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Poster
2012-11-25T23:58:39-02:00
2012-11-25T23:58:39-02:00
2012-11-25T23:58:39-02:00
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h
S
Q
Q
BT
0 0 0 1 k
/T1_0 1 Tf
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T*
[(t)-5(he tem)21(p)-8(o)12(ral exp)14(r)12(es)5(sio)13(n p)13(r)13(o)12(f)-11(ile o)13(f a g)9(ene a)10(nd i)12(ts b)13(io)8(log)-6(ical f)-5(unc)-8(t)-7(io)13(n a)10(nd t)-5(ha)18(t i)12(t co)11(uld b)-7(e p)-7(os)5(sib)9(le to p)13(r)12(edic)-7(t a g)9(ene)51(\037)87(s f)-6(unc)-8(t)-7(io)13(n f)-11(r)13(o)12(m )]TJ
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22 0 0 22 510.6777 1288.0938 Tm
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0 -1.2 TD
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0 -1.2 TD
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0 -1.2 TD
[(o)12(f )-50(exp)13(r)13(es)5(sio)13(n. )-50(I)35(t)22(\037)87(s )-50(enr)-6(ic)5(hed )-50(in )-50(a )-50(f)8(e)-5(w )-50(v)9(er)-27(y )-50(g)8(eneral )]TJ
0 -1.2 TD
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0 -1.2 TD
[(mo)19(v)9(emen)20(t)22(\035 a)10(nd \036)75(g)-7(l)8(y)9(co)8(l)8(ysis)39(\035)148(.)]TJ
T*
[(Ther)13(e)51(\037)87(s )-80(no )-80(enr)-6(ic)5(hmen)21(t )-81(in )-80(a)9(n)25(y )-80(p)12(r)13(o)-8(ces)5(s)-6(es )-80(dir)13(ec)-8(t)-5(l)8(y )]TJ
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[(r)12(ela)18(ted to t)-5(he ner)-26(v)9(o)11(us sys)6(tem.)]TJ
-19.327 8.4 Td
[(Cl)12(us)5(ter )-443(1 )-443(is )-442(enr)-6(ic)5(hed )-443(in )-442(g)8(eneral )-442(b)13(io)8(log)-6(ical )]TJ
0 -1.2 TD
[(p)12(r)12(o)-8(ces)5(s)-7(es )-1579(as )-1578(\036)-9(b)-7(o)-8(d)8(y )-1579(mo)12(r)-10(p)8(hog)8(enesis)38(\035)148(, )]TJ
0 -1.2 TD
[(\036)75(o)15(xida)18(t)-7(io)13(n-r)12(ed)11(uc)-8(t)-7(io)13(n )-409(p)12(r)13(o)-8(ces)5(s)-7(es)38(\035 )-409(a)9(nd )-409(\036)75(def)8(en)10(s)-6(e )]TJ
0 -1.2 TD
[(r)12(es)5(p)-8(o)12(n)10(s)-7(e)51(\035)148(. )-361(I)16(n)20(ter)12(es)5(t)-7(in)7(g)-7(l)8(y)67(, )-361(i)12(ts )-361(exp)13(r)12(es)5(sio)13(n )-361(p)12(r)12(o)12(f)-11(ile )]TJ
0 -1.2 TD
[(sho)20(ws )-275(a )-276(p)-8(eak )-276(in )-275(eac)5(h )-276(o)12(f )-276(t)-5(he )-276(t)-5(hr)13(ee )-276(s)5(t)-7(a)6(g)8(es )-276(o)12(f )]TJ
0 -1.2 TD
[(de)-5(v)9(elo)11(p)12(men)20(t. )]TJ
T*
[(Ther)13(e)51(\037)87(s )-73(no )-73(enr)-6(ic)5(hmen)21(t )-73(in )-72(a)9(n)25(y )-73(p)12(r)12(o)-8(ces)5(s)-7(es )-73(dir)13(ec)-8(t)-5(l)8(y )]TJ
0 -1.2 TD
[(r)12(ela)18(ted to t)-5(he ner)-26(v)9(o)11(us sys)6(tem.)]TJ
26 0 0 26 85.0825 2132.8179 Tm
[(W)88(e us)-6(ed RN)35(A)38(-s)-7(eq p)-7(o)8(liA \(t)-4(he RN)35(A t)-5(ha)18(t will b)-6(e t)-7(ra)9(n)10(sla)18(ted to p)12(r)12(o)11(tein)10(s\) da)18(t)-7(a f)-10(r)12(o)12(m )]TJ
0 -1.2 TD
[(G)8(ra)19(v)9(ele)-5(y a)18(t al. 2011 \(7\). The us)-5(ed da)17(t)-7(a co)20(v)9(er)7(s 30 t)-6(ime p)-7(o)12(in)21(ts alo)13(n)6(g em)9(b)13(r)-27(y)9(o)12(nic, la)11(r)-27(val, )]TJ
0 -1.2 TD
[(p)11(u)11(pal a)10(nd ad)12(ul)11(t s)5(t)-7(a)6(g)8(es. E)-9(ac)5(h sa)10(m)20(p)8(le co)13(n)10(sis)6(ts o)13(f RN)35(A is)-6(o)8(la)18(ted f)-11(r)12(o)12(m 30 w)-6(ho)8(le a)10(nimals. )]TJ
0 -1.2 TD
[(The le)-4(v)9(el o)13(f exp)13(r)12(es)5(sio)13(n f)8(o)12(r eac)6(h g)9(ene is r)14(ep)-8(o)12(r)-9(ted as a RPKM val)15(ue, a met)-4(ho)-7(d o)12(f )]TJ
0 -1.2 TD
[(q)8(ua)9(n)20(t)-7(if)-16(yin)7(g g)8(ene exp)13(r)13(es)5(sio)13(n f)-11(r)13(o)12(m RN)35(A s)-6(eq)8(uencin)7(g da)18(t)-7(a b)20(y no)13(r)-7(malizin)8(g f)8(o)12(r to)11(t)-7(al r)13(ead )]TJ
0 -1.2 TD
[(len)6(gt)-5(h a)10(nd t)-5(he n)21(um)9(b)-7(er o)13(f s)-6(eq)8(uencin)7(g r)13(eads.)]TJ
0.044 31.581 Td
[(I)16(n r)13(ecen)20(t y)9(ea)9(r)7(s t)-4(her)13(e ha)19(v)9(e b)-7(een g)-5(r)13(ea)17(t ad)8(va)9(nces in D)8(N)34(A a)9(nd RN)35(A s)-6(eq)8(uencin)7(g )]TJ
T*
