%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Benedikt Zacher, Margaux Michel, Björn Schwalb, Patrick Cramer, Achim Tresch, Julien Gagneur
Accurate Promoter and Enhancer Identification in 127 ENCODE and Roadmap Epigenomics Cell Types and Tissues by GenoSTAN
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 10 0 R/Annots 11 0 R/Contents 12 0 R/TrimBox[0 0 612 792]>>
endobj
11 0 obj
[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 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]
endobj
13 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref003)>>
endobj
14 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref005)>>
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref006)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref010)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref011)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref012)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref013)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref014)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref015)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref016)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref006)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref010)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref017)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref020)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref008)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref009)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref011)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref013)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref021)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref024)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref025)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref008)>>
endobj
35 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref021)>>
endobj
36 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref026)>>
endobj
37 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref027)>>
endobj
38 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref009)>>
endobj
39 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref022)>>
endobj
40 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref028)>>
endobj
41 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref028)>>
endobj
42 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref011)>>
endobj
43 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref011)>>
endobj
44 0 obj
<>/Border[0 0 0]/Dest(Rpone.0169249.ref028)>>
endobj
12 0 obj
[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 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R 62 0 R 63 0 R 64 0 R 65 0 R 66 0 R]
endobj
45 0 obj
<>stream
q
0.83 0.64 0.02 0 k
508.7055 680.315 m
