 1 Tf 9.9626 0 0 9.9626 74.0976 737.4045 Tm [(4)-30877.7(BEN)-10(NER)-339.2(AND)-338.4(VINGR)-8.9(ON)]TJ ET endstream endobj 68 0 obj <>stream Adobed         s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz ?N*UثWb]v*fy`0!v@"tb*V/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTW/qTT9M/1jsk 8-cŝicFǠ)BךwO.Lk]CM&K ]dhGB1Twob7Owob7Owob7Owob7Oi>)K7UQVc 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1 Tf .5008 0 TD [(.)-256.5(T)0(h)-7(e)-252.9(outpu)-6.6(t)-259.6(o)0(f)-253.9(the)-262.9(classiers)-268(are)-258.2(the)-262.9(genome-)-8.7(wide)-261.9(predictio)-9.3(ns)-258.8(of)-253.9(chromat)-11.5(in)]TJ -12.6615 -1.195 TD [(states,)-244.1(that)-249.4(is,)-239.2(predict)-10.7(ion)]TJ /F6 1 Tf 9.9528 0 TD (c)Tj 6.9738 0 0 6.9738 211.2377 702.0281 Tm (t)Tj /F1 1 Tf 9.9626 0 0 9.9626 213.8456 703.5588 Tm (\()Tj /F6 1 Tf .3357 0 TD (s)Tj /F1 1 Tf .387 0 TD [(\))-236.1(yields)-246.4(the)-245.8(assessm)-11.5(ent)-240.1(of)-242.5(the)-240.2(exper)-9.4(t)-236.8(for)-245.2(chromat)-11.5(in)-237.6(state)]TJ /F6 1 Tf 22.4947 0 TD (s)Tj /F1 1 Tf .626 0 TD [(that)-243.7(genomic)-248.5(position)]TJ /F6 1 Tf -34.5075 -1.2007 TD (t)Tj /F1 1 Tf .717 0 TD [(is)-438(in)-436.8(this)-436.6(state.)-441.3(In)-441.7(the)-433.6(supra)-8.8(-Bayes)-10.3(ian)-433.6(appro)-7.6(ach,)-438.7(exper)-9.4(t)-436(predictio)-9.3(ns)-435.2(are)-440.3(treat)-9.2(ed)-435.8(as)-437(obser)-8.8(vations)-440.6(and)-442.3(a)]TJ -.717 -1.2007 TD [(separat)-10.9(e)-252.9(mode)-8.4(l,)-254.3(the)-262.9(decision)-261.1(mak)-7.6(er,)-256.1(is)-261.6(construc)-9.9(ted)-257.2(to)-260.4(reach)-261.5(a)-258.6(nal)-257.2(deci)-9.4(sion.)-257.8(Here,)-263.3(we)-257.6(deci)-9.4(ded)-254.5(to)-260.4(impleme)-10.1(nt)]TJ T* [(the)-240.2(decisi)-9.2(on)-240.5(maker)-240.5(as)-243.5(an)-242.3(HMM)-243.4(in)-237.6(which)-245.6(each)-247.4(chromati)-9.3(n)-234.1(sta)-8(te)]TJ /F6 1 Tf 25.0043 0 TD (s)Tj /F1 1 Tf .626 0 TD [(is)-238.8(associa)-10.2(ted)-240.2(with)-240.1(one)-243.1(or)-242.5(more)-243.7(hidden)-242.4(states)]TJ /F6 1 Tf -25.6302 -1.2007 TD (s)Tj /F7 1 Tf 6.9738 0 0 6.9738 111.4582 659.3384 Tm (0)Tj 9.9626 0 0 9.9626 116.6173 655.7101 Tm .2772 Tc (2S)Tj 6.9738 0 0 6.9738 132.3779 659.3384 Tm 0 Tc (0)Tj /F5 1 Tf 9.9626 0 0 9.9626 136.4031 655.7101 Tm (=)Tj /F7 1 Tf .717 0 TD (f)Tj /F1 1 Tf .5065 0 TD [(PA)-166.7(EA)-173(EA)]TJ 6.9738 0 0 6.9738 197.8582 654.2361 Tm (1)Tj 9.9626 0 0 9.9626 201.8267 655.7101 Tm .1678 Tc [(E)167.8(A)]TJ 6.9738 0 0 6.9738 220.1385 654.2361 Tm 0 Tc (2)Tj 9.9626 0 0 9.9626 224.107 655.7101 Tm ()Tj /F8 1 Tf .6715 0 TD .1682 Tc [(..)5.7(.)]TJ /F7 1 Tf 1.1438 0 TD 0 Tc (g)Tj /F1 1 Tf .5008 0 TD [(.)-449.9(For)-447.3(the)-450.7(emiss)-8.6(ion)-448.9(model)-450.1(several)-454.8(choi)-7.6(ces)-450.9(would)-448.7(be)-452.9(conceiva)-10.3(ble.)-445.4(Fo)-6.4(r)]TJ -14.0101 -1.2007 TD [(instanc)-9.9(e,)-293.1(the)-297.1(famil)-10.9(y)-291(o)0(f)-299.4(beta)-299.6(distribut)-9.7(ions)-297.2(is)-295.7(frequent)-10.7(ly)-294.5(used)-296.2(to)-300.2(model)-296.4(p)-6.5(robabilitie)-10.7(s.)-292.6(Howeve)-10.3(r,)-299(to)-294.5(reduce)-302.1(the)]TJ T* [(numb)-6.6(er)-272.7(of)-276.7(parame)-9.7(ters)-278.2(that)-277.8(must)-278(be)-276.5(estimated)-281.3(from)-278(data)-282.5(we)-274.7(decided)-280.9(to)-277.4(use)-278.4(a)-275.7(likelihoo)-8.3(d)-273.9(model)-279.3(that)-277.8(contain)-8.7(s)]TJ T* [(no)-365.7(free)-363.4(para)-8.6(meters)-370.4(and)-362.6(inco)-7.6(rporates)-370.4(the)-365.3(classi)-10.3(er)-363.8(predictio)-9.3(ns)-361.2(as)-368.7(they)-366.1(are.)-366.7(We)-364.4(dene)-370.8(the)-365.3(emission)-372.1(distri-)]TJ 0 -1.195 TD [(bution)-340.2(of)-333.6(state)]TJ /F6 1 Tf 6.2482 0 TD (s)Tj /F7 1 Tf 6.9738 0 0 6.9738 173.707 611.4896 Tm (0)Tj /F1 1 Tf 9.9626 0 0 9.9626 179.433 607.918 Tm [(in)-334.3(terms)-339.4(of)-333.6(the)-336.9(density)-338.2(functi)-8.2(on)]TJ /F6 1 Tf 12.2461 -1.9234 TD (f)Tj 6.9738 0 0 6.9738 304.2708 587.2817 Tm (s)Tj /F7 1 Tf 4.9813 0 0 4.9813 306.9353 589.266 Tm (0)Tj /F1 1 Tf 9.9626 0 0 9.9626 309.3164 588.7557 Tm (\()Tj /F6 1 Tf .3357 0 TD (x)Tj /F1 1 Tf .4439 0 TD (\))Tj /F7 1 Tf .6146 0 TD (/)Tj /F6 1 Tf 1.0471 0 TD (x)Tj /F1 1 Tf .552 0 TD ()Tj -23.2402 -1.9006 TD (where)Tj /F6 1 Tf 2.7827 0 TD (x)Tj /F5 1 Tf .6203 0 TD (=)Tj /F6 1 Tf .717 0 TD (c)Tj 6.9738 0 0 6.9738 153.1275 568.3463 Tm (t)Tj /F1 1 Tf 9.9626 0 0 9.9626 155.7354 569.8203 Tm (\()Tj /F6 1 Tf .3357 0 TD (s)Tj /F1 1 Tf .3813 0 TD [(\))-338.5(and)]TJ /F6 1 Tf 2.4526 0 TD (s)Tj /F7 1 Tf 6.9738 0 0 6.9738 191.1685 573.4487 Tm (0)Tj /F1 1 Tf 9.9626 0 0 9.9626 196.8944 569.8203 Tm [(is)-329.8(assoc)-9.8(iated)-337.3(with)-336.9(chrom)-11.1(atin)-334.7(state)]TJ /F6 1 Tf 14.1752 0 TD (s)Tj /F1 1 Tf .387 0 TD (.)Tj /F6 1 Tf 10.959 0 0 10.959 117.5811 545.8959 Tm [(2.1.3.)-497(Transition)-278.8(rates.)]TJ /F1 1 Tf 9.9626 0 0 9.9626 230.9669 545.8959 Tm [(In)-259.6(ty)18.5(pi)18.5(ca)17.7(l)-271(H)0(M)15.3(M)0(s)18.1(,)-273.5(t)13.5(r)0(a)17.5(n)0(s)14.4(i)0(t)21.4(i)0(o)18.5(n)-273.9(ra)17.5(te)16.7(s)-269.4(a)0(r)17.5(e)-270(es)18.3(ti)15.7(m)12.8(a)0(t)16.7(e)0(d)-265.1(f)0(r)17.3(o)0(m)-261.1(d)0(a)19.4(t)0(a)-262.2(a)0(n)19.4(d)-273.9(re)17.5()11.4(e)0(c)17.7(t)-271(co)13.8(nt)18.5(ex)19.4(t-)]TJ -12.3826 -1.195 TD [(de)19.4(pe)13.8(nd)21.2(en)13.8(t)-373.4(s)0(t)17.3(a)0(t)22.4(e)-378.1(pr)19.3(ev)19.4(al)16.7(en)13.8(ce)17.7(s.)-366.5(T)10.8(h)0(e)-367.5(s)0(i)17.3(t)13.5(ua)13.8(t)13.5(i)0(o)18.5(n)-376.3(is)-364(di)18.5(ff)17.3(er)17.5(en)13.8(t)-373.4(i)13.5(n)-376.3(o)0(u)21.2(r)-378.3(ca)17.7(se)18.3(,)-376(w)12.4(he)13.8(re)-363.8(cl)16.7(as)18.3(si)17.3(e)14.5(rs)-363.2(ar)17.5(e)-372.4(u)0(s)14.4(e)0(d)-367.5(t)13.5(o)-376.3(o)0(p)21.2(t)0(i)15.7(m)0(a)15.9(l)0(l)21.4(y)]TJ 0 -1.2007 TD [(di)18.5(sc)18.3(ri)16.5(mi)20.6(na)13.8(te)-284.9(be)19.4(tw)14.5(ee)17.7(n)-296.7(c)0(h)19.4(r)0(o)19.3(m)0(a)15.9(t)0(i)15.7(n)-296.7(st)23(at)16.7(es)-289(an)19.4(d)-296.7(t)0(o)-283.1(a)0(c)17.7(c)0(o)13.8(u)0(n)21.2(t)-299.4(f)14.3(o)0(r)-288(p)0(r)19.3(e)0(v)13.8(a)0(l)22.4(e)0(n)13.8(c)0(e)17.7(s)0(.)-286.9(B)11.6(y)-296.7(n)0(a)19.4(i)0(v)12.8(e)0(l)22.4(y)-296.7(in)18.5(te)16.7(gr)19.3(at)16.7(in)18.5(g)-296.7(c)0(l)16.7(a)0(s)18.3(s)0(i)17.3()11.4(er)17.5(s)-297.9(i)13.5(nt)18.5(o)]TJ T* [(an)-287.8(H)12.4(M)0(M)11.6(,)-290.6(re)17.5(su)14.4(l)13.5(t)0(s)-284.3(o)0(f)-288(c)0(l)16.7(a)0(s)18.3(s)0(i)17.3()11.4(ca)17.7(ti)15.7(on)-286.1(ma)15.9(y)-291(g)0(e)13.8(t)-293.7(ov)21.2(er)17.5(ru)19.3(le)16.7(d)-296.7(b)0(y)-286.1(t)13.5(ra)17.5(ns)14.4(it)21.4(io)18.5(n)-296.7(r)0(a)17.5(t)0(e)16.7(s)0(,)-281.2(m)0(a)15.9(k)0(i)18.5(n)0(g)-286.1(i)0(t)-285.9(m)0(o)17.7(r)0(e)-284.1(d)0(i)18.5(f)0()14.4(c)0(u)19.4(l)0(t)-285.9(t)0(o)-283.1(c)0(o)19.4(m)0(b)12(i)13.5(ne)]TJ T* [(cl)16.7(as)18.3(si)17.3()11.4(e)0(r)17.5(s)-349.1(in)18.5(to)-340(a)-349.7(w)0(e)15.5(l)0(l)15.7(-)0(f)17.3(u)0(n)21.2(c)0(t)16.7(i)0(o)18.5(n)0(i)18.5(n)0(g)-343(m)12.8(od)15.5(el)16.7(.)-347.5(F)11.4(or)-339.2(in)18.5(st)17.3(an)13.8(ce)17.7(,)-347.5(w)0(h)17.3(e)0(t)16.7(h)0(e)19.4(r)-349.9(a)-349.7(r)0(e)17.5(g)0(i)18.5(o)0(n)-343(i)0(s)-341.2(c)0(l)22.4(a)0(s)12.6(s)0(i)23()0(e)14.5(d)-347.9(as)-340.3(ac)12(t)13.5(i)0(v)18.5(e)-349.7(en)13.8(ha)19.4(nc)19.4(er)-341(or)]TJ T* [(pr)19.3(im)14.9(ed)-464.2(sh)20(ou)15.5(ld)-465.2(be)-469.9(m)12.8(o)0(s)14.4(t)0(l)21.4(y)-478.8(de)19.4(ci)16.7(de)19.4(d)-478.8(b)0(a)19.4(s)0(e)18.3(d)-473.1(on)-468.2(wh)17.3(at)-467(cl)16.7(as)18.3(si)17.3()11.4(e)0(r)-471.9(s)0(h)20(o)0(w)17.3(s)-474.3(th)18.5(e)-474.9(h)0(i)18.5(g)0(h)15.5(e)0(r)-466.2(p)0(r)19.3(o)0(b)15.5(a)0(b)19.4(i)0(l)15.7(i)0(t)21.4(y)-478.8(\(F)20(ig)18.5(.)-472.7(3)0(\))13.6(.)-472.7(S)11.4(t)0(i)15.7(l)0(l)21.4(,)]TJ T* [(tr)16.5(an)19.4(si)17.3(ti)21.4(on)-314.5(ra)17.5(te)16.7(s)-326.3(a)0(r)17.5(e)-326.9(va)19.4(lu)18.5(ab)19.4(le)-319.1(pa)19.4(ra)17.5(me)15.9(te)16.7(rs)-317.7(an)19.4(d)-325.1(w)0(e)-314.5(u)0(s)14.4(e)-321.2(th)18.5(em)-319.8(to)-311.6(mo)17.7(de)13.8(l)-322.2(t)0(h)18.5(e)-326.9(ex)19.4(pe)19.4(ct)16.7(ed)-316.3(le)16.7(ng)15.5(t)13.5(h)-325.1(of)-316.5(ch)19.4(ro)13.6(m)12.8(a)0(t)16.7(i)0(n)-317.3(s)0(t)17.3(a)0(t)16.7(e)0(s)18.3(.)]TJ 1.0015 -1.2007 TD [(Two)-273.5(types)-277(of)-271(const)-9.6(raints)-276.8(are)-275.3(impose)-8.2(d)-268.2(o)0(n)-274.7(the)-274.3(transi)-9.4(tion)-270.3(matrix)]TJ /F9 1 Tf 25.1465 0 TD (S)Tj /F1 1 Tf .6658 0 TD [(.)-273.5(First,)-279.6(the)-274.3(structure)-277.2(of)-276.7(the)-274.3(HMM)-277.6(forbids)]TJ -26.8139 -1.2007 TD [(certain)-262.9(transitions)-264.6(resulting)-259.1(in)-260.4(entries)-262.3(that)-255.1(must)-260.9(remain)-261.1(zero)-259(during)-259.7(learning.)-262.2(Second,)-258.1(transi)-9.4(tion)-259(rates)-258(should)]TJ 0 -1.195 TD [(only)-284.7(accou)-9.2(nt)-283.1(for)-290.8(the)-285.7(average)-293.3(leng)-7.6(th)-283.1(of)-288(chromati)-9.3(n)-285.3(states.)-289.6(To)-285.9(accompl)-11.3(ish)-285.1(this,)-289(it)-285.9(is)-284.3(neces)-10.4(sary)-286.8(to)-283.1(const)-9.6(rain)-288.4(all)]TJ 0 -1.2007 TD [(nonzero)-323.9(off-di)-7.6(agonal)-323.9(entrie)-10(s)-320.6(within)-324.1(a)-315.5(row)-326.9(to)-317.3(share)-323.5(the)-325.5(same)-324.3(value.)-323.5(More)-321.7(speci)-11.3(cally,)-320.6(ModH)-8.9(MM)-318.4(u)-6.5(ses)-319.4(the)]TJ T* [(transition)-342.3(matrix)]TJ /F9 1 Tf 7.0961 0 TD (S)Tj /F5 1 Tf .8308 0 TD (=)Tj /F1 1 Tf .7227 0 TD (\()Tj /F10 1 Tf .3357 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 202.6204 412.9511 Tm (ij)Tj /F1 1 Tf 9.9626 0 0 9.9626 207.0425 414.4251 Tm [(\))-332.8(with)]TJ /F10 1 Tf 1.673 -3.2095 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 229.2094 380.9196 Tm (ij)Tj /F5 1 Tf 9.9626 0 0 9.9626 235.2755 382.4503 Tm (=)Tj /F10 1 Tf 1.9405 1.195 TD (d)Tj /F6 1 Tf 6.9738 0 0 6.9738 259.5968 392.8818 Tm (i)Tj /F1 1 Tf 9.9626 0 0 9.9626 325.9275 394.3558 Tm (if)Tj /F6 1 Tf 1.0015 0 TD (i)Tj /F5 1 Tf .4496 0 TD (=)Tj /F6 1 Tf .7227 0 TD (j)Tj /F1 1 Tf .3813 0 TD ()Tj /F11 1 Tf -9.7081 -1.195 TD ()Tj /F6 1 Tf 6.9738 0 0 6.9738 259.5401 380.9196 Tm (i)Tj /F1 1 Tf 9.9626 0 0 9.9626 272.0125 382.4503 Tm (if)Tj /F6 1 Tf 1.0015 0 TD (i)Tj /F7 1 Tf .5634 0 TD (6)Tj T* ()Tj /F6 1 Tf 1.0471 0 TD (j)Tj /F1 1 Tf .6146 0 TD [(and)-339.8(transition)-342.3(is)-335.5(feasible)-111.2()]TJ -4.8483 -1.2007 TD [(0)-5924.6(otherw)-9.3(ise)]TJ /F11 1 Tf 10.4251 0 TD (:)Tj /F12 1 Tf -11.7681 3.2379 TD (8)Tj 0 -.8934 TD (<)Tj 0 -1.7925 TD (:)Tj ET q 420.151 0 0 193.266 112.705 140.655 cm /Im3 Do Q BT /F2 1 Tf 8.9663 0 0 8.9663 107.6031 124.7244 Tm [(FIG.)-315.8(3.)]TJ /F1 1 Tf 4.0909 0 TD [(Transition)-316.7(rates)-313.7(interfering)-316.5(with)-319.2(classications.)-314.8(The)-316.9(gure)-311(shows)-313.1(a)-318.1(region)-309.6(with)-319.2(histone)-311.7(modication)-317.1(signals)]TJ -4.0909 -1.2203 TD [(\(omitted\))-360.3(of)-362(an)-361.8(active)-360.1(enhancer.)-365.4(The)-361.2(active)-360.1(enhancer)-362.5(classier)-362.2(\(EA\))-366.8(also)-359.8(shows)-357.3(the)-365.4(highest)-362.3(probability.)-360.1(The)-361.2(primed)]TJ 0 -1.2266 TD [(state)-403.6(classier)-400.2(\(PR\))-404.9(shows)-401.6(a)-400.3(smaller)-402.5(peak)-401.2(while)-403.3(the)-403.3(probability)-401.4(for)-402.1(an)-399.8(active)-404.4(promoter)-403.3(\(PA\))-403.5(is)-396.3(very)-401.4(low.)-407.1(The)-399.1(rst)]TJ 0 -1.2203 TD [(segmentation)-410.2(\(s1\))-402.8(is)-408.9(computed)-406.8(with)-407.7(an)-406.1(unconstrained)-404.8(transition)-409.4(matrix.)-408.6(The)-405.4(region)-404.5(is)-408.9(classied)-403.9(as)-407.3(primed)-408(because)]TJ T* [(transition)-460(rates)-465.5(overrule)-459.1(classier)-469.7(assessments.)-460.9(The)-462.3(second)-464.7(segmentation)-460.8(\(s2\))-466(has)-457.4(constrained)-462.7(transition)-466.3(rates)-459.1(and)]TJ 0 -1.2266 TD [(correctly)-338.6(classies)-335.5(the)-333.8(region)-334.9(as)-331.4(active)-341.2(enhancer.)]TJ /F2 1 Tf 9.9626 0 0 9.9626 107.6031 737.4045 Tm (M)Tj 7.1731 0 0 7.1731 117.0708 737.4045 Tm (OD)Tj 9.9626 0 0 9.9626 127.8425 737.4045 Tm [(HMM:)-338(SUPR)-9.9(A-BAY)-10.9(ESIAN)-341.2(GENOM)-10.7(E)-335.5(SEGMEN)-11.8(TATION)-14981.3(5)]TJ ET endstream endobj 75 0 obj <>stream Adobed       k  s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz ?N*UثWb]v*UثWb|a)@۪9 FÓUVI8+T婵;En'k3-wM1Ty{CB -vE"WY?:i7tJg..!*%` 3ӍxqVI7yμZm@m?ɸN*_YصzpF`O\U+"$2֗,V,+4R05ΉuK$I1;i'X #*'զwl~$4~=b6AUZ$Ōqeop+MHTt~8 _}b Gqs)99*-ǩ;b_ãRo4¿\Ӎwኪy[Yҵmdk;YLrh2|U40K;>dTw/ki!dQ԰/eP/M2H88tX+q82[@p.41E j'|U4Pc1ZO@U?0Pz1QKш1T>mi iag9BJT*ke,HYjT}&#@ԤKBDu JѩR⫵}gO-~|x#ŨHP1튡6C^\ֽ7P6u5~KkƵ*-oL.keb'W@&b/MdԯI~$ oVMTk+;k%xXRJ}*/._hM+[Yge@yY |KNU?9W*iɂTҤX?Y?ܧbgGQ{W[{/*) Y. % P]Vj_Ӯ4[ج;(+D j9Tb4b.s0i\-/R_9ĐlU0765u[eB=A8] GnRF4Ɠ Ӊ*cb=~ 3D_)ǩ銲?4izFuۍ2+[C%S/qVi< 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%~lUWb]J|dov*UثWb]v*UثWbX/gKo'3[pC|ݚ7v*UثWb]v*UثWb]v*UثWb]v*UثWbD|Z=徫\h6ޡKvXPDzMY?YfZ?)i;),A~.ey'c.K,ǔd;6H0.