[(met)-5(ho)-7(ds a)10(nd t)-5(he n)21(um)8(b)-7(er o)13(f a)19(va)9(ila)8(b)8(le tem)20(p)-8(o)12(ral s)-5(er)-7(ies o)13(f g)8(eno)12(mic exp)13(r)13(es)5(sio)13(n da)18(t)-7(a is )]TJ
0 -1.2 TD
[(ra)18(p)12(idl)8(y incr)14(easin)7(g \(1\). )]TJ
0 -2.4 TD
[(This kind o)14(f da)18(t)-7(a ca)10(n b)-7(e us)-6(ed to c)5(ha)10(rac)-7(ter)-7(ize t)-4(he f)-6(unc)-8(t)-7(io)13(n o)13(f s)6(p)-8(ecif)-11(ic g)9(enes, )]TJ
0 -1.2 TD
[(r)12(ela)18(t)-7(io)13(n)10(shi)12(ps b)-7(etw)9(een g)9(enes, i)13(ts r)13(egula)17(t)-7(io)13(n, co)-7(o)12(r)12(dina)18(t)-7(io)13(n a)10(nd e)-4(v)9(en c)6(linic im)22(p)8(lica)18(t)-7(io)13(n)10(s )]TJ
T*
[(o)12(f dif)-10(f)8(er)13(en)20(t)-7(ial exp)14(r)13(es)5(sio)13(n \(2\). S)-11(o)12(me s)5(t)8(udies ha)20(v)9(e s)6(ug)-7(g)8(es)5(ted t)-5(he co)-7(o)12(r)13(dina)18(ted )]TJ
0 -1.2 TD
[(exp)13(r)12(es)5(sio)13(n o)13(f g)8(enes d)12(ur)-7(in)7(g t)-5(he de)-4(v)9(elo)11(p)12(men)20(t o)12(f )]TJ
/T1_3 1 Tf
[(D)-5(r)20(o)6(so)8(p)10(h)15(i)5(l)5(a m)7(e)16(l)5(a)13(n)7(ogas)8(t)9(er)]TJ
/T1_0 1 Tf
( \(3, 4, 5, 6\). )Tj
0 -1.2 TD
[(N)22(e)-5(v)9(er)-9(t)-5(heles)6(s t)-4(he)-4(y limi)13(t to v)9(er)-26(y g)9(eneral as)7(p)-8(ec)-8(ts o)13(f b)-7(o)-8(d)8(y mo)13(r)-10(p)8(hog)8(enesis.)]TJ
0 -2.4 TD
[(H)23(er)13(e w)10(e sho)20(w t)-4(he r)13(es)5(ul)11(ts o)13(f a)18(p)11(p)8(l)8(yin)7(g t)-5(he K-mea)9(n)10(s alg)9(o)12(r)-7(i)12(t)-5(hm to c)6(l)11(us)5(ter t)-5(he )]TJ
0 -1.2 TD
[(de)-5(v)9(elo)11(p)12(men)20(t)-7(al t)-6(ra)9(n)10(s)-6(cr)-7(i)12(p)11(to)12(me o)12(f Dr)13(os)-7(o)11(p)8(hila mela)11(nogas)6(ter a)10(nd a f)-6(unc)-8(t)-7(io)13(nal )]TJ
0 -1.2 TD
[(c)5(ha)10(rac)-7(ter)-7(iza)18(t)-7(io)13(n o)13(f t)-5(he ob)12(t)-7(a)9(ined c)6(l)11(us)5(ter)7(s. W)89(e a)10(r)12(e s)-6(ea)9(r)13(c)5(hin)7(g co)8(her)13(en)20(t wa)19(v)9(es o)13(f g)8(enet)-7(ic )]TJ
0 -1.2 TD
[(exp)13(r)12(es)5(sio)13(n wi)13(t)-5(h s)6(p)-8(ecial in)22(ter)12(es)5(t in t)-4(he de)-4(v)9(elo)11(p)12(men)20(t o)12(f t)-5(he ner)-25(v)9(o)11(us sys)6(tem. Our )]TJ
0 -1.2 TD
[(h)25(yp)-7(o)11(t)-5(hesis is t)-2(ha)18(t t)-5(her)13(e is a tem)22(p)-8(o)12(ral co)13(r)-7(r)12(es)5(p)-8(o)12(ndence b)-7(etw)9(een t)-4(he s)6(t)-7(a)6(g)8(es o)13(f ner)-26(v)9(o)11(us )]TJ
0 -1.2 TD
[(sys)6(tem de)-5(v)9(elo)11(p)12(men)20(t a)9(nd t)-5(he exp)13(r)12(es)5(sio)13(n o)13(f c)5(l)11(us)5(ter)7(s o)13(f g)8(enes d)12(ur)-7(in)7(g eac)6(h o)13(f t)-5(hes)-6(e )]TJ
0 -1.2 TD
[(s)5(t)-7(a)6(g)8(es. Our f)-9(inal ob)13(j)-6(ec)-8(t)-7(i)8(v)9(e is to ob)13(t)-7(a)9(in a ca)19(t)-7(alogue o)13(f g)8(enes wi)13(t)-5(h b)13(io)8(log)-6(ical r)14(ele)-5(va)9(nce )]TJ
0 -1.2 TD
[(to t)-5(he syna)19(ps)-6(e as)6(s)-7(em)9(b)8(l)8(y)67(.)]TJ
1 1 1 1 k
/T1_1 1 Tf
48 0 0 48 85.9023 1906.626 Tm
[(RES)14(UL)57(T)-7(S)]TJ
0 0 0 1 k
/T1_0 1 Tf
22 0 0 22 933.1685 1178.0938 Tm
[(Cl)12(us)5(ter )24(3 )24(f)8(ea)17(t)8(ur)12(es )24(a )24(\036)25(ma)17(ter)-7(nal)22(\035 )24(exp)13(r)12(es)5(sio)13(n )24(p)12(r)12(o)12(f)-11(ile, )]TJ
0 -1.2 TD
[(wi)12(t)-5(h )-455(hig)-6(h )-455(le)-5(v)9(els )-455(o)12(f )-455(exp)13(r)13(es)5(sio)13(n )-455(a)17(t )-455(t)-5(he )-455(v)9(er)-26(y )]TJ
0 -1.2 TD
[(b)-7(eg)-6(innin)7(g )35(o)12(f )35(em)9(b)13(r)-27(y)9(o)12(nic )35(lif)9(e. )35(This )35(is )35(c)5(ha)10(rac)-7(ter)-7(is)6(t)-7(ic )]TJ
0 -1.2 TD
[(f)8(o)12(r )-129(g)8(enes )-128(w)-6(hos)-6(e )-129(mRN)34(A )-129(is )-128(inher)-5(i)12(ted )-129(b)19(y )-128(t)-5(he )-128(eg)-7(g )]TJ
0 -1.2 TD
[(f)-11(r)12(o)12(m )-320(t)-5(he )-319(mo)11(t)-5(her)58(. )-319(The )-319(c)5(l)11(us)5(ter )-319(is )-319(enr)-6(ic)5(hed )-319(in )]TJ
0 -1.2 TD
[(g)8(eneral )-330(b)13(io)8(log)-6(ical )-330(p)12(r)13(o)-8(ces)5(s)-6(es )-331(as )-331(\036)24(r)13(egula)17(t)-7(io)13(n )-331(o)12(f )]TJ
T*