513.4677 680.315 l
h
f*
518.6835 680.315 m
523.4457 680.315 l
h
f*
424.8 641.3102 m
429.5622 641.3102 l
h
f*
434.7213 641.3102 m
444.2457 641.3102 l
h
f*
530.8724 602.3055 m
540.3969 602.3055 l
h
f*
544.8756 602.3055 m
554.3433 602.3055 l
h
f*
318.7276 589.3228 m
328.252 589.3228 l
h
f*
394.6394 589.3228 m
404.1638 589.3228 l
h
f*
474.6331 589.3228 m
484.1575 589.3228 l
h
f*
488.5795 589.3228 m
498.1039 589.3228 l
h
f*
377.8016 563.3008 m
382.5638 563.3008 l
h
f*
386.9858 563.3008 m
396.5102 563.3008 l
h
f*
555.7039 537.3354 m
565.1717 537.3354 l
h
f*
200.0126 524.2961 m
209.537 524.2961 l
h
f*
333.4677 472.3087 m
338.2299 472.3087 l
h
f*
342.7087 472.3087 m
347.4709 472.3087 l
h
f*
351.8929 472.3087 m
361.4173 472.3087 l
h
f*
365.8394 472.3087 m
375.3638 472.3087 l
h
f*
379.8425 472.3087 m
389.3669 472.3087 l
h
f*
394.526 472.3087 m
404.0504 472.3087 l
h
f*
336.1323 420.3213 m
345.6567 420.3213 l
h
f*
353.9339 394.2992 m
358.6961 394.2992 l
h
f*
363.1181 394.2992 m
372.6425 394.2992 l
h
f*
377.1213 394.2992 m
386.6457 394.2992 l
h
f*
395.7732 303.3071 m
405.2976 303.3071 l
h
f*
448.1008 303.3071 m
452.863 303.3071 l
h
f*
457.3417 303.3071 m
466.8661 303.3071 l
h
f*
512.2772 238.337 m
521.8016 238.337 l
h
f*
250.1858 134.3055 m
259.6535 134.3055 l
h
f*
217.1339 108.3402 m
226.6583 108.3402 l
h
f*
340.5543 108.3402 m
350.0787 108.3402 l
h
f*
483.3071 108.3402 m
492.7748 108.3402 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(functional)Tj
4.3086 0 Td
(definition)Tj
4.1612 0 Td
(of)Tj
1.0148 0 Td
(enhancers)Tj
4.2803 0 Td
(and)Tj
1.7348 0 Td
(promoters)Tj
4.3937 0 Td
(leads)Tj
2.211 0 Td
(to)Tj
1.0261 0 Td
(practical)Tj
3.634 0 Td
(difficulties)Tj
4.405 0 Td
(for)Tj
1.389 0 Td
(their)Tj
-32.5585 -1.3039 Td
(genome-wide)Tj
5.6579 0 Td
(identification)Tj
5.5842 0 Td
(because)Tj
3.3222 0 Td
(the)Tj
1.4683 0 Td
(direct)Tj
2.5342 0 Td
(measurement)Tj
5.6692 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(regulatory)Tj
4.3199 0 Td
(activity)Tj
3.1181 0 Td
(of)Tj
1.0148 0 Td
(geno-)Tj
-35.172 -1.2982 Td
(mic)Tj
1.7291 0 Td
(regions)Tj
3.1634 0 Td
(is)Tj
0.8504 0 Td
(hard,)Tj
2.3017 0 Td
(with)Tj
2.0013 0 Td
(current)Tj
3.1804 0 Td
(approaches)Tj
4.7395 0 Td
(leading)Tj
3.1295 0 Td
(to)Tj
1.0261 0 Td
(contradicting)Tj
5.6012 0 Td
(results)Tj
2.812 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(].)Tj
-29.3384 -1.2983 Td
(Since)Tj
2.3527 0 Td
(the)Tj
1.4683 0 Td
(direct)Tj
2.5229 0 Td
(measurement)Tj
5.6635 0 Td
(of)Tj
1.0092 0 Td
(cis-regulatory)Tj
5.7203 0 Td
(activity)Tj
3.1124 0 Td
(is)Tj
0.839 0 Td
(challenging,)Tj
5.0343 0 Td
(a)Tj
0.652 0 Td
(biochemical)Tj
5.057 0 Td
(charac-)Tj
-34.6278 -1.2983 Td
(terization)Tj
4.0478 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(chromatin)Tj
4.4164 0 Td
(at)Tj
0.9524 0 Td
(these)Tj