㤌˴r#M\Py麍֝tnlx&SSQNHCdXv*UثWb]v*UثWb]v*UثWb]v*UثG¡m?a`K>zHfIWb]v*UثWb]h8)V~ʷrz$jA>79f\Dm͖"_Cy?N6qq#J+j!M {Wb]v*UثWb]v*UثWb]v*UثWb]z*`h4pFdv*UثWb]v*UثVC#S,UثT5֙ݺդ7+K"⫦QfUR0{TmLӡI 1H::F¾bUثWb]>exS2qV7v*UثWb]v*UثWbWNf.vG49Ni8:TxVQӪ>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 [(Th)-7(e)-264.3(parameter)]TJ /F10 1 Tf 6.123 0 TD (d)Tj /F6 1 Tf 6.9738 0 0 6.9738 140.0882 713.9904 Tm (i)Tj /F1 1 Tf 9.9626 0 0 9.9626 145.1338 715.4644 Tm [(mode)-8.4(ls)-261.6(the)-268.6(expected)-272.1(length)-268(of)-265.3(the)]TJ /F6 1 Tf 13.8679 0 TD (i)Tj /F1 1 Tf .2845 0 TD [(th)-260.4(chromat)-11.5(in)-260.4(sta)-8(te,)-262.5(whe)-8(reas)]TJ /F11 1 Tf 11.2957 0 TD ()Tj /F6 1 Tf 6.9738 0 0 6.9738 403.54 713.9904 Tm (i)Tj /F1 1 Tf 9.9626 0 0 9.9626 408.6424 715.4644 Tm [(represents)-272.5(the)-262.9(transi)-9.4(tion)]TJ -33.5799 -1.195 TD [(rat)-8.8(e)-378.1(into)-384.2(another)-383.5(sta)-8(te.)-382(In)-379.1(addition)-386.1(to)-379.9(the)-382.4(above)-388.7(constraints,)-389.2(we)-382.8(also)-384.4(assume)-383.9(that)-385.9(the)-382.4(expec)-9.2(ted)-382.4(length)-381.8(of)]TJ 0 -1.2007 TD [(chrom)-11.1(atin)-442.8(sta)-8(tes)-446.2(is)-443.7(context)-446.9(inde)-7.6(penden)-8.1(t,)-442.1(that)-448.5(is,)]TJ /F10 1 Tf 20.6453 0 TD (d)Tj /F6 1 Tf 6.9738 0 0 6.9738 284.7684 690.066 Tm (i)Tj /F5 1 Tf 9.9626 0 0 9.9626 288.907 691.5967 Tm (=)Tj /F10 1 Tf .717 0 TD (d)Tj /F6 1 Tf 6.9738 0 0 6.9738 301.0393 690.066 Tm (j)Tj /F1 1 Tf 9.9626 0 0 9.9626 307.8991 691.5967 Tm (for)Tj /F6 1 Tf 1.6161 0 TD (i)Tj /F1 1 Tf .2788 0 TD ()Tj /F6 1 Tf .5008 0 TD (j)Tj /F7 1 Tf .5577 0 TD .2829 Tc (2f)Tj /F1 1 Tf 1.4397 0 TD 0 Tc [(EA)-173(EA)]TJ 6.9738 0 0 6.9738 383.244 690.066 Tm (1)Tj 9.9626 0 0 9.9626 387.2692 691.5967 Tm .1678 Tc [(E)167.8(A)]TJ 6.9738 0 0 6.9738 405.5243 690.066 Tm 0 Tc (2)Tj /F7 1 Tf 9.9626 0 0 9.9626 409.5495 691.5967 Tm (g)Tj /F1 1 Tf .5008 0 TD (,)Tj /F6 1 Tf .6942 0 TD (i)Tj /F1 1 Tf .2788 0 TD ()Tj /F6 1 Tf .5008 0 TD (j)Tj /F7 1 Tf .5634 0 TD .2772 Tc (2f)Tj /F1 1 Tf 1.434 0 TD 0 Tc [(BI)-170.3(BI)]TJ 6.9738 0 0 6.9738 474.066 690.066 Tm (1)Tj 9.9626 0 0 9.9626 478.0345 691.5967 Tm .1678 Tc [(B)167.8(I)]TJ 6.9738 0 0 6.9738 493.0014 690.066 Tm 0 Tc (2)Tj /F7 1 Tf 9.9626 0 0 9.9626 497.0266 691.5967 Tm (g)Tj /F1 1 Tf .5008 0 TD (,)Tj /F6 1 Tf -42.9523 -1.2007 TD (i)Tj /F1 1 Tf .2845 0 TD ()Tj /F6 1 Tf .5008 0 TD (j)Tj /F7 1 Tf .5577 0 TD .2829 Tc (2f)Tj /F1 1 Tf 1.4397 0 TD 0 Tc [(PR)-167.5(PR)]TJ 6.9738 0 0 6.9738 131.1307 678.1038 Tm (1)Tj 9.9626 0 0 9.9626 135.0992 679.6345 Tm .1678 Tc [(P)167.8(R)]TJ 6.9738 0 0 6.9738 152.2771 678.1038 Tm 0 Tc (2)Tj /F7 1 Tf 9.9626 0 0 9.9626 156.2456 679.6345 Tm (g)Tj /F1 1 Tf .5008 0 TD [(,)-256.5(and)]TJ /F6 1 Tf 2.2079 0 TD (i)Tj /F1 1 Tf .2845 0 TD ()Tj /F6 1 Tf .5008 0 TD (j)Tj /F7 1 Tf .5577 0 TD .2773 Tc (2f)Tj /F1 1 Tf 1.4397 0 TD 0 Tc (TR)Tj 6.9738 0 0 6.9738 223.7102 678.1038 Tm (1)Tj 9.9626 0 0 9.9626 227.7354 679.6345 Tm .1621 Tc [(T)162.1(R)]TJ 6.9738 0 0 6.9738 245.4802 678.1038 Tm 0 Tc (2)Tj /F7 1 Tf 9.9626 0 0 9.9626 249.4487 679.6345 Tm (g)Tj /F1 1 Tf .5065 0 TD [(.)-250.8(For)-259.6(each)-258.8(row)]TJ /F6 1 Tf 6.0547 0 TD (i)Tj /F1 1 Tf .2788 0 TD [(,)-256.5(diagonal)-259.9(entrie)-10(s)]TJ /F10 1 Tf 7.1587 0 TD (d)Tj /F6 1 Tf 6.9738 0 0 6.9738 393.9023 678.1038 Tm (i)Tj /F1 1 Tf 9.9626 0 0 9.9626 398.8912 679.6345 Tm [(and)-260.2(off-diagona)-9.3(l)-253.9(entr)-9.6(ies)]TJ /F11 1 Tf 9.8617 0 TD ()Tj /F6 1 Tf 6.9738 0 0 6.9738 502.0723 678.1038 Tm (i)Tj /F1 1 Tf 9.9626 0 0 9.9626 74.0976 667.6722 Tm [(mus)-7(t)-379.1(b)0(e)-384.6(chose)-8.6(n)-376.3(such)-387.3(that)-385.9(the)-382.4(row)-383.8(sum)-382.6(is)-386.7(equal)-385.7(to)-379.9(1.)-382.4(The)-385.2(constra)-9.2(ints)-385.3(that)-380.2(are)-389.1(imposed)-384.5(on)-382.8(the)-382.4(transi)-9.4(tion)]TJ 0 -1.2007 TD [(matri)-10.9(x)]TJ /F9 1 Tf 2.8737 0 TD (S)Tj /F5 1 Tf .8365 0 TD (=)Tj /F1 1 Tf .717 0 TD (\()Tj /F10 1 Tf .3357 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 127.0488 654.2361 Tm (ij)Tj /F1 1 Tf 9.9626 0 0 9.9626 131.4708 655.7101 Tm [(\))-241.7(com)-7.6(plicate)-246.6(the)-245.8(estimat)-10.5(ion)-244.1(step,)-248.2(which)-245.6(led)-245.8(us)-241.7(to)-243.3(develop)-250.7(a)-241.6(modied)-251.6(Baum)-8.1(Welch)-246(algo)-7.6(rithm.)]TJ /F6 1 Tf 10.959 0 0 10.959 74.0976 631.7856 Tm [(2.2.)-502(Algorithm)-326.9(for)-334.2(estimating)-331.9(transition)-327.4(rates)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 613.8707 Tm [(ModH)-8.9(MM)-318.4(inco)-7.6(rporates)-324.9(predict)-10.7(ions)-320(from)-323.5(a)-321.2(set)-321(of)-316.5(classi)-10.4(ers)-320.2(through)-323.1(a)-321.2(simpl)-8.4(e)-315.5(para)-8.6(meter-f)-9.7(ree)-320.8(likelihoo)-8.3(d)]TJ -1.0015 -1.2007 TD [(mode)-8.4(l.)-242.9(Hen)-8(ce,)-244.5(the)-245.8(only)-244.8(para)-8.6(meters)-250.9(that)-243.7(mus)-7(t)-242.5(b)0(e)-248(estimated)-252.8(are)-246.8(the)-245.8(transi)-9.4(tion)-241.9(rates)-252.3(of)-242.5(the)-245.8(unobse)-7.6(rved)-245.8(Mar)-8(kov)]TJ T* [(proce)-9.4(ss.)-323(Given)-325.3(the)-319.8(amoun)-9.1(t)-316.5(o)0(f)-322.2(data)-322.4(availa)-9.8(ble)-319.8(for)-319.2(com)-7.6(puting)-323.1(genome)-324.7(segm)-9.6(entations,)-327.6(we)-320.2(ref)-8(rain)-322.6(from)-323.5(using)]TJ T* [(highl)-9.3(y)-370.7(sophist)-7.6(icated)-379.7(Bayesian)-384.3(estimation)-379.8(methods)-8.9(.)-376(Instead)-9.1(,)-370.3(w)0(e)-377.1(utilize)-378.5(the)-376.7(common)-377.6(max)-7.6(imum)-377.1(likelihoo)-8.3(d)]TJ T* [(appro)-7.6(ach.)-421.7(As)-416.4(an)-418.7(instanc)-9.9(e)-412.3(o)0(f)-418.9(the)-416.6(expec)-9.2(tation-m)-10.3(aximizati)-9.7(on)-416.9(\(EM\))-418.5(algo)-7.6(rithm)-418.9(the)-416.6(Baum)-8.1(Welch)-422.4(algo)-7.6(rithm)]TJ 0 -1.195 TD [(max)-7.6(imizes)-280.2(the)-274.3(likelihoo)-8.3(d)-273.9(function)-277.2(itera)-9.2(tively)-276.4(until)-273.9(a)-275.7(stationar)-10.5(y)-268.2(point)-276.8(is)-272.9(found.)-279.3(To)-274.5(satisfy)-278.8(our)-271.7(const)-9.6(raints)-276.8(on)]TJ 0 -1.2007 TD [(the)-302.7(transition)-302.5(matrix)]TJ /F9 1 Tf 8.5472 0 TD (S)Tj /F5 1 Tf .8308 0 TD (=)Tj /F1 1 Tf .7227 0 TD (\()Tj /F10 1 Tf .3357 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 183.5716 540.6235 Tm (ij)Tj /F1 1 Tf 9.9626 0 0 9.9626 187.9937 542.1542 Tm [(\))-293(w)0(e)-303.2(employ)-297.2(a)-298.5(modied)-302.8(Baum)-8.2(Welch)-302.9(algorithm)-301.3(that)-300.6(allows)-301.5(arbitrar)-9.7(y)-296.7(equality)]TJ -11.4323 -1.2007 TD [(const)-9.6(raints.)-288.6(Gi)-8.2(ven)-288.6(a)-287.1(seque)-8.6(nce)-290.4(of)]TJ /F6 1 Tf 13.4525 0 TD (T)Tj /F1 1 Tf .8422 0 TD [(observat)-9.9(ions,)-291.9(the)-285.7(updat)-8.4(ed)-287.8(transition)-296.8(matrix)-290.5(at)-290.6(iteration)]TJ /F6 1 Tf 22.2614 0 TD (n)Tj /F5 1 Tf .6658 0 TD (+)Tj /F1 1 Tf .717 0 TD [(1)-291(i)0(s)-284.3(give)-7.6(n)-285.3(b)0(y)]TJ /F9 1 Tf -27.8097 -2.8851 TD (S)Tj /F6 1 Tf 6.9738 0 0 6.9738 181.7007 499.9747 Tm (n)Tj /F5 1 Tf .6666 0 TD (+)Tj /F1 1 Tf .7154 0 TD (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 197.0078 501.4487 Tm (=)Tj /F1 1 Tf .8877 0 TD [(arg)-336.1(max)]TJ /F9 1 Tf 6.9738 0 0 6.9738 220.1952 493.0014 Tm (S)Tj /F12 1 Tf 9.9626 0 0 9.9626 240.8881 510.9164 Tm (X)Tj /F6 1 Tf 6.9738 0 0 6.9738 244.2897 490.8471 Tm (i)Tj /F1 1 Tf .2845 0 TD ()Tj /F6 1 Tf .504 0 TD (j)Tj /F10 1 Tf 9.9626 0 0 9.9626 256.8188 501.4487 Tm (n)Tj /F6 1 Tf 6.9738 0 0 6.9738 261.8078 499.5211 Tm (ij)Tj /F1 1 Tf 9.9626 0 0 9.9626 267.9306 501.4487 Tm (log)Tj /F10 1 Tf 1.4511 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 287.8865 499.9747 Tm (ij)Tj /F1 1 Tf 9.9626 0 0 9.9626 293.329 501.4487 Tm [()-1163.6(whe)-8(re)]TJ /F10 1 Tf 4.9508 0 TD (n)Tj /F6 1 Tf 6.9738 0 0 6.9738 347.6408 499.5211 Tm (ij)Tj /F5 1 Tf 9.9626 0 0 9.9626 353.707 501.4487 Tm (=)Tj /F12 1 Tf .8877 .9503 TD (X)Tj /F6 1 Tf 6.9738 0 0 6.9738 362.6645 512.9006 Tm (T)Tj /F5 1 Tf .8048 0 TD (-)Tj /F1 1 Tf .7154 0 TD (1)Tj /F6 1 Tf -.6585 -3.1379 TD (t)Tj /F10 1 Tf 9.9626 0 0 9.9626 378.5385 501.4487 Tm (n)Tj /F6 1 Tf 6.9738 0 0 6.9738 383.5274 499.5211 Tm (ij)Tj /F1 1 Tf 9.9626 0 0 9.9626 387.9495 501.4487 Tm (\()Tj /F6 1 Tf .3357 0 TD (t)Tj /F1 1 Tf .3016 0 TD .0995 Tc (\))Tj -32.1402 -2.9534 TD 0 Tc (and)Tj /F10 1 Tf 1.8779 0 TD (n)Tj /F6 1 Tf 6.9738 0 0 6.9738 97.7952 470.0975 Tm (ij)Tj /F1 1 Tf 9.9626 0 0 9.9626 102.2173 472.0251 Tm (\()Tj /F6 1 Tf .3357 0 TD (t)Tj /F1 1 Tf .3016 0 TD [(\))-429.5(i)0(s)-426.6(the)-433.6(posterior)-434.7(proba)-7.6(bility)-431(of)-424.6(a)-429.3(transi)-9.4(tion)-429.7(from)-431.6(state)]TJ /F6 1 Tf 23.3654 0 TD (i)Tj /F1 1 Tf .7113 0 TD (to)Tj /F6 1 Tf 1.2064 0 TD (j)Tj /F1 1 Tf .7113 0 TD [(at)-427.2(posi)-7(tion)]TJ /F6 1 Tf 4.8199 0 TD (t)Tj /F1 1 Tf .7056 0 TD [(com)-7.6(puted)-429.5(usin)-7(g)-427.6(the)]TJ -34.9798 -1.2007 TD [(tra)-8.8(nsition)-270.9(matrix)]TJ /F9 1 Tf 6.9652 0 TD (S)Tj /F6 1 Tf 6.9738 0 0 6.9738 150.1795 458.5322 Tm (n)Tj /F1 1 Tf 9.9626 0 0 9.9626 154.148 460.0629 Tm [(.)-267.8(The)-271.3(optim)-7.2(ization)-273.3(probl)-8.6(em)-268.6(is)-272.9(solved)-272.1(by)-269(nding)-274(the)-274.3(stationary)-278.7(points)-273.1(of)-265.3(the)-274.3(Lagran)-9.9(gian)]TJ /F7 1 Tf 4.6776 -2.9136 TD (L)Tj /F1 1 Tf .6886 0 TD (\()Tj /F9 1 Tf .3301 0 TD (S)Tj /F1 1 Tf .6715 0 TD ()Tj /F10 1 Tf .5008 0 TD (k)Tj /F1 1 Tf .5008 0 TD (\))Tj /F5 1 Tf .5008 0 TD (=)Tj /F12 1 Tf .882 .9446 TD (X)Tj /F6 1 Tf 6.9738 0 0 6.9738 244.7999 420.3778 Tm (i)Tj /F1 1 Tf .2845 0 TD ()Tj /F6 1 Tf .4959 0 TD (j)Tj /F10 1 Tf 9.9626 0 0 9.9626 257.3291 431.0361 Tm (n)Tj /F6 1 Tf 6.9738 0 0 6.9738 262.318 429.1086 Tm (ij)Tj /F1 1 Tf 9.9626 0 0 9.9626 268.4409 431.0361 Tm (log)Tj /F10 1 Tf 1.4511 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 288.3968 429.5054 Tm (ij)Tj /F5 1 Tf 9.9626 0 0 9.9626 294.4629 431.0361 Tm (-)Tj /F12 1 Tf .8877 .9446 TD (X)Tj /F6 1 Tf 6.9738 0 0 6.9738 309.4865 420.3778 Tm (i)Tj /F10 1 Tf 9.9626 0 0 9.9626 319.2944 431.0361 Tm (k)Tj /F6 1 Tf 6.9738 0 0 6.9738 324.2834 429.5054 Tm (i)Tj /F12 1 Tf 9.9626 0 0 9.9626 332.4471 440.4471 Tm (X)Tj /F6 1 Tf 6.9738 0 0 6.9738 338.6267 420.3778 Tm (j)Tj /F10 1 Tf 9.9626 0 0 9.9626 348.4345 431.0361 Tm (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 353.9338 429.5054 Tm (ij)Tj /F5 1 Tf 9.9626 0 0 9.9626 359.9999 431.0361 Tm (-)Tj /F1 1 Tf .7227 0 TD (1)Tj /F12 1 Tf -4.0631 1.7129 TD 3.9918 Tc ("#)Tj /F1 1 Tf -25.3571 -4.6719 TD 0 Tc [(wi)-8.2(th)-334.3(multiplie)-8.9(rs)]TJ /F10 1 Tf 6.8173 0 TD (k)Tj /F6 1 Tf 6.9738 0 0 6.9738 147.0047 400.0818 Tm (i)Tj /F1 1 Tf 9.9626 0 0 9.9626 149.4425 401.5558 Tm [(.)-336.1(W)0(e)-335.9(explain)-338.8(the)-336.9(gener)-9.4(al)-336.1(solution)-339.9(on)-331.6(a)-338.3(small)-340.2(example)-341.3(with)-336.9(transiti)-10.7(on)-331.6(matrix)]TJ /F9 1 Tf 7.2725 -3.4769 TD (S)Tj /F5 1 Tf .8365 0 TD (=)Tj /F10 1 Tf 1.7072 1.5251 TD (r)Tj /F1 1 Tf 6.9738 0 0 6.9738 252.7936 380.5794 Tm (11)Tj /F10 1 Tf 9.9626 0 0 9.9626 270.1983 382.1101 Tm (r)Tj /F1 1 Tf 6.9738 0 0 6.9738 275.7543 380.5794 Tm (12)Tj /F10 1 Tf 9.9626 0 0 9.9626 247.2377 370.1479 Tm (r)Tj /F1 1 Tf 6.9738 0 0 6.9738 252.7936 368.6739 Tm (21)Tj /F10 1 Tf 9.9626 0 0 9.9626 270.1983 370.1479 Tm (r)Tj /F1 1 Tf 6.9738 0 0 6.9738 275.7543 368.6739 Tm (22)Tj 9.9626 0 0 9.9626 298.7716 382.2802 Tm (0)Tj /F10 1 Tf 1.7242 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 321.4487 380.8062 Tm (q)Tj /F10 1 Tf 9.9626 0 0 9.9626 296.5038 370.318 Tm (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 302.0031 368.844 Tm (q)Tj /F10 1 Tf 9.9626 0 0 9.9626 315.9495 370.318 Tm (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 321.4487 368.844 Tm (q)Tj /F7 1 Tf 9.9626 0 0 9.9626 337.096 376.1007 Tm .1682 Tc ()Tj /F8 1 Tf -7.3465 -2.0714 TD 0 Tc (.)Tj 0 -.3983 TD (.)Tj 0 .7967 TD (.)Tj 4.5866 -.3983 TD (.)Tj .404 -.3983 TD (.)Tj -.8024 .7967 TD (.)Tj 3.5964 -.3983 TD (.)Tj T* (.)Tj 0 .7967 TD (.)Tj /F12 1 Tf -10.4478 3.0274 TD (2)Tj 0 -1.747 TD (6)Tj 0 -.5918 TD (4)Tj 11.3242 2.3388 TD (3)Tj 0 -1.747 TD (7)Tj 0 -.5918 TD (5)Tj /F1 1 Tf -27.713 -3.4029 TD [(that)-260.7(cont)-7.6(ains)-259.2(two)-259.4(types)-259.9(of)-259.6(constraint)-11.3(s.)-252.7(Firs)-8.2(t,)]TJ /F10 1 Tf 17.8 0 TD (r)Tj /F1 1 Tf 6.9738 0 0 6.9738 256.9322 330.9164 Tm (13)Tj 9.9626 0 0 9.9626 266.9669 332.3905 Tm [(is)-255.9(set)-258.4(to)-260.4(zero)-259(so)-258.8(that)-260.7(transitions)-264.6(from)-260.9(state)-258.8(one)-260.2(to)-260.4(state)-258.8(three)]TJ -19.3592 -1.2007 TD [(are)-246.8(not)-238.4(allow)-9.4(ed.)-242.7(Second,)-246.7(all)-237.2(othe)-7.6(r)-236.1(transi)-9.4(tions)-243.8(from)-243.8(the)-240.1(rst)-241.5(two)-242.3(states)-243.7(to)-243.3(states)-243.7(thr)-7(ee)-238.4(and)-243.1(four)-240.3(are)-246.8(constra)-9.1(ined)]TJ T* [(to)-340(have)-336.7(the)-336.9(same)-335.7(rate)]TJ /F10 1 Tf 9.1618 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 170.8724 306.992 Tm (q)Tj /F1 1 Tf 9.9626 0 0 9.9626 174.8409 308.4661 Tm [(,)-336.1(that)-334.7(is,)]TJ /F10 1 Tf 3.6818 0 TD (r)Tj /F1 1 Tf 6.9738 0 0 6.9738 217.0771 306.992 Tm (14)Tj /F5 1 Tf 9.9626 0 0 9.9626 226.2047 308.4661 Tm (=)Tj /F10 1 Tf .717 0 TD (r)Tj /F1 1 Tf 6.9738 0 0 6.9738 238.9039 306.992 Tm (23)Tj /F5 1 Tf 9.9626 0 0 9.9626 248.0314 308.4661 Tm (=)Tj /F10 1 Tf .717 0 TD (r)Tj /F1 1 Tf 6.9738 0 0 6.9738 260.7307 306.992 Tm (24)Tj /F5 1 Tf 9.9626 0 0 9.9626 269.8582 308.4661 Tm (=)Tj /F10 1 Tf .717 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 282.5574 306.992 Tm (q)Tj /F1 1 Tf 9.9626 0 0 9.9626 286.5259 308.4661 Tm [(.)