[(g)8(ene )-671(exp)13(r)12(es)5(sio)13(n)74(\035 )-671(a)9(nd )-671(\036)75(cell )-671(dif)-11(f)8(er)13(en)20(t)-7(ia)18(t)-7(io)13(n)75(\035)148(. )]TJ
0 -1.2 TD
[(Rega)9(r)12(din)6(g )-32(ner)-26(v)9(o)11(us )-32(sys)6(tem )-32(is )-31(enr)-6(ic)5(hed )-31(in )-31(va)9(r)-7(io)12(us )]TJ
0 -1.2 TD
[(p)12(r)12(o)-8(ces)5(s)-7(es )-13(t)-5(ha)18(t )-13(t)-7(ak)9(e )-13(p)8(lace )-12(a)18(t )-13(t)-5(he )-12(v)9(er)-27(y )-13(b)-7(eg)-6(innin)8(g )-13(o)12(f )]TJ
0 -1.2 TD
[(i)12(ts )-15(de)-5(v)9(elo)11(p)12(men)20(t, )-16(s)5(uc)5(h )-15(as )-15(\036)25(neur)13(og)8(enesis)38(\035)148(, )-15(\036)24(neur)13(o)12(n )]TJ
0 -1.2 TD
[(dif)-11(f)8(er)13(en)20(t)-7(ia)18(t)-7(io)13(n)74(\035 a)10(nd \036)25(neur)13(ob)8(las)6(t di)8(visio)13(n)74(\035)148(.)]TJ
19.364 12 Td
[(Cl)12(us)5(ter )-1(4 )-1(is enr)-6(ic)5(hed )-1(in g)8(eneral p)12(r)13(o)-8(ces)5(s)-7(es )-1(s)5(uc)5(h )-1(as )]TJ
T*
[(\036)28(t)-7(ra)9(n)10(smem)9(b)13(ra)9(ne )-90(t)-7(ra)9(n)10(s)5(p)-8(o)12(r)-9(t)22(\035)148(, )-90(\036)-7(io)13(n )-90(t)-7(ra)9(n)10(s)5(p)-8(o)12(r)-10(t)22(\035 )-90(a)9(nd )]TJ
0 -1.2 TD
[(\036)49(sig)-5(nal )-23(t)-7(ra)9(n)10(s)-7(d)11(uc)-8(t)-7(io)13(n)74(\035)148(. )-23(A)24(cco)12(r)12(din)6(g)-7(l)8(y)67(, )-23(is )-23(enr)-6(ic)5(hed )-23(in )]TJ
0 -1.2 TD
[(ter)-7(m)10(s )4(r)12(ela)18(ted )4(to )4(t)-5(he )5(f)-7(unc)-8(t)-7(io)13(nin)7(g )4(o)12(f )4(t)-5(he )5(as)5(s)-7(em)9(b)8(led )]TJ
0 -1.2 TD
[(syna)18(ps)-6(e, )-276(s)5(uc)5(h )-276(as )-276(\036)25(neur)13(o)11(t)-7(ra)9(n)10(smi)12(t)8(ter )-276(t)-7(ra)9(n)10(s)5(p)-8(o)12(r)-9(t)22(\035)148(, )]TJ
0 -1.2 TD
[(\036)49(syna)18(p)11(t)-7(ic )-386(t)-7(ra)9(n)10(smis)6(sio)13(n)75(\035 )-386(a)9(nd )-386(\036)49(syna)18(p)11(t)-7(ic )-386(v)9(esic)6(le )]TJ
T*
[(ex)8(o)-8(c)-12(ytosis)38(\035)148(. )-185(I)35(ts )-185(exp)13(r)13(es)5(sio)13(n )-185(p)12(r)13(o)12(f)-11(ile, )-184(t)-5(ha)18(t )-185(has )-184(lo)19(w )]TJ
0 -1.2 TD
[(le)-5(v)9(els )-174(a)17(t )-175(t)-5(he )-174(b)-7(eg)-6(innin)7(g )-174(o)12(f )-174(em)9(b)13(r)-27(y)9(o)12(nic )-174(lif)8(e, )-174(r)-7(is)-6(es )]TJ
0 -1.2 TD
[(co)8(her)13(en)20(t)-5(l)8(y )-88(d)11(ur)-7(in)7(g )-88(t)-5(he )-88(ho)12(ur)7(s )-88(in )-88(w)-6(hic)6(h )-88(is )-88(alr)13(ead)8(y )]TJ
0 -1.2 TD
[(w)9(ell )-136(des)-7(cr)-6(ib)-7(ed )-136(t)-5(ha)18(t )-136(t)-5(he )-135(f)-11(ir)8(s)5(t )-136(syna)18(ps)-6(es )-136(b)-7(eg)-6(in )-135(t)-5(he )]TJ
0 -1.2 TD
[(t)-7(ra)9(n)10(smis)6(sio)13(n o)13(f ax)9(o)12(n p)-7(o)11(ten)20(t)-7(ials. )]TJ
19.414 12.091 Td
[(Cl)12(us)5(ter )-11(5 )-11(is )-10(enr)-6(ic)5(hed )-11(in )-10(g)8(eneral )-10(p)12(r)12(o)-8(ces)5(s)-7(es )-11(r)13(ela)18(ted )]TJ
T*
[(to )-244(t)-5(he )-243(s)5(pa)18(t)-7(ial )-243(o)12(r)10(ga)9(niza)19(t)-7(io)13(n )-244(o)12(f )-244(t)-5(he )-243(cell )-244(a)9(nd )-244(i)12(ts )]TJ
0 -1.2 TD
[(in)21(ter)-7(nal )-487(o)12(r)10(ga)9(niza)18(t)-7(io)13(n, )-488(s)5(uc)5(h )-488(as )-487(\036)75(c)-12(ytosk)9(eleto)12(n )]TJ
0 -1.2 TD
[(o)12(r)10(ga)9(niza)18(t)-7(io)13(n)75(\035 )-761(a)9(nd )-761(\036)75(o)12(r)10(ga)9(nelle )-761(o)12(r)10(ga)9(niza)18(t)-7(io)13(n)74(\035)148(. )]TJ
0 -1.2 TD
[(Rega)9(r)12(din)6(g )-504(ner)-26(v)9(o)11(us )-504(sys)6(tem, )-504(i)12(ts )-504(enr)-6(ic)5(hed )-504(in )]TJ
0 -1.2 TD
[(p)12(r)12(o)-8(ces)5(s)-7(es )-706(t)-5(ha)18(t )-707(t)-7(ak)9(e )-707(p)8(lace )-706(a)9(f)-7(ter )-707(neur)13(o)12(nal )]TJ
T*
[(dif)-11(f)8(er)13(en)20(t)-7(ia)18(t)-7(io)13(n )-25(b)12(u)11(t )-26(b)-7(ef)8(o)12(r)13(e )-25(t)-5(he )-25(syna)18(ps)-6(es )-25(a)9(r)12(e )-25(r)12(ead)8(y)67(, )]TJ
0 -1.2 TD
[(s)5(uc)5(h )-93(as )-93(\036)25(r)12(egula)17(t)-7(io)13(n )-93(o)12(f )-93(dendr)-7(i)12(te )-93(mo)12(r)-9(p)8(hog)8(enesis)39(\035 )]TJ
0 -1.2 TD
[(a)9(nd )-11(\036)59(ax)8(o)12(nog)8(enesis)38(\035)148(. )-11(I)19(s )-11(als)-6(o )-11(enr)-6(ic)5(hed )-11(in )-10(p)12(r)12(o)-8(ces)5(s)-7(es )]TJ