2.2564 0 Td
(elements)Tj
3.7644 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2755 0 Td
(histone)Tj
3.1522 0 Td
(modifications,)Tj
5.964 0 Td
(DNA)Tj
2.3754 0 Td
(accessibil-)Tj
-33.1594 -1.3039 Td
(ity,)Tj
1.4626 0 Td
(and)Tj
1.7291 0 Td
(transcription)Tj
5.4369 0 Td
(factor)Tj
2.5398 0 Td
(binding)Tj
3.3505 0 Td
(has)Tj
1.5421 0 Td
(been)Tj
2.1259 0 Td
(proposed)Tj
3.9515 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(].)Tj
3.0671 0 Td
(This)Tj
1.9899 0 Td
(approach)Tj
3.9514 0 Td
(leverages)Tj
-31.1468 -1.2982 Td
(extensive)Tj
3.8834 0 Td
(genome-wide)Tj
5.6636 0 Td
(datasets)Tj
3.3562 0 Td
(of)Tj
1.0148 0 Td
(chromatin-immunoprecipitation)Tj
13.3964 0 Td
(followed)Tj
3.651 0 Td
(by)Tj
1.1792 0 Td
(sequencing)Tj
-32.1446 -1.2983 Td
(\(ChIP-Seq\))Tj
4.7451 0 Td
(of)Tj
1.0148 0 Td
(transcription)Tj
5.4312 0 Td
(factors)Tj
2.9083 0 Td
(\(TFs\),)Tj
2.6249 0 Td
(histone)Tj
3.1521 0 Td
(modifications,)Tj
5.9583 0 Td
(or)Tj
1.0999 0 Td
(Cap)Tj
1.8368 0 Td
(analysis)Tj
3.3222 0 Td
(gene)Tj
2.0806 0 Td
(expres-)Tj
-34.1742 -1.3039 Td
(sion)Tj
1.9048 0 Td
(\(CAGE\))Tj
3.532 0 Td
(that)Tj
1.7744 0 Td
(have)Tj
2.0637 0 Td
(been)Tj
2.1203 0 Td
(generated)Tj
4.1385 0 Td
(by)Tj
1.1792 0 Td
(collaborative)Tj
5.3405 0 Td
(projects)Tj
3.3788 0 Td
(such)Tj
2.058 0 Td
(as)Tj
1.0148 0 Td
(ENCODE)Tj
4.2406 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7404 0 Td
(12)Tj
0 g
(],)Tj
-34.486 -1.2983 Td
(NIH)Tj
2.0636 0 Td
(Roadmap)Tj
4.0818 0 Td
(Epigenomics)Tj
5.3858 0 Td
([)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(],)Tj
2.0806 0 Td
(BLUEPRINT)Tj
5.5105 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(])Tj
1.8482 0 Td
(and)Tj
1.7348 0 Td
(FANTOM)Tj
4.4164 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(16)Tj
0 g
(].)Tj
-27.6603 -1.2983 Td
(In)Tj
1.1111 0 Td
(this)Tj
1.6725 0 Td
(context,)Tj
3.4129 0 Td
(the)Tj
1.4683 0 Td
(computational)Tj
6.0491 0 Td
(approaches)Tj
4.7338 0 Td
(employed)Tj
4.1442 0 Td
(to)Tj
1.0205 0 Td
(classify)Tj
3.0557 0 Td
(genomic)Tj
3.6737 0 Td
(regions)Tj
3.1635 0 Td
(as)Tj
-34.7015 -1.3039 Td
(enhancers)Tj
4.2802 0 Td
(or)Tj
1.0999 0 Td
(promoters)Tj
4.3936 0 Td
(play)Tj
1.8709 0 Td
(a)Tj
0.6576 0 Td
(decisive)Tj
3.3676 0 Td
(role)Tj
1.7688 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(10)Tj
0 g
(].)Tj
1.7404 0 Td
(As)Tj
1.2643 0 Td
(the)Tj
1.4683 0 Td
(experimental)Tj
5.4595 0 Td
(data)Tj
1.9105 0 Td
(are)Tj
1.4514 0 Td
(heteroge-)Tj
-31.9916 -1.2982 Td
(neous,)Tj
2.8119 0 Td
(we)Tj
1.3266 0 Td
(generally)Tj
3.8324 0 Td
(refer)Tj
2.092 0 Td
(to)Tj
1.0261 0 Td
(them)Tj
2.2904 0 Td
(as)Tj
1.0091 0 Td
(tracks.)Tj
2.829 0 Td
(Several)Tj
3.05 0 Td
(studies)Tj
2.9821 0 Td
(used)Tj
2.0579 0 Td
(supervised)Tj
4.456 0 Td
(learning)Tj
3.5206 0 Td
(techniques)Tj
-33.2841 -1.2983 Td
(to)Tj
1.0261 0 Td