-336.1(Finding)-334.4(the)-336.9(sta)-8(tionary)-339(points)-335.7(of)]TJ /F7 1 Tf 13.8565 0 TD (L)Tj /F1 1 Tf 1.0186 0 TD [(we)-337.3(obta)-7.6(in)]TJ /F10 1 Tf -26.057 -3.2095 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 180.6236 275.0173 Tm (ij)Tj /F5 1 Tf 9.9626 0 0 9.9626 186.6897 276.4913 Tm (=)Tj ET 219.798 288.17 6.8031 .39685 re f BT /F10 1 Tf 6.9738 0 0 6.9738 219.7984 291.2881 Tm (n)Tj /F6 1 Tf 4.9813 0 0 4.9813 223.2566 289.9275 Tm (ij)Tj /F10 1 Tf 6.9738 0 0 6.9738 220.4787 282.444 Tm (k)Tj /F6 1 Tf 4.9813 0 0 4.9813 223.9936 281.4236 Tm (i)Tj /F1 1 Tf 9.9626 0 0 9.9626 263.3385 285.8456 Tm [(if)-251(\()]TJ /F6 1 Tf 1.2007 0 TD (i)Tj /F1 1 Tf .2788 0 TD ()Tj /F6 1 Tf .5008 0 TD (j)Tj /F1 1 Tf .2845 0 TD (\))Tj /F7 1 Tf .6089 0 TD (2)Tj /F6 1 Tf .9389 0 TD (p)Tj /F5 1 Tf .6658 0 TD (=)Tj /F7 1 Tf .717 0 TD (f)Tj /F1 1 Tf .5008 0 TD [(1)-168.5(2)]TJ /F7 1 Tf 1.5023 0 TD (g)Tj /F5 1 Tf .6715 0 TD ()Tj /F7 1 Tf .717 0 TD (f)Tj /F1 1 Tf .5008 0 TD [(1)-168.5(2)]TJ /F7 1 Tf 1.5023 0 TD (g)Tj ET 206.022 272.353 34.299 .39685 re f BT /F10 1 Tf 6.9738 0 0 6.9738 219.9117 275.4708 Tm (n)Tj /F6 1 Tf 4.9813 0 0 4.9813 223.4267 274.1668 Tm (q)Tj /F12 1 Tf 9.9626 0 0 9.9626 206.022 271.9558 Tm (P)Tj /F6 1 Tf 4.9813 0 0 4.9813 216.5102 261.7511 Tm (k)Tj /F7 1 Tf 6.9738 0 0 6.9738 220.5354 265.2661 Tm (j)Tj /F10 1 Tf .2683 0 TD (r)Tj /F6 1 Tf 4.9813 0 0 4.9813 226.2614 264.1889 Tm (q)Tj /F7 1 Tf 6.9738 0 0 6.9738 229.2661 265.2661 Tm (j)Tj /F6 1 Tf 4.9813 0 0 4.9813 231.1369 263.3385 Tm (k)Tj /F10 1 Tf 6.9738 0 0 6.9738 233.9716 265.2661 Tm (k)Tj /F6 1 Tf 4.9813 0 0 4.9813 237.4865 264.1889 Tm (k)Tj /F1 1 Tf 9.9626 0 0 9.9626 250.2991 270.085 Tm [(if)-251(\()]TJ /F6 1 Tf 1.2007 0 TD (i)Tj /F1 1 Tf .2788 0 TD ()Tj /F6 1 Tf .5008 0 TD (j)Tj /F1 1 Tf .2845 0 TD (\))Tj /F7 1 Tf .6089 0 TD (2)Tj /F6 1 Tf .9333 0 TD (q)Tj /F5 1 Tf .6715 0 TD (=)Tj /F7 1 Tf .717 0 TD (f)Tj /F1 1 Tf .5008 0 TD [(\(1)-171.3(4\))-171.3(\(2)-165.6(3\))-171.3(\(2)-171.3(4\))]TJ /F7 1 Tf 7.5172 0 TD (g)Tj /F12 1 Tf -18.8756 2.6859 TD (8)Tj 0 -.8991 TD (<)Tj 0 -1.7868 TD (:)Tj /F1 1 Tf 20.5429 .643 TD ()Tj -32.567 -3.1924 TD [(whe)-8(re)]TJ /F10 1 Tf 2.868 0 TD (n)Tj /F6 1 Tf 6.9738 0 0 6.9738 107.6598 242.8157 Tm (q)Tj /F5 1 Tf 9.9626 0 0 9.9626 113.2724 244.6866 Tm (=)Tj /F12 1 Tf .8877 .7511 TD (P)Tj /F1 1 Tf 6.9738 0 0 6.9738 132.6047 241.8519 Tm (\()Tj /F6 1 Tf .3333 0 TD (i)Tj /F1 1 Tf .2845 0 TD ()Tj /F6 1 Tf .4959 0 TD (j)Tj /F1 1 Tf .2845 0 TD (\))Tj /F7 1 Tf .3333 0 TD (2)Tj /F6 1 Tf .6585 0 TD (q)Tj /F10 1 Tf 9.9626 0 0 9.9626 154.9417 244.6866 Tm (n)Tj /F6 1 Tf 6.9738 0 0 6.9738 159.9306 242.8157 Tm (ij)Tj /F1 1 Tf 9.9626 0 0 9.9626 164.3527 244.6866 Tm (.)Tj /F7 1 Tf .6601 0 TD (j)Tj /F10 1 Tf .2731 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 179.1496 243.2125 Tm (q)Tj /F7 1 Tf 9.9626 0 0 9.9626 183.118 244.6866 Tm (j)Tj /F6 1 Tf 6.9738 0 0 6.9738 185.8393 241.9653 Tm (k)Tj /F1 1 Tf 9.9626 0 0 9.9626 193.6629 244.6866 Tm [(denot)-8.4(es)-414.2(the)-410.9(numb)-6.6(er)-415(of)]TJ /F10 1 Tf 9.8446 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 297.2975 243.2125 Tm (q)Tj /F1 1 Tf 9.9626 0 0 9.9626 305.3479 244.6866 Tm [(entrie)-10(s)-411.7(i)0(n)]TJ /F9 1 Tf 4.285 0 TD (S)Tj /F1 1 Tf 1.0812 0 TD [(at)-410.1(row)]TJ /F6 1 Tf 3.107 0 TD (k)Tj /F1 1 Tf .4496 0 TD [(.)-410.1(I)0(n)-413.2(this)-413.8(exampl)-8.7(e)-412.3(w)0(e)-411.3(have)]TJ /F7 1 Tf -32.1345 -1.2007 TD (j)Tj /F10 1 Tf .2731 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 82.3181 231.2503 Tm (q)Tj /F7 1 Tf 9.9626 0 0 9.9626 86.3433 232.7244 Tm (j)Tj /F1 1 Tf 6.9738 0 0 6.9738 89.0078 230.0031 Tm (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 94.6771 232.7244 Tm (=)Tj /F1 1 Tf .7227 0 TD [(1)-330.8(and)]TJ /F7 1 Tf 2.6177 0 TD (j)Tj /F10 1 Tf .2675 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 136.1196 231.2503 Tm (q)Tj /F7 1 Tf 9.9626 0 0 9.9626 140.1448 232.7244 Tm (j)Tj /F1 1 Tf 6.9738 0 0 6.9738 142.8661 230.0031 Tm (2)Tj /F5 1 Tf 9.9626 0 0 9.9626 148.4787 232.7244 Tm (=)Tj /F1 1 Tf .7227 0 TD [(2.)-331.2(Th)-7(e)-332.6(Lagra)-9.2(nge)-334.1(multipl)-8.5(iers)-335.1(are)-337.9(obta)-7.6(ined)-337.7(as)-334.6(a)-332.6(solu)-7(tion)-332.9(to)-334.3(the)-336.9(const)-9.6(raints)]TJ ET 221.839 208.743 12.472 .39687 re f BT /F10 1 Tf 9.9626 0 0 9.9626 221.8393 213.222 Tm (n)Tj /F1 1 Tf 6.9738 0 0 6.9738 226.8283 211.3511 Tm (11)Tj /F10 1 Tf 9.9626 0 0 9.9626 223.5968 199.6157 Tm (k)Tj /F1 1 Tf 6.9738 0 0 6.9738 228.5858 198.1417 Tm (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 237.5999 206.4755 Tm (+)Tj ET 246.444 208.743 12.472 .39687 re f BT /F10 1 Tf 9.9626 0 0 9.9626 246.444 213.222 Tm (n)Tj /F1 1 Tf 6.9738 0 0 6.9738 251.433 211.3511 Tm (12)Tj /F10 1 Tf 9.9626 0 0 9.9626 248.2015 199.6157 Tm (k)Tj /F1 1 Tf 6.9738 0 0 6.9738 253.1905 198.1417 Tm (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 262.2614 206.4755 Tm (+)Tj ET 271.105 208.743 43.313 .39687 re f BT /F7 1 Tf 9.9626 0 0 9.9626 278.8157 213.6188 Tm (j)Tj /F10 1 Tf .2675 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 287.0361 212.1448 Tm (q)Tj /F7 1 Tf 9.9626 0 0 9.9626 291.0046 213.6188 Tm (j)Tj /F1 1 Tf 6.9738 0 0 6.9738 293.7259 210.8976 Tm (1)Tj /F10 1 Tf 9.9626 0 0 9.9626 297.6944 213.6188 Tm (n)Tj /F6 1 Tf 6.9738 0 0 6.9738 302.6834 211.6913 Tm (q)Tj /F12 1 Tf 9.9626 0 0 9.9626 271.1054 207.0992 Tm (P)Tj /F6 1 Tf 6.9738 0 0 6.9738 281.5369 196.781 Tm (k)Tj /F7 1 Tf 9.9626 0 0 9.9626 286.9794 199.6157 Tm (j)Tj /F10 1 Tf .2731 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 295.1999 198.1417 Tm (q)Tj /F7 1 Tf 9.9626 0 0 9.9626 299.1684 199.6157 Tm (j)Tj /F6 1 Tf 6.9738 0 0 6.9738 301.8897 196.8945 Tm (k)Tj /F10 1 Tf 9.9626 0 0 9.9626 305.6314 199.6157 Tm (k)Tj /F6 1 Tf 6.9738 0 0 6.9738 310.6771 198.1417 Tm (k)Tj /F5 1 Tf 9.9626 0 0 9.9626 317.707 206.4755 Tm (+)Tj /F8 1 Tf .8877 0 TD .1682 Tc (...)Tj /F5 1 Tf 1.4795 0 TD 0 Tc (=)Tj /F1 1 Tf .7227 0 TD (1)Tj ET 221.839 180.397 12.472 .39685 re f BT /F10 1 Tf 9.9626 0 0 9.9626 221.8393 184.8755 Tm (n)Tj /F1 1 Tf 6.9738 0 0 6.9738 226.8283 183.0047 Tm (21)Tj /F10 1 Tf 9.9626 0 0 9.9626 223.5968 171.2692 Tm (k)Tj /F1 1 Tf 6.9738 0 0 6.9738 228.5858 169.7952 Tm (2)Tj /F5 1 Tf 9.9626 0 0 9.9626 237.5999 178.1291 Tm (+)Tj ET 246.444 180.397 12.472 .39685 re f BT /F10 1 Tf 9.9626 0 0 9.9626 246.444 184.8755 Tm (n)Tj /F1 1 Tf 6.9738 0 0 6.9738 251.433 183.0047 Tm (22)Tj /F10 1 Tf 9.9626 0 0 9.9626 248.2015 171.2692 Tm (k)Tj /F1 1 Tf 6.9738 0 0 6.9738 253.1905 169.7952 Tm (2)Tj /F5 1 Tf 9.9626 0 0 9.9626 262.2614 178.1291 Tm (+)Tj ET 271.105 180.397 43.313 .39685 re f BT /F7 1 Tf 9.9626 0 0 9.9626 278.8157 185.2724 Tm (j)Tj /F10 1 Tf .2675 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 287.0361 183.7983 Tm (q)Tj /F7 1 Tf 9.9626 0 0 9.9626 291.0046 185.2724 Tm (j)Tj /F1 1 Tf 6.9738 0 0 6.9738 293.7259 182.5511 Tm (2)Tj /F10 1 Tf 9.9626 0 0 9.9626 297.6944 185.2724 Tm (n)Tj /F6 1 Tf 6.9738 0 0 6.9738 302.6834 183.4016 Tm (q)Tj /F12 1 Tf 9.9626 0 0 9.9626 271.1054 178.7527 Tm (P)Tj /F6 1 Tf 6.9738 0 0 6.9738 281.5369 168.4346 Tm (k)Tj /F7 1 Tf 9.9626 0 0 9.9626 286.9794 171.2692 Tm (j)Tj /F10 1 Tf .2731 0 TD (r)Tj /F6 1 Tf 6.9738 0 0 6.9738 295.1999 169.7952 Tm (q)Tj /F7 1 Tf 9.9626 0 0 9.9626 299.1684 171.2692 Tm (j)Tj /F6 1 Tf 6.9738 0 0 6.9738 301.8897 168.548 Tm (k)Tj /F10 1 Tf 9.9626 0 0 9.9626 305.6314 171.2692 Tm (k)Tj /F6 1 Tf 6.9738 0 0 6.9738 310.6771 169.7952 Tm (k)Tj /F5 1 Tf 9.9626 0 0 9.9626 317.707 178.1291 Tm (+)Tj /F8 1 Tf .8877 0 TD .1682 Tc (...)Tj /F5 1 Tf 1.4795 0 TD 0 Tc (=)Tj /F1 1 Tf .7227 0 TD (1)Tj .6658 .6203 TD ()Tj -28.2081 -4.8427 TD [(whe)-8(re)-289.8(dots)-291.5(mark)-294.9(addition)-10.5(al)-290.6(constraint)-11.3(s)-286.5(stemmi)-8.7(ng)-291.7(from)-289.4(the)-291.4(remai)-10(ning)-290.3(parts)-296.1(of)-288(the)-291.4(matrix)]TJ /F9 1 Tf 36.1976 0 TD (S)Tj /F1 1 Tf .6658 0 TD [(.)-290.6(Newton)-11.3(s)-289.2(root)]TJ -36.8634 -1.2007 TD [(n)-6.4(ding)-335.9(method)-337(\(G)-7.4(ill)-334.9(et)-336.1(al.,)-336.9(1981\))-335.8(is)-335.5(used)-336.1(to)-334.3(solv)-7(e)-332.6(this)-334.1(set)-338.1(of)-333.6(equat)-10.1(ions)-337.1(numerical)-11.9(ly.)]TJ /F6 1 Tf 10.959 0 0 10.959 74.0976 99.8929 Tm [(2.3.)-502(Default)-328.7(chromatin)-331.8(state)-330.5(classiers)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 81.9212 Tm [(ModH)-8.9(MM)-346.9(take)-9.4(s)-349.1(a)0(s)-345.9(input)-356.5(the)-348.3(genom)-9.1(e-wide)-352.6(predict)-10.7(ions)-348.4(of)-350.6(a)-349.7(set)-349.5(of)-350.6(classiers)-11.9(.)-347.5(I)0(n)-350.6(principle)-9.3(,)-347.5(any)-351.2(type)-349(of)]TJ -1.0015 -1.2007 TD [(cla)-8.6(ssier)-388.3(can)-387.1(be)-390.3(used;)-390.8(however)-9.1(,)-381.7(ModH)-8.9(MM)-386.7(impleme)-10.1(nts)-387.5(a)-383.8(defa)-8.6(ult)-383.4(classi)-10.4(er)-386.5(set)-389.3(to)-385.6(simplify)-391(usage)-8.6(.)-381.7(These)]TJ /F2 1 Tf 0 66.9948 TD [(6)-30877.7(BEN)-10(NER)-339.2(AND)-338.4(VINGR)-8.9(ON)]TJ ET endstream endobj 88 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 [(engineer)-10.5(ed)-310.6(classi)-10.4(ers)-308.8(requi)-10.3(re)-306.9(no)-314.5(training)-314.1(data)-316.7(and)-311.4(consi)-9.6(st)-307.1(of)-310.8(two)-316.3(layers.)-316.1(First,)-313.7(a)-309.8(sing)-7(le-feature)-322.1(classier)-317.2(is)]TJ 0 -1.195 TD [(construc)-9.9(ted)-280(for)-279.4(each)-287.2(feature)-284.9(that)-283.5(determin)-9.3(es)-277.7(the)-280(proba)-7.6(bility)-283.1(of)-276.6(enrichm)-11.5(ent)-280(at)-279.2(each)-287.2(genomic)-282.7(posi)-7(tion.)-282.1(These)]TJ 0 -1.2007 TD [(single-fe)-9.7(ature)-370.6(classi)-10.3(ers)-365.7(are)-366.3(then)-371.8(combine)-9.5(d)-365(into)-367.1(a)-361.1(set)-372.2(of)-362(naiv)-7.6(e)-361.1(B)0(a)-8(yesian)-370.6(multife)-9.5(ature)-364.9(cla)-8.6(ssiers)-373.2(\()-82.4(Maron,)]TJ T* [(1961;)-257(Duda)-259.2(and)-260.2(Hart,)-264.3(1973;)-257(Mitche)-9.9(ll,)-252.1(199)-8(7;)-254.7(Russell)-264.4(and)-254.5(Nor)-8.2(vig,)-255.8(2016\),)-256.5(each)-264.5(specializ)-12.1(ed)-253.7(in)-260.4(the)-257.2(detection)-265.2(of)]TJ T* [(a)-332.6(sing)-7(le)-336.1(chromati)-9.3(n)-330.8(state.)]TJ /F6 1 Tf 10.959 0 0 10.959 117.5811 643.7479 Tm [(2.3.1.)-497(Single-feature)-364.5(classiers.)]TJ /F1 1 Tf 9.9626 0 0 9.9626 270.4818 643.7479 Tm [(The)-379.5(purpose)-380.2(of)-379.1(a)-378.1(single-fe)-9.7(ature)-382(classi)-10.3(er)-375.2(is)-381.1(to)-374.2(asse)-9(ss)-373.8(the)-382.4(enrich-)]TJ -16.3489 -1.2007 TD [(ment)-426.5(of)-418.9(a)-423.7(featur)-9.2(e)-423.7(genome-)-8.7(wide.)-427.3(Since)-424.8(it)-422.5(assigns)-428.9(a)-423.7(proba)-7.6(bility)-425.4(to)-419.7(each)-429.5(genomic)-430.6(position,)-425.7(we)-428.3(may)-423(also)]TJ T* [(interp)-8.2(ret)-441.3(thi)-7.8(s)-440.1(step)-447(as)-448.4(a)-446.4(normaliz)-9.3(ation)-449.3(step)-447(that)-442.8(decoup)-8.1(les)-446.2(the)-450.7(denition)-448.6(of)-447.4(the)-445(engi)-7.6(neered)-450.1(multifeat)-9.9(ure)]TJ 0 -1.195 TD [(classi)-10.3(ers)-434(from)-437.3(the)-433.6(actual)-442.2(observation)-9.3(s.)-434.8(Such)-436.5(classi)-10.3(ers)-434(are)-434.6(the)-433.6(basi)-8.8(c)-429.3(ingr)-7.8(edient)-434.8(of)-436(many)-435.2(peak)-439.1(calling)]TJ 0 -1.2007 TD [(methods)-8.9(,)-472.7(impleme)-10.1(nting)-476(a)-474.9(large)-478.8(vari)-9.6(ety)-473.5(of)-475.8(different)-482.8(statist)-9.2(ical)-478.8(models)-480.5(\(Wilbanks)-480.8(and)-476.4(Fa)-8.2(cciotti,)-481.3(2010\),)]TJ T* [(ranging)-267.9(from)-260.9(Po)-6.4(isson)-265(\()-82.4(Mortaz)-9.1(avi)-262.9(et)-262.1(al.,)-262.9(2008;)-262.6(Valoue)-9.2(v)-262.5(e)0(t)-262.1(al.,)-262.9(2008\))-267.6(or)-259.6(local)-269(Poisson)-265.8(\(Zhang)-264.2(et)-262.2(al.,)-262.9(20)-7.2(08\))-260.3(to)]TJ T* [(HMMs)-342.1(\(Spyrou)-338.6(et)-336.1(al.,)-336.9(2009\).)]TJ 1.0015 -1.2007 TD [(Our)-281.3(appro)-7.6(ach)-279(dif)-7(fers)-283.1(in)-277.4(that)-283.5(we)-280.4(do)-286.1(not)-278.2(assume)-287.2(the)-280(sam)-8.8(e)-281.4(model)-285(for)-279.4(all)-282.7(featur)-9.2(es)-277.7(but)-283.9(rather)-282.3(accou)-9.2(nt)-283.1(for)-279.4(the)]TJ -1.0015 -1.2007 TD [(high)-421.2(heteroge)-10.5(neity.)-421.2(More)-424.2(speci)-11.3(cally,)-423(we)-422.7(rst)-423.6(compute)-424.9(the)-422.3(cover)-9.4(age)-421.3(along)-423.8(the)-422.3(genome)-427.1(in)-419.7(200)-167.3(bp)-422.6(bins)]TJ T* [(\(Secti)-9.2(on)-269(3.5\).)-278.2(The)-277(coverage)-282.7(values)-279.6(are)-275.3(then)-275.1(modele)-8.7(d)-273.9(b)0(y)-269(a)-275.7(featur)-9.2(e-specic)-280.9(mixtu)-7.2(re)-272.7(di)18.5(st)17.3(ri)16.5(bu)21.2(ti)15.7(on)21.2(.)-262.1(C)0(o)16.5(n)0(s)14.4(i)13.5(de)13.8(r)-258.8(a)0(n)]TJ T* [(ev)19.4(en)13.8(t)]TJ /F7 1 Tf 2.4128 0 TD (f)Tj /F6 1 Tf .5008 0 TD (X)Tj /F10 1 Tf 6.9738 0 0 6.9738 143.1496 529.0015 Tm (u)Tj /F6 1 Tf -.0569 -.9674 TD (t)Tj /F5 1 Tf 9.9626 0 0 9.9626 149.9527 524.1826 Tm (=)Tj /F6 1 Tf .7227 0 TD (x)Tj /F7 1 Tf .4496 0 TD (g)Tj /F1 1 Tf .7796 0 TD [(w)12.4(i)0(t)15.7(h)-268.2(co)13.8(ve)19.4(ra)17.5(ge)-265.1(va)19.4(lu)18.5(e)]TJ /F6 1 Tf 8.2684 0 TD (x)Tj /F1 1 Tf .717 0 TD [(fr)17.3(om)-261.1(a)-270(f)0(e)17.5(a)0(t)16.7(u)0(r)19.3(e)]TJ /F10 1 Tf 5.9182 0 TD (u)Tj /F7 1 Tf .9446 0 TD .2773 Tc (2f)Tj /F1 1 Tf 1.434 0 TD 0 Tc [(AT)17.5(AC)-166.5(H)12.4(3)0(K)17.3(4)0(m)12(e1)]TJ /F8 1 Tf 7.9782 0 TD .1568 Tc (...)Tj /F7 1 Tf 1.1267 0 TD 0 Tc (g)Tj /F1 1 Tf .7796 0 TD [(at)-284.9(bin)]TJ /F6 1 Tf 2.5778 0 TD (t)Tj /F1 1 Tf .2845 0 TD [(.)