%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Eman Badr, Mahmoud ElHefnawi, Lenwood S. Heath
Computational Identification of Tissue-Specific Splicing Regulatory Elements in Human Genes from RNA-Seq Data
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 9 0 R/Annots 10 0 R/Contents 11 0 R/TrimBox[0 0 612 792]>>
endobj
10 0 obj
[12 0 R 13 0 R 14 0 R 15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R]
endobj
12 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref003)>>
endobj
13 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref005)>>
endobj
14 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref006)>>
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref004)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref007)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref008)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref003)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref009)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref010)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref010)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref010)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref011)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref012)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref003)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref013)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref014)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref015)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref016)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref017)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref008)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref018)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref009)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref010)>>
endobj
35 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref019)>>
endobj
11 0 obj
[36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R]
endobj
36 0 obj
<>stream
q
0.83 0.64 0.02 0 k
374.0031 667.3323 m
378.7654 667.3323 l
h
f*
383.1874 667.3323 m
387.9496 667.3323 l
h
f*
392.4283 667.3323 m
397.1906 667.3323 l
h
f*
328.0819 641.3102 m
332.8441 641.3102 l
h
f*
337.3228 641.3102 m
342.085 641.3102 l
h
f*
346.5071 641.3102 m
351.2693 641.3102 l
h
f*
505.7008 628.3276 m
510.463 628.3276 l
h
f*
514.9417 628.3276 m
519.6472 628.3276 l
h
f*
330.8031 602.3055 m
340.3276 602.3055 l
h
f*
203.4142 563.3008 m
212.9386 563.3008 l
h
f*
382.6772 550.3181 m
392.2016 550.3181 l
h
f*
352.063 511.3134 m
361.5874 511.3134 l
h
f*
226.885 485.348 m
236.4094 485.348 l
h
f*
438.2929 446.3433 m
443.0551 446.3433 l
h
f*
255.8551 420.3213 m
265.3795 420.3213 l
h
f*
455.7543 342.3118 m
465.2787 342.3118 l
h
f*
264.8126 303.3071 m
274.2803 303.3071 l
h
f*
271.1622 264.3024 m
280.6866 264.3024 l
h
f*
203.4142 251.3197 m
212.9386 251.3197 l
h
f*
458.3055 251.3197 m
463.0677 251.3197 l
h
f*
264.6425 212.315 m
274.1669 212.315 l
h
f*
272.7496 160.3276 m
277.5118 160.3276 l
h
f*
264.6425 147.3449 m
274.1669 147.3449 l
h
f*
276.0945 108.3402 m
285.6189 108.3402 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(proteins,)Tj
3.736 0 Td
(called)Tj
2.5228 0 Td
(splicing)Tj
3.3165 0 Td
(factors.)Tj
3.1295 0 Td
(They)Tj
2.2336 0 Td
(bind)Tj
2.075 0 Td
(to)Tj
1.0205 0 Td
(certain)Tj
2.9876 0 Td
(short)Tj
2.2848 0 Td
(sequences)Tj
4.2179 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(pre-mRNA,)Tj
4.9662 0 Td
(called)Tj
-35.24 -1.3039 Td
(splicing)Tj
3.3165 0 Td
(regulatory)Tj
4.3199 0 Td
(elements)Tj
3.7644 0 Td
(\(SREs\).)Tj
3.1521 0 Td
(Identifying)Tj
4.6488 0 Td
(these)Tj
2.2507 0 Td
(SREs)Tj
2.2507 0 Td
(and)Tj
1.7291 0 Td
(their)Tj
2.109 0 Td
(combinatorial)Tj
5.8507 0 Td
(effects)Tj
2.7269 0 Td
(are)Tj
-36.1188 -1.2982 Td
(crucial)Tj
2.9139 0 Td
(to)Tj
1.0262 0 Td
(understanding)Tj
6.0661 0 Td
(AS.)Tj
1.6044 0 Td
(SREs)Tj
2.2507 0 Td
(are)Tj
1.4456 0 Td
(classified)Tj
3.8211 0 Td
(as)Tj
1.0148 0 Td
(enhancers)Tj
4.2803 0 Td
(if)Tj
0.7767 0 Td
(they)Tj
1.9219 0 Td
(promote)Tj
3.668 0 Td
(exon)Tj
2.16 0 Td
(inclusion)Tj
-32.9497 -1.2983 Td
(and)Tj
1.7291 0 Td
(silencers)Tj
3.6453 0 Td
(if)Tj
0.7767 0 Td
(they)Tj
1.9219 0 Td
(inhibit)Tj
2.9026 0 Td
(exon)Tj
2.1657 0 Td
(inclusion)Tj
3.9174 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(5)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
0.9241 0 Td
(6)Tj
0 g
(].)Tj
1.2586 0 Td
(Accurate)Tj
3.8097 0 Td
(splicing)Tj
3.3109 0 Td
(is)Tj
0.8504 0 Td
(crucial,)Tj
3.1407 0 Td
(as)Tj
1.0148 0 Td
(it)Tj
0.7824 0 Td
(is)Tj
0.8504 0 Td
(believed)Tj
-34.2593 -1.2983 Td
(that)Tj
1.7744 0 Td
(mutations)Tj
4.286 0 Td
(either)Tj
2.5285 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(core)Tj
1.9445 0 Td
(splicing)Tj
3.3166 0 Td
(signals)Tj
2.9026 0 Td
(or)Tj
1.0998 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(SREs)Tj
2.245 0 Td
(contribute)Tj
4.3937 0 Td
(to)Tj
1.0261 0 Td
(approximately)Tj
-30.5289 -1.3039 Td
(50%)Tj
1.9275 0 Td
(of)Tj
1.0148 0 Td
(human)Tj