(predict)Tj
3.0444 0 Td
(enhancers)Tj
4.2859 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(tracks)Tj
2.6022 0 Td
(such)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(histone)Tj
3.1521 0 Td
(modifications)Tj
5.7373 0 Td
(or)Tj
1.0942 0 Td
(P300)Tj
2.2053 0 Td
(binding)Tj
3.3505 0 Td
(\(e.g.)Tj
1.9049 0 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
-35.2287 -1.3039 Td
(20)Tj
0 g
(]\).)Tj
2.0749 0 Td
(However,)Tj
4.0762 0 Td
(a)Tj
0.6576 0 Td
(training)Tj
3.4186 0 Td
(set)Tj
1.3039 0 Td
(of)Tj
1.0148 0 Td
(validated)Tj
3.8324 0 Td
(enhancers)Tj
4.2803 0 Td
(is)Tj
0.8504 0 Td
(needed)Tj
3.0954 0 Td
(in)Tj
1.0318 0 Td
(this)Tj
1.6781 0 Td
(case,)Tj
2.0863 0 Td
(which)Tj
2.6476 0 Td
(is)Tj
0.8503 0 Td
(hard)Tj
2.0807 0 Td
(to)Tj
-34.9793 -1.2983 Td
(define)Tj
2.6985 0 Td
(since)Tj
2.2394 0 Td
(only)Tj
1.9785 0 Td
(few)Tj
1.6158 0 Td
(enhancers)Tj
4.2803 0 Td
(have)Tj
2.0636 0 Td
(been)Tj
2.1203 0 Td
(validated)Tj
3.8324 0 Td
(experimentally)Tj
6.1625 0 Td
(so)Tj
1.0885 0 Td
(far)Tj
1.3096 0 Td
(and)Tj
1.7291 0 Td
(these)Tj
2.2564 0 Td
(might)Tj
2.5965 0 Td
(be)Tj
-35.9714 -1.2982 Td
(biased)Tj
2.7382 0 Td
(towards)Tj
3.4016 0 Td
(specific)Tj
3.1917 0 Td
(enhancer)Tj
3.9232 0 Td
(subclasses.)Tj
4.4503 0 Td
(Alternatively,)Tj
5.5956 0 Td
(unsupervised)Tj
5.5332 0 Td
(learning)Tj
3.5206 0 Td
(algorithms)Tj
-32.3544 -1.2983 Td
(were)Tj
2.1203 0 Td
(developed)Tj
4.2746 0 Td
(to)Tj
1.0204 0 Td
(identify)Tj
3.2995 0 Td
(promoters)Tj
4.3937 0 Td
(and)Tj
1.7291 0 Td
(enhancers)Tj
4.286 0 Td
(from)Tj
2.2053 0 Td
(combinations)Tj
5.709 0 Td
(of)Tj
1.0148 0 Td
(histone)Tj
3.1521 0 Td
(marks)Tj
2.6985 0 Td
(and)Tj
-35.9033 -1.3039 Td
(protein-DNA)Tj
5.6579 0 Td
(interactions)Tj
4.9719 0 Td
(alone)Tj
2.3754 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2643 0 Td
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
0.9184 0 Td
(11)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(13)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.4003 0 Td
(21)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(].)Tj
3.2032 0 Td
(These)Tj
2.5681 0 Td
(unsupervised)Tj
5.5332 0 Td
(methods)Tj
3.685 0 Td
(perform)Tj
-32.9723 -1.2983 Td
(genome)Tj
3.4072 0 Td
(segmentation,)Tj
5.8393 0 Td
(i.e.)Tj
1.3606 0 Td
(they)Tj
1.9219 0 Td
(model)Tj
2.7496 0 Td
(the)Tj
1.4683 0 Td
(genome)Tj
3.4073 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6519 0 Td
(succession)Tj
4.422 0 Td
(of)Tj
1.0148 0 Td
(segments)Tj
3.9232 0 Td
(in)Tj
1.0374 0 Td
(different)Tj
-32.2183 -1.2983 Td
(chromatin)Tj
4.4163 0 Td
(states)Tj
2.3981 0 Td
(defined)Tj
3.2258 0 Td
(by)Tj
1.1792 0 Td
(characteristic)Tj
5.5445 0 Td
(combinations)Tj
5.709 0 Td
(of)Tj
1.0148 0 Td
(histone)Tj
3.1521 0 Td
(marks)Tj
2.7042 0 Td
(and)Tj
1.7291 0 Td
(protein-DNA)Tj
-31.0731 -1.3039 Td
(interactions)Tj