0 -1.2 TD
[(r)12(ela)18(ted )-154(to )-154(t)-5(he )-153(lo)-8(caliza)19(t)-7(io)13(n )-154(a)9(nd )-154(t)-7(ra)9(n)10(s)5(p)-8(o)12(r)-9(t )-154(o)12(f )-154(t)-5(he )]TJ
0 -1.2 TD
[(syna)18(p)11(t)-7(ic v)10(esic)6(les. )]TJ
ET
1 1 1 1 k
907.321 2855.326 -821.102 8.999 re
f
2182.212 2855.326 -1246.005 8.999 re
f
BT
/T1_1 1 Tf
48 0 0 48 86.2188 2876.7275 Tm
[(INTR)11(O)9(D)7(UCTI)8(O)9(N)]TJ
0.005 -14.068 Td
[(D)42(A)64(T)71(A)]TJ
17.677 13.974 Td
[(METH)8(O)9(DS)]TJ
0 0 0 1 k
/T1_0 1 Tf
26 0 0 26 936.2065 2797.915 Tm
[(W)88(e s)-6(et aside t)-4(he g)9(enes t)-4(ha)18(t ha)19(v)9(e no exp)13(r)13(es)5(sio)13(n alo)13(n)6(g t)-5(he t)-4(hr)13(ee de)-5(v)9(elo)11(p)12(men)20(t)-7(al s)6(t)-7(a)6(g)8(es \(g)8(enes t)-4(ha)18(t a)9(r)13(e t)-7(ra)9(n)10(sla)18(ted o)12(nl)8(y in t)-3(he ad)12(ul)11(t )]TJ
0 -1.2 TD
[(a)9(nimal\) s)-5(o o)11(ur f)-11(inal da)19(t)-7(a s)-6(et co)12(n)10(sis)6(ts in 27 s)7(ucces)5(si)9(v)9(e exp)13(r)12(es)5(sio)13(n val)12(ues f)8(o)12(r 13,767 g)8(enes. B)-18(eca)18(us)-7(e w)10(e a)10(r)12(e mo)12(r)12(e in)21(ter)12(es)5(ted in t)-4(he )]TJ
0 -1.2 TD
[(wa)19(y g)9(enes c)6(ha)10(n)6(g)8(e t)-5(heir le)-3(v)9(els o)13(f exp)13(r)12(es)5(sio)13(n alo)13(n)6(g t)-7(ime t)-4(ha)10(n in t)-3(he a)8(bs)-6(o)8(l)11(u)11(te val)12(ues o)13(f exp)13(r)13(es)5(sio)13(n, w)10(e de)-5(vided eac)6(h val)12(ue o)12(f )]TJ
0 -1.2 TD
[(exp)13(r)12(es)5(sio)13(n b)20(y t)-4(he maxim)21(um val)12(ue t)-5(ha)18(t t)-5(he g)9(ene r)13(eac)5(h t)-4(hr)13(o)11(ug)-7(h t)-4(he co)13(n)10(sider)13(ed t)-7(ime la)18(ps)-6(e. )]TJ
0 -2.4 TD
[(Then w)10(e a)18(p)11(p)8(lied hiera)11(r)12(c)5(hical \(W)117(ARD\) a)9(nd no)13(n-hiera)10(r)13(c)5(hical \(K-mea)10(n)10(s, P)18(a)9(m, Cla)10(ra, F)19(a)9(nn)25(y\) c)6(l)11(us)5(ter)-7(in)7(g met)-5(ho)-7(ds usin)7(g R pac)6(k)5(a)6(g)8(es. )]TJ
0 -1.2 TD
[(T)86(o co)13(m)20(pa)9(r)12(e t)-5(he ob)12(t)-7(a)9(ined r)13(es)5(ul)11(ts w)10(e us)-6(ed S)6(il)12(uet)-7(a. The mo)13(r)12(e ho)13(mog)8(eno)11(us c)5(l)11(us)5(ter)7(s w)10(er)13(e f)8(o)11(und to b)-7(e t)-5(hos)-6(e ob)12(t)-7(a)9(ined a)18(p)11(p)8(l)8(yin)7(g t)-5(he )]TJ
0 -1.2 TD
[(K-mea)9(n)10(s alg)9(o)12(r)-7(i)12(t)-5(hm , c)6(l)11(us)5(ter)-7(in)7(g t)-5(he da)18(t)-7(a in 5 g)-4(r)12(o)11(u)11(ps. )]TJ
0 -2.4 TD
[(T)86(o c)5(ha)10(rac)-7(ter)-7(ize t)-4(he c)6(l)11(us)5(ter)7(s w)10(e p)-7(er)-6(f)8(o)12(r)-7(med f)-7(unc)-8(t)-7(io)13(nal enr)-5(ic)5(hmen)21(t a)9(nal)8(ysis o)14(f G)-7(ene On)21(to)7(log)-20(y ter)-6(m)10(s usin)7(g t)-5(he GO)7(RILL)-7(A p)8(la)18(t)-7(f)8(o)12(r)-7(m )]TJ
0 -1.2 TD
[(\(8\). Enr)-6(ic)5(hmen)21(t is def)-10(ined as \(b/n\) / \(B/N\), w)-3(her)13(e N is t)-3(he to)12(t)-7(al n)21(um)8(b)-7(er o)13(f g)8(enes, B is t)-2(he to)12(t)-7(al n)21(um)8(b)-7(er o)13(f g)8(enes as)6(s)-7(o)-8(cia)18(ted wi)12(t)-5(h )]TJ
T*
[(a s)6(p)-8(ecif)-11(ic GO ter)-6(m, n is t)-3(he n)21(um)8(b)-7(er o)13(f g)8(enes in t)-3(he a)10(nal)9(ys)-6(ed lis)6(t a)9(nd b is t)-3(he in)22(ter)7(s)-7(ec)-8(t)-7(io)13(n b)-7(etw)9(een n a)10(nd B)16(. The 'P)39(-val)11(ue' is t)-3(he )]TJ
0 -1.2 TD
[(enr)-6(ic)5(hmen)21(t p-val)12(ue co)12(m)20(p)12(u)11(ted acco)13(r)12(din)6(g to t)-5(he H)10(G mo)-8(del. )]TJ
0 -2.4 TD
[(W)88(e als)-6(o la)8(b)-7(eled eac)6(h g)9(ene as b)-6(ein)7(g o)13(r no)12(t b)-7(ein)7(g o)19(v)9(er)22(-exp)12(r)12(es)5(s)-6(ed in f)-10(i)8(v)9(e dif)-10(f)8(er)13(en)20(t t)-7(is)6(s)5(ues; cen)21(t)-7(ral ner)-25(v)9(o)11(us sys)6(tem, fa)18(t b)-7(o)-8(dies, )]TJ
0 -1.2 TD
[(midgu)11(t, sali)9(val g)-6(la)9(nds a)10(nd t)-5(he ca)10(r)12(cas)6(s, a)10(nd t)-5(hen s)6(t)8(udied t)-5(he dis)6(t)-7(r)-7(ib)12(u)11(t)-7(io)13(n o)13(f t)-5(he la)8(b)-7(els. W)89(e la)8(b)-7(eled a g)9(ene as b)-6(ein)7(g \036)75(o)19(v)9(er)22(-exp)12(r)12(es)5(s)-6(ed)21(\035 )]TJ
0 -1.2 TD