3.0784 0 Td
(genetic)Tj
3.0671 0 Td
(diseases)Tj
3.3788 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2643 0 Td
(7)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
0.9184 0 Td
(8)Tj
0 g
(].)Tj
-13.4531 -1.2982 Td
(Alternative)Tj
4.6714 0 Td
(splicing)Tj
3.3165 0 Td
(plays)Tj
2.2337 0 Td
(a)Tj
0.652 0 Td
(key)Tj
1.5987 0 Td
(role)Tj
1.7632 0 Td
(in)Tj
1.0374 0 Td
(generating)Tj
4.4674 0 Td
(tissue-specific)Tj
5.777 0 Td
(proteins)Tj
3.5149 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2643 0 Td
(9)Tj
0 g
(].)Tj
1.2585 0 Td
(Tissue-spe-)Tj
-32.7512 -1.2983 Td
(cific)Tj
1.8878 0 Td
(alternative)Tj
4.422 0 Td
(splicing)Tj
3.3109 0 Td
(is)Tj
0.8504 0 Td
(regulated)Tj
3.9401 0 Td
(by)Tj
1.1792 0 Td
(a)Tj
0.652 0 Td
(combination)Tj
5.3517 0 Td
(of)Tj
1.0148 0 Td
(tissue-specific)Tj
5.777 0 Td
(and)Tj
1.7291 0 Td
(ubiquitously)Tj
-30.115 -1.3039 Td
(expressed)Tj
4.0932 0 Td
(RNA-binding)Tj
5.7429 0 Td
(factors)Tj
2.9027 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(].)Tj
2.0749 0 Td
(They)Tj
2.2394 0 Td
(interact)Tj
3.2825 0 Td
(with)Tj
2.0012 0 Td
(the)Tj
1.4684 0 Td
(splicing)Tj
3.3165 0 Td
(regulatory)Tj
4.3199 0 Td
(elements)Tj
3.7644 0 Td
(to)Tj
-35.206 -1.2983 Td
(affect)Tj
2.3754 0 Td
(the)Tj
1.4683 0 Td
(spliceosome)Tj
5.074 0 Td
(assembly)Tj
3.8267 0 Td
(\(splicing)Tj
3.6567 0 Td
(machinery\))Tj
4.8302 0 Td
(and)Tj
1.7348 0 Td
(consequently)Tj
5.4878 0 Td
(the)Tj
1.4684 0 Td
(transcribed)Tj
4.7508 0 Td
(iso-)Tj
-34.6731 -1.2983 Td
(forms.)Tj
2.7892 0 Td
(There)Tj
2.5795 0 Td
(are)Tj
1.4457 0 Td
(several)Tj
2.9367 0 Td
(splicing)Tj
3.3165 0 Td
(factors)Tj
2.9026 0 Td
(that)Tj
1.7802 0 Td
(activate)Tj
3.2541 0 Td
(or)Tj
1.0942 0 Td
(repress)Tj
3.0501 0 Td
(splicing)Tj
3.3165 0 Td
(in)Tj
1.0375 0 Td
(different)Tj
3.6566 0 Td
(contexts)Tj
-33.1594 -1.3039 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(].)Tj
2.0749 0 Td
(Skipping)Tj
3.7757 0 Td
(exons)Tj
2.5228 0 Td
(is)Tj
0.8504 0 Td
(one)Tj
1.7008 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(notable)Tj
3.1862 0 Td
(alternative)Tj
4.4163 0 Td
(splicing)Tj
3.3165 0 Td
(events)Tj
2.7269 0 Td
(between)Tj
3.532 0 Td
(different)Tj
3.6567 0 Td
(tissues)Tj
-34.2423 -1.2982 Td
(that)Tj
1.7744 0 Td
(results)Tj
2.8063 0 Td
(in)Tj
1.0375 0 Td
(different)Tj
3.651 0 Td
(proteins.)Tj
3.736 0 Td
(Wang,)Tj
2.8573 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1225 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(])Tj
1.8539 0 Td
(suggested)Tj
4.0705 0 Td
(that)Tj
1.7745 0 Td
(having)Tj
2.914 0 Td
(this)Tj
1.6724 0 Td
(switch-like)Tj
4.5638 0 Td
(regula-)Tj
-34.7752 -1.2983 Td
(tion)Tj
1.8425 0 Td
(between)Tj
3.5262 0 Td
(tissues)Tj
2.8177 0 Td
(requires)Tj
3.4752 0 Td
(additional)Tj
4.2746 0 Td
(splicing)Tj
3.3165 0 Td
(regulatory)Tj
4.32 0 Td
(elements)Tj
3.7644 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(present.)Tj
3.3902 0 Td
(Most)Tj
2.2791 0 Td
(work)Tj
-35.1834 -1.3039 Td
(in)Tj
1.0318 0 Td
(mammalian)Tj
5.0456 0 Td
(systems)Tj
3.2995 0 Td
(revealed)Tj
3.5263 0 Td
(that)Tj
1.7745 0 Td
(AS)Tj
1.3833 0 Td
(decisions)Tj
3.9061 0 Td
(are)Tj
1.4456 0 Td
(often)Tj
2.2847 0 Td
(made)Tj
2.4265 0 Td
(by)Tj
1.1792 0 Td
(a)Tj
0.6576 0 Td
(combinatorial)Tj
5.8507 0 Td
(action)Tj
2.6986 0 Td
(of)Tj
-36.51 -1.2983 Td
(general)Tj
3.1294 0 Td
(and)Tj
1.7291 0 Td
(tissue-specific)Tj
5.7826 0 Td
(regulators)Tj
4.2236 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(].)Tj
2.0807 0 Td
(Even)Tj
2.2166 0 Td
(simple)Tj
2.8517 0 Td
(tissue-specific)Tj
5.7826 0 Td
(decisions)Tj
3.9061 0 Td
(can)Tj
1.6271 0 Td
(involve)Tj
-33.3295 -1.2982 Td
(additional)Tj
4.2746 0 Td
(layers)Tj
2.5114 0 Td
(of)Tj
1.0148 0 Td
(complexity,)Tj
4.8699 0 Td
(where)Tj
2.6476 0 Td
(regulatory)Tj
4.32 0 Td
(elements)Tj
3.7643 0 Td
(cooperate)Tj
4.1273 0 Td
(or)Tj
1.0998 0 Td
(compete)Tj
3.6283 0 Td
(with)Tj
2.0013 0 Td
(each)Tj
-34.2593 -1.2983 Td
(other)Tj
2.347 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(].)Tj
-1.1508 -1.3039 Td
(Several)Tj
3.05 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
2.058 0 Td
(identified)Tj
4.0591 0 Td
(tissue-specific)Tj
5.7827 0 Td
(regulatory)Tj
4.32 0 Td
(elements.)Tj
3.9854 0 Td
(Mouse)Tj
2.9367 0 Td
(RNA-Seq)Tj
4.0139 0 Td
(data)Tj
1.9162 0 Td
(for)Tj
-36.3059 -1.2983 Td
(three)Tj
2.262 0 Td
(tissues)Tj
2.8233 0 Td
(\(brain,)Tj
2.9083 0 Td
(liver)Tj
1.9842 0 Td
(and)Tj
1.7292 0 Td
(skeletal)Tj
3.1521 0 Td
(muscle\))Tj
3.3618 0 Td
(were)Tj
2.1203 0 Td
(utilized)Tj
3.1918 0 Td
(to)Tj
1.0262 0 Td
(calculate)Tj
3.6736 0 Td
(the)Tj
1.474 0 Td
(expression)Tj
4.4618 0 Td
(level)Tj
2.0182 0 Td
(of)Tj
-36.1868 -1.2983 Td
(each)Tj
2.0295 0 Td
(isoform)Tj
3.3392 0 Td
(of)Tj
1.0148 0 Td
(genes)Tj
2.4435 0 Td
(for)Tj
1.3833 0 Td
(a)Tj
0.6519 0 Td
(set)Tj
1.304 0 Td
(of)Tj
1.0148 0 Td
(predefined)Tj
4.541 0 Td
(cassette)Tj
3.2429 0 Td
(exons)Tj
2.5228 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(].)Tj
1.6044 0 Td
(The)Tj
1.7801 0 Td
(authors)Tj
3.2485 0 Td
(identified)Tj
4.0592 0 Td
(456)Tj
-34.1799 -1.3039 Td