-279.2(W)-9(e)-281.4(assum)-11.5(e)-281.4(that)]TJ /F6 1 Tf -18.113 -2.1169 TD (X)Tj /F10 1 Tf 6.9738 0 0 6.9738 294.6897 507.2314 Tm (u)Tj /F6 1 Tf -.065 -.9918 TD (t)Tj /F9 1 Tf 9.9626 0 0 9.9626 299.7921 503.0928 Tm (*)Tj /F12 1 Tf 1.5251 .9503 TD (X)Tj /F6 1 Tf 6.9738 0 0 6.9738 311.4708 492.2644 Tm (k)Tj /F7 1 Tf .4634 0 TD (2)Tj /F6 1 Tf .6585 0 TD (F)Tj /F7 1 Tf .6585 0 TD ([)Tj /F6 1 Tf .6585 0 TD (B)Tj /F10 1 Tf 9.9626 0 0 9.9626 334.4314 503.0928 Tm (p)Tj /F6 1 Tf 6.9738 0 0 6.9738 339.9306 501.6188 Tm (k)Tj 9.9626 0 0 9.9626 343.729 503.0928 Tm (p)Tj 6.9738 0 0 6.9738 348.718 501.6188 Tm (k)Tj /F1 1 Tf 9.9626 0 0 9.9626 352.4597 503.0928 Tm ()Tj -24.5775 -2.8567 TD (where)Tj /F6 1 Tf 2.7144 0 TD (p)Tj 7.4718 0 0 6.641 139.6346 472.9321 Tm (k)Tj /F1 1 Tf 9.9626 0 0 9.9626 145.644 474.6329 Tm [(is)-261.6(the)]TJ /F6 1 Tf 2.4242 0 TD (k)Tj /F1 1 Tf .4496 0 TD [(th)-266.1(com)-7.6(ponent)-265.2(of)-271(the)-262.9(featur)-9.2(e-speci)-10.9(c)-264.3(mixtu)-7.2(re)-267.1(distributio)-8.3(n)-262.5(with)-268.6(weight)]TJ /F10 1 Tf 28.1739 0 TD (p)Tj /F6 1 Tf 6.9738 0 0 6.9738 460.4597 473.1022 Tm (k)Tj /F1 1 Tf 9.9626 0 0 9.9626 464.2581 474.6329 Tm (.)Tj /F6 1 Tf .5121 0 TD (F)Tj /F1 1 Tf .882 0 TD (and)Tj /F6 1 Tf 1.7129 0 TD (B)Tj /F1 1 Tf .882 0 TD (partition)Tj -39.7883 -1.2007 TD [(the)-297.1(set)]TJ /F7 1 Tf 2.942 0 TD (f)Tj /F6 1 Tf .5008 0 TD (p)Tj 6.9738 0 0 6.9738 146.8913 461.14 Tm (k)Tj /F7 1 Tf 9.9626 0 0 9.9626 150.633 462.6707 Tm (g)Tj /F1 1 Tf .7967 0 TD [(into)-298.8(fore)-8.8(ground)]TJ /F7 1 Tf 6.6181 0 TD (f)Tj /F6 1 Tf .5008 0 TD (p)Tj 6.9738 0 0 6.9738 234.4818 461.14 Tm (k)Tj /F7 1 Tf 9.9626 0 0 9.9626 238.2235 462.6707 Tm (j)Tj /F6 1 Tf .2731 0 TD (k)Tj /F7 1 Tf .7455 0 TD (2)Tj /F6 1 Tf .9333 0 TD (F)Tj /F7 1 Tf .6601 0 TD (g)Tj /F1 1 Tf .7967 0 TD [(and)-300(background)-303.4(com)-7.6(ponents)]TJ /F7 1 Tf 11.9274 0 TD (f)Tj /F6 1 Tf .5008 0 TD (p)Tj 6.9738 0 0 6.9738 400.9889 461.14 Tm (k)Tj /F7 1 Tf 9.9626 0 0 9.9626 404.7873 462.6707 Tm (j)Tj /F6 1 Tf .2731 0 TD (k)Tj /F7 1 Tf .7455 0 TD (2)Tj /F6 1 Tf .9333 0 TD (B)Tj /F7 1 Tf .6146 0 TD (g)Tj /F1 1 Tf .5008 0 TD [(.)-296.3(A)0(s)-302.6(a)0(n)-299.2(exampl)-8.7(e,)-298.8(we)-297.5(take)]TJ -32.8971 -1.2007 TD [(the)-280(ATAC-se)-11.3(q)-273.9(featur)-9.2(e,)-276.1(which)-279.7(mea)-9.4(sures)-277.4(the)-280(accessi)-11.9(bility)-277.4(of)-276.7(chromat)-11.5(in.)-277.8(The)-277(foregrou)-8.1(nd)-280.4(component)-284.2(consist)-9.3(s)]TJ T* [(of)-373.4(two)-378.9(geometri)-9.3(c)-372.4(distribut)-9.7(ions,)-371.6(whe)-8(reas)-379.7(the)-371(backgr)-10.1(ound)-372.9(is)-375.4(mode)-8.4(led)-376.7(by)-371.4(a)-372.4(delta)-377.1(distri)-10.3(bution)-374.3(posi)-7(tioned)-376.1(at)]TJ T* [(zero,)-333.3(a)-332.6(P)0(o)-6.4(isson)-333.3(and)-334.1(a)-332.6(geomet)-8.7(ric)-333.2(distributio)-8.3(n)-330.8(\(Fig.)-337.4(4\).)-328.2(Whet)-10.1(her)-330.4(a)-332.6(com)-7.6(ponent)-333.5(belo)-7.6(ngs)-333.5(to)-328.7(the)-336.9(foregrou)-8.1(nd)-331.6(or)]TJ T* [(backgroun)-12.4(d)-330.8(i)0(s)-341.2(a)-332.6(subj)-7(ective)-339.8(choi)-7.6(ce)-335.2(and)-339.8(must)-340.6(be)-339.1(determin)-9.3(ed)-333.4(by)-337.3(visu)-7(al)-336.1(inspect)-9.9(ion)-335.1(of)-339.2(the)-336.9(data.)-339.8(The)-339.6(parame)-9.7(-)]TJ T* [(ters)-335.1(of)-327.9(the)-331.2(mixtu)-7.2(re)-329.7(distri)-10.3(bution)-334.5(are)-332.2(estimated)-338.2(by)-331.6(maxim)-9.7(um)-329.4(likelihoo)-8.3(d)-330.8(using)-332.1(the)-331.2(EM)-333.4(algo)-7.6(rithm)-333.5(\(Demp)-9.3(ster)]TJ T* [(et)-336.1(al.,)-336.9(1977\).)]TJ 1.0015 -1.195 TD [(Once)-249.6(a)-247.2(mixtu)-7.2(re)-250(distribut)-9.7(ion)-244.1(for)-250.9(a)-247.2(featur)-9.2(e)]TJ /F10 1 Tf 16.4684 0 TD (u)Tj /F1 1 Tf .9162 0 TD [(is)-244.5(d)-6.5(etermined,)-256.9(the)-245.8(p)-6.5(robability)-255.7(that)-249.4(a)-247.2(given)-253.1(bin)]TJ /F6 1 Tf 18.5455 0 TD (t)Tj /F1 1 Tf .5235 0 TD [(of)-248.2(the)-251.5(genom)-9.1(e)]TJ -37.4552 -1.2007 TD [(with)-336.9(cover)-9.4(age)-335.9(value)]TJ /F6 1 Tf 8.5984 0 TD (x)Tj /F1 1 Tf .7796 0 TD [(is)-335.5(enriche)-9.7(d)-330.8(i)0(s)-335.5(give)-7.6(n)-330.8(b)0(y)-337.3(the)-336.9(posterior)-343.7(probability)]TJ /F6 1 Tf 7.2099 -2.6176 TD (q)Tj 6.9738 0 0 6.9738 277.8519 339.4771 Tm (t)Tj /F1 1 Tf 9.9626 0 0 9.9626 280.4598 340.9511 Tm (\()Tj /F10 1 Tf .3357 0 TD (u)Tj /F1 1 Tf .6658 0 TD (\))Tj /F5 1 Tf .5008 0 TD (=)Tj ET 304.271 343.219 63.099 .39685 re f BT /F12 1 Tf 9.9626 0 0 9.9626 308.6928 355.3511 Tm (P)Tj /F6 1 Tf 6.9738 0 0 6.9738 319.181 345.033 Tm (k)Tj /F7 1 Tf .4715 0 TD (2)Tj /F6 1 Tf .6504 0 TD (F)Tj /F10 1 Tf 9.9626 0 0 9.9626 333.7511 347.8676 Tm (p)Tj /F6 1 Tf 6.9738 0 0 6.9738 339.2503 346.3936 Tm (k)Tj 9.9626 0 0 9.9626 343.0487 347.8676 Tm (p)Tj 6.9738 0 0 6.9738 348.0377 346.3936 Tm (k)Tj /F1 1 Tf 9.9626 0 0 9.9626 351.7794 347.8676 Tm (\()Tj /F6 1 Tf .3357 0 TD (x)Tj /F1 1 Tf .4496 0 TD (\))Tj /F12 1 Tf -5.554 -.6317 TD (P)Tj /F6 1 Tf 6.9738 0 0 6.9738 314.759 331.2566 Tm (k)Tj /F7 1 Tf .4634 0 TD (2)Tj /F6 1 Tf .6585 0 TD (F)Tj /F7 1 Tf .6585 0 TD ([)Tj /F6 1 Tf .6585 0 TD (B)Tj /F10 1 Tf 9.9626 0 0 9.9626 338.1731 334.0912 Tm (p)Tj /F6 1 Tf 6.9738 0 0 6.9738 343.729 332.6172 Tm (k)Tj 9.9626 0 0 9.9626 347.4708 334.0912 Tm (p)Tj 6.9738 0 0 6.9738 352.4597 332.6172 Tm (k)Tj /F1 1 Tf 9.9626 0 0 9.9626 356.2582 334.0912 Tm (\()Tj /F6 1 Tf .3301 0 TD (x)Tj /F1 1 Tf .4496 0 TD (\))Tj /F11 1 Tf .6032 .6886 TD (:)Tj /F1 1 Tf -25.34 -2.6404 TD [(In)-327.9(this)-334.1(way,)-332.7(a)-332.6(single-fe)-9.7(ature)-336.5(classier)-340(is)-329.8(construc)-9.9(ted)-331.2(for)-330.6(all)-334(featur)-9.2(es.)-329.2(Ev)-7(ery)-330.4(such)-336.1(classier)-340(consists)-335.7(of)-333.6(a)]TJ -1.0015 -1.2007 TD [(mixtu)-7.2(re)-335.3(of)-333.6(Poisson,)-340.1(geomet)-8.7(ric,)-333.6(and)-339.8(delta)-337.3(distribut)-9.7(ions.)]TJ /F6 1 Tf 10.959 0 0 10.959 117.5811 278.759 Tm [(2.3.2.)-497(Multifeature)-254.5(classiers.)]TJ /F1 1 Tf 9.9626 0 0 9.9626 261.9779 278.759 Tm [(Multifeatur)-11.8(e)-252.9(classi)-10.4(ers)-257.6(are)-258.2(dened)-263.4(as)-254.9(simpl)-8.4(e)-252.9(comb)-8.4(inations)-262.1(of)-253.9(single-)]TJ -15.4954 -1.2007 TD [(featur)-9.2(e)-344(cla)-8.6(ssiers.)-350.8(Con)-7(sider)-353(the)-348.3(case)-351(of)-350.6(active)-351.2(prom)-8.6(oters)-353(that)-346.1(are)-355(known)-349.2(to)-351.4(be)-350.4(accessible)-360.2(and)-345.5(mark)-10.3(ed)-344.7(by)]TJ T* [(H3K27a)-8.5(c)-366.7(and)-374(H3K4m)-9.5(e3)-367.5(as)-374.4(well)-372.8(as)-368.7(a)-366.7(high)-375.7(H3K4me3-)-9.9(to-me)-8.2(1)-365(ratio)-371.6(\(H)-7.4(3K4me3)-8.1(/1\).)-371.6(A)-368.9(classi)-10.3(er)-369.5(for)-370.4(active)]TJ T* [(promot)-7.1(ers)-399.9(shoul)-7.8(d)-399.1(assign)-409.8(high)-404.2(probabiliti)-8.9(es)-402.8(to)-402.6(regions)-405.7(whe)-8(re)-397.9(thos)-7(e)-400.9(three)-404.8(featur)-9.2(es)-402.8(co-occur)-9.7(.)-398.7(There)-9.2(fore,)-401.8(a)]TJ T* [(naive)-340.2(Bayesian)-344.5(promot)-7.1(er)-335.3(model)-336.2(is)-335.5(given)-338.4(by)]TJ ET q 336.132 0 0 116.164 154.715 96.831 cm /Im4 Do Q BT /F2 1 Tf 8.9663 0 0 8.9663 107.6031 80.9008 Tm [(FIG.)-290.5(4.)]TJ /F1 1 Tf 4.072 0 TD [(Mixture)-294.9(distribution)-296.2(used)-292.5(to)-293.9(model)-292.1(ATAC-seq)-298(data.)-294.4(Both)-291.3(plots)-297.6(show)-293.4(the)-289.5(empirical)-299.3(distribution)-289.9(in)-293.9(black.)]TJ /F2 1 Tf 42.5405 0 TD (\(A\))Tj /F1 1 Tf -46.6125 -1.2266 TD [(Components)-333.5(of)-336.7(the)-333.8(mixture)-335.6(distribution.)]TJ /F2 1 Tf 16.7873 0 TD (\(B\))Tj /F1 1 Tf 1.6692 0 TD [(Foreground)-330.1(and)-336.1(background)-337.7(components)-331.2(are)-334.8(merged.)]TJ /F2 1 Tf 9.9626 0 0 9.9626 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[(regul)-10.3(atory)-380.2(ele)-8.6(ments)-383(as)-385.8(oppose)-7.6(d)-376.3(t)0(o)-385.6(H3K4me3)-388.4(that)-380.2(show)-8.2(s)-383.2(a)-378.1(highe)-8.4(r)-378.3(enrichm)-11.5(ent)-382.4(at)-381.7(promot)-7.1(ers)-382.8(toward)-384.9(tran-)]TJ T* [(scribed)-350.6(regio)-10.3(ns)-338.5(du)-7.2(e)-338.3(t)0(o)-345.7(its)-344.7(role)-345.3(in)-345.7(preinitiat)-9.9(ion)-346.5(complex)-345.3(format)-10.9(ion)-340.8(\(Laube)-9.9(rth)-342.8(et)-347.5(al.,)-342.6(201)-8(3\).)-339.6(Th)-7(e)-338.3(sym)-7(metric)]TJ T* [(str)-8.2(ucture)-337.2(of)-333.6(a)-338.3(feature)-341.8(is)-335.5(captured)-340.6(by)]TJ /F6 1 Tf 14.05 -1.9177 TD (s)Tj 6.9738 0 0 6.9738 217.9275 500.7117 Tm (t)Tj /F5 1 Tf .4634 0 TD (-)Tj /F1 1 Tf .7235 0 TD (1)Tj /F8 1 Tf .4959 0 TD (:)Tj /F6 1 Tf .2764 0 TD (t)Tj /F5 1 Tf .4634 0 TD (+)Tj /F1 1 Tf .7235 0 TD (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 245.5369 502.1857 Tm (=)Tj /F6 1 Tf .717 0 TD (q)Tj 6.9738 0 0 6.9738 257.6692 500.7117 Tm (t)Tj /F5 1 Tf .4715 0 TD (-)Tj /F1 1 Tf .7154 0 TD (1)Tj /F7 1 Tf 9.9626 0 0 9.9626 272.1826 502.1857 Tm ()Tj /F6 1 Tf .4951 0 TD (q)Tj 6.9738 0 0 6.9738 282.1039 500.7117 Tm (t)Tj /F5 1 Tf .4634 0 TD (+)Tj /F1 1 Tf .7235 0 TD (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 295.9936 502.1857 Tm (+)Tj ET 303.194 507.742 41.669 .39685 re f BT /F6 1 Tf 9.9626 0 0 9.9626 303.1936 502.1857 Tm (q)Tj 6.9738 0 0 6.9738 308.1826 500.7117 Tm (t)Tj /F5 1 Tf .4715 0 TD (-)Tj /F1 1 Tf .7154 0 TD (1)Tj /F7 1 Tf 9.9626 0 0 9.9626 322.696 502.1857 Tm ()Tj /F6 1 Tf .4894 0 TD (q)Tj 6.9738 0 0 6.9738 332.5605 500.7117 Tm (t)Tj /F5 1 Tf .4715 0 TD (+)Tj /F1 1 Tf .7235 0 TD (1)Tj /F7 1 Tf 9.9626 0 0 9.9626 347.0739 502.1857 Tm ()Tj /F6 1 Tf .4951 0 TD (q)Tj 6.9738 0 0 6.9738 356.9952 500.7117 Tm (t)Tj /F1 1 Tf 9.9626 0 0 9.9626 359.6031 502.1857 Tm ()Tj -28.6576 -1.9006 TD [(whe)-8(re)]TJ ET 190.885 469.701 41.669 .39685 re f BT /F6 1 Tf 9.9626 0 0 9.9626 190.885 464.1447 Tm (q)Tj 6.9738 0 0 6.9738 195.8739 462.614 Tm (t)Tj /F5 1 Tf .4715 0 TD (-)Tj /F1 1 Tf .7154 0 TD (1)Tj /F7 1 Tf 9.9626 0 0 9.9626 210.3873 464.1447 Tm ()Tj /F6 1 Tf .4894 0 TD (q)Tj 6.9738 0 0 6.9738 220.2519 462.614 Tm (t)Tj /F5 1 Tf .4715 0 TD (+)Tj /F1 1 Tf .7154 0 TD (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 234.1983 464.1447 Tm (=)Tj /F6 1 Tf .7227 0 TD (q)Tj 6.9738 0 0 6.9738 246.3873 462.614 Tm (t)Tj /F5 1 Tf .4634 0 TD (-)Tj /F1 1 Tf .7235 0 TD (1)Tj /F7 1 Tf 9.9626 0 0 9.9626 260.844 464.1447 Tm ()Tj /F8 1 Tf .5406 .0057 TD ()Tj /F6 1 Tf -.0455 -.0057 TD (q)Tj 6.9738 0 0 6.9738 270.7653 462.614 Tm (t)Tj /F5 1 Tf .4715 0 TD (+)Tj /F1 1 Tf .7154 0 TD (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 284.7117 464.1447 Tm (+)Tj /F8 1 Tf .7682 .0057 TD ()Tj /F6 1 Tf -.0512 -.0057 TD (q)Tj 6.9738 0 0 6.9738 296.844 462.614 Tm (t)Tj /F5 1 Tf .4715 0 TD (-)Tj /F1 1 Tf .7235 0 TD (1)Tj /F7 1 Tf 9.9626 0 0 9.9626 311.3574 464.1447 Tm ()Tj /F6 1 Tf .4951 0 TD (q)Tj 6.9738 0 0 6.9738 321.2787 462.614 Tm (t)Tj /F5 1 Tf .4715 0 TD (+)Tj /F1 1 Tf .7154 0 TD (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 335.2251 464.1447 Tm (+)Tj /F8 1 Tf .7625 .0057 TD ()Tj /F6 1 Tf -.0455 -.0057 TD (q)Tj 6.9738 0 0 6.9738 347.3574 462.614 Tm (t)Tj /F5 1 Tf .4715 0 TD (-)Tj /F1 1 Tf .7154 0 TD (1)Tj /F7 1 Tf 9.9626 0 0 9.9626 361.8708 464.1447 Tm ()Tj /F8 1 Tf .5406 .0057 TD ()Tj /F6 1 Tf -.0455 -.0057 TD (q)Tj 6.9738 0 0 6.9738 371.792 462.614 Tm (t)Tj /F5 1 Tf .4634 0 TD (+)Tj /F1 1 Tf .7235 0 TD (1)Tj /F11 1 Tf 9.9626 0 0 9.9626 385.0582 464.1447 Tm (:)Tj /F1 1 Tf -31.2127 -1.9006 TD [(Th)-7(e)-332.6(classi)-10.4(er)-335.3(require)-9.9(s)-332(a)0(n)-333.4(enrichm)-11.5(ent)-336.9(at)-336.1(bins)]TJ /F6 1 Tf 18.5853 0 TD (t)Tj /F5 1 Tf .4666 0 TD (-)Tj /F1 1 Tf .7227 0 TD [(1)-330.8(and)]TJ /F6 1 Tf 2.6177 0 TD (t)Tj /F5 1 Tf .4666 0 TD (+)Tj /F1 1 Tf .717 0 TD [(1)-336.5(o)0(r)-333.6(a)0(n)-339.1(enrichment)-342.7(at)-336.1(the)-336.9(center)-339(bin)]TJ /F6 1 Tf 15.1881 0 TD (t)Tj /F1 1 Tf .2845 0 TD (.)Tj -38.047 -1.2007 TD [(In)-293.7(this)-288.6(man)-7.6(ner,)-291(a)-292.8(multife)-9.5(ature)-291(cla)-8.6(ssier)-291.5(is)-295.7(constructe)-10.3(d)-291(for)-290.8(every)-293.9(chromat)-11.5(in)-288.8(state.)-299(The)-288.4(cla)-8.6(ssiers)-293.5(are)-298.1(then)]TJ -1.0015 -1.2007 TD [(assi)-10(gned)-255.2(to)-254.7(states)-255.1(of)-253.9(the)-257.2(HMM,)-255.2(whe)-8(re)-255.7(some)-254.2(cla)-8.6(ssiers)-259.3(may)-252.3(als)-8(o)-251.2(b)0(e)-253.7(shared)-261.7(among)-253.8(sever)-10.6(al)-250.8(sta)-8(tes.)-253.1(This)-257.2(is,)-256.2(for)]TJ T* [(instanc)-9.9(e,)-315.9(the)-319.8(case)-322.6(for)-319.2(the)-314.1(act)-8.6(ive)-314.1(enhanc)-9.9(er)-318.3(states)-323.3(EA,)-318.6(EA)]TJ 6.9738 0 0 6.9738 302.7401 407.8487 Tm (1)Tj 9.9626 0 0 9.9626 306.7086 409.3228 Tm [(,)-313.4(and)-322.8(EA)]TJ 6.9738 0 0 6.9738 343.2188 407.8487 Tm (2)Tj 9.9626 0 0 9.9626 347.244 409.3228 Tm [(,)-313.4(a)0(s)-317.5(well)-321.6(as)-317.5(the)-319.8(bivalent)-319.6(sta)-8(tes)-315.3(BI,)-321.6(BI)]TJ 6.9738 0 0 6.9738 498.0471 407.8487 Tm (1)Tj 9.9626 0 0 9.9626 502.0156 409.3228 Tm (,)Tj -42.9523 -1.2007 TD [(and)-339.8(BI)]TJ 6.9738 0 0 6.9738 101.8771 395.8865 Tm (2)Tj 9.9626 0 0 9.9626 105.8456 397.3605 Tm [(.)