[(in a t)-5(is)6(s)5(ue w)-6(hen t)-4(he le)-4(v)9(el o)13(f exp)13(r)13(es)5(sio)13(n o)13(f t)-5(ha)18(t g)8(ene in t)-3(ha)18(t t)-7(is)6(s)5(ue is a)19(t leas)6(t 5 t)-7(imes hig)-5(her t)-4(ha)10(n t)-4(he mea)10(n le)-4(v)9(el o)13(f exp)13(r)12(es)5(sio)13(n o)13(f t)-5(h)1(e )]TJ
0 -1.2 TD
[(g)8(ene in t)-3(he w)-6(ho)8(le o)13(r)10(ga)9(nism. W)89(e us)-6(ed da)17(t)-7(a o)13(f t)-7(is)6(s)5(ue s)5(p)-8(ecif)-11(ic exp)13(r)12(es)5(sio)13(n d)12(ur)-7(in)7(g t)-5(hir)13(d la)9(r)-27(val s)6(t)-7(a)6(g)8(e, a)19(va)9(ila)8(b)8(le f)8(o)12(r 10.000 g)8(enes in )]TJ
0 -1.2 TD
[(Fl)8(yA)39(t)-5(las, t)-4(he Dr)13(os)-7(o)11(p)8(hila g)10(ene exp)13(r)13(es)5(sio)13(n a)18(t)-5(las \(9\).)]TJ
ET
1 1 1 1 k
2182.678 1887.431 -2098.142 8.998 re
f
904.017 2182.433 -818.935 8.999 re
f
BT
0 0 0 1 k
/T1_0 1 Tf
18 0 0 18 939.3447 273.5508 Tm
[(1 - B)-8(a)9(r)-7(r)13(et)8(t et al. N)6(CBI GEO: a)10(r)12(c)5(hi)9(v)9(e f)8(o)12(r f)-6(unc)-8(t)-7(io)13(nal g)9(eno)12(mics da)18(t)-7(a s)-6(ets 10 y)10(ea)9(r)7(s o)13(n. N)33(uc)5(leic A)25(cids Res, 2011.)]TJ
0 -1.2 TD
[(2 - B)-8(a)9(r)22(-J)16(os)-7(ep)8(h et al. S)16(t)8(ud)7(yin)7(g a)10(nd mo)-8(dellin)7(g d)8(yna)10(mic b)13(io)8(log)-6(ical p)14(r)13(o)-8(ces)5(s)-6(es usin)7(g t)-7(ime-s)-7(er)-6(ies g)9(ene exp)13(r)12(es)5(sio)13(n da)18(t)-7(a. N)25(a)17(t)8(ur)12(e Re)-4(vie)-4(ws G)-6(enet)-7(ics, 2012.)]TJ
0 -1.2 TD
[(3 - F)17(er)-6(r)12(eir)13(o et al. W)14(ho)8(le t)-6(ra)9(n)10(s)-6(cr)-7(i)12(p)11(to)12(me a)9(nal)9(ysis o)14(f a r)14(e)-5(v)9(er)7(sib)9(le neur)13(o)-8(deg)8(enera)18(t)-7(i)8(v)9(e p)13(r)13(o)-8(ces)5(s in Dr)14(os)-7(o)11(p)8(hila r)14(e)-5(v)9(eals p)-6(o)11(ten)20(t)-7(ial neur)14(o)11(p)12(r)12(o)11(tec)-8(t)-7(i)8(v)9(e g)8(enes. BM)9(C G)-6(eno)12(mics, 2012.)]TJ
0 -1.2 TD
[(4 - Arb)-7(ei)12(t)-7(ma)9(n et al. G)-5(ene exp)13(r)12(es)5(sio)13(n d)12(ur)-7(in)7(g t)-5(he lif)9(e c)-12(y)9(c)5(le o)13(f Dr)13(os)-7(o)11(p)8(hila mela)11(nogas)6(ter)57(. S)-12(cience, 2002.)]TJ
0 -1.2 TD
[(5 - H)23(o)-8(o)11(p)-8(er et al. I)25(den)20(t)-7(if)-11(ica)18(t)-7(io)13(n o)13(f t)-7(ig)-6(h)21(t)-5(l)8(y r)13(egula)17(ted g)-6(r)12(o)11(u)11(ps o)13(f g)8(enes d)12(ur)-7(in)7(g Dr)13(os)-7(o)11(p)8(hila mela)11(nogas)6(ter em)9(b)13(r)-27(y)9(og)8(enesis. M)26(o)8(l S)16(ys)6(t B)7(io)8(l , 2007.)]TJ
0 -1.2 TD
[(6 - P)18(a)17(pa)18(ts)-7(enk)9(o et al. T)87(em)20(p)-8(o)12(ral wa)20(v)9(es o)13(f co)8(her)13(en)20(t g)8(ene exp)13(r)12(es)5(sio)13(n d)12(ur)-7(in)7(g Dr)13(os)-7(o)11(p)8(hila em)10(b)13(r)-27(y)9(og)8(enesis. B)8(io)13(inf)9(o)12(r)-7(ma)17(t)-7(ic, 2010.)]TJ
T*
[(7 - G)8(ra)19(v)9(ele)-5(y et al. The de)-3(v)9(elo)11(p)12(men)20(t)-7(al t)-6(ra)9(n)10(s)-7(cr)-6(i)12(p)11(to)12(me o)12(f Dr)13(os)-7(o)11(p)8(hila mela)11(nogas)6(ter)57(. N)25(a)17(t)8(ur)12(e, 2011)]TJ
0 -1.2 TD
[(8 - Eden et al. GOr)-5(illa: A T)88(o)-8(o)8(l F)17(o)12(r Dis)-6(co)19(v)9(er)-27(y And V)47(is)6(ualiza)19(t)-7(io)13(n o)13(f Enr)-6(ic)5(hed GO T)87(er)-6(m)10(s in R)-13(a)9(nk)9(ed G)-7(ene Lis)6(ts. BM)8(C B)7(io)13(inf)9(o)12(r)-7(ma)17(t)-7(ics, 2009.)]TJ
0 -1.2 TD
[(9 \226 Chin)22(t)-7(a)17(palli et al. U)51(sin)7(g Fl)8(yA)39(t)-5(las to iden)22(t)-7(if)-16(y b)-7(et)8(ter Dr)13(os)-7(o)11(p)8(hila mo)-6(dels o)13(f h)21(uma)9(n dis)-6(eas)-6(e. N)25(a)17(t)8(ur)12(e G)-7(enet)-7(ics, 2007.)]TJ
0 0 0 0 k
30 0 0 30 769.6177 3060.2529 Tm
[(Fla)18(vio P)18(azos, R)-13(a)9(m\363)12(n Al)8(va)9(r)12(ez, G)17(us)5(t)-7(a)18(v)9(o G)16(uerb)-7(er)13(o)12(f)-11(f, R)-14(a)9(fael C)-6(a)9(n)20(tera)]TJ
23 0 0 23 87.625 3032.6528 Tm