(putative)Tj
3.4412 0 Td
(enhancers)Tj
4.2803 0 Td
(and)Tj
1.7291 0 Td
(silencers.)Tj
3.8721 0 Td
(Among)Tj
3.2428 0 Td
(these,)Tj
2.4831 0 Td
(45)Tj
1.1679 0 Td
(were)Tj
2.126 0 Td
(common)Tj
3.8437 0 Td
(to)Tj
1.0262 0 Td
(all)Tj
1.1452 0 Td
(tissues.)Tj
-27.1614 -1.2982 Td
(Kim)Tj
1.9842 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1225 0 Td
([)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(])Tj
1.8539 0 Td
(utilized)Tj
3.1917 0 Td
(a)Tj
0.652 0 Td
(distribution-based)Tj
7.5741 0 Td
(quantitative)Tj
4.9776 0 Td
(association)Tj
4.6262 0 Td
(rule)Tj
1.7914 0 Td
(mining)Tj
3.1351 0 Td
(to)Tj
1.0262 0 Td
(find)Tj
-34.0722 -1.2983 Td
(exonic)Tj
2.8516 0 Td
(and)Tj
1.7348 0 Td
(intronic)Tj
3.4469 0 Td
(sequence)Tj
3.8607 0 Td
(motifs)Tj
2.761 0 Td
(in)Tj
1.0374 0 Td
(10)Tj
1.1679 0 Td
(mouse)Tj
2.8573 0 Td
(tissues.)Tj
3.0444 0 Td
(Combinatorial)Tj
/F10 1 Tf
6.0945 0 Td
[()1()-4()]TJ
/F5 1 Tf
(-regulatory)Tj
5.6352 0 Td
(motifs)Tj
-34.4917 -1.3039 Td
(were)Tj
2.1203 0 Td
(also)Tj
1.7688 0 Td
(discovered.)Tj
4.7338 0 Td
(The)Tj
1.7801 0 Td
(author)Tj
2.8857 0 Td
(identified)Tj
4.0592 0 Td
(statistically)Tj
4.6091 0 Td
(significant)Tj
4.388 0 Td
(associations)Tj
4.9889 0 Td
(between)Tj
-31.3339 -1.2983 Td
(sequence)Tj
3.855 0 Td
(motifs)Tj
2.761 0 Td
(and)Tj
1.7348 0 Td
(tissue-specific)Tj
5.7769 0 Td
(exon)Tj
2.1657 0 Td
(skipping)Tj
3.6567 0 Td
(rates.)Tj
2.3357 0 Td
(Ninety-seven)Tj
5.5105 0 Td
(interesting)Tj
4.4901 0 Td
(association)Tj
-32.2864 -1.2983 Td
(rules)Tj
2.1486 0 Td
(were)Tj
2.1203 0 Td
(identified,)Tj
4.286 0 Td
(of)Tj
1.0148 0 Td
(which)Tj
2.6475 0 Td
(three)Tj
2.2677 0 Td
(contain)Tj
3.2485 0 Td
(multiple)Tj
3.5659 0 Td
(7-mers.)Tj
-20.1031 -1.2982 Td
(Focusing)Tj
3.8494 0 Td
(on)Tj
1.2756 0 Td
(human)Tj
3.0784 0 Td
(tissues,)Tj
3.0444 0 Td
(a)Tj
0.6519 0 Td
(varying)Tj
3.2202 0 Td
(effect)Tj
2.364 0 Td
(regression)Tj
4.32 0 Td
(model)Tj
2.7439 0 Td
(on)Tj
1.2756 0 Td
(splicing)Tj
3.3165 0 Td
(elements)Tj
-30.3361 -1.3039 Td
(\(VERSE\))Tj
3.8267 0 Td
(was)Tj
1.7008 0 Td
(developed)Tj
4.2746 0 Td
(to)Tj
1.0205 0 Td
(predict)Tj
3.05 0 Td
(genome-wide)Tj
5.6636 0 Td
(intronic)Tj
3.4469 0 Td
(SREs)Tj
2.2507 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(],)Tj
2.075 0 Td
(where)Tj
2.6532 0 Td
(RNA-Seq)Tj
4.0195 0 Td
(data)Tj
1.9105 0 Td
(for)Tj
-35.892 -1.2983 Td
(16)Tj
1.1678 0 Td
(human)Tj
3.0784 0 Td
(tissues)Tj
2.8233 0 Td
(was)Tj
1.6951 0 Td
(used.)Tj
2.2847 0 Td
(Approximately)Tj
6.2305 0 Td
(half)Tj
1.7122 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(SREs)Tj
2.2507 0 Td
(\(55.68%\))Tj
3.787 0 Td
(were)Tj
2.1203 0 Td
(found)Tj
2.6192 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(signifi-)Tj
-34.4293 -1.2983 Td
(cant)Tj
1.9218 0 Td
(only)Tj
1.9786 0 Td
(in)Tj
1.0375 0 Td
(one)Tj
1.6951 0 Td
(tissue.)Tj
-5.4368 -1.3039 Td
(Castle,)Tj
2.8743 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1282 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(])Tj
1.8481 0 Td
(designed)Tj
3.7644 0 Td
(microarrays)Tj
5.0343 0 Td
(monitoring)Tj
4.8189 0 Td
(exons)Tj
2.5285 0 Td
(and)Tj
1.7291 0 Td
(exon-exon)Tj
4.4617 0 Td
(junctions)Tj
3.9571 0 Td
(in)Tj
-34.2819 -1.2982 Td
(17,939)Tj
2.8232 0 Td
(human)Tj
3.0784 0 Td
(genes.)Tj
2.6646 0 Td
(For)Tj
1.6271 0 Td
(the)Tj
1.4683 0 Td
(regulatory)Tj
4.32 0 Td
(elements,)Tj
3.9911 0 Td
(they)Tj
1.9219 0 Td
(extracted)Tj
3.8891 0 Td
(sequences)Tj
4.218 0 Td
(in)Tj
1.0318 0 Td
(eight)Tj
2.2053 0 Td
(neighbor-)Tj
-33.2388 -1.2983 Td
(hoods)Tj
2.6475 0 Td
(around)Tj
3.1351 0 Td
(regulated)Tj
3.9401 0 Td
(exons)Tj
2.5228 0 Td
(where)Tj
2.6533 0 Td
(135)Tj
1.644 0 Td
(motifs)Tj
2.761 0 Td
(were)Tj
2.1259 0 Td
(identified.)Tj
-20.2335 -1.3039 Td
(Brudno,)Tj
3.5092 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1282 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(])Tj
1.8482 0 Td
(identified)Tj
4.0592 0 Td
(intronic)Tj
3.4526 0 Td
(regulatory)Tj
4.3199 0 Td
(elements)Tj
3.7644 0 Td
(that)Tj
1.7802 0 Td
(are)Tj
1.4456 0 Td
(brain-specific,)Tj
5.896 0 Td
(while,)Tj
2.5966 0 Td
(in)Tj
-35.9374 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(],)Tj
2.0749 0 Td
(the)Tj
1.4683 0 Td
(identified)Tj
4.0592 0 Td
(regulatory)Tj
4.32 0 Td
(elements)Tj
3.7644 0 Td
(were)Tj
2.1203 0 Td
(muscle-specific.)Tj
6.5706 0 Td
(In)Tj
1.1112 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(],)Tj
1.5988 0 Td
(a)Tj
0.6519 0 Td
(probabilistic)Tj
5.1931 0 Td
(approach)Tj
-32.9327 -1.2983 Td
(was)Tj
1.6951 0 Td
(utilized)Tj
3.1917 0 Td
(and)Tj
1.7292 0 Td
(several)Tj
2.9366 0 Td
(intronic)Tj
3.4526 0 Td
(regulatory)Tj
4.32 0 Td
(elements)Tj
3.7644 0 Td
(in)Tj
1.0318 0 Td
(different)Tj
3.6567 0 Td
(human)Tj
3.0784 0 Td
(tissues)Tj
2.8233 0 Td
(were)Tj
-31.6798 -1.3039 Td
(identified.)Tj
1.1962 -1.2982 Td
(Wang,)Tj
2.8629 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1225 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8539 0 Td
(developed)Tj
4.2689 0 Td
(a)Tj
0.6577 0 Td
(linear)Tj
2.5115 0 Td
(regression)Tj
4.3143 0 Td
(model)Tj