-336.1(A)-334.8(full)-334.9(speci)-11.3(cation)-338(of)-333.6(the)-336.9(classi)-10.4(ers)-337.3(is)-335.5(given)-338.4(in)-334.3(Table)-340(1.)]TJ /F6 1 Tf 10.959 0 0 10.959 74.0976 373.4928 Tm [(2.4.)-502(Supervised)-331.2(shape)-327(classier)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 355.5212 Tm [(As)-319.6(an)-316.3(alter)-9.2(native)-321(to)-317.3(the)-319.8(engineer)-10.5(ed)-316.3(defa)-8.6(ult)-315.1(classi)-10.4(ers)-320.2(we)-320.2(consider)-322.9(a)-315.5(super)-8.8(vised)-316.8(method)-325.6(that)-317.7(mode)-8.4(ls)-318.5(the)]TJ -1.0015 -1.2007 TD [(shape)-332.9(of)-322.2(features)-326.7(aroun)-7.6(d)-325.1(chromati)-9.3(n)-319.4(states)-329(\(Secti)-9.2(on)-320.2(3.4\).)-323.7(Th)-7(e)-321.2(method)-325.6(is)-324.2(insp)-7(ired)-322.6(by)-325.9(DFilter)-327.8(\(Kuma)-9.3(r)-321.4(e)0(t)-324.7(al.,)]TJ 0 -1.195 TD [(20)-7.2(13\),)-357.5(a)-355.4(peak)-359.4(cal)-8.6(ling)-355.7(method)-365.5(that)-357.5(imple)-9(ments)-360.2(a)-355.4(Hot)-9(elling)-356.1(lt)-7(er.)-358.5(In)-356.3(its)-356.1(esse)-9(nce,)-359.1(the)-359.7(method)-365.5(models)-361(fore-)]TJ 0 -1.2007 TD .0209 Tc [(ground)-372.5(and)-372.5(b)-2.6(ackground)-372.5(as)-373.7(multivariate)-374.3(normal)-369.6(distri)]TJ 22.7793 0 TD .0206 Tc [(butions,)-366.7(s)-4.1(haring)-372.8(the)-368.9(s)-4.1(am)]TJ 10.5389 0 TD .0216 Tc [(e)-373.6(c)2(ovariance)-367.9(m).2(atrix.)-365.7(A)]TJ -33.3182 -1.2007 TD 0 Tc [(li)-7.1(kelih)-11.1(ood-r)-7.8(atio)-312(tes)-8(t)-299.4(i)0(s)-307.1(then)-314.9(used)-307.6(to)-305.9(cal)-8.6(l)-305.1(peaks)-315.9(\(linea)-10(r)-304.3(disc)-8.8(rimi)-8.4(nan)-9.8(t)-299.4(a)0(n)-9(alys)-8.8(is\).)-310.2(We)-307.5(modi)-9.3(ed)-304.9(the)-308.4(met)-10.4(hod)-309.6(and)]TJ T* [(u)-6.5(sed)-415(sev)-11(eral)-421.1(com)-7.6(ponen)-11.3(ts)-415.2(for)-416(the)-422.2(backgr)-10.1(ou)-7.2(nd)-416.9(distri)-10.3(buti)-8.6(on.)-417.3(More)-418.5(sp)-8.4(eci)-8.6(cally,)-423(at)-415.8(each)-423.8(geno)-10.5(mic)-420.1(bin)]TJ /F6 1 Tf 41.3362 0 TD (t)Tj /F1 1 Tf .6942 0 TD (we)Tj -42.0304 -1.2007 TD [(co)-9(nsid)-7(er)-278.4(for)-279.4(all)-277.1(feat)-11.4(ures)-281.2(the)-280(ob)-7.2(serv)-8(ation)-11.1(s)-275.1(insid)-10.5(e)-275.7(a)-275.7(wind)-9.7(ow)-278.6(of)-276.6(siz)-8(e)-275.7(2)]TJ /F6 1 Tf 27.1155 0 TD (n)Tj /F5 1 Tf .6658 0 TD (+)Tj /F1 1 Tf .717 0 TD [(1)-6.5(.)-273.5(Unde)-8.8(r)-275.9(the)-280(fore)-8.8(groun)-11.5(d)-273.9(mode)-8.4(l)-276.7(each)]TJ -28.4983 -1.2007 TD [(ran)-11.7(dom)-335.9(vari)-9.6(able)-345.1(from)-340.6(the)-336.9(set)]TJ /F7 1 Tf 12.303 0 TD (f)Tj /F6 1 Tf .5008 0 TD (X)Tj /F10 1 Tf 6.9738 0 0 6.9738 208.233 276.6613 Tm (u)Tj /F6 1 Tf -.0569 -1.0731 TD (t)Tj /F5 1 Tf .4634 0 TD (+)Tj /F6 1 Tf .7235 0 TD (j)Tj /F7 1 Tf 9.9626 0 0 9.9626 218.5511 271.8424 Tm (g)Tj /F1 1 Tf .8365 0 TD (with)Tj /F6 1 Tf 2.1226 0 TD (j)Tj /F7 1 Tf .5577 0 TD .2772 Tc (2f)Tj /F5 1 Tf 1.6047 0 TD 0 Tc (-)Tj /F6 1 Tf .717 0 TD (n)Tj /F1 1 Tf .5008 0 TD ()Tj /F5 1 Tf .6715 0 TD (-)Tj /F6 1 Tf .717 0 TD (n)Tj /F5 1 Tf .6658 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 /F6 1 Tf .5008 0 TD (n)Tj /F7 1 Tf .5008 0 TD (g)Tj /F1 1 Tf .8365 0 TD [(is)-335.5(dist)-9.8(rib)-7(uted)-337.7(as)]TJ ET 74.098 236.806 430.413 .51022 re f 74.098 101.367 430.413 .51025 re f 74.098 218.381 430.413 .51022 re f BT /F3 1 Tf 8.9663 0 0 8.9663 195.307 242.9858 Tm (Table)Tj /F1 1 Tf 3.0034 0 TD (1.)Tj /F3 1 Tf 1.2456 0 TD [(Multifeature)-334.6(Classier)-337.4(Denitions)]TJ /F6 1 Tf -10.5466 -2.0233 TD [(PA)-2508.8(EA)-4468.9(PR)-6359.5(BI)-4414.8(TL)-2310.4(TR)-2273.7(CL)-2272.2(NS)-2305.3(R1)-2325.7(R2)]TJ /F1 1 Tf -7.2208 -2.0739 TD (ATAC)Tj /F13 1 Tf 7.2334 0 TD (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 146.4377 204.7181 Tm (c)Tj /F13 1 Tf 8.9663 0 0 8.9663 170.2488 206.2488 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 177.7322 204.7181 Tm (c)Tj /F13 1 Tf 8.9663 0 0 8.9663 205.7952 206.2488 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 213.222 204.7181 Tm (c)Tj /F13 1 Tf 8.9663 0 0 8.9663 236.9763 206.2488 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 244.4598 204.7181 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 339.2503 206.2488 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 344.9196 204.7181 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 370.0912 206.2488 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 375.8172 204.7181 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 433.1904 206.2488 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 438.8597 204.7181 Tm (c)Tj /F1 1 Tf 8.9663 0 0 8.9663 74.0976 195.2503 Tm (H3K27ac)Tj /F13 1 Tf 7.2334 0 TD (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 146.4377 193.7763 Tm (s)Tj /F13 1 Tf 8.9663 0 0 8.9663 170.2488 195.2503 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 177.7322 193.7763 Tm (s)Tj /F14 1 Tf 8.9663 0 0 8.9663 205.7952 195.2503 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 211.4645 193.7763 Tm (a)Tj /F14 1 Tf 8.9663 0 0 8.9663 236.9763 195.2503 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 242.7023 193.7763 Tm (a)Tj /F14 1 Tf 8.9663 0 0 8.9663 433.1904 195.2503 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 438.8597 193.7763 Tm (c)Tj /F1 1 Tf 8.9663 0 0 8.9663 74.0976 184.3086 Tm (H3K4me1)Tj /F13 1 Tf 10.7237 0 TD (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 177.7322 182.8346 Tm (s,)Tj /F1 1 Tf .6407 0 TD (3)Tj /F13 1 Tf 8.9663 0 0 8.9663 236.9763 184.3086 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 244.4598 182.8346 Tm (s,)Tj /F1 1 Tf .6407 0 TD (3)Tj /F13 1 Tf 8.9663 0 0 8.9663 303.7606 184.3086 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 311.1873 182.8346 Tm (s,)Tj /F1 1 Tf .6407 0 TD (3)Tj /F14 1 Tf 8.9663 0 0 8.9663 433.1904 184.3086 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 438.8597 182.8346 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 463.1243 184.3086 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 468.8503 182.8346 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 494.0219 184.3086 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 499.6912 182.8346 Tm (c)Tj /F1 1 Tf 8.9663 0 0 8.9663 74.0976 173.3669 Tm (H3K4me3)Tj /F13 1 Tf 7.2334 0 TD (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 146.4377 171.8362 Tm (a)Tj /F13 1 Tf 8.9663 0 0 8.9663 205.7952 173.3669 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 213.222 171.8362 Tm (a)Tj /F13 1 Tf 8.9663 0 0 8.9663 272.5228 173.3669 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 279.9495 171.8362 Tm (a)Tj /F14 1 Tf 8.9663 0 0 8.9663 339.2503 173.3669 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 344.9196 171.8362 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 370.0912 173.3669 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 375.8172 171.8362 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 433.1904 173.3669 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 438.8597 171.8362 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 463.1243 173.3669 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 468.8503 171.8362 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 494.0219 173.3669 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 499.6912 171.8362 Tm (c)Tj /F1 1 Tf 8.9663 0 0 8.9663 74.0976 162.3684 Tm (H3K4me3/1)Tj /F13 1 Tf 7.2334 0 TD (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 146.4377 160.8945 Tm (a)Tj /F14 1 Tf 8.9663 0 0 8.9663 170.2488 162.3684 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 175.9747 160.8945 Tm (a)Tj /F1 1 Tf 8.9663 0 0 8.9663 74.0976 151.4267 Tm (H3K27me3)Tj /F14 1 Tf 14.6881 0 TD ()Tj /F6 1 Tf 6.7246 0 0 5.9768 211.4645 149.9527 Tm (a)Tj /F14 1 Tf 8.9663 0 0 8.9663 236.9763 151.4267 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 242.7023 149.9527 Tm (a)Tj /F13 1 Tf 8.9663 0 0 8.9663 272.5228 151.4267 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 279.9495 149.9527 Tm (s)Tj /F13 1 Tf 8.9663 0 0 8.9663 303.7606 151.4267 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 311.1873 149.9527 Tm (s)Tj /F14 1 Tf 8.9663 0 0 8.9663 433.1904 151.4267 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 438.8597 149.9527 Tm (c)Tj /F13 1 Tf 8.9663 0 0 8.9663 463.1243 151.4267 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 470.6078 149.9527 Tm (c)Tj /F1 1 Tf 8.9663 0 0 8.9663 74.0976 140.485 Tm (H3K9me3)Tj /F14 1 Tf 40.0493 0 TD ()Tj /F6 1 Tf 6.7246 0 0 5.9768 438.8597 138.9543 Tm (c)Tj /F13 1 Tf 8.9663 0 0 8.9663 494.0219 140.485 Tm (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 501.5054 138.9543 Tm (c)Tj /F1 1 Tf 8.9663 0 0 8.9663 74.0976 129.4866 Tm (RNA)Tj /F13 1 Tf 33.0119 0 TD (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 377.5747 128.0126 Tm (c)Tj /F14 1 Tf 8.9663 0 0 8.9663 433.1904 129.4866 Tm ()Tj /F6 1 Tf 6.7246 0 0 5.9768 438.8597 128.0126 Tm (c)Tj /F1 1 Tf 8.9663 0 0 8.9663 74.0976 118.5448 Tm [(RNA)-338.6(\(low\))]TJ /F13 1 Tf 29.5723 0 TD (X)Tj /F6 1 Tf 6.7246 0 0 5.9768 346.7338 117.0708 Tm (c)Tj /F1 1 Tf 8.9663 0 0 8.9663 74.0976 107.6031 Tm (Control)Tj /F14 1 Tf 7.2334 0 TD ()Tj /F6 1 Tf 6.7246 0 0 5.9768 144.6236 106.0724 Tm (a)Tj /F14 1 Tf 8.9663 0 0 8.9663 170.2488 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[(For)-276.6(all)-282.7(three)-279.6(methods)-287.7(a)-275.7(bin)-278.2(size)-283.7(of)-276.7(200)-173(bp)-274.7(was)-282.3(used.)-279.6(The)-282.7(ModHMM)-287.5(segmentat)-11.1(ion)-278.2(is)-278.6(compute)-9.5(d)-273.9(a)0(s)-283.3(the)-274.3(mos)-7(t)]TJ T* .0112 Tc [(likely)-359.5(s)-2.1(equence)-361.2(o)-.9(f)-361.4(h)4.7(i)-3.7(d)4.7(den)-359.5(s)-2.1(tat)-3.7(e)3(s,)-359.1(that)-356.5(i)-3.7(s)3.5(,)-359.1(t)2(he)-361.2(V)-4.9(ite)]TJ 20.7421 0 TD .0114 Tc [(rbi)-362(p)4.9(ath.)-358.9(ChromHMM)-361.2(and)-359.3(E)-.6(piCSeg)-359.3(use)-361(t)2.2(he)-361(posterior)]TJ -20.7421 -1.2007 TD [(decod)4.9(i)-3.5(ng)-330.8(algo)4.9(rithm)-334.3(t)2.2(o)-336.5(c)3.2(ompute)-332.6(segmentations.)]TJ 1.0015 -1.195 TD 0 Tc [(We)-358.7(evaluat)-10.5(ed)-356.1(all)-362.4(three)-359.2(methods)-367.4(on)-354.3(ENCO)-9.8(DE)-358.1(\(EN)-8(CODE)-362.6(Project)-362.8(Con)-7(sortium,)-359.4(2012\))-364.3(data)-362.2(from)-357.7(mous)-7.8(e)]TJ -1.0015 -1.2007 TD [(embryoni)-10.5(c)-332.6(liver)-343.2(at)-336.1(day)-339.8(12.5)-338.4(and)-334.1(emb)-7.6(ryonic)-341.2(lung)-335.9(at)-341.8(day)-334.1(16.5.)-338.8(For)-339.2(a)-338.3(rst)-338.2(qualitat)-9.3(ive)-336.9(comparison)-9.3(,)-336.1(Figur)-7.8(e)-332.6(5)]TJ T* [(shows)-317.4(a)-309.8(small)-317.4(region)-312.7(within)-318.4(chromos)-8.1(ome)-314.9(1)-308.1(that)-317.6(contain)-8.7(s)-309.3(three)-313.7(act)-8.6(ively)-312.7(transcr)-11.1(ibed)-309.2(genes)-8.6(,)-313.4(a)0(s)-311.8(indicated)-316.4(by)]TJ T* [(the)-274.3(data.)-277.2(Th)-7(e)-270(ModH)-8.9(MM)-272.9(segm)-9.6(entation)-279.7(correct)-11.7(ly)-271.7(detect)-9.8(s)-269.4(the)-280(promoters)-281.8(and)-277.2(transcrib)-9.7(ed)-270.8(regio)-10.3(ns.)-270.6(In)-276.7(addition,)]TJ T* 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0 -1.195 TD [(distribut)-9.7(ion)-352.2(of)-350.6(features)-360.8(around)-355.5(regulatory)-356.4(ele)-8.6(ments.)-354.9(Figure)-357.4(6)-347.9(shows)-357.3(state)-355.5(equival)-8.7(ences)-351.8(b)-6.5(etween)-358.1(the)-348.3(thr)-7(ee)]TJ 0 -1.2007 TD [(methods)-8.9(.)-267.8(I)0(n)-271(gener)-9.4(al,)-268.2(there)-279.6(is)-267.2(a)-270(low)-276.4(overlap)-275.4(betwee)-10.9(n)-268.2(states)-10.4(.)-267.8(Since)-276.8(we)-269(used)-273.5(mor)-7.8(e)-270(states)-277.8(for)-268(Chrom)-8.3(HMM)-277.6(and)]TJ T* [(EpiCSeg,)-275.8(it)-263.1(is)-267.2(clear)-270(that)-272.1(a)-264.3(single)-269.2(ModH)-8.9(MM)-267.2(state)-270.2(must)-266.6(be)-270.8(represe)-10.2(nted)-269.4(by)-263.3(multipl)-8.5(e)-264.3(states)-272.1(from)-266.6(Chr)-9(omHMM)]TJ T* [(and)-356.9(EpiCSeg.)-361.1(Howeve)-10.3(r,)-355.9(there)-359.2(are)-355(also)-355.9(multipl)-8.5(e)-355.4(recombinat)-12.6(ions,)-354.5(for)-353.4(instanc)-9.9(e,)-355.7(Chrom)-8.3(HMM)-357.3(state)-361.2(9)-353.6(corre-)]TJ T* [(sponds)-337(to)-334.3(ModH)-8.9(MM)-335.5(active)-339.8(prom)-8.6(oter)-333.9(\(PA)-7.4(\))-332.8(and)-334.1(enhanc)-9.9(er)-335.3(\(EA)-8(\))-332.8(states.)]TJ /F6 1 Tf 10.959 0 0 10.959 107.6031 207.3826 Tm [(3.1.)-496.9(Enhancer)-333.5(predictions)]TJ /F1 1 Tf 9.9626 0 0 9.9626 117.5811 189.4676 Tm [(To)-337.1(compare)-346.2(the)-342.6(predictiv)-9.3(e)-338.3(performanc)-11.1(e)-338.3(o)0(f)-339.2(segment)-10.7(ation)-341.2(methods)-344.7(we)-337.3(const)-9.6(ructed)-342.9(a)-338.3(test)-341.6(set)-338.1(with)-342.6(active)]TJ -1.0015 -1.2007 TD [(enhanc)-9.9(ers)-320.2(identied)-325.2(by)-314.5(the)-319.8(FANT)-9.9(OM)-320.4(consortium)-323.2(\(A)-7.4(ndersson)-319.5(et)-319.1(al.,)-319.8(2014\).)-324.8(Enhance)-10.5(rs)-317.7(are)-320.8(experiment)-12.6(ally)]TJ T* [(detect)-9.8(ed)-424.4(as)-431.3(origins)-429.4(of)-430.3(bidirectiona)-10.5(l)-424.6(cappe)-9.2(d)-427.6(transcrip)-9.7(ts)-426.6(using)-428.9(CAG)-9.2(E)-421.7(\(Shi)-7(raki)-430.7(et)-427.2(al.,)-427.9(2003\).)