4.9662 0 Td
(found)Tj
2.6192 0 Td
(recurrently)Tj
4.6828 0 Td
(throughout)Tj
4.7735 0 Td
(the)Tj
1.474 0 Td
(genome.)Tj
3.6284 0 Td
(All)Tj
1.4003 0 Td
(popular)Tj
3.3392 0 Td
(genome)Tj
3.4072 0 Td
(segmentations)Tj
5.9754 0 Td
(are)Tj
-36.2662 -1.2982 Td
(based)Tj
2.4717 0 Td
(on)Tj
1.2756 0 Td
(hidden)Tj
3.0444 0 Td
(Markov)Tj
3.3732 0 Td
(models)Tj
3.1068 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(],)Tj
2.0749 0 Td
(or)Tj
1.0999 0 Td
(their)Tj
2.1089 0 Td
(generalized)Tj
4.7622 0 Td
(form)Tj
2.2053 0 Td
(\(dynamic)Tj
4.0365 0 Td
(Bayesian)Tj
3.7247 0 Td
(networks\).)Tj
-33.2841 -1.2983 Td
(However,)Tj
4.0761 0 Td
(these)Tj
2.2564 0 Td
(methods)Tj
3.6794 0 Td
(differ)Tj
2.3867 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(way)Tj
1.7915 0 Td
(the)Tj
1.474 0 Td
(distribution)Tj
4.9663 0 Td
(of)Tj
1.0148 0 Td
(ChIP-seq)Tj
3.9515 0 Td
(signals)Tj
2.9026 0 Td
(for)Tj
1.389 0 Td
(each)Tj
2.0239 0 Td
(chro-)Tj
-34.418 -1.3039 Td
(matin)Tj
2.5851 0 Td
(state)Tj
2.0353 0 Td
(is)Tj
0.8504 0 Td
(modeled.)Tj
3.9174 0 Td
(ChromHMM)Tj
5.6636 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
(21)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.4003 0 Td
(26)Tj
0 g
(],)Tj
1.7348 0 Td
(one)Tj
1.7008 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7121 0 Td
(methods)Tj
3.685 0 Td
(applied)Tj
3.1521 0 Td
(by)Tj
1.1793 0 Td
(the)Tj
-33.3579 -1.2983 Td
(ENCODE)Tj
4.2406 0 Td
(consortium,)Tj
5.0739 0 Td
(requires)Tj
3.4753 0 Td
(binarized)Tj
3.9798 0 Td
(ChIP-seq)Tj
3.9515 0 Td
(signals)Tj
2.9026 0 Td
(that)Tj
1.7802 0 Td
(are)Tj
1.4456 0 Td
(then)Tj
2.0183 0 Td
(modeled)Tj
3.6964 0 Td
(with)Tj
1.9955 0 Td
(inde-)Tj
-34.5597 -1.2983 Td
(pendent)Tj
3.5035 0 Td
(Bernoulli)Tj
3.9402 0 Td
(distributions)Tj
5.3291 0 Td
(\(conditioning)Tj
5.7373 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(hidden)Tj
3.0444 0 Td
(state\).)Tj
2.5965 0 Td
(Consequently,)Tj
5.9584 0 Td
(the)Tj
1.4683 0 Td
(perfor-)Tj
-34.3216 -1.2982 Td
(mance)Tj
2.8686 0 Td
(of)Tj
1.0148 0 Td
(ChromHMM)Tj
5.6636 0 Td
(depends)Tj
3.5489 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4684 0 Td
(non-trivial)Tj
4.5127 0 Td
(choice)Tj
2.7949 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(proper)Tj
2.9253 0 Td
(binarization)Tj
5.0853 0 Td
(cutoff.)Tj
-32.8249 -1.3039 Td
(Although)Tj
4.0024 0 Td
(the)Tj
1.4684 0 Td
(default)Tj
2.965 0 Td
(binarization)Tj
5.0853 0 Td
(cutoff)Tj
2.5512 0 Td
(proposed)Tj
3.9515 0 Td
(by)Tj
1.1848 0 Td
(ChromHMM)Tj
5.658 0 Td
(performs)Tj
3.8834 0 Td
(relatively)Tj
3.8381 0 Td
(well)Tj
1.8198 0 Td
(in)Tj
-36.4079 -1.2983 Td
(practice,)Tj
3.5999 0 Td
(the)Tj
1.474 0 Td
(quantitative)Tj
4.9776 0 Td
(information)Tj
5.074 0 Td
(is)Tj
0.8504 0 Td
(lost)Tj
1.6328 0 Td
(with)Tj
1.9955 0 Td
(this)Tj
1.6725 0 Td
(approach.)Tj
4.1782 0 Td