2.7439 0 Td
(to)Tj
1.0261 0 Td
(estimate)Tj
3.549 0 Td
(the)Tj
1.4683 0 Td
(effect)Tj
2.3641 0 Td
(of)Tj
1.0148 0 Td
(various)Tj
3.1407 0 Td
(splic-)Tj
-35.0359 -1.2983 Td
(ing)Tj
1.5023 0 Td
(factors)Tj
2.9027 0 Td
(on)Tj
1.2755 0 Td
(exon)Tj
2.16 0 Td
(inclusion)Tj
3.9175 0 Td
(between)Tj
3.5319 0 Td
(two)Tj
1.7065 0 Td
(tissues,)Tj
3.0444 0 Td
(and,)Tj
1.9559 0 Td
(hence,)Tj
2.7949 0 Td
(the)Tj
1.4683 0 Td
(binding)Tj
3.3506 0 Td
(sites)Tj
1.9332 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2507 0 Td
(splic-)Tj
-34.8092 -1.2983 Td
(ing)Tj
1.5023 0 Td
(factors)Tj
2.9027 0 Td
(are)Tj
1.4456 0 Td
(predicted.)Tj
4.2236 0 Td
(They)Tj
2.2394 0 Td
(applied)Tj
3.1521 0 Td
(their)Tj
2.1089 0 Td
(model)Tj
2.744 0 Td
(on)Tj
1.2755 0 Td
(data)Tj
1.9163 0 Td
(from)Tj
2.2053 0 Td
(liver)Tj
1.9842 0 Td
(and)Tj
1.7292 0 Td
(heart)Tj
2.2733 0 Td
(tissues)Tj
2.8176 0 Td
(and)Tj
-34.52 -1.3039 Td
(predicted)Tj
3.9968 0 Td
(15)Tj
1.1735 0 Td
(motifs)Tj
2.7609 0 Td
(that)Tj
1.7802 0 Td
(contribute)Tj
4.388 0 Td
(to)Tj
1.0261 0 Td
(exon)Tj
2.1657 0 Td
(skipping)Tj
3.6623 0 Td
(events.)Tj
2.9537 0 Td
(The)Tj
1.7801 0 Td
(work)Tj
2.2791 0 Td
(was)Tj
1.7008 0 Td
(extended)Tj
3.8551 0 Td
(to)Tj
1.0261 0 Td
(11)Tj
-34.5484 -1.2983 Td
(human)Tj
3.0784 0 Td
(tissues)Tj
2.8176 0 Td
(in)Tj
1.0374 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(].)Tj
-5.7372 -1.2982 Td
(Wang,)Tj
2.8629 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1225 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(],)Tj
2.0807 0 Td
(analyzed)Tj
3.702 0 Td
(10)Tj
1.1679 0 Td
(human)Tj
3.0784 0 Td
(tissues.)Tj
3.0443 0 Td
(A)Tj
0.9071 0 Td
(high)Tj
2.0069 0 Td
(frequency)Tj
4.1896 0 Td
(of)Tj
1.0148 0 Td
(tissue-specific)Tj
5.777 0 Td
(regulation)Tj
-33.0914 -1.3039 Td
(was)Tj
1.6951 0 Td
(observed)Tj
3.7984 0 Td
(for)Tj
1.3833 0 Td
(each)Tj
2.0296 0 Td
(of)Tj
1.0147 0 Td
(various)Tj
3.1465 0 Td
(alternative)Tj
4.4163 0 Td
(splicing)Tj
3.3165 0 Td
(event)Tj
2.3698 0 Td
(types,)Tj
2.5001 0 Td
(including)Tj
4.0422 0 Td
(over)Tj
1.9786 0 Td
(60%)Tj
1.9275 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-34.6334 -1.2983 Td
(analyzed)Tj
3.702 0 Td
(skipped)Tj
3.3278 0 Td
(exons.)Tj
-5.8336 -1.2983 Td
(Ke)Tj
1.3209 0 Td
(and)Tj
1.7291 0 Td
(Chasin)Tj
3.0217 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(])Tj
1.8539 0 Td
(utilized)Tj
3.1861 0 Td
(a)Tj
0.6576 0 Td
(hypergeometric)Tj
6.514 0 Td
(test)Tj
1.5987 0 Td
(to)Tj
1.0262 0 Td
(discover)Tj
3.5546 0 Td
(sequence)Tj
3.8608 0 Td
(pairs)Tj
2.1713 0 Td
(that)Tj
1.7745 0 Td
(are)Tj
1.4513 0 Td
(over-)Tj
-34.9169 -1.3039 Td
(represented)Tj
4.9095 0 Td
(in)Tj
1.0318 0 Td
(intronic)Tj
3.4526 0 Td
(regions)Tj
3.1635 0 Td
(flanking)Tj
3.5149 0 Td
(human)Tj
3.0784 0 Td
(exons.)Tj
2.7496 0 Td
(They)Tj
2.2393 0 Td
(identified)Tj
4.0592 0 Td
(more)Tj
2.3414 0 Td
(than)Tj
2.0296 0 Td
(60,000)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 397.3039 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Splicing)Tj
3.6496 0 Td
(Regulator)Tj
4.252 0 Td
(y)Tj
0.7157 0 Td
(Elemen)Tj
3.3308 0 Td
(ts)Tj
0.9921 0 Td
(and)Tj
1.8567 0 Td
(Tissue)Tj
3.1182 0 Td
(Specificity)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.4748 0 Td
(DOI:10.137)Tj
5.0387 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.0166)Tj
3.5434 0 Td
(978)Tj
2.6362 0 Td
(November)Tj
4.7622 0 Td
(18,)Tj
1.5874 0 Td
(2016)Tj
36.7515 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
37 0 obj
<>stream
endstream
endobj
38 0 obj
<>stream
endstream
endobj
39 0 obj
<>stream
endstream
endobj
40 0 obj
<>stream
endstream
endobj
41 0 obj
<>stream
endstream
endobj
42 0 obj
<>stream
endstream
endobj
43 0 obj
<>stream
endstream
endobj
44 0 obj
<>stream
endstream
endobj
45 0 obj
<>stream
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
endstream
endobj
49 0 obj
<>stream
endstream
endobj
50 0 obj
<>stream
endstream
endobj
51 0 obj
<>stream
endstream
endobj
52 0 obj
<>stream
endstream
endobj
53 0 obj
<>stream
BT
66.402 0 Td
(18)Tj
ET
Q
endstream
endobj
54 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 9 0 R/Annots 58 0 R/Contents 59 0 R/TrimBox[0 0 612 792]>>
endobj
58 0 obj
[60 0 R 61 0 R 62 0 R 63 0 R 64 0 R 65 0 R 66 0 R 67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R 74 0 R 75 0 R 76 0 R 77 0 R 78 0 R 79 0 R 80 0 R 81 0 R 82 0 R 83 0 R 84 0 R 85 0 R 86 0 R]
endobj
60 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref020)>>
endobj
61 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref008)>>
endobj
62 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref014)>>
endobj
63 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref016)>>
endobj
64 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref017)>>
endobj
65 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref009)>>
endobj
66 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref018)>>
endobj
67 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref021)>>
endobj
68 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref028)>>
endobj