-433(We)-427(took)-426.9(all)]TJ T* [(enhanc)-9.9(ers)-320.2(that)-329(showed)-330.2(at)-324.7(least)-327.1(5)-319.4(CAG)-9.2(E)-319.3(read)-8.6(s)-320.6(i)0(n)-323(liver)-326.1(at)-324.7(emb)-7.6(ryonic)-324.1(day)-328.4(12)-320.2(resu)-8(lting)-325.1(in)-323(only)-324.5(537)-321(regi)-9.6(ons.)]TJ 0 -1.195 TD [(With)-335.5(such)-341.8(a)-332.6(low)-339(detection)-339.2(thr)-7(eshold)-334.7(on)-337.3(the)-336.9(numb)-6.6(er)-335.3(of)-333.6(counts)-340.4(many)-338.4(false)-337.7(positiv)-9.1(es)-334.6(ought)-336.6(to)-334.3(be)-333.4(expec)-9.2(ted.)]TJ 0 -1.2007 TD [(Indeed,)-397.5(about)-395.3(half)-396.5(of)-390.5(the)-399.5(regions)-394.3(did)-397.7(not)-392(show)-395.1(the)-393.8(desired)-401.8(histone)-395.1(modi)-9.3(cation)-394.9(patter)-10(ns.)-390.1(To)-394(lter)-399.3(false)]TJ T* [(positives,)-429.4(we)-428.3(cluste)-9.2(red)-421.5(the)-427.9(enhanc)-9.9(er)-420.7(region)-11.1(s)-423.1(using)-423.2(deepToo)-8.7(ls2)-427.3(\(Ram)]TJ 28.8852 .0398 TD ()Tj .3016 -.0398 TD [(rez)-423.2(et)-427.2(al.,)-427.9(2016\).)-427.3(We)-427(dropped)-424.5(all)]TJ -29.1868 -1.2007 TD [(cluste)-9.2(rs)-277.8(that)-289.2(either)-283.1(show)-8.2(ed)-282.2(no)-286.1(histone)-287(marks)-285.4(or)-282.3(high)-284.7(levels)-288(of)-282.3(H3K4m)-9.5(e3,)-282.5(result)-9.4(ing)-278.2(in)-283.1(265)-286.8(positive)-284.8(regi)-9.6(ons.)]TJ T* 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U/yGY˦ynDYn#شiɛႏƼK|Uo|eui)\42Oo,R[3F-WZ-qV_miz~uy[ͮkڪNqs%"W7HZbv*UثVwc}~cc~Ah>i]P>v܌Ua-y Fo@Ж@yig^CcŤ*1WS/SOUt;hmyt9G^Ԯ*Ƽ]w˖mET[k9 D bӯc r"bF궺jznoKIOMG壄HUTuovDkI<)*⩶*UثWb]v*U endstream endobj 123 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 [(are)-434.6(rarely)-436(observed.)-440(For)-430.3(ChromHM)-10.1(M)-429.5(active)-436.6(promot)-7.1(ers)-428.3(are)-434.6(mode)-8.4(led)-427.9(by)-428.3(sta)-8(te)-427.2(16,)-434.4(which)-433.4(represe)-10.1(nts)-427.3(en-)]TJ 0 -1.195 TD [(ric)-8.8(hment)-273.6(in)-277.4(ATAC-se)-11.3(q,)-274.3(H3K27a)-8.5(c,)-276.1(H3K4me3,)-280.7(and)-277.2(RNA-se)-10.7(q.)-274.3(Howeve)-10.3(r,)-270.6(the)-274.3(regi)-9.6(on)-269(repr)-8.8(esented)-282.1(by)-274.7(this)-271.5(sta)-8(te)]TJ 0 -1.2007 TD [(is)-238.8(muc)-7.6(h)-239.8(narrow)-8.6(er)-238.6(and)-237.4(it)-240.4(is)-238.8(frequent)-10.7(ly)-237.6(anked)-246.4(by)-240.5(a)-235.9(dive)-7.6(rse)-240.6(set)-241.3(of)-236.8(states)-10.4(.)-233.7(One)-241.3(of)-242.5(them)-238.8(is)-238.8(sta)-8(te)-239.4(9,)-240.2(which)-239.9(mode)-8.4(ls)]TJ T* [(enri)-9.6(chment)-367.2(in)-368.5(ATAC)-9.7(-seq,)-366.9(H3K27a)-8.5(c,)-367.1(H3K4m)-9.5(e1,)-362.2(and)-368.3(H3K4m)-9.5(e3.)-367.9(It)-364.8(is)-364(als)-8(o)-365(frequently)-373.5(found)-370(at)-364.6(enhanc)-9.9(ers)]TJ T* [(that)-334.7(show)-326.8(enri)-9.6(chment)-333.1(in)-323(H3K)-10.2(4me3)-327(above)-337.4(the)-325.5(bina)-7.6(rization)-332.9(threshol)-10.9(d)-325.1(set)-326.7(by)-331.6(ChromHM)-10.1(M.)-327.5(The)-328.3(situat)-10.1(ion)-329.4(is)]TJ T* 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[(prom)-8.6(oters)-335.9(typi)-8.6(cally)-337.3(show)-338.2(char)-8.6(acteristic)-11.9(s)-332(o)0(f)-339.2(enhanc)-9.9(ers.)-337.7(Both)-334.9(Chrom)-8.3(HMM)-340.2(and)-339.8(EpiCSeg)-343.7(do)-337.3(not)-335.1(model)-341.9(the)]TJ 0 -1.2007 TD [(spat)-8.8(ial)-481.9(distribut)-9.7(ion)-477.4(of)-481.5(featur)-9.2(es)-482.5(aroun)-7.6(d)-478.8(promot)-7.1(ers)-485.2(and)-482.1(enhancers)-489.5(and,)-482.5(theref)-9.2(ore,)-484.4(often)-482.7(fail)-484.7(to)-482.3(correctly)]TJ T* [(disc)-8.8(riminate)-342.1(between)-341.7(them.)]TJ /F6 1 Tf 10.959 0 0 10.959 74.0976 562.0534 Tm [(3.3.)-502(Bivalent)-327.2(state)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 544.1384 Tm [(During)-303.5(the)-302.7(developm)-10.3(ent)-297.1(of)-299.4(ModH)-8.9(MM,)-296(we)-303.2(observed)-308.7(that)-300.6(the)-297.1(H3K4m)-9.5(e1-to-me3)-305.2(ratio)-303.3(has)-301.2(low)-299.2(predict)-10.7(ive)]TJ -1.0015 -1.2007 TD [(po)-7.2(wer)-328.7(for)-324.9(disc)-8.8(riminating)-333.3(betwee)-10.9(n)-325.1(bivalen)-8.7(t)-322.2(prom)-8.6(oters)-330.2(and)-328.4(poised)-329(enhanc)-9.9(ers.)-332(This)-331.2(led)-325.5(us)-327.1(to)-328.6(represe)-10.1(nt)-323(both)]TJ T* [(chrom)-11.1(atin)-266.4(sta)-8(tes)-269.8(by)-269(a)-270(single)-269.2(biva)-7.6(lent)-272.1(state.)-270.6(To)-268.8(quant)-8.4(ify)-268.8(this)-271.5(observat)-9.9(ion,)-267.2(we)-274.7(consider)-271.7(all)-271.4(biva)-7.6(lent)-266.4(regi)-9.6(ons)-265.2(in)]TJ T* [(the)-382.4(ModHMM)-384.3(segm)-9.6(entation)-382.2(of)-379.1(mouse)-380.2(emb)-7.6(ryonic)-381(liver)-383(at)-376(day)-379.7(12.5.)-378.6(The)-379.5(H3K4)-10.9(me1-to-me3)-383.5(ratio)-383(is)-381.1(then)]TJ T* [(used)-484(to)-476.6(separat)-10.9(e)-474.9(promot)-7.1(ers)-479.6(from)-477.2(the)-479.2(remai)-10(ning)-478.1(regions)-485.4(\(i.e.,)-476.6(puta)-7.6(tive)-477(pois)-7(ed)-475.6(enhanc)-9.9(ers\).)-477(All)-484.1(bivalent)]TJ T* [(regi)-9.6(ons)-356.3(overl)-10.3(apping)-361.9(annotat)-8.7(ed)-361.8(UCSC)-362.8(refGe)-9.6(ne)-356.1(prom)-8.6(oters)-364.3(\(500)-170.1(bp)-360(regions)-365.9(around)-361.2(transcr)-11.1(iption)-360(sta)-8(rt)-359.1(sites\))]TJ 0 -1.195 TD [(are)-343.6(dened)-337.4(as)-340.2(true)-339.6(positives.)-344.1(This)-336.9(leads)-341.4(to)-334.3(an)-339.1(area)-340.4(under)-337.6(the)-336.9(prec)-8.6(ision)-334.9(recall)-341.8(curve)-339.4(\(PR)-8.2(-AUC\))-339(of)]TJ /F9 1 Tf 40.198 0 TD (*)Tj /F1 1 Tf 1.0015 0 TD (0.84.)Tj -41.1996 -1.2007 TD [(Th)-7(e)-292.8(m)0(i)-7.8(nimal)-299.2(PR-AUC)-307.6(achieved)-306.2(by)-297.4(a)-292.8(rando)-7.6(m)-300.2(classier)-305.8(is)]TJ /F9 1 Tf 23.5873 0 TD (*)Tj /F1 1 Tf 1.0015 0 TD [(0.63.)-299(As)-296.9(a)-298.5(com)-7.6(parison,)-303.7(we)-297.5(took)-301.7(all)-294.1(region)-11.1(s)-292.2(o)0(f)]TJ -24.5889 -1.2007 TD [(the)-371(ModHMM)-372.9(segment)-10.7(ation)-363.9(that)-368.9(are)-366.3(either)-374.2(labeled)-369(as)-368.7(active)-368.3(prom)-8.6(oter)-368.1(or)-362(enhanc)-9.9(er.)-364.2(Here,)-371.4(the)-365.3(sam)-8.8(e)-361.1(p)-6.5(ro-)]TJ T* [(cedur)-9.4(e)-332.6(lea)-8.6(ds)-332.8(to)-334.3(a)-332.6(PR-)-8.2(AUC)-339.2(of)]TJ /F9 1 Tf 12.4794 0 TD (*)Tj /F1 1 Tf 1.0015 0 TD [(0.96,)-338.8(wherea)-10.1(s)-332(a)-332.6(rando)-7.6(m)-334.3(classi)-10.3(er)-335.3(achieves)-341.6(a)-338.3(performanc)-11.1(e)-332.6(o)0(f)-339.2(0.46.)]TJ /F6 1 Tf 10.959 0 0 10.959 74.0976 414.5952 Tm [(3.4.)-502(Supervised)-331.2(cross-tissue)-329.9(enhancer)-329.8(predictions)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 396.6802 Tm [(The)-248.6(modular)-243(str)-8.2(ucture)-246.2(of)-242.5(ModHMM)-247.7(allow)-9.4(s)-241(u)0(s)-241.7(t)0(o)-243.3(gradually)-251.2(improv)-7.1(e)-241.6(the)-240.2(segm)-9.6(entation)-245.6(by)-246.2(replacing)-247.3(sing)-7(le)]TJ -1.0015 -1.2007 TD [(cla)-8.6(ssiers)-9(.)-449.9(Here,)-462.5(we)-451.1(graf)-8.8(t)-453.1(a)-452.1(super)-8.8(vised)-453.4(cla)-8.6(ssier)-456.6(into)-458.1(ModHMM)-463.9(that)-454.2(models)-457.7(the)-456.4(shape)-458.1(of)-458.7(features)-463.2(at)]TJ T* [(enhanc)-9.9(ers)-297.5(\(Secti)-9.2(on)-291.7(2.4\).)-295.2(We)-296.1(use)-295.5(the)-297.1(FAN)-9.4(TOM)-298.2(enhancers)-301.7(from)-295.1(emb)-7.6(ryonic)-295.6(liv)-7.8(er)-289.8(at)-296.3(day)-300(12.5)-292.9(as)-294.7(training)-302.7(set)]TJ T* [(and)-356.9(test)-353(the)-354(method)-359.8(on)-354.3(lung)-352.9(at)-353.2(day)-356.9(16.5,)-355.9(for)-353.4(which)-353.7(a)-355.4(validati)-9.3(on)-348.7(set)-355.2(has)-358.1(been)-353.7(gener)-9.4(ated)-350.8(in)-357.1(the)-354(same)-352.8(way)]TJ 0 -1.195 TD [(\(Sect)-11.3(ion)-335.1(3.1\).)]TJ 1.0015 -1.2007 TD [(Typic)-8.2(ally)-283.5(there)-279.6(is)-278.6(muc)-7.6(h)-279.6(variabilit)-9.9(y)-279.6(between)-284.8(data)-282.5(sets,)-283.5(which)-285.4(prevent)-286.8(a)-275.7(direct)-283.1(appl)-7.6(ication)-284.6(of)-276.7(the)-285.7(model)-279.3(to)]TJ -1.0015 -1.2007 TD [(dif)-7(ferent)-373.4(tissues.)-369.4(In)-367.7(mos)-7(t)-362(case)-9.6(s)-366.2(i)0(t)-365.6(would)-374.7(be)-367.5(necessar)-11.9(y)-365(t)0(o)-368.5(re-estimat)-12.9(e)-366.7(the)-365.3(para)-8.6(meters)-370.4(of)-367.7(the)-371(single-fe)-9.7(ature)]TJ T* [(cla)-8.6(ssiers)-9(.)-324.7(Owing)-333.1(to)-323(the)-331.2(uniform)-334.3(experimental)-337.4(protocol)-9.7(s)-326.3(and)-328.4(processi)-11.1(ng)-325.9(steps)-329.4(of)-327.9(ENCO)-9.8(DE)-329.6(data)-328.1(we)-331.6(may,)]TJ T* [(ho)-7.2(wever,)-247(skip)-251.7(this)-248.8(step.)-248.2(Still,)-247.8(there)-251.1(remain)-249.7(som)-7(e)-241.6(sta)-8(tistical)-252.3(difference)-12.1(s)-246.7(between)-250.7(the)-251.5(data)-248.4(sets)-249(that)-249.4(we)-246.3(remove)]TJ T* [(by)-280.4(quantile)-285.4(normaliz)-9.3(ing)-278.2(\(Ama)-8.6(ratunga)-281.1(and)-277.2(Ca)-8(brera,)-279.2(2001;)-279.7(Bolst)-9.6(ad)-276.5(et)-279.2(al.,)-280(2003\))-278.9(the)-280(coverage)-288.4(values)-279.6(of)-276.7(each)]TJ T* [(featur)-9.2(e.)]TJ 1.0015 -1.2007 TD [(To)-354.2(establish)-356.8(a)-355.4(baseline,)-360(we)-348.7(rst)-355.3(tested)-356.3(how)-353.3(well)-355.7(ModH)-8.9(MM)-352.6(with)-353.9(its)-350.4(defa)-8.6(ult)-349.2(chromat)-11.5(in)-351.4(state)-355.5(classi)-10.3(ers)]TJ -1.0015 -1.195 TD [(perf)-8.8(orms)-294.3(across)-297(tissue)-8.6(s.)-292.6(We)-290.4(als)-8(o)-291(trained)-295.2(a)-292.8(Chrom)-8.3(HMM)-294.7(and)-294.3(EpiCSeg)-298.2(mode)-8.4(l)-288.1(o)0(n)-291.7(data)-299.6(from)-295.1(embryonic)-297.5(lung)]TJ 0 -1.2007 TD [(at)-256.5(day)-254.5(16.5.)-253.4(Howeve)-10.3(r,)-253.5(we)-257.6(kept)-252.3(for)-256.6(both)-250.5(method)-12.6(s)-246.6(the)-257.2(numb)-6.6(er)-250(of)-253.9(states)-260.7(that)-255.1(was)-253.9(optim)-7.2(al)-256.5(for)-250.9(the)-257.2(liver)-252.1(data)-259.8(set.)]TJ T* [(Compa)-8.1(red)-347.5(with)-342.6(the)-342.6(liver)-343.1(data,)-345.5(the)-342.6(classi)-10.4(cation)-343.7(perf)-8.8(ormance)-346.2(of)-339.2(ModH)-8.9(MM)-341.2(droppe)-8.3(d)-342.2(slightly,)-343.1(but)-346.5(also)-344.5(the)]TJ T* [(op)-7.2(timal)-347.5(com)-7.6(bination)-351.9(of)-344.9(sta)-8(tes)-343.8(for)-353.4(ChromHM)-10.1(M)-344.2(and)-351.2(EpiCSeg)-355.1(showed)-352.9(a)-344(muc)-7.6(h)-347.9(lower)-350(classi)-10.4(cation)-349.4(perf)-8.8(or-)]TJ T* [(man)-7.6(ce)-249.8(\(Fig)-7(.)-245.1(9A\))-8.2(.)-245.1(Nex)-8(t,)-248.6(we)-251.9(tested)-259.6(the)-251.5(classicat)-13.3(ion)-249.7(performanc)-11.1(e)-252.9(o)0(f)-248.2(the)-251.5(super)-8.8(vised)-254.2(shape)-253.3(classi)-10.3(er)-250(for)-250.9(which)]TJ T* [(we)-348.7(used)-341.8(a)-344(window)-350.9(size)-346.3(of)-339.2(10)-343(bins)-348.4(and)-345.5(ATAC-se)-11.3(q,)-342.6(H3K27a)-8.5(c,)-338.7(H3K)-10.2(4me1,)-344.5(and)-345.5(H3K4m)-9.5(e3/1)-343.3(as)-345.9(well)-344.3(as)-345.9(the)]TJ T* [(cont)-7.6(rol)-365.5(data)-362.2(as)-363(featur)-9.2(es.)-363.4(In)-362(gener)-9.4(al,)-365(the)-359.7(perf)-8.8(ormance)-369(of)-362(the)-365.3(shape)-367.1(classi)-10.4(er)-363.8(is)-364(better)-362.8(than)-366.1(the)-365.3(engi)-7.6(neered)]TJ T* [(cla)-8.6(ssier)-263.1(\(Fig.)-263.5(9B\).)-259.7(Integra)-9.9(ted)-257.2(into)-259(ModH)-8.9(MM)-261.5(the)-257.2(perf)-8.8(ormance)-266.6(stays)-261.1(appro)-7.6(ximatel)-9.3(y)-256.8(the)-257.2(sam)-8.8(e,)-259(showing)-263.6(that)]TJ 0 -1.195 TD [(othe)-7.6(r)-332.8(classi)-10.4(ers)-337.3(do)-331.6(not)-335.1(interf)-10.1(ere.)]TJ /F6 1 Tf 10.959 0 0 10.959 74.0976 135.6661 Tm [(3.5.)-502(Data)-328.9(preparation)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 117.7511 Tm [(ENCO)-9.7(DE)-284.1(BAM)-280.3(acce)-10.2(ssion)-282.1(numb)-6.6(ers)-280.4(are)-286.7(given)-281.5(in)-283.1(Table)-283.1(2.)-280(For)-282.3(emb)-7.6(ryonic)-284.2(lung)-279(at)-284.9(day)-282.9(16.5)-281.5(no)-280.4(ATAC)-9.8(-seq)]TJ -1.0015 -1.2007 TD [(BAM)-263.3(les)-252.7(were)-262.9(available)-10.9(.)-250.8(W)0(e)-256.2(down)-7(loaded)-261.3(fastq)-256.2(les)-258.4(from)-255.2(ENCO)-9.7(DE)-255.7(with)-257.2(accession)-263.8(nos.)-254.2(ENCFF)-10.7(577XAL,)]TJ T* [(ENC)-10.7(FF224TA)-7.5(O,)-289.6(ENCFF)-10.7(872IZI,)-293.2(and)-294.3(ENCFF427H)-12(TC.)-291(Bowt)-8.8(ie2)-291.4(\(Langmea)-11.1(d)-285.3(and)-294.3(Salzb)-9.4(erg,)-291(2012\))-290.3(was)-293.7(used)]TJ T* [(to)-283.1(align)-284.3(read)-8.6(s)-280.8(t)0(o)-277.4(the)-285.7(refere)-10.2(nce)-284.7(genome)-284.8(mm10.)-289.3(Picard)-285.2(and)-282.9(samtoo)-8.2(ls)-278.6(\(Li)-285.7(et)-279.2(al.,)-285.7(2009\))-284.6(were)-285.7(used)-284.9(to)-283.1(mark)-283.5(and)]TJ T* [(lt)-7(er)-335.3(duplica)-8.7(tes.)]TJ /F2 1 Tf 0 67.0005 TD [(12)-30377.7(BEN)-10(NER)-339.2(AND)-338.4(VINGR)-8.9(ON)]TJ ET endstream endobj 127 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 117.5811 547.5967 Tm 0 0 0 rg 0 Tc 0 Tw [(ENCODE)-248.3(data)-248.4(are)-246.8(availa)-9.8(ble)-240.2(as)-243.5(either)-249(sing)-7(le-)-242.1(or)-242.5(paired-)-9.9(end.)-243.5(ATA)-10(C-seq)-246.8(data)-242.7(wer)-10(e)-241.6(generat)-9.7(ed)-242.3(using)-246.8(paired-)]TJ -1.0015 -1.2007 TD [(end)-368.3(seque)-8.6(ncing;)-370.4(however)-9.1(,)-364.6(since)-375.5(we)-365.7(are)-372(only)-370(interest)-9.7(ed)-367.5(in)-362.8(acce)-10.2(ssible)-372.8(regions)-371.6(we)-371.4(treated)-371(it)-365.6(as)-368.7(sing)-7(le)-364.6(end.)]TJ T* [(For)-333.5(histone)-338.2(modica)-8.7(tions)-334.9(single-end)-338.6(seque)-8.6(ncin)-7.6(g)-330.8(was)-333.6(used.)-336.5(We)-335.9(processe)-10.1(d)-330.8(this)-334.1(data)-333.7(by)-331.6(rst)-338.2(estimating)-339.9(the)]TJ T* [(fragme)-9.9(nt)-277.4(leng)-7.6(th)-283.1(with)-285.7(a)-281.4(cross-c)-9.6(orrelation)-290.9(analysis)-290.7(of)-282.3(forward)-284.4(and)-288.6(reverse)-289(strand)-285.4(read)-8.6(s.)