(This)Tj
1.9899 0 Td
(is)Tj
0.8447 0 Td
(especially)Tj
4.0195 0 Td
(important)Tj
-32.309 -1.2983 Td
(for)Tj
1.3832 0 Td
(distinguishing)Tj
5.9188 0 Td
(promoters)Tj
4.3993 0 Td
(from)Tj
2.2053 0 Td
(enhancers)Tj
4.2803 0 Td
(since)Tj
2.245 0 Td
(these)Tj
2.2564 0 Td
(elements)Tj
3.7644 0 Td
(are)Tj
1.4457 0 Td
(both)Tj
2.0579 0 Td
(marked)Tj
3.2938 0 Td
(with)Tj
-33.2501 -1.3039 Td
(H3K4me1)Tj
4.3313 0 Td
(and)Tj
1.7291 0 Td
(H3K4me3,)Tj
4.5581 0 Td
(but)Tj
1.5533 0 Td
(at)Tj
0.9525 0 Td
(different)Tj
3.6566 0 Td
(ratios)Tj
2.4548 0 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(].)Tj
2.0807 0 Td
(Segway)Tj
3.1521 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2642 0 Td
(22)Tj
0 g
(],)Tj
1.7348 0 Td
(the)Tj
1.4683 0 Td
(other)Tj
2.3528 0 Td
(method)Tj
3.3222 0 Td
(applied)Tj
-34.6108 -1.2982 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.4683 0 Td
(ENCODE)Tj
4.2463 0 Td
(consortium,)Tj
5.0739 0 Td
(uses)Tj
1.8936 0 Td
(independent)Tj
5.2724 0 Td
(Gaussian)Tj
3.8721 0 Td
(distributions)Tj
5.3291 0 Td
(of)Tj
1.0148 0 Td
(transformed)Tj
5.1703 0 Td
(\(by)Tj
1.5194 0 Td
(the)Tj
-36.0394 -1.2983 Td
(hyperbolic)Tj
4.4617 0 Td
(sine)Tj
1.8198 0 Td
(function\))Tj
3.9741 0 Td
(and)Tj
1.7292 0 Td
(smoothed)Tj
4.1895 0 Td
(ChIP-seq)Tj
3.9515 0 Td
(signal.)Tj
2.7666 0 Td
(Although)Tj
4.0082 0 Td
(Segway)Tj
3.1521 0 Td
(preserves)Tj
3.9288 0 Td
(some)Tj
-33.9815 -1.3039 Td
(quantitative)Tj
4.9776 0 Td
(information,)Tj
5.3007 0 Td
(the)Tj
1.4683 0 Td
(transformation)Tj
6.2759 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(original)Tj
3.3279 0 Td
(count)Tj
2.5228 0 Td
(data)Tj
1.9162 0 Td
(leads)Tj
2.211 0 Td
(to)Tj
1.0262 0 Td
(variance)Tj
3.5773 0 Td
(esti-)Tj
-35.087 -1.2983 Td
(mation)Tj
3.0954 0 Td
(difficulties)Tj
4.405 0 Td
(for)Tj
1.3833 0 Td
(very)Tj
1.9275 0 Td
(low)Tj
1.6554 0 Td
(counts.)Tj
3.1125 0 Td
(Therefore,)Tj
4.3936 0 Td
(Segway)Tj
3.1521 0 Td
(further)Tj
3.0331 0 Td
(makes)Tj
2.7496 0 Td
(the)Tj
1.474 0 Td
(strong)Tj
2.7666 0 Td
(assump-)Tj
-33.1481 -1.2983 Td
(tion)Tj
1.8425 0 Td
(that)Tj
1.7744 0 Td
(for)Tj
1.389 0 Td
(a)Tj
0.652 0 Td
(given)Tj
2.3811 0 Td
(track,)Tj
2.4661 0 Td
(all)Tj
1.1452 0 Td
(states)Tj
2.3981 0 Td
(have)Tj
2.0579 0 Td
(the)Tj
1.474 0 Td
(same)Tj
2.2564 0 Td
(variance.)Tj
3.804 0 Td
(Recently,)Tj
3.8835 0 Td
(EpicSeg)Tj
3.3619 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(])Tj
1.8481 0 Td
(used)Tj
2.0636 0 Td
(a)Tj
-34.7978 -1.3039 Td
(negative)Tj
3.5319 0 Td
(multinomial)Tj
5.2044 0 Td
(distribution)Tj
4.9662 0 Td
(to)Tj
1.0262 0 Td
(directly)Tj
3.2315 0 Td
(model)Tj
2.7439 0 Td
(the)Tj
1.4683 0 Td
(read)Tj
1.9786 0 Td
(counts)Tj
2.8856 0 Td
(without)Tj
3.3336 0 Td
(the)Tj
1.4683 0 Td
(need)Tj
2.143 0 Td
(for)Tj
1.3833 0 Td
(data)Tj
-35.3648 -1.2982 Td
(transformations.)Tj
6.8597 0 Td