69 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref021)>>
endobj
70 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref019)>>
endobj
71 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref020)>>
endobj
72 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref020)>>
endobj
73 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref019)>>
endobj
74 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref029)>>
endobj
75 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref030)>>
endobj
76 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref021)>>
endobj
77 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref031)>>
endobj
78 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref029)>>
endobj
79 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref022)>>
endobj
80 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref023)>>
endobj
81 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref024)>>
endobj
82 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref025)>>
endobj
83 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref026)>>
endobj
84 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref027)>>
endobj
85 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref028)>>
endobj
86 0 obj
<>/Border[0 0 0]/Dest(Rpone.0166978.ref025)>>
endobj
59 0 obj
[87 0 R 88 0 R 89 0 R 90 0 R 91 0 R 92 0 R 93 0 R 94 0 R 95 0 R 96 0 R 97 0 R 98 0 R 99 0 R 100 0 R 101 0 R 102 0 R 103 0 R 104 0 R 105 0 R 106 0 R 107 0 R 108 0 R]
endobj
87 0 obj
<>stream
q
0.83 0.64 0.02 0 k
439.7102 667.3323 m
449.178 667.3323 l
h
f*
316.6866 602.3055 m
321.3921 602.3055 l
h
f*
325.8709 602.3055 m
335.3953 602.3055 l
h
f*
339.8173 602.3055 m
349.3417 602.3055 l
h
f*
353.8205 602.3055 m
363.3449 602.3055 l
h
f*
423.8362 602.3055 m
428.5984 602.3055 l
h
f*
433.0205 602.3055 m
442.5449 602.3055 l
h
f*
556.0441 576.3402 m
565.5685 576.3402 l
h
f*
200.0126 563.3008 m
209.537 563.3008 l
h
f*
251.6031 537.3354 m
261.1276 537.3354 l
h
f*
511.6535 524.2961 m
521.1213 524.2961 l
h
f*
525.6 524.2961 m
535.1244 524.2961 l
h
f*
557.4614 524.2961 m
566.9858 524.2961 l
h
f*
546.1795 511.3134 m
555.7039 511.3134 l
h
f*
233.5748 459.326 m
243.0992 459.326 l
h
f*
375.7606 459.326 m
385.285 459.326 l
h
f*
373.2094 446.3433 m
382.7339 446.3433 l
h
f*
448.4976 446.3433 m
458.022 446.3433 l
h
f*
458.5323 289.9276 m
468.0567 289.9276 l
h
f*
252.6803 224.9008 m
262.2047 224.9008 l
h
f*
329.2157 198.9354 m
338.7402 198.9354 l
h
f*
377.9717 146.948 m
387.4394 146.948 l
h
f*
331.3134 133.9087 m
340.7811 133.9087 l
h
f*
225.4677 120.926 m
234.9921 120.926 l
h
f*
507.2882 120.926 m
516.8126 120.926 l
h
f*
517.7197 94.9039 m
527.2441 94.9039 l
h
f*
203.4142 81.9213 m
212.9386 81.9213 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(5-mer)Tj
2.6588 0 Td
(sequence)Tj
3.8608 0 Td
(pairs)Tj
2.1713 0 Td
(with)Tj
/F10 1 Tf
1.9956 0 Td
[()]TJ
/F11 1 Tf
0 Tc
0.6973 0 Td
()Tj
/F5 1 Tf
-0.004 Tc
0.9865 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 333.2409 711.8362 cm
BT
/F12 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()]TJ
/F5 1 Tf
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 341.0645 707.4141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(.)Tj
0.4478 0 Td
(They)Tj
2.2337 0 Td
(showed)Tj
3.2542 0 Td
(that)Tj
1.7744 0 Td
(some)Tj
2.3358 0 Td
(pairs)Tj
2.1656 0 Td
(are)Tj
1.4514 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9955 0 Td
(tissue-)Tj
-34.0211 -1.3039 Td
(specific)Tj
3.1918 0 Td
(genes.)Tj
-1.9955 -1.2982 Td
(Taking)Tj
3.0443 0 Td
(into)Tj
1.8426 0 Td
(consideration)Tj
5.7032 0 Td
(the)Tj
1.4684 0 Td
(combinatorial)Tj
5.8505 0 Td
(effect)Tj
2.3641 0 Td
(of)Tj
1.0148 0 Td
(SREs,)Tj
2.4775 0 Td
(a)Tj
0.6519 0 Td
(biophysical)Tj
4.7339 0 Td
(principals)Tj
4.1725 0 Td
(based)Tj
-34.52 -1.2983 Td
(regression)Tj
4.32 0 Td
(model)Tj
2.7439 0 Td
(for)Tj
1.3833 0 Td
(the)Tj
1.4684 0 Td
(regulation)Tj
4.3085 0 Td
(of)Tj
1.0148 0 Td
(AS)Tj
1.3833 0 Td
(was)Tj
1.7008 0 Td
(developed)Tj
4.2689 0 Td
(in)Tj
1.0375 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(].)Tj
2.0749 0 Td
(It)Tj
0.8561 0 Td
(captures)Tj
3.5773 0 Td
(both)Tj
2.0636 0 Td
(the)Tj
1.4684 0 Td
(main)Tj
-33.6697 -1.2983 Td
(effects)Tj
2.727 0 Td
(of)Tj
1.0148 0 Td
(individual)Tj
4.2859 0 Td
(SREs)Tj
2.245 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4684 0 Td
(combinatorial)Tj
5.8505 0 Td
(effects)Tj
2.7269 0 Td
(of)Tj
1.0148 0 Td
(SRE)Tj
1.8822 0 Td
(pairs.)Tj
2.3981 0 Td
(Overall,)Tj
3.3676 0 Td
(619)Tj
1.6497 0 Td
(different)Tj
-32.3657 -1.3039 Td
(SREs)Tj
2.2451 0 Td
(and)Tj
1.7291 0 Td
(196)Tj
1.6497 0 Td
(SRE)Tj
1.8879 0 Td
(pairs)Tj
2.1713 0 Td
(were)Tj
2.1203 0 Td
(detected)Tj
3.5659 0 Td
(from)Tj
2.2053 0 Td
(different)Tj
3.6567 0 Td
(tissues.)Tj
3.0444 0 Td
(Their)Tj
2.4208 0 Td
(model)Tj
2.7439 0 Td
(was)Tj
1.7008 0 Td
(limited)Tj
3.067 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
-35.2344 -1.2982 Td
(interaction)Tj
4.6035 0 Td
(of)Tj
1.0148 0 Td
(at)Tj
0.9524 0 Td
(most)Tj
2.211 0 Td
(two)Tj
1.7065 0 Td
(SREs.)Tj