[(1 - D)-7(epa)9(r)-10(t)-7(a)9(men)20(to de B)7(io)8(log)-6(\355a del N)24(eur)12(o)-8(desa)9(r)-7(r)13(o)8(llo del I)17(n)10(s)5(t)-7(i)12(t)8(uo de I)16(n)25(v)9(es)5(t)-7(igacio)13(nes B)7(io)8(l\363g)-6(icas Clemen)22(te Es)5(t)-7(a)7(b)8(le , 2 - I)17(n)10(s)5(t)-7(i)12(t)8(u)11(to de Es)5(t)-7(ad\355)1(s)5(t)-7(i)1(ca de la F)18(ac)-8(ul)11(t)-7(ad de Cienci)1(as Eco)12(n\363)12(micas, )1(3 - I)16(n)10(s)5(t)-7(i)12(t)8(u)11(to de M)16(a)17(tem\341)17(t)-7(ica y Es)5(t)-7(ad\355s)5(t)-7(ica de la F)18(ac)-8(ul)11(t)-7(ad de I)16(n)6(g)8(eni)1(er)-7(\355)1(a )]TJ
0.836 0.817 0.761 0.965 k
/T1_1 1 Tf
18 0 0 18 84.9155 1535.2275 Tm
[(T)87(o)9(t)-4(a)-4(l enr)-3(iche)-9(d GO t)9(emrs: 70)]TJ
0 0 0 1 k
/T1_0 1 Tf
T*
[(S)-12(elec)-7(ted ter)-7(m)10(s )-409( )-1797( )-1797( )-1797(P)38(-val)11(ue )-1018( E )]TJ
16 0 0 16 84.9155 1494.4277 Tm
[(r)12(ep)13(r)12(o)-8(d)11(uc)-8(t)-7(io)13(n )-1643( )-2047( )-2047( )-2047(2.12E-37 )-961(4.60 )]TJ
0 -1.2 TD
[(b)-7(o)-8(d)8(y mo)13(r)-10(p)8(hog)8(enesis )-1012( )-2047( )-2047(1.7E-11 )-1412(4.66)]TJ
T*
[(r)12(ed-o)15(x p)13(r)13(o)-8(ces)5(s )-1118( )-2047( )-2047( )-2047(6.33E-10 )-961(1.57 )]TJ
0 -1.2 TD
[(def)8(en)10(s)-6(e r)13(es)5(p)-8(o)12(n)10(s)-7(e )-269( )-2047( )-2047( )-2047(5.9E-9 )-1863(1.93 )]TJ
0 -2.55 TD
[(N)22(o)12(ne)]TJ
0.836 0.817 0.761 0.965 k
/T1_1 1 Tf
18 0 0 18 510.8579 1535.168 Tm
[(T)87(o)9(t)-4(a)-4(l enr)-3(iche)-9(d GO t)9(emrs: 23)]TJ
0 0 0 1 k
/T1_0 1 Tf
0 -1.2 TD
[(S)-12(elec)-7(ted ter)-7(m)10(s )-409( )-1797( )-1797( )-1797(P)38(-val)11(ue )-1018( E )]TJ
16 0 0 16 510.8579 1494.3682 Tm
[(micr)13(o)11(t)8(ub)11(ule-bas)-6(ed mo)19(v)9(emen)20(t )146( )-2047(8.59E-8 )-1412(2.36 )]TJ
0 -1.2 TD
[(male ga)10(mete g)8(enera)18(t)-7(io)13(n )67( )-2047( )-2047(1.85E-6 )-1412(2.43 )]TJ
T*
[(detec)-8(t)-7(io)13(n o)13(f c)5(hemical s)7(t)-7(im)20(ul)11(us )-1955(1.47E-6 )-1412(2.31 )]TJ
0 -1.2 TD
[(g)-7(l)8(y)9(co)8(l)8(ysis )-738( )-2047( )-2047( )-2047( )-2047(4.12E-6 )-1412(3.61 )]TJ
0 -2.4 TD
[(N)22(o)12(ne)]TJ
0.836 0.817 0.761 0.965 k
/T1_1 1 Tf
18 0 0 18 936.521 1534.8398 Tm
[(T)87(o)9(t)-4(a)-4(l enr)-3(iche)-9(d GO t)9(emrs: 548)]TJ
0 0 0 1 k
/T1_0 1 Tf
0 -1.2 TD
[(S)-12(elec)-7(ted ter)-7(m)10(s )-409( )-1797( )-1797( )-1797(P)38(-val)11(ue )-1018( E )]TJ
16 0 0 16 936.521 1494.04 Tm
[(micr)13(o)11(t)8(ub)11(ule-bas)-6(ed mo)19(v)9(emen)20(t )146( )-2047(8.59E-8 )-1412(2.36 )]TJ
0 -1.2 TD
[(male ga)10(mete g)8(enera)18(t)-7(io)13(n )67( )-2047( )-2047(1.85E-6 )-1412(2.43 )]TJ
T*
[(detec)-8(t)-7(io)13(n o)13(f c)5(hemical s)7(t)-7(im)20(ul)11(us )-1955(1.47E-6 )-1412(2.31 )]TJ
0 -1.2 TD
[(g)-7(l)8(y)9(co)8(l)8(ysis )-738( )-2047( )-2047( )-2047( )-2047(4.12E-6 )-1412(3.61 )]TJ
18 0 0 18 936.521 1414.8398 Tm
( )Tj
16 0 0 16 936.521 1395.6396 Tm
[(neur)13(og)8(enesis )-1668( )-2047( )-2047( )-2047(1.07E-60 )-961(2.2)]TJ
0 -1.2 TD
[(neur)13(o)12(n p)13(r)12(o)11(j)-6(ec)-8(t)-7(io)13(n mo)12(r)-9(p)8(hog)8(enesis )-663(4.38E-12 )-961(1.97)]TJ
0 -1.2 TD
[(neur)13(o)12(n dif)-10(f)8(er)13(en)20(t)-7(ia)18(t)-7(io)13(n )-551( )-2047( )-2047(6.25E-9 )-1412(2.56)]TJ
0 -1.2 TD
[(ner)-26(v)9(o)11(us sys)6(tem de)-5(v)9(elo)11(p)12(men)20(t )-255( )-2047(1.19E-8 )-1412(2.06)]TJ
0 -1.2 TD
[(p)-8(er)-7(i)12(p)8(heral ner)-25(v)67(. sys)6(tem de)-5(v)9(elo)11(p)26(. )-1337(2.69E-8 )-1412(2.18)]TJ
T*
[(neur)13(ob)8(las)6(t di)8(visio)13(n )-1680( )-2047( )-2047(3.63E-8 )-1412(2.93 )]TJ
T*
[(cen)20(t)-7(ral ner)-25(v)67(. sys)6(tem de)-5(v)9(elo)11(p)26(. )-368( )-2047(2.23E-6 )-1412(2.00)]TJ
0 -1.2 TD
[(ax)8(o)12(n guida)10(nce )-1157( )-2047( )-2047( )-2047(2.25E-6 )-1412(1.63)]TJ
0 -1.2 TD
[(r)12(egula)17(t)-7(io)13(n o)13(f neur)13(og)8(enesis )-1234( )-2047(2.63E-6 )-1412(1.87)]TJ
0 -1.2 TD
[(neur)13(o)12(n fa)18(te co)12(mmi)11(t)-7(men)20(t )-1752( )-2047(9.28E-5 )-1412(2.09)]TJ
0.836 0.817 0.761 0.965 k
/T1_1 1 Tf
18 0 0 18 1360.793 1535.168 Tm
[(T)87(o)9(t)-4(a)-4(l enr)-3(iche)-9(d GO t)9(emrs: 115)]TJ
0 0 0 1 k
/T1_0 1 Tf
0 -1.2 TD
[(S)-12(elec)-7(ted ter)-7(m)10(s )-409( )-1797( )-1797( )-1797(P)38(-val)11(ue )-1018( E )]TJ