-281.2(Afterw)-9.6(ard,)-279.6(read)-8.6(s)-280.8(are)]TJ T* [(extended)-350(in)-345.7(3)]TJ /F7 1 Tf 6.9738 0 0 6.9738 163.3889 503.3763 Tm (0)Tj /F1 1 Tf 9.9626 0 0 9.9626 169.1716 499.7479 Tm [(direct)-10(ion)-340.8(to)-345.7(match)-349.4(the)-342.6(estimat)-10.5(ed)-344.7(fragme)-9.9(nt)-340(leng)-7.6(th.)-340.4(No)-346.9(special)-347.5(proce)-9.4(ssing)-344.7(of)-344.9(RNA)-9.2(-seq)-343.8(data)]TJ -6.1799 -1.2007 TD [(was)-339.2(required.)]TJ 1.0015 -1.195 TD [(The)-265.7(coverage)]TJ /F6 1 Tf 5.719 0 TD (C)Tj 7.4718 0 0 6.641 181.1905 474.1794 Tm (n)Tj /F1 1 Tf 9.9626 0 0 9.9626 187.5968 475.8802 Tm [(of)-259.6(each)-270.2(featur)-9.2(e)-264.3(i)0(s)-261.6(com)-7.6(puted)-264.4(by)-263.3(rst)-270(tiling)-266(the)-262.9(genom)-9.1(e)-264.3(into)-264.7(a)-264.3(set)-264.1(of)-265.3(bins)-263.1(of)-265.3(size)]TJ /F6 1 Tf 31.702 0 TD (n)Tj /F1 1 Tf .5008 0 TD [(.)-262.1(G)0(i)-8.2(ven)]TJ -40.2322 -1.2007 TD [(a)-326.9(set)-326.7(of)-327.9(reads)]TJ /F6 1 Tf 5.8157 0 TD (R)Tj /F1 1 Tf .6146 0 TD [(,)-324.7(for)-330.6(each)]TJ /F6 1 Tf 4.2451 0 TD (r)Tj /F7 1 Tf .6942 0 TD (2)Tj /F6 1 Tf .9333 0 TD (R)Tj /F1 1 Tf .9389 0 TD [(the)-331.2(value)-328.8(of)-327.9(all)-328.3(bins)-325.7(that)-329(overlap)-332.3(with)]TJ /F6 1 Tf 15.8425 0 TD (r)Tj /F1 1 Tf .7113 0 TD [(is)-324.2(increm)-10.7(ented)-328.8(by)-325.9(the)-331.2(number)-330.5(of)]TJ -29.7957 -1.2007 TD [(overlapp)-8.7(ing)-272.5(nucleot)-8.7(ides.)-270.9(The)-271.3(nal)-274.3(coverage)-277(is)-272.9(the)-268.6(total)-275.7(number)-273.6(of)-271(overlapp)-8.7(ing)-272.5(nucleot)-8.7(ides)-270.6(for)-268(all)-271.4(read)-8.6(s)-269.4(per)]TJ T* [(bin)-261.1(size)]TJ /F6 1 Tf 3.3688 0 TD (n)Tj /F1 1 Tf .5008 0 TD [(.)-256.5(T)0(h)-7(e)-258.6(advantage)-272.8(of)-259.6(this)-260.2(binnin)-10.1(g)-256.8(scheme)-270.7(is)-261.6(that)-260.7(a)-264.3(coverage)]TJ /F6 1 Tf 23.3768 0 TD (C)Tj 7.4718 0 0 6.641 385.7385 438.3495 Tm (m)Tj /F1 1 Tf 9.9626 0 0 9.9626 393.6755 439.9936 Tm [(with)-262.9(bin)-261.1(siz)-8(e)]TJ /F6 1 Tf 5.4117 0 TD (m)Tj /F1 1 Tf .9788 0 TD [(can)-261.9(be)-265.1(compute)-9.5(d)-256.8(b)0(y)]TJ -35.105 -1.2007 TD [(increas)-10.9(ing)-335.1(the)-336.9(bin)-335.1(size)-334.9(of)-339.2(another)-338(cover)-9.4(age)]TJ /F6 1 Tf 18.0277 0 TD (C)Tj 7.4718 0 0 6.641 293.8393 426.3873 Tm (n)Tj /F1 1 Tf 9.9626 0 0 9.9626 300.9259 428.0314 Tm [(as)-334.6(long)-335.9(as)]TJ /F6 1 Tf 4.45 0 TD (m)Tj /F1 1 Tf 1.0528 0 TD [(is)-335.5(a)-338.3(multiple)-341.1(of)]TJ /F6 1 Tf 6.6466 0 TD (n)Tj /F1 1 Tf .5008 0 TD (.)Tj -31.0533 -1.2007 TD [(The)-368.1(featur)-9.2(e)-361.1(H3K)-10.2(4me3/1)-371.2(was)-367.7(com)-7.6(puted)-366.9(from)-369(the)-371(coverages)-375.7(of)-367.7(H3K4m)-9.5(e1)-367.5(and)-368.3(H3K4me3.)-371.7(At)-372.4(bin)]TJ /F6 1 Tf 40.3175 0 TD (t)Tj /F1 1 Tf .6487 0 TD (the)Tj -41.9678 -1.2007 TD [(ratio)-337.5(is)-335.5(given)-338.4(by)]TJ /F6 1 Tf 12.9688 -2.612 TD (z)Tj 6.9738 0 0 6.9738 240.6613 376.6109 Tm (t)Tj /F5 1 Tf 9.9626 0 0 9.9626 244.9133 378.085 Tm (=)Tj /F1 1 Tf .7227 0 TD [(round)-734.2(10)]TJ /F7 1 Tf 4.2907 0 TD ()Tj ET 299.792 380.409 72.057 .39685 re f BT /F6 1 Tf 9.9626 0 0 9.9626 306.7086 384.8881 Tm (x)Tj 6.9738 0 0 6.9738 311.1873 383.3574 Tm (t)Tj /F5 1 Tf .4634 0 TD (-)Tj /F1 1 Tf .7235 0 TD (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 325.0771 384.8881 Tm (+)Tj /F6 1 Tf .7227 0 TD (x)Tj 6.9738 0 0 6.9738 336.7558 383.3574 Tm (t)Tj /F5 1 Tf 9.9626 0 0 9.9626 341.0078 384.8881 Tm (+)Tj /F6 1 Tf .7227 0 TD (x)Tj 6.9738 0 0 6.9738 352.6298 383.3574 Tm (t)Tj /F5 1 Tf .4715 0 TD (+)Tj /F1 1 Tf .7235 0 TD (1)Tj /F6 1 Tf 9.9626 0 0 9.9626 299.7921 371.2818 Tm (y)Tj 6.9738 0 0 6.9738 304.2708 369.7511 Tm (t)Tj /F5 1 Tf .4634 0 TD (-)Tj /F1 1 Tf .7235 0 TD (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 318.2172 371.2818 Tm (+)Tj /F6 1 Tf .717 0 TD (y)Tj 6.9738 0 0 6.9738 329.8393 369.7511 Tm (t)Tj /F5 1 Tf 9.9626 0 0 9.9626 334.0912 371.2818 Tm (+)Tj /F6 1 Tf .7227 0 TD (y)Tj 6.9738 0 0 6.9738 345.77 369.7511 Tm (t)Tj /F5 1 Tf .4634 0 TD (+)Tj /F1 1 Tf .7235 0 TD (1)Tj /F5 1 Tf 9.9626 0 0 9.9626 359.6598 371.2818 Tm (+)Tj /F1 1 Tf .7227 0 TD (1)Tj ET 373.493 380.409 23.017 .39685 re f BT /F12 1 Tf 9.9626 0 0 9.9626 373.4928 392.3716 Tm (P)Tj /F6 1 Tf 6.9738 0 0 6.9738 383.981 382.0534 Tm (s)Tj 9.9626 0 0 9.9626 388.8566 384.8881 Tm (y)Tj 6.9738 0 0 6.9738 393.2786 383.4141 Tm (s)Tj /F12 1 Tf 9.9626 0 0 9.9626 373.4928 378.7653 Tm (P)Tj /F6 1 Tf 6.9738 0 0 6.9738 383.981 368.4471 Tm (s)Tj 9.9626 0 0 9.9626 388.8566 371.2818 Tm (x)Tj 6.9738 0 0 6.9738 393.2786 369.7511 Tm (s)Tj /F12 1 Tf 9.9626 0 0 9.9626 275.4141 392.1448 Tm 11.426 Tc ()Tj /F1 1 Tf 12.8834 -1.4113 TD 0 Tc ()Tj -29.7274 -2.629 TD (where)Tj /F7 1 Tf 2.7827 0 TD (f)Tj /F6 1 Tf .5008 0 TD (x)Tj 6.9738 0 0 6.9738 144.7936 350.4188 Tm (t)Tj /F7 1 Tf 9.9626 0 0 9.9626 147.4015 351.8928 Tm (g)Tj /F1 1 Tf .8365 0 TD [(are)-337.9(the)-336.9(coverage)-339.6(valu)-7.6(es)-334.6(of)-333.6(H3K4)-10.9(me3)-337.7(and)]TJ /F7 1 Tf 17.4529 0 TD (f)Tj /F6 1 Tf .5008 0 TD (y)Tj 6.9738 0 0 6.9738 339.0802 350.4188 Tm (t)Tj /F7 1 Tf 9.9626 0 0 9.9626 341.6881 351.8928 Tm (g)Tj /F1 1 Tf .8308 0 TD [(thos)-7(e)-332.6(o)0(f)-333.6(H3K)-10.2(4me1.)]TJ /F2 1 Tf 10.959 0 0 10.959 282.6708 316.0629 Tm [(4.)-496.7(DISCUSSION)]TJ /F1 1 Tf 9.9626 0 0 9.9626 117.5811 292.1385 Tm [(Traditiona)-9.9(l)-248.2(genome)-256.4(segmentat)-11.1(ion)-249.7(methods)-8.9(,)-245.1(such)-250.7(as)-249.2(Chr)-9(omHMM)-9.5(,)-245.1(EpiCSeg,)-258.7(or)-248.2(Segway,)-256.4(are)-252.5(unsupervi)-8.9(sed)]TJ -1.0015 -1.2007 TD [(methods)-475.5(and)-465(can)-472.5(be)-469.9(used)-472.7(to)-465.2(detect)-470.7(k)-6.5(nown)-467.9(and)-470.7(unknow)-8.5(n)-461.7(patter)-10(ns)-469.3(in)-465.2(genom)-9.1(ics)-469(data.)-470.7(They)-471.3(have)-473.3(been)]TJ T* [(extensi)-9.9(vely)-297.8(used)-301.9(in)-294.5(the)-297.1(past)-304.7(to)-294.5(analyze)-305.5(the)-297.1(epig)-7.6(enetic)-300(land)-7.6(scape)-300.6(of)-299.4(a)-292.8(larg)-9.6(e)-292.8(variet)-10(y)-296.7(o)0(f)-293.7(cel)-8.6(l)-293.7(types)-299.8(and)-300(tissue)-8.6(s)]TJ T* [(\(Hoff)-8(man)-280.7(et)-284.9(al.,)-280(201)-8(2b;)-278.2(Kund)-7(aje)-281.8(et)-284.9(al.,)-285.7(2015;)-279.7(Ernst)-288.4(and)-282.9(Kell)-8.6(is,)-279(2017\).)-285(Howeve)-10.3(r,)-282(nowa)-8.8(days)-284.9(much)-281.5(is)-284.3(known)]TJ 0 -1.195 TD [(about)-332.7(the)-325.5(epig)-7.6(enetic)-328.4(land)-7.6(scape)-334.7(and)-328.4(the)-325.5(featur)-9.2(es)-328.9(that)-329(mark)-329(regulat)-10.7(ory)-328.6(elements)-10.3(.)-324.7(This)-331.2(extensive)-331.9(kn)-7.2(owledge)]TJ 0 -1.2007 TD [(questio)-8.2(ns,)-316.1(at)-319.1(least)-321.4(to)-311.6(som)-7(e)-315.5(extent,)-321.3(the)-319.8(traditi)-8.8(onal)-314.9(appro)-7.6(ach)-318.8(to)-317.3(genome)-324.7(segmentat)-11.1(ion.)-318.4(Instead,)-322.5(we)-314.5(used)-324.7(this)]TJ T* [(know)-7(ledge)-271.9(to)-277.4(construct)-280.9(a)-270(segment)-10.7(ation)-272.9(method)-280.1(that)-272.1(outpe)-8.4(rform)-7.6(s)-269.4(the)-274.3(traditi)-8.8(onal)-275.1(methods)-276.4(in)-271.7(sever)-10.6(al)-273.5(aspects.)]TJ ET q 300.076 0 0 106.072 172.743 616.195 cm /Im9 Do Q BT /F2 1 Tf 8.9663 0 0 8.9663 107.6031 600.2077 Tm [(FIG.)-315.8(9.)]TJ /F1 1 Tf 4.0972 0 TD [(Cross-tissue)-316.5(predictive)-320.5(performance.)]TJ /F2 1 Tf 15.175 0 TD (\(A\))Tj /F1 1 Tf 1.7009 0 TD [(Predictive)-319.1(performance)-319.1(of)-317.8(ModHMM,)-315.2(ChromHMM,)-318.1(and)-317.1(EpiCSeg)]TJ -20.9731 -1.2203 TD [(on)-403.7(data)-405.2(from)-411.5(embryonic)-402.6(lung)-406.7(at)-410.1(day)-405.6(16.5.)]TJ /F2 1 Tf 18.1151 0 TD (\(B\))Tj /F1 1 Tf 1.7388 0 TD [(ModHMM)-407.1(performance)-407.7(on)-410(lung)-400.4(at)-410.1(day)-405.6(16.5)-406.1(with)-407.7(supervised)-407.3(shape)]TJ -19.8539 -1.2266 TD (classier.)Tj ET 107.603 184.139 430.356 .51024 re f 107.603 70.583 430.356 .51025 re f 107.603 165.713 430.356 .51022 re f BT /F3 1 Tf 8.9663 0 0 8.9663 223.8802 190.3181 Tm (Table)Tj /F1 1 Tf 3.0034 0 TD (2.)Tj /F3 1 Tf 1.2456 0 TD [(ENCODE)-340.1(BAM)-336(File)-329.4(Accession)-338.8(Numbers)]TJ /F6 1 Tf -3.0729 -2.0233 TD [(Embryonic)-331.2(liver)-340.4(day)-329.7(12.5)-11262.6(Embryonic)-337.6(lung)-337.2(day)-329.7(16.5)]TJ /F1 1 Tf -14.1444 -2.0802 TD [(ATAC)-9449.3(ENCFF929LOH,)-331.4(ENCFF848NLJ)-14812.2()]TJ 0 -1.2203 TD [(H3K27ac)-8335.3(ENCFF524ZFV,)-333(ENCFF322QGS)-8230.9(ENCFF431CSN,)-338(ENCFF149TQU)]TJ T* [(H3K27me3)-7501.3(ENCFF811DWT,)-336.4(ENCFF171KAM)-7499.6(ENCFF079QHR,)-336.4(ENCFF788UXL)]TJ T* [(H3K4me1)-8001.3(ENCFF788JMC,)-331.6(ENCFF340ACH)-8066.4(ENCFF151AXQ,)-334.9(ENCFF440VFN)]TJ 0 -1.2266 TD [(H3K4me3)-8001.3(ENCFF211WGC,)-335(ENCFF587PZE)-7990(ENCFF844DSD,)-336.5(ENCFF437ESL)]TJ 0 -1.2203 TD [(H3K9me3)-8001.3(ENCFF293UCG,)-336.4(ENCFF777XFH)-8009.6(ENCFF740KNN,)-334.9(ENCFF380FIJ)]TJ T* [(RNA)-10063.3(ENCFF405LEY,)-334.3(ENCFF627PCS)-8385.7(ENCFF502KFQ,)-336.5(ENCFF371ONT)]TJ 0 -1.2266 TD [(Control)-9104.3(ENCFF865QGZ,)-331.4(ENCFF438RYK)-7952.5(ENCFF018HYW,)-333.6(ENCFF855ISH)]TJ /F2 1 Tf 9.9626 0 0 9.9626 107.6031 737.4045 Tm (M)Tj 7.1731 0 0 7.1731 117.0708 737.4045 Tm 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V]W~])柩~/?}G_Spx銤>ZmjusN)AD~?@ Xzv劲}k+ VcbOGվJzp'By1ƇW6R\ K׏~L~rVڸۯK(u揪l\[zDOpU%uA~o\}럼7VW\Uv<?S~>ilU[v*UثWb]v*UثWb]v*UثWb]v*UثWb]_=KLr#?ўNz<\_1U/8,>y~TruDBdA}g"?8|\bHkΩi#A>n=$_T>/UI?]gEϡXyƿX)•U/OR:Z_?T}C_T?GzXy/=_Д/}Pvxzv^*|/a揪~W$}O)*1Wb]v*UثWb] endstream endobj 132 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 [(ModH)-8.9(MM)-426.5(has)-426.4(a)-423.7(highe)-8.4(r)-423.8(predictio)-9.3(n)-421.9(accuracy)-438.1(and)-425.2(the)-427.9(segmentat)-11.1(ions)-422.4(show)-429.3(a)-423.7(better)-431.1(balance)-430.7(of)-424.6(p)-6.5(recision)]TJ 0 -1.195 TD [(and)-243.1(re)17.5(ca)17.7(ll)15.7(.)-228(W)0(i)21.6(t)0(h)-220.5(e)0(a)17.7(c)0(h)-219.6(h)0(i)18.5(d)0(d)15.5(e)0(n)-219.6(s)0(t)17.3(a)0(t)22.4(e)-230.2(of)-219.7(Mo)19.3(dH)17.3(MM)-221.7(a)-230.2(c)0(l)16.7(a)0(s)18.3(s)0(i)17.3()11.4(er)-221.5(is)-216(as)18.3(so)14.4(ci)16.7(at)16.7(ed)-219.6(t)13.5(h)0(a)13.8(t)-225.5(de)19.4(te)16.7(ct)16.7(s)-229.6(a)-224.5(we)15.5(ll)15.7(-d)19.3(e)14.5(ne)19.4(d)-228.4(c)0(h)19.4(r)0(o)19.3(m)0(a)15.9(t)0(i)15.7(n)]TJ 0 -1.2007 TD [(st)17.3(at)16.7(e.)-264.7(Th)15.7(is)-261.6(le)16.7(ad)13.8(s)-269.4(t)0(o)-266.1(s)0(e)18.3(g)0(m)17.7(e)0(n)13.8(t)0(a)16.7(t)13.5(io)12.8(ns)-264.5(t)13.5(h)0(a)13.8(t)-271(ar)17.5(e)-275.7(s)0(u)20(p)0(e)13.8(r)0(i)22.2(o)0(r)-265.3(i)0(n)-266.1(q)0(u)15.5(a)0(l)22.4(i)0(t)15.7(a)0(t)16.7(i)0(v)18.5(e)-275.7(as)18.3(pe)19.4(ct)16.7(s.)-264.1(Fu)16.3(nc)19.4(ti)15.7(on)21.2(al)-267.8(el)16.7(em)15.9(en)19.4(ts)17.3(,)-273.5(s)0(u)20(c)0(h)-265.1(a)0(s)-266.3(a)0(c)17.7(t)0(i)15.7(v)0(e)]TJ T* [(pr)13.6(om)17.7(ot)18.5(er)17.5(s)-314.9(o)0(r)-305.1(e)0(n)19.4(h)0(a)19.5(n)0(c)13.8(e)0(r)17.5(s)0(,)-303.9(a)0(r)17.5(e)-315.5(t)13.5(y)0(p)15.5(i)0(c)16.7(a)0(l)16.7(l)13.5(y)-313.7(c)0(o)13.8(n)0(t)18.5(a)0(i)16.7(n)0(e)19.4(d)-313.7(in)-305.9(a)-315.5(s)0(i)23(n)0(g)15.5(l)0(e)-307.7(s)0(e)18.3(g)0(m)17.7(e)0(n)19.5(t)0(,)-305.5(w)0(h)17.3(i)0(c)16.7(h)-313.7(is)-301.4(no)15.5(t)-310.8(t)0(h)12.8(e)-309.8(ca)12(se)-300.4(fo)13.6(r)-310(C)0(h)16.5(r)0(o)19.3(m)0(H)13.8(M)0(M)]TJ T* [(an)-9(d)-330.8(E)0(p)-7(iCS)-9(eg.)]TJ 1.0015 -1.2007 TD [(Inspire)-9.3(d)-353.6(b)0(y)-348.7(the)-359.7(supra-Baye)-11.5(sian)-355.9(appro)-7.6(ach,)-353.4(ModH)-8.9(MM)-352.6(integr)-8.2(ates)-357.7(predictio)-9.3(ns)-349.8(o)-6.5(f)-349.9(a)-355.4(set)-355.2(of)-350.6(exper)-9.4(ts)-352.6(or)-350.6(clas-)]TJ -1.0015 -1.2007 TD [(sie)-8(rs.)-238.4(Using)-245(the)-240.2(outpu)-6.6(t)-236.8(o)0(f)-236.8(classi)-10.4(ers)-240.5(as)-237.8(input)-242.6(to)-237.6(the)-240.2(HM)-7.4(M)-236(has)-244.3(certain)-245.8(advantage)-11.1(s)-235.3(o)-6.5(ver)-239.4(classical)-246.6(HM)-7.4(Ms)-238(that)]TJ T* [(mode)-8.4(l)-305.1(obser)-8.8(vations)-309.7(direct)-10(ly.)-306.3(For)-310.8(instance,)-314.5(a)-304.2(cla)-8.6(ssier)-308.6(may)-314.9(cherry-pic)-10.3(k)-308.1(only)-307.4(a)-304.1(subse)-8(t)-305.1(o)0(f)-310.8(the)-308.4(availa)-9.8(ble)-308.4(data.)]TJ T* [(Th)-7(e)-355.4(cover)-9.4(age)-358.7(of)-362(RNA-se)-10.7(q)-353.6(read)-8.6(s)-354.8(i)0(n)-362.8(a)-355.4(sing)-7(le)-358.9(genom)-9.1(ic)-358.9(bin)-357.9(already)-368.2(provides)-360.9(enough)-364.9(inform)-9.1(ation)-358.2(to)-362.8(decide)]TJ 0 -1.195 TD [(whe)-8(ther)-260(the)-257.2(region)-261.5(is)-255.9(transcrib)-9.7(ed.)-254.1(In)-259.6(contras)-9.1(t,)-254.3(classi)-10.3(cation)-258.4(of)-259.6(active)-260.2(promot)-7.1(ers)-257.6(and)-260.2(enhancers)-261.9(requi)-10.3(res)-257.6(data)]TJ 0 -1.2007 TD [(from)-340.6(multipl)-8.5(e)-332.6(featur)-9.2(es)-334.6(and)-334.1(sever)-10.5(al)-336.1(surroundi)-9.1(ng)-331.6(bins)-7(.)]TJ 1.0015 -1.2007 TD [(ModH)-8.9(MM)-329.8(uses)-331.6(a)-332.6(default)-335.1(set)-332.4(of)-327.9(engineer)-10.5(ed)-327.7(cla)-8.6(ssiers)-333.3(to)-328.7(dete)-9.4(ct)-324.7(chrom)-11.1(atin)-329(states)-10.4(.)