-9.2919 -1.2983 Td
(As)Tj
1.2699 0 Td
(discussed)Tj
3.9968 0 Td
(above,)Tj
2.7723 0 Td
(most)Tj
2.2053 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(human)Tj
3.0783 0 Td
(tissue-specific)Tj
5.7827 0 Td
(studies)Tj
2.982 0 Td
(focus)Tj
2.3301 0 Td
(on)Tj
1.2756 0 Td
(identifying)Tj
4.575 0 Td
(individ-)Tj
-33.9474 -1.3039 Td
(ual)Tj
1.4287 0 Td
(SREs)Tj
2.245 0 Td
(in)Tj
1.0375 0 Td
(intronic)Tj
3.4526 0 Td
(regions)Tj
3.1634 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(14)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(16)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.4002 0 Td
(17)Tj
0 g
(].)Tj
1.7348 0 Td
(Wang,)Tj
2.8573 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1282 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(18)Tj
0 g
(])Tj
1.5137 0 Td
(identified)Tj
4.0592 0 Td
(SREs)Tj
2.245 0 Td
(in)Tj
1.0375 0 Td
(both)Tj
2.0579 0 Td
(intronic)Tj
-34.2139 -1.2983 Td
(and)Tj
1.7292 0 Td
(exonic)Tj
2.8573 0 Td
(regions.)Tj
3.3845 0 Td
(However,)Tj
4.0762 0 Td
(the)Tj
1.474 0 Td
(focus)Tj
2.3243 0 Td
(was)Tj
1.7008 0 Td
(only)Tj
1.9729 0 Td
(on)Tj
1.2756 0 Td
(individual)Tj
4.2916 0 Td
(regulatory)Tj
4.32 0 Td
(elements)Tj
3.7644 0 Td
(as)Tj
1.0148 0 Td
(well.)Tj
-34.1856 -1.2983 Td
(There)Tj
2.5739 0 Td
(are)Tj
1.4513 0 Td
(other)Tj
2.3471 0 Td
(studies)Tj
2.9877 0 Td
(that)Tj
1.7801 0 Td
(identify)Tj
3.2938 0 Td
(individual)Tj
4.2859 0 Td
(SREs)Tj
2.2507 0 Td
(in)Tj
1.0318 0 Td
(both)Tj
2.0636 0 Td
(exonic)Tj
2.8517 0 Td
(and)Tj
1.7291 0 Td
(intronic)Tj
3.4526 0 Td
(regions)Tj
3.1634 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
-35.2627 -1.3039 Td
(28)Tj
0 g
(],)Tj
1.7348 0 Td
(which)Tj
2.6532 0 Td
(we)Tj
1.3267 0 Td
(use)Tj
1.5307 0 Td
(for)Tj
1.3889 0 Td
(comparing)Tj
4.5694 0 Td
(our)Tj
1.627 0 Td
(results.)Tj
3.0331 0 Td
(However,)Tj
4.0762 0 Td
(the)Tj
1.474 0 Td
(focus)Tj
2.3244 0 Td
(in)Tj
1.0374 0 Td
(these)Tj
2.2507 0 Td
(studies)Tj
2.9877 0 Td
(was)Tj
1.7008 0 Td
(not)Tj
1.5704 0 Td
(on)Tj
-35.2854 -1.2982 Td
(tissue-specific)Tj
5.777 0 Td
(SREs.)Tj
2.4718 0 Td
(For)Tj
1.6271 0 Td
(more)Tj
2.3414 0 Td
(detailed)Tj
3.3674 0 Td
(review)Tj
2.846 0 Td
(about)Tj
2.4945 0 Td
(these)Tj
2.2563 0 Td
(approaches,)Tj
4.9606 0 Td
(please)Tj
2.6249 0 Td
(refer)Tj
2.0976 0 Td
(to)Tj
1.0262 0 Td
(our)Tj
1.627 0 Td
(pre-)Tj
-35.5178 -1.2983 Td
(vious)Tj
2.3358 0 Td
(paper)Tj
2.4831 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(].)Tj
-3.6226 -1.3039 Td
(The)Tj
1.7858 0 Td
(tissue-specific)Tj
5.7769 0 Td
(studies)Tj
2.9877 0 Td
(that)Tj
1.7802 0 Td
(focus)Tj
2.3243 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(combinatorial)Tj
5.8507 0 Td
(SRE)Tj
1.8878 0 Td
(effect)Tj
2.3641 0 Td
(were)Tj
2.126 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(20)Tj
0 g
(].)Tj
1.7348 0 Td
(In)Tj
1.1111 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(],)Tj
-35.4044 -1.2983 Td
(out)Tj
1.5534 0 Td
(of)Tj
1.0148 0 Td
(196)Tj
1.6441 0 Td
(identified)Tj
4.0592 0 Td
(SRE)Tj
1.8878 0 Td
(pairs,)Tj
2.3981 0 Td
(only)Tj
1.9728 0 Td
(two)Tj
1.7122 0 Td
(pairs)Tj
2.1713 0 Td
(have)Tj
2.0579 0 Td
(both)Tj
2.058 0 Td
(SREs)Tj
2.2507 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(exonic)Tj
2.8516 0 Td
(region.)Tj
3.0274 0 Td
(In)Tj
1.1112 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(],)Tj
-34.2763 -1.2982 Td
(the)Tj
1.4684 0 Td
(identified)Tj
4.0592 0 Td
(pairs)Tj
2.1713 0 Td
(reside)Tj
2.5908 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(intronic)Tj
3.4524 0 Td
(regions.)Tj
-15.0517 -1.2983 Td
(In)Tj
1.1111 0 Td
(this)Tj
1.6725 0 Td
(work,)Tj
2.5058 0 Td
(we)Tj
1.3266 0 Td
(performed)Tj
4.473 0 Td
(genome-wide)Tj
5.6578 0 Td
(analysis)Tj
3.3279 0 Td
(to)Tj
1.0261 0 Td
(study)Tj
2.3868 0 Td
(alternative)Tj
4.422 0 Td
(splicing)Tj
3.3165 0 Td
(on)Tj
1.2756 0 Td
(multiple)Tj
-33.698 -1.3039 Td
(tissues)Tj
2.8177 0 Td
(\(brain,)Tj
2.914 0 Td
(heart,)Tj
2.5001 0 Td
(liver,)Tj
2.211 0 Td
(and)Tj
1.7291 0 Td
(muscle\).)Tj
3.5829 0 Td
(The)Tj
1.7858 0 Td
(RNA-Seq)Tj
4.0195 0 Td
(data)Tj
1.9106 0 Td
(set)Tj
1.3039 0 Td
(from)Tj
2.2053 0 Td
(the)Tj
1.4684 0 Td
(Human)Tj
3.3222 0 Td
(BodyMap)Tj
-31.7705 -1.2983 Td
(project)Tj
3.0161 0 Td
([)Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(])Tj
1.8538 0 Td
(was)Tj
1.6951 0 Td
(utilized.)Tj
3.4186 0 Td
(We)Tj
1.6101 0 Td
(used)Tj
2.0579 0 Td
(DEXSeq)Tj
3.5829 0 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(])Tj
1.8538 0 Td
(to)Tj
1.0262 0 Td
(identify)Tj
3.2938 0 Td
(differential)Tj
4.6034 0 Td
(exons)Tj
2.5229 0 Td
(across)Tj
2.6815 0 Td
(tissues.)Tj
-33.2161 -1.2983 Td
(Then,)Tj
2.5569 0 Td
(we)Tj
1.3266 0 Td
(applied)Tj
3.1521 0 Td
(our)Tj
1.6271 0 Td
(algorithms,)Tj
4.7395 0 Td
(GenSRE)Tj
3.5772 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(])Tj
1.8481 0 Td
(and)Tj
1.7348 0 Td
(CoSREM)Tj
3.9458 0 Td
([)Tj
0.83 0.64 0.02 0 k
(31)Tj
0 g
(],)Tj
2.0807 0 Td
(to)Tj
1.0204 0 Td
(identify)Tj
3.2995 0 Td
(both)Tj
2.058 0 Td
(individual)Tj
-32.9667 -1.3039 Td
(and)Tj
1.7292 0 Td
(combinatorial)Tj