16 0 0 16 1360.793 1494.3682 Tm
[(t)-7(ra)9(n)10(smem)9(b)13(ra)9(ne t)-6(ra)9(n)10(s)5(p)-8(o)12(r)-10(t )-1485( )-2047(1.12E-41 )-961(2.59 )]TJ
0 -1.2 TD
[(io)13(n t)-6(ra)9(n)10(s)5(p)-8(o)12(r)-9(t )-1663( )-2047( )-2047( )-2047(4.54E-28 )-961(2.47 )]TJ
T*
[(elec)-7(t)-7(r)12(o)12(n t)-6(ra)9(n)10(s)5(p)-8(o)12(r)-10(t c)5(ha)10(in )145( )-2047( )-2047(3.33E-21 )-961(3.98 )]TJ
0 -1.2 TD
[(sig)-5(nal t)-6(ra)9(n)10(s)-7(d)11(uc)-8(t)-7(io)13(n )-1637( )-2047( )-2047(6.93E-6 )-1412(1.32 )]TJ
0 -2.55 TD
[(K io)13(n t)-6(ra)9(n)10(smem)9(b)13(ra)9(ne t)-6(ra)9(n)10(s)5(p)-8(o)12(r)-9(t )-1486(1.33E-6 )-1412(4.73 )]TJ
0 -1.2 TD
[(b)-7(eha)19(vio)13(r )-1042( )-2047( )-2047( )-2047( )-2047(2.26E-4 )-1412(1.39)]TJ
0 -1.2 TD
[(syna)18(p)11(t)-7(ic t)-6(ra)9(n)10(smis)6(sio)13(n )-715( )-2047( )-2047(4.67E-4 )-1412(1.94 )]TJ
0 -1.2 TD
[(r)12(eg)-6(. o)13(f neur)13(o)11(t)-7(ra)9(n)10(s. le)-4(v)9(els )-1991( )-2047(4.95E-4 )-1412(1.78 )]TJ
T*
[(r)12(eg)-6(. o)13(f neur)13(o)11(t)-7(ra)9(n)10(s. t)-6(ra)9(n)10(s)5(p)-8(o)12(r)-10(t )-573( )-2047(5.11E-4 )-1412(3.49 )]TJ
T*
[(r)12(eg)-6(. o)13(f neur)13(o)11(t)-7(ra)9(n)10(s. s)-6(ecr)13(et)-7(io)13(n )-649( )-2047(5.11E-4 )-1412(3.49 )]TJ
0 -1.2 TD
[(la)9(r)-27(val lo)-7(co)12(mo)11(to)12(r)-27(y b)-7(eha)19(vio)13(r )-952( )-2047(5.57E-4 )-1412(2.98 )]TJ
0 -1.2 TD
[(syna)18(p)11(t)-7(ic v)10(esic)6(le ex)9(o)-8(c)-12(ytosis )-1259( )-2047(9.39E-4 )-1412(2.84)]TJ
0 -1.2 TD
[(r)12(eg)-6(. o)13(f calci)13(um io)13(n t)-6(ra)9(n)10(s)5(p)-8(o)12(r)-9(t via)]TJ
T*
[(v)9(o)8(l)11(t)-7(a)6(g)8(e-ga)17(ted C)-7(a c)6(ha)10(nnel ac)-6(t)-7(i)8(vi)12(ty )-1018(9.65E-4 )-1412(5.67 )]TJ
0.836 0.817 0.761 0.965 k
/T1_1 1 Tf
18 0 0 18 1786.6875 1536.168 Tm
[(T)87(o)9(t)-4(a)-4(l enr)-3(iche)-9(d GO t)9(emrs: 302)]TJ
0 0 0 1 k
/T1_0 1 Tf
0 -1.2 TD
[(S)-12(elec)-7(ted ter)-7(m)10(s )-409( )-1797( )-1797( )-1797(P)38(-val)11(ue )-1018( E )]TJ
16 0 0 16 1786.6875 1495.3682 Tm
[(cell)12(ula)9(r co)13(m)20(p)-8(o)12(nen)21(t o)12(r)10(ga)9(niza)19(t)-7(io)13(n )-1247(3.27E-24 )-961(1.44 )]TJ
0 -1.2 TD
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T*
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T*
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T*
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(20 )Tj
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W n
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f*
q
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h
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S
Q
BT
0.855 0.848 0.785 1 k
/T1_0 1 Tf
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(0 )Tj
-0.5 3.133 Td
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(40 )Tj
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(60 )Tj
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(80 )Tj
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ET
q
493.734 1570.326 424.797 263.083 re
W n
q
0 g
0 G
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Q
Q
q
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W n
q
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f*
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f*
q
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W n
q
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0 G
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Q
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h
f
Q
q
949.871 1599.529 381.514 217.733 re
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h
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S
Q
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(60 )Tj
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(80 )Tj
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T*
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ET
q
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W n