-324.7(T)0(h)-7(e)-326.9(basis)-335.1(of)-327.9(which)-336.7(is)]TJ -1.0015 -1.2007 TD [(a)-463.5(single-fe)-9.7(ature)-461.7(enrichment)-467.9(analysi)-9.9(s)-457.2(with)-462.1(a)-457.8(mixture)-462(mode)-8.4(l)-453.1(tail)-7.4(ored)-462.1(to)-459.5(each)-458(featur)-9.2(e.)-458.2(This)-462.1(is)-460.7(unique)-458.7(to)]TJ T* [(ModH)-8.9(MM)-267.2(as)-260.6(mos)-7(t)-259.6(peak)-268.4(callin)-10.7(g)-262.5(methods)-265(im)-7.8(plement)-268.3(a)-264.3(single)-269.2(model.)-268.3(Applying)-265.9(ModH)-8.9(MM)-267.2(to)-260.4(a)-264.3(new)-264.1(d)-6.5(ata)-264.7(set)]TJ T* [(requi)-10.3(res)-337.3(to)-334.3(perform)-340.9(the)-336.9(enrichm)-11.5(ent)-336.9(analysi)-9.9(s)-332(d)0(e)-339.1(novo.)-339.2(Alternati)-10.3(vely,)-338(ModH)-8.9(MM)-335.5(may)-337.7(quant)-8.4(ile)-334(norm)-8.6(alize)-339.1(a)]TJ T* [(new)-440.5(data)-441.9(set)-434.8(to)-436.8(a)-440.7(known)-440.2(reference)-442.8(for)-438.7(which)-444.8(single-fe)-9.7(ature)-438.9(mode)-8.4(ls)-432.3(already)-442.2(exis)-8.8(t.)-436.4(We)-438.3(have)-439.1(shown)-441.4(on)]TJ T* [(dif)-7(ferent)-270.9(tissues)-266.6(that)-272.1(this)-265.8(approach)-275.2(leads)-267.4(to)-266.1(good)-264.8(resu)-8(lts.)-265.5(Unlike)-271.9(ChromHM)-10.1(M)-264.5(and)-265.8(EpiCSeg,)-275.8(ModHMM)-270.4(has)]TJ 0 -1.195 TD [(well)-8.6(-dene)-9.3(d)-234.1(hidde)-8.4(n)-234.1(states)-243.7(that)-238(do)-240.5(not)-238.4(change)-243.2(when)-242.1(applied)-242.1(across)-245.8(different)-243.8(cell)-239.8(types)-242.9(or)-236.8(tissue)-8.6(s.)-235.6(This)-240.1(makes)]TJ 0 -1.2007 TD [(ModH)-8.9(MM)-335.5(idea)-9.4(l)-333.6(for)-336.3(differentia)-10.9(l)-333.6(analysi)-9.9(s.)]TJ 1.0015 -1.2007 TD [(Compa)-8.1(red)-302(with)-302.7(traditional)-306.6(segment)-10.7(ation)-301.3(methods)-8.9(,)-296.3(ModHMM)-304.6(is)-301.4(much)-304.3(more)-300.6(exib)-7.6(le)-296.3(and)-300(provi)-8.6(des)-295.5(man)-7.6(y)]TJ -1.0015 -1.2007 TD [(leve)-9.4(rage)-281.7(points)-284.4(to)-277.4(const)-9.6(ruct)-282.7(high-quali)-8.3(ty)-277.4(segm)-9.6(entations.)-287.7(For)-276.6(instanc)-9.9(e,)-281.8(any)-282.9(of)-276.7(the)-280(chrom)-11.1(atin)-277.8(sta)-8(te)-279.2(classi)-10.3(ers)]TJ T* [(from)-255.2(the)-251.5(default)-255.4(set)-252.7(can)-250.6(be)-253.7(replaced)-257(by)-251.9(more)-249.3(accur)-11.1(ate)-247.6(alter)-9.2(natives,)-255(allow)-9.4(ing)-249.7(to)-249(incorpor)-8.9(ate)-253.3(predictio)-9.3(ns)-247.4(from)]TJ T* [(sta)-8(te-of-the)-10.5(-art)-284.7(methods)-287.7(such)-284.9(as)-283.3(REPTI)-9.3(LE)-280(\(H)-7.4(e)-281.4(e)0(t)-279.2(al.,)-285.7(2017\).)-285(To)-285.9(improv)-7.1(e)-281.4(a)-281.4(given)-287.2(segmentat)-11.1(ion,)-284.3(ModHMM)]TJ T* [(allow)-9.4(s)-332(visual)-331.7(insp)-7(ection)-338(of)-327.9(all)-334(classi)-10.4(er)-329.6(predict)-10.7(ions,)-331.7(which)-336.7(may)-332(serv)-8(e)-332.6(a)0(s)-328.9(a)-332.6(powe)-8.8(rful)-328.4(tool)-332.9(to)-334.3(decide)-337.1(which)]TJ T* [(cla)-8.6(ssiers)-339(mus)-7(t)-333.6(b)0(e)-333.4(replace)-11.5(d.)-331.2(The)-339.6(softw)-8(are)-332.2(is)-335.5(fre)-8(ely)-336.9(available)-341(at)-336.1(\(https://gi)-8.3(thub.com)-8.1(/pbenner)-8.7(/modhm)-8.7(m\).)]TJ /F2 1 Tf 10.959 0 0 10.959 228.5291 392.7117 Tm -.0003 Tc (ACKNOWLEDGMENTS)Tj /F1 1 Tf 9.9626 0 0 9.9626 84.0755 368.7873 Tm 0 Tc [(We)-341.6(than)-7.6(k)-336.5(Anna)-344.5(Ramisch)-9.7(,)-336.1(T)0(o)-7(bias)-338.8(Zehnder)-10.7(,)-336.1(and)-345.5(Verena)-345.9(Heinr)-8.6(ich)-336.9(for)-342(their)-343.2(comme)-8.7(nts)-342(on)-337.3(the)-342.6(article)-345.3(and)]TJ -1.0015 -1.2007 TD [(man)-7.6(y)-330.8(insp)-7(iring)-335.7(discu)-9.6(ssions.)]TJ /F2 1 Tf 10.959 0 0 10.959 191.9055 320.9952 Tm [(AUTHOR)-330.8(DISCLOSURE)-328.8(STATEMENT)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 297.0708 Tm [(The)-339.6(authors)-337.4(decl)-9.4(are)-337.9(they)-337.7(have)-336.7(no)-331.6(com)-7.6(peting)-336.2(n)-6.4(ancial)-339.8(interest)-9.7(s.)]TJ /F2 1 Tf 10.959 0 0 10.959 221.3291 262.2047 Tm [(FUNDING)-329.8(INFORMATION)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 238.2802 Tm [(P.B.)-262.3(was)-265.3(suppor)-7.7(ted)-257.2(by)-263.3(the)-262.9(German)-268(Ministry)-264.2(of)-259.6(Educat)-10.7(ion)-261.1(and)-260.2(Research)-271.5(\(BMBF,)-267.2(grant)-260.7(no.)-263.7(01IS180)-6.5(37G\).)]TJ /F2 1 Tf 10.959 0 0 10.959 252.6236 203.4141 Tm [(REFERENC)5.5(ES)]TJ /F1 1 Tf 8.9663 0 0 8.9663 74.0976 179.4897 Tm [(Amaratunga,)-309.6(D.,)-305.8(and)-304.5(Cabrera,)-307.5(J.)-307.1(2001.)-304.5(Analysis)-303.1(of)-305.1(data)-304.1(from)-310.3(viral)-301.5(DNA)-305.6(microchips.)]TJ /F6 1 Tf 34.8076 0 TD [(J)-305.4(A)0(m)-305.6(Stat)-303.3(Assoc)]TJ /F1 1 Tf 6.892 0 TD [(96,)-305.4(11611170.)]TJ -41.6996 -1.2203 TD [(Andersson,)-287.4(R.,)-282(Gebhard,)-282.1(C.,)-275.6(Miguel-Escalada,)-289.6(I.,)-279.8(et)-283.7(al.)-280.3(2014.)-279.2(An)-280.5(atlas)-283.5(of)-279.8(active)-284.2(enhancers)-287.3(across)-278.8(human)-281.7(cell)-282.8(types)-283.4(and)]TJ 1.0053 -1.2203 TD (tissues.)Tj /F6 1 Tf 3.25 0 TD (Nature)Tj /F1 1 Tf 3.1109 0 TD [(507,)-330.2(455.)]TJ -7.3662 -1.2266 TD [(Barski,)-286.8(A.,)-286.9(Cuddapah,)-280.5(S.,)-282.1(Cui,)-288.4(K.,)-280.5(et)-283.7(al.)-286.6(2007.)-279.2(High-resolution)-286.4(proling)-283.5(of)-286.2(histone)-280.1(methylations)-285.3(in)-287.6(the)-283.2(human)-281.7(genome.)]TJ /F6 1 Tf 1.0053 -1.2203 TD (Cell)Tj /F1 1 Tf 2.0044 0 TD [(129,)-336.6(823837.)]TJ -3.0097 -1.2203 TD [(Bolstad,)-376.3(B.M.,)-373.6(Irizarry,)-378.7(R.A.,)-376.2(A)]TJ 12.7027 .2339 TD ()Tj .5185 -.2339 TD [(strand,)-376.9(M.,)-372.8(and)-374(Speed,)-376.9(T.P.)-376.3(2003.)-367.7(A)-375.9(comparison)-378(of)-374.7(normalization)-377.2(methods)-374.5(for)-370.5(high)]TJ -12.2159 -1.2266 TD [(density)-330.7(oligonucleotide)-336.2(array)-336.4(data)-335.7(based)-332.4(on)-334.1(variance)-341.2(and)-329.7(bias.)]TJ /F6 1 Tf 25.8797 0 TD (Bioinformatics)Tj /F1 1 Tf 6.2913 0 TD [(19,)-330.7(185193.)]TJ -33.1763 -1.2203 TD [(Buenrostro,)-388.6(J.D.,)-379(Giresi,)-384.3(P.G.,)-382.7(Zaba,)-378.7(L.C.,)-385.4(et)-378.5(al.)-381.4(2013.)-380.3(Transposition)-386(of)-381(native)-383(chromatin)-381.3(for)-383.1(fast)-381.3(and)-380.3(sensitive)-387.9(epi-)]TJ 1.0053 -1.2203 TD [(genomic)-331.4(proling)-334.1(of)-336.7(open)-329.3(chromatin,)-340(dna-binding)-330.2(proteins)-339.1(and)-329.7(nucleosome)-339.9(position.)]TJ /F6 1 Tf 35.1238 0 TD [(Nat)-336.1(Methods)]TJ /F1 1 Tf 5.5642 0 TD [(10,)-330.7(1213.)]TJ -41.6933 -1.2266 TD [(Buenrostro,)-401.3(J.D.,)-391.6(Wu,)-395.9(B.,)-395.8(Chang,)-393.3(H.Y.,)-400.1(and)-393(Greenleaf,)-400.1(W.J.)-393.7(2015.)-393(Atac-seq:)-397.4(A)-394.8(method)-399.1(for)-395.8(assaying)-393(chromatin)-400.3(ac-)]TJ 1.0053 -1.2203 TD [(cessibility)-331.8(genome-wide.)]TJ /F6 1 Tf 10.4455 0 TD [(Curr)-333.9(Protoc)-333.3(Mol)-333.5(Biol)]TJ /F1 1 Tf 9.2884 0 TD [(109,)-330.2(2129.)]TJ /F2 1 Tf 9.9626 0 0 9.9626 74.0976 737.4045 Tm [(14)-30377.7(BEN)-10(NER)-339.2(AND)-338.4(VINGR)-8.9(ON)]TJ ET endstream endobj 137 0 obj <>stream /GS1 gs BT /F1 1 Tf 8.9663 0 0 8.9663 107.6031 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(Burge,)-250.5(C.,)-256.7(and)-247.5(Karlin,)-256.6(S.)-247.6(1997.)-253.9(Prediction)-253.5(of)-254.5(complete)-248.9(gene)-255.8(structures)-255.9(in)-249.6(human)-256.4(genomic)-249.2(DNA.)]TJ /F6 1 Tf 38.7531 0 TD [(J)-254.8(Mol)-251.3(Biol)]TJ /F1 1 Tf 4.4956 0 TD [(268,)-254.4(7894.)]TJ -43.2487 -1.2203 TD [(Calo,)-334.6(E.,)-334(and)-336.1(Wysocka,)-329.9(J.)-338.7(2013.)-329.8(Modication)-333.3(of)-336.7(enhancer)-337.2(chromatin:)-334.3(What,)-338.1(how,)-333.5(and)-329.7(why?)]TJ /F6 1 Tf 38.2346 0 TD [(Mol)-333.5(Cell)]TJ /F1 1 Tf 3.9581 0 TD [(49,)-330.7(825837.)]TJ -42.1928 -1.2203 TD (Cappe)Tj 2.1751 .0379 TD ()Tj .3857 -.0379 TD [(,)-236.9(O.,)-236.3(Moulines,)-232.7(E.,)-239.1(and)-234.9(Ryde)]TJ 10.9703 .0379 TD ()Tj .3857 -.0379 TD [(n,)-230.1(T.)-236.2(2005.)]TJ /F6 1 Tf 4.5651 0 TD [(Inference)-240.7(in)-237(Hidden)-234.4(Markov)-239.2(Models)]TJ /F1 1 Tf 14.5237 0 TD [(,)-236.9(volume)-234.7(6.)-236.4(Springer,)-236.9(New)-235.2(York,)-240.8(NY,)]TJ -32.0066 -1.2203 TD (USA.)Tj -.999 -1.2266 TD [(Coetzee,)-466.8(S.G.,)-458.6(Ramjan,)-466(Z.,)-460.4(Dinh,)-463.5(H.Q.,)-463.3(et)-460.7(al.)-463.6(2018.)-462.5(Statehub-statepaintr:)-471.2(Rapid)-464(and)-462.5(reproducible)-463.6(chromatin)-463.5(state)]TJ .999 -1.2203 TD [(evaluation)-336.9(for)-332.5(custom)-337(genome)-334.2(annotation.)]TJ /F6 1 Tf 17.5777 0 TD (F1000Research)Tj /F1 1 Tf 6.677 0 TD (7.)Tj -25.2537 -1.2203 TD [(ENCODE)-276.9(Project)-269.9(Consortium.)-277.4(2012.)-272.9(An)-267.9(integrated)-276.3(encyclopedia)-279.8(of)-267.2(DNA)-274(elements)-275.3(in)-274.9(the)-270.5(human)-275.4(genome.)]TJ /F6 1 Tf 43.1981 0 TD (Nature)Tj /F1 1 Tf 3.054 0 TD (489,)Tj -45.2531 -1.2266 TD (5774.)Tj -.999 -1.2203 TD [(Creyghton,)-315.8(M.P.,)-316.9(Cheng,)-323.8(A.W.,)-316.5(Welstead,)-320.9(G.G.,)-317.9(et)-315.3(al.)-318.2(2010.)-317.1(Histone)-321.4(h3k27ac)-317.6(separates)-324.1(active)-322.2(from)-316.6(poised)-314.5(enhancers)]TJ .999 -1.2203 TD [(and)-336.1(predicts)-335.2(developmental)-335.1(state.)]TJ /F6 1 Tf 13.9673 0 TD [(Proc)-336.6(Natl)-333.3(Acad)-335.4(Sci)-333.8(U)-331.6(S)-334.6(A)]TJ /F1 1 Tf 11.1346 0 TD [(107,)-330.2(2193121936.)]TJ -26.101 -1.2266 TD [(Dempster,)-271.4(A.P.,)-268.9(Laird,)-274.9(N.M.,)-271(and)-272.8(Rubin,)-268.5(D.B.)-272.1(1977.)-266.5(Maximum)-270(likelihood)-272.9(from)-272.3(incomplete)-270.9(data)-272.5(via)-270.5(the)-270.5(EM)-271.4(algorithm.)]TJ /F6 1 Tf .999 -1.2203 TD [(J)-337(R)-328.1(Stat)-334.9(Soc)-336.1(B)-334.4(\()-84.3(Methodol\))]TJ /F1 1 Tf 11.2801 0 TD (138.)Tj -12.2791 -1.2203 TD [(Duda,)-354.4(R.O.,)-357.2(and)-355(Hart,)-361.1(P.E.)-351(1973.)]TJ /F6 1 Tf 14.0811 0 TD [(Pattern)-355.8(Classication)-354.4(and)-358.9(Scene)-358.9(Analysis)]TJ /F1 1 Tf 17.1793 0 TD [(.)-350.7(A)-356.9(Wiley-Interscience)-361.5(Publication,)-358.5(New)]TJ -30.2615 -1.2203 TD (York.)Tj -.999 -1.2266 TD [(Ernst,)-292.6(J.,)-291.1(and)-285.5(Kellis,)-297.2(M.)-287.7(2012.)-291.8(ChromHMM:)-287.1(Automating)-294.6(chromatin-state)-293.9(discovery)-292.8(and)-291.8(characterization.)]TJ /F6 1 Tf 42.8124 0 TD [(Nat)-291.8(Methods)]TJ /F1 1 Tf -41.8134 -1.2203 TD [(9,)-331.2(215.)]TJ -.999 -1.2203 TD -.0134 Tc [(Er)-13.4(n)10.3(s)-13.4(t)7.7(,)-262.9(J)-13.4(.)8.3(,)-269.2(a)-13.4(n)10.5(d)-265.8(K)-13.4(e)7.1(ll)-13.4(i)11.2(s)-13.4(,)-257.3(M)-1(.)-269.2(2017.)-269.2(Ch)-13.4(r)10.3(o)-13.4(m)9.3(a)-13.4(t)6.4(i)2(n)-13.4(-)10.3(s)-13.4(t)7.7(a)-13.4(t)6.4(e)-261.9(d)-13.4(i)8.8(s)-13.4(c)9.3(ove)-13.4(r)7.8(y)-265.8(a)-13.4(n)10.4(d)-272.1(g)-.3(e)-13.4(n)10.5(om)-13.4(e)-258.6(a)3.6(n)-13.4(n)6.5(ot)-13.4(a)6.4(t)2(i)-13.4(o)8.9(n)-265.8(w)-13.4(i)11.9(t)-13.4(h)-256.7(C)-13.4(h)8.1(r)-13.4(o)10.3(m)2.5(H)-13.4(M)8.9(M.)]TJ /F6 1 Tf 39.7205 0 TD 0 Tc [(N)14.7(a)0(t)-243.3(P)13.3(ro)18.8(t)15.4(o)13.1(c)]TJ /F1 1 Tf 4.5968 0 TD -.0131 Tc [(12)-13.1(,)-255.8(2)0(4)-13.1(7)6.8(8.)]TJ -44.3173 -1.2266 TD 0 Tc [(Galassi,)-340.5(U.,)-337.4(Giordana,)-336.2(A.,)-337.4(and)-342.4(Saitta,)-337.9(L.)-337.4(2007.)-336.1(Structured)-340.6(hidden)-338.6(Markov)-337.9(model:)-339.9(A)-331.6(general)-345.6(framework)-337.6(for)-338.9(modeling)]TJ .999 -1.2203 TD [(complex)-280.9(sequences,)-282.5(290301.)-277.7(In)]TJ /F6 1 Tf 13.4678 0 TD [(Congress)-278.7(of)-274.9(the)-283.2(Italian)-276.8(Association)-283.2(for)-275.6(Articial)-280.7(Intelligence)]TJ /F1 1 Tf 24.5645 0 TD [(.)-281.1(Springer,)-274.8(New)-279.4(York,)]TJ -38.0323 -1.2203 TD [(NY,)-337.3(USA.)]TJ -.999 -1.2266 TD [(Gelfand,)-336.7(A.E.,)-333.4(Mallick,)-339.6(B.K.,)-338.3(and)-336.1(Dey,)-336(D.K.)-333.9(1995.)-336.1(Modeling)-336(expert)-337.3(opinion)-333.4(arising)-339.6(as)-337.7(a)-330.7(partial)-338.6(probabilistic)-338.5(speci-)]TJ .999 -1.2203 TD (cation.)Tj /F6 1 Tf 3.0413 0 TD [(J)-337(A)0(m)-330.9(Stat)-334.9(Assoc)]TJ /F1 1 Tf 7.0121 0 TD [(90,)-330.7(598604.)]TJ -11.0525 -1.2203 TD [(Genest,)-310.5(C.,)-313.6(and)-317.1(Zidek,)-310.2(J.V.)-312.8(1986.)-310.8(Combining)-309.1(probability)-319.2(distributions:)-313.1(A)-312.6(critique)-312.8(and)-310.8(an)-311.3(annotated)-314.4(bibliography.)]TJ /F6 1 Tf 46.4355 0 TD (Stat)Tj -45.4364 -1.2266 TD (Sci)Tj /F1 1 Tf 1.5618 0 TD [(1,)-331.2(114135.)]TJ -2.5608 -1.2203 TD [(Gill,)-332.5(P.E.,)-335(Murray,)-337.1(W.,)-329.7(and)-336.1(Wright,)-335(M.H.)-331.3(1981.)]TJ /F6 1 Tf 19.9867 0 TD [(Practical)-336(Optimization)]TJ /F1 1 Tf 9.301 0 TD [(.)-331.7(Academic)-339.1(Press,)-335.3(London,)-328.6(UK.)]TJ -29.2877 -1.2203 TD [(Gorkin,)-452.5(D.,)-457.6(Barozzi,)-454.4(I.,)-456.9(Zhang,)-458(Y.,)-451.3(et)-454.4(al.)-457.3(2017.)-456.2(Systematic)-454(mapping)-455.5(of)-456.9(chromatin)-457.2(state)-454.2(landscapes)-460.1(during)-452.6(mouse)]TJ .999 -1.2203 TD (development.)Tj /F6 1 Tf 5.7728 0 TD (bioRxiv)Tj /F1 1 Tf 3.4017 0 TD (166652.)Tj -10.1736 -1.2266 TD [(He,)-311.2(Y.,)-305.8(Gorkin,)-313.4(D.U.,)-305.2(Dickel,)-313.3(D.E.,)-308.1(et)-309(al.)-311.9(2017.)-304.5(Improved)-310.8(regulatory)-310.4(element)-312.6(prediction)-311.8(based)-307.1(on)-308.8(tissue-specic)-316.8(local)]TJ .999 -1.2203 TD [(epigenomic)-336.4(signatures.)]TJ /F6 1 Tf 9.6677 0 TD 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