5.8506 0 Td
(exonic)Tj
2.8517 0 Td
(regulatory)Tj
4.3198 0 Td
(elements)Tj
3.7644 0 Td
(responsible)Tj
4.7565 0 Td
(for)Tj
1.3833 0 Td
(exons)Tj
2.5285 0 Td
(that)Tj
1.7745 0 Td
(exist)Tj
2.0353 0 Td
(in)Tj
1.0374 0 Td
(one)Tj
1.7008 0 Td
(tissue)Tj
2.4548 0 Td
(but)Tj
-36.1868 -1.2982 Td
(not)Tj
1.5704 0 Td
(in)Tj
1.0375 0 Td
(other)Tj
2.3471 0 Td
(tissues.)Tj
3.0444 0 Td
(Putative)Tj
3.4866 0 Td
(tissue-specific)Tj
5.7768 0 Td
(exonic)Tj
2.8573 0 Td
(enhancers)Tj
4.2803 0 Td
(were)Tj
2.1203 0 Td
(discovered)Tj
4.5071 0 Td
(and)Tj
1.7348 0 Td
(a)Tj
0.6519 0 Td
(compli-)Tj
-33.4145 -1.2983 Td
(cated)Tj
2.3244 0 Td
(exonic)Tj
2.8573 0 Td
(enhancer)Tj
3.9175 0 Td
(regulatory)Tj
4.32 0 Td
(network)Tj
3.5488 0 Td
(was)Tj
1.7008 0 Td
(revealed.)Tj
3.7474 0 Td
(Multiple)Tj
3.6396 0 Td
(exonic)Tj
2.8573 0 Td
(enhancers)Tj
4.2803 0 Td
(were)Tj
-33.1934 -1.3039 Td
(found)Tj
2.6192 0 Td
(across)Tj
2.6759 0 Td
(multiple)Tj
3.566 0 Td
(tissues,)Tj
3.0444 0 Td
(while)Tj
2.3696 0 Td
(some)Tj
2.3301 0 Td
(were)Tj
2.126 0 Td
(found)Tj
2.6135 0 Td
(only)Tj
1.9786 0 Td
(in)Tj
1.0374 0 Td
(specific)Tj
3.1918 0 Td
(tissues.)Tj
3.0444 0 Td
(Putative)Tj
3.4809 0 Td
(combi-)Tj
-34.0778 -1.2983 Td
(natorial)Tj
3.3279 0 Td
(exonic)Tj
2.8516 0 Td
(enhancers)Tj
4.2803 0 Td
(and)Tj
1.7348 0 Td
(silencers)Tj
3.6452 0 Td
(were)Tj
2.1203 0 Td
(discovered)Tj
4.5071 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(that)Tj
1.7802 0 Td
(may)Tj
1.9275 0 Td
(be)Tj
1.1509 0 Td
(responsible)Tj
4.7508 0 Td
(for)Tj
-34.9112 -1.2983 Td
(exon)Tj
2.1657 0 Td
(inclusion)Tj
3.9118 0 Td
(or)Tj
1.0998 0 Td
(exclusion)Tj
3.9912 0 Td
(across)Tj
2.6759 0 Td
(tissues.)Tj
3.0443 0 Td
(This)Tj
1.9899 0 Td
(is,)Tj
1.0715 0 Td
(to)Tj
1.0261 0 Td
(our)Tj
1.6271 0 Td
(knowledge,)Tj
4.7678 0 Td
(the)Tj
1.4683 0 Td
(first)Tj
1.8029 0 Td
(analysis)Tj
3.3278 0 Td
(to)Tj
1.0262 0 Td
(focus)Tj
-34.9963 -1.2982 Td
(only)Tj
1.9729 0 Td
(on)Tj
1.2756 0 Td
(discovering)Tj
4.8416 0 Td
(exonic)Tj
2.8516 0 Td
(regulatory)Tj
4.3199 0 Td
(elements)Tj
3.7644 0 Td
(\(individual)Tj
4.6261 0 Td
(and)Tj
1.7348 0 Td
(combinatorial\))Tj
6.1851 0 Td
(across)Tj
2.6816 0 Td
(tissues.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 325.9842 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(Methods)Tj
/F0 1 Tf
-6.4961 -1.4976 Td
(Data)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 291.0047 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(RNA-Seq)Tj
4.0195 0 Td
(data)Tj
1.9105 0 Td
(from)Tj
2.2053 0 Td
(the)Tj
1.474 0 Td
(Human)Tj
3.3166 0 Td
(BodyMap)Tj
4.1328 0 Td
(2.0)Tj
1.3947 0 Td
(project)Tj
3.016 0 Td
(is)Tj
0.8504 0 Td
(utilized)Tj
3.1918 0 Td
([)Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(].)Tj
2.0749 0 Td
(This)Tj
1.99 0 Td
(data)Tj
1.9105 0 Td
(originates)Tj
-31.487 -1.2982 Td
(from)Tj
2.2053 0 Td
(16)Tj
1.1679 0 Td
(different)Tj
3.6566 0 Td
(human)Tj
3.0784 0 Td
(tissues.)Tj
3.0444 0 Td
(It)Tj
0.8617 0 Td
(contains)Tj
3.6057 0 Td
(50)Tj
1.1735 0 Td
(bp)Tj
1.2416 0 Td
(paired-end)Tj
4.6148 0 Td
(reads,)Tj
2.5625 0 Td
(75)Tj
1.1678 0 Td
(bp)Tj
1.2473 0 Td
(single-end)Tj
4.3823 0 Td
(reads,)Tj
-34.0098 -1.3039 Td
(and)Tj
1.7291 0 Td
(100)Tj
1.6441 0 Td
(bp)Tj
1.2472 0 Td
(single-end)Tj
4.3823 0 Td
(reads.)Tj
2.5625 0 Td
(We)Tj
1.6101 0 Td
(focus)Tj
2.3244 0 Td
(on)Tj
1.2756 0 Td
(four)Tj
1.9162 0 Td
(tissues,)Tj
3.0444 0 Td
(namely,)Tj
3.3732 0 Td
(brain,)Tj
2.5738 0 Td
(heart,)Tj
2.5002 0 Td
(liver,)Tj
2.2053 0 Td
(and)Tj
1.7291 0 Td
(muscle.)Tj
-34.1175 -1.2983 Td
(All)Tj
1.3946 0 Td
(the)Tj
1.4683 0 Td
(samples)Tj
3.3846 0 Td
(provided)Tj
3.8154 0 Td
(for)Tj
1.3889 0 Td
(tissues)Tj
2.8177 0 Td
(of)Tj
1.0148 0 Td
(interest)Tj
3.2144 0 Td
(have)Tj
2.058 0 Td
(been)Tj
2.1203 0 Td
(utilized.)Tj
-21.4808 -1.2983 Td
(For)Tj
1.627 0 Td
(comparing)Tj
4.5751 0 Td
(our)Tj
1.6271 0 Td
(results)Tj
2.8063 0 Td
(with)Tj
2.0012 0 Td
(previously)Tj
4.3484 0 Td
(published)Tj
4.1272 0 Td
(results,)Tj
3.033 0 Td
(several)Tj
2.931 0 Td
(databases)Tj
4.0025 0 Td
(are)Tj
1.4514 0 Td
(utilized.)Tj
-33.7264 -1.3039 Td
(SpliceAid-F)Tj
4.9265 0 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(])Tj
1.8539 0 Td
(is)Tj
0.8504 0 Td
(a)Tj
0.6519 0 Td
(recent)Tj
2.7099 0 Td
(comprehensive)Tj
6.2872 0 Td
(database)Tj
3.6397 0 Td
(that)Tj
1.7801 0 Td
(includes)Tj
3.5433 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4684 0 Td
(experimentally)Tj
6.1624 0 Td
(veri-)Tj
-35.0189 -1.2982 Td
(fied)Tj
1.7234 0 Td
(splicing)Tj
3.3165 0 Td
(factors)Tj
2.9027 0 Td
(and)Tj
1.7291 0 Td
(their)Tj
2.109 0 Td
(binding)Tj
3.3505 0 Td
(sites.)Tj
2.16 0 Td
(It)Tj
0.856 0 Td
(contains)Tj
3.6114 0 Td
(71)Tj
1.1678 0 Td
(splicing)Tj
3.3165 0 Td
(factors)Tj
2.9027 0 Td
(and)Tj
1.7291 0 Td
(655)Tj
1.6498 0 Td
(binding)Tj
3.3505 0 Td
(sites)Tj
-35.875 -1.2983 Td
(for)Tj
1.3776 0 Td
(human.)Tj
3.2938 0 Td
(We)Tj
1.5987 0 Td
(also)Tj
1.7632 0 Td
(used)Tj
2.0523 0 Td
(AEdb)Tj
2.5001 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(],)Tj
2.0636 0 Td
(which)Tj
2.6419 0 Td
(is)Tj
0.839 0 Td
(a)Tj