q
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Q
Q
q
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W n
q
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0 G
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Q
Q
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f*
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f*
q
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W n
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BT
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(40 )Tj
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(60 )Tj
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(80 )Tj
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(100 )Tj
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(120 )Tj
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(140 )Tj
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(160 )Tj
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(4 )Tj
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(5 )Tj
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(9 )Tj
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ET
q
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W n
q
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Q
Q
BT
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[(RPKM \(le)-3(v)9(el o)13(f exp)13(r)12(es)5(sio)13(n\))]TJ
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[(RPKM \(le)-3(v)9(el o)13(f exp)13(r)12(es)5(sio)13(n\))]TJ
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[(RP)1(KM \(le)-5(v)9(el o)12(f exp)12(r)12(es)5(si)1(o)12(n\))]TJ
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[(me)-5(a)5(n e)3(xp)10(r)9(es)4(s)4(io)10(n o)10(f 2.987 g)3(enes in )]TJ
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[(CL)28(US)9(TER )]TJ
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[(CL)28(US)9(TER )]TJ
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(2)Tj
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[(me)-5(a)5(n e)3(xp)10(r)9(es)4(s)4(io)10(n o)10(f 3.061 g)3(enes in )]TJ
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[(CL)28(US)9(TER )]TJ
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(3)Tj
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[(CL)28(US)9(TER )]TJ
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(4)Tj
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[(me)-5(a)5(n e)3(xp)10(r)9(es)4(s)4(io)10(n o)10(f 2.849 g)3(enes in )]TJ
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[(D)9(ISCUSS)11(I)8(O)9(N a)6(nd P)3(ERS)12(P)3(ECTIVES)]TJ
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f
BT
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[(F)18(a)17(t B)-19(o)-8(dies)]TJ
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ET
q
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W n
q
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Q
Q
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f*
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f*
q
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q
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Q
Q
q
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W n
q
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/Im0 Do
Q
Q
q
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W n
q
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Q
Q
q
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W n
q
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Q
Q
q
408.456 917.209 48 109.872 re
W n
q
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Q
Q
q
259.456 917.209 48.001 94.872 re
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[(N)32(um)9(b)-7(er o)13(f o)19(v)9(er exp)13(r)12(es)5(s)-7(ed g)8(enes )]TJ
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