0.6463 0 Td
(database)Tj
3.634 0 Td
(for)Tj
1.3776 0 Td
(alternative)Tj
4.4107 0 Td
(exons)Tj
2.5172 0 Td
(and)Tj
1.7234 0 Td
(their)Tj
2.0977 0 Td
(proper-)Tj
-34.5371 -1.3039 Td
(ties)Tj
1.5703 0 Td
(from)Tj
2.2054 0 Td
(various)Tj
3.1407 0 Td
(species;)Tj
3.2202 0 Td
(it)Tj
0.788 0 Td
(is)Tj
0.8504 0 Td
(the)Tj
1.4683 0 Td
(manually)Tj
3.9288 0 Td
(curated)Tj
3.2258 0 Td
(component)Tj
4.8132 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(Alternative)Tj
4.6658 0 Td
(Splicing)Tj
-32.3657 -1.2983 Td
(Database)Tj
3.8437 0 Td
(\(ASD\).)Tj
3.0217 0 Td
(The)Tj
1.7858 0 Td
(exon)Tj
2.1657 0 Td
(data)Tj
1.9105 0 Td
(in)Tj
1.0375 0 Td
(AEdb)Tj
2.5058 0 Td
(have)Tj
2.0636 0 Td
(been)Tj
2.1203 0 Td
(experimentally)Tj
6.1568 0 Td
(verified.)Tj
-25.4152 -1.2983 Td
(In)Tj
1.1111 0 Td
(addition,)Tj
3.8211 0 Td
(we)Tj
1.3266 0 Td
(compared)Tj
4.2463 0 Td
(our)Tj
1.6271 0 Td
(putative)Tj
3.4412 0 Td
(exonic)Tj
2.8516 0 Td
(splicing)Tj
3.3166 0 Td
(enhancers)Tj
4.2859 0 Td
(\(ESEs\))Tj
2.8743 0 Td
(with)Tj
1.9956 0 Td
(five)Tj
1.6554 0 Td
(other)Tj
-33.749 -1.2982 Td
(computational)Tj
6.049 0 Td
(data)Tj
1.9106 0 Td
(sets.)Tj
1.8935 0 Td
(The)Tj
1.7802 0 Td
(RESCUE-ESE)Tj
5.8223 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(])Tj
1.8482 0 Td
(data)Tj
1.9162 0 Td
(set)Tj
1.3039 0 Td
(contains)Tj
3.6056 0 Td
(238)Tj
1.6441 0 Td
(6-mers)Tj
3.0217 0 Td
(for)Tj
1.389 0 Td
(human)Tj
-32.1843 -1.3039 Td
(exons.)Tj
2.7495 0 Td
(Another)Tj
3.583 0 Td
(data)Tj
1.9105 0 Td
(set)Tj
1.304 0 Td
(is)Tj
0.8504 0 Td
(PESE)Tj
2.3924 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(],)Tj
2.0749 0 Td
(where)Tj
2.6476 0 Td
(2096)Tj
2.126 0 Td
(8-mers)Tj
3.0217 0 Td
(were)Tj
2.1203 0 Td
(identified.)Tj
4.2859 0 Td
(The)Tj
1.7802 0 Td
(third)Tj
2.2166 0 Td
(data)Tj
1.9106 0 Td
(set)Tj
1.3039 0 Td
(is)Tj
-36.2775 -1.2983 Td
(from)Tj
2.2053 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(])Tj
1.8482 0 Td
(and)Tj
1.7348 0 Td
(contains)Tj
3.6056 0 Td
(4-)Tj
1.0488 0 Td
(and)Tj
1.7291 0 Td
(5-mers)Tj
3.0218 0 Td
(as)Tj
1.0148 0 Td
(potential)Tj
3.7587 0 Td
(ESEs.)Tj
2.4207 0 Td
(In)Tj
1.1112 0 Td
(the)Tj
1.4684 0 Td
(data)Tj
1.9105 0 Td
(set)Tj
1.3039 0 Td
(from)Tj
2.2054 0 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(],)Tj
2.0806 0 Td
(the)Tj
1.4683 0 Td
(authors)Tj
-33.9361 -1.2983 Td
(concentrated)Tj
5.4481 0 Td
(on)Tj
1.2756 0 Td
(5-mer)Tj
2.6589 0 Td
(putative)Tj
3.4412 0 Td
(ESEs.)Tj
-11.6276 -1.3039 Td
(For)Tj
1.627 0 Td
(exonic)Tj
2.8573 0 Td
(splicing)Tj
3.3166 0 Td
(silencers)Tj
3.6453 0 Td
(\(ESSs\),)Tj
3.0047 0 Td
(we)Tj
1.3266 0 Td
(compared)Tj
4.2463 0 Td
(our)Tj
1.6271 0 Td
(results)Tj
2.8062 0 Td
(with)Tj
2.0013 0 Td
(FAS-ESS)Tj
3.7757 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(],)Tj
2.075 0 Td
(and)Tj
1.7347 0 Td
(PESS)Tj
-35.24 -1.2982 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(].)Tj
2.0749 0 Td
(The)Tj
1.7801 0 Td
(FAS-ESS)Tj
3.7814 0 Td
(data)Tj
1.9162 0 Td
(set)Tj
1.2983 0 Td
(contains)Tj
3.6113 0 Td
(130)Tj
1.6441 0 Td
(10-mer)Tj
3.1408 0 Td
(sequences)Tj
4.2179 0 Td
(that)Tj
1.7745 0 Td
(were)Tj
2.1259 0 Td
(identified)Tj
4.0592 0 Td
(utilizing)Tj
3.5206 0 Td
(the)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 397.3039 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Splicing)Tj
3.6496 0 Td
(Regulator)Tj
4.252 0 Td
(y)Tj
0.7157 0 Td
(Elemen)Tj
3.3308 0 Td
(ts)Tj
0.9921 0 Td
(and)Tj
1.8567 0 Td
(Tissue)Tj
3.1182 0 Td
(Specificity)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.4748 0 Td
(DOI:10.137)Tj
5.0387 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.0166)Tj
3.5434 0 Td
(978)Tj
2.6362 0 Td
(November)Tj
4.7622 0 Td
(18,)Tj
1.5874 0 Td
(2016)Tj
36.7515 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
88 0 obj
<>stream
endstream
endobj
89 0 obj
<>stream
endstream
endobj
90 0 obj
<>stream
endstream
endobj
91 0 obj
<>stream
endstream
endobj
92 0 obj
<>stream
endstream
endobj
93 0 obj
<>stream
endstream
endobj
94 0 obj
<>stream
endstream
endobj
95 0 obj
<>stream
endstream
endobj
96 0 obj
<>stream
endstream
endobj
97 0 obj
<>stream
endstream
endobj
98 0 obj
<>stream
endstream
endobj
99 0 obj
<>stream
endstream
endobj
100 0 obj
<>stream
endstream
endobj
101 0 obj
<>stream
endstream
endobj
102 0 obj
<>stream
endstream
endobj
103 0 obj
<>stream
endstream
endobj
104 0 obj
<>stream
endstream
endobj
105 0 obj
<>stream
endstream
endobj
106 0 obj
<>stream
endstream
endobj
107 0 obj
<>stream
endstream
endobj
108 0 obj
<>stream
BT
66.402 0 Td
(18)Tj
ET
Q
endstream
endobj
109 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 9 0 R/Annots 112 0 R/Contents 113 0 R/TrimBox[0 0 612 792]>>
endobj
111 0 obj
<>stream
JFIF C
$, !$4.763.22:ASF:=N>22HbINVX]^]8EfmeZlS[]Y C**Y;2;YYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY ("
} !1AQa"q2#BR$3br
%&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz
w !1AQaq"2B #3Rbr
$4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ? (
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
*裒k>Mt|8Ic+HҜHW6h{ny?_ij̎翶_w?/֏Tdt4W=s