(However,)Tj
4.0762 0 Td
(the)Tj
1.4684 0 Td
(EpicSeg)Tj
3.3618 0 Td
(model)Tj
2.744 0 Td
(leads)Tj
2.211 0 Td
(to)Tj
1.0261 0 Td
(a)Tj
0.6576 0 Td
(common)Tj
3.8438 0 Td
(dispersion)Tj
4.371 0 Td
(\(the)Tj
1.8085 0 Td
(parameter)Tj
-32.4281 -1.2983 Td
(adjusting)Tj
3.9061 0 Td
(the)Tj
1.4683 0 Td
(variance)Tj
3.5773 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(negative)Tj
3.5377 0 Td
(multinomial\))Tj
5.5388 0 Td
(for)Tj
1.389 0 Td
(all)Tj
1.1452 0 Td
(tracks.)Tj
2.8289 0 Td
(Moreover,)Tj
4.3994 0 Td
(EpicSeg)Tj
3.3562 0 Td
(does)Tj
2.0409 0 Td
(not)Tj
-35.6709 -1.2983 Td
(provide)Tj
3.2881 0 Td
(other)Tj
2.3471 0 Td
(way)Tj
1.7915 0 Td
(to)Tj
1.0261 0 Td
(correct)Tj
3.0387 0 Td
(for)Tj
1.389 0 Td
(sequencing)Tj
4.7112 0 Td
(depth)Tj
2.5171 0 Td
(than)Tj
2.0296 0 Td
(down-sampling,)Tj
6.7181 0 Td
(which)Tj
2.6532 0 Td
(makes)Tj
2.7552 0 Td
(it)Tj
0.7824 0 Td
(inap-)Tj
-35.0473 -1.3039 Td
(propriate)Tj
3.9231 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.474 0 Td
(analysis)Tj
3.3222 0 Td
(of)Tj
1.0148 0 Td
(data)Tj
1.9162 0 Td
(sets)Tj
1.6611 0 Td
(with)Tj
2.0012 0 Td
(multiple)Tj
3.566 0 Td
(cell)Tj
1.5591 0 Td
(types)Tj
2.2733 0 Td
(with)Tj
1.9956 0 Td
(varying)Tj
3.2201 0 Td
(library)Tj
2.8687 0 Td
(sizes.)Tj
2.2734 0 Td
(\(Down-)Tj
-34.0949 -1.2983 Td
(sampling,)Tj
4.1045 0 Td
(i.e.)Tj
1.3606 0 Td
(restricting)Tj
4.3143 0 Td
(all)Tj
1.1452 0 Td
(libraries)Tj
3.4696 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(size)Tj
1.6837 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(smallest)Tj
3.4129 0 Td
(one)Tj
1.7007 0 Td
(discards)Tj
3.4923 0 Td
(relevant)Tj
3.4186 0 Td
(informa-)Tj
-33.0801 -1.2982 Td
(tion)Tj
1.8425 0 Td
(from)Tj
2.2053 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4683 0 Td
(better)Tj
2.5399 0 Td
(covered)Tj
3.3562 0 Td
(libraries\).)Tj
4.0308 0 Td
(Also,)Tj
2.245 0 Td
(EpicSeg)Tj
3.3619 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.1203 0 Td
(applied)Tj
3.1521 0 Td
(only)Tj
1.9786 0 Td
(to)Tj
1.0261 0 Td
(three)Tj
2.2621 0 Td
(cell)Tj
-34.2763 -1.3039 Td
(types)Tj
2.2733 0 Td
(so)Tj
1.0885 0 Td
(far)Tj
1.3153 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(].)Tj
2.0749 0 Td
(These)Tj
2.5682 0 Td
(methods)Tj
3.685 0 Td
(not)Tj
1.5704 0 Td
(only)Tj
1.9786 0 Td
(differ)Tj
2.3867 0 Td
(in)Tj
1.0318 0 Td
(their)Tj
2.109 0 Td
(modeling)Tj
4.0252 0 Td
(assumptions)Tj
5.2214 0 Td
(but)Tj
1.5533 0 Td
(also)Tj
1.7688 0 Td
(lead)Tj
1.8539 0 Td
(to)Tj
-36.5043 -1.2983 Td
(very)Tj
1.9162 0 Td
(different)Tj
3.6453 0 Td
(results.)Tj
3.0217 0 Td
(In)Tj
1.0998 0 Td
(the)Tj
1.4627 0 Td
(K562)Tj
2.3131 0 Td
(cell)Tj
1.5477 0 Td
(line)Tj
1.6951 0 Td
(for)Tj
1.3776 0 Td
(instance,)Tj
3.7417 0 Td
(ChromHMM)Tj
5.6523 0 Td
(identified)Tj
4.0478 0 Td
(22,323)Tj
2.8176 0 Td
(enhanc-)Tj
-34.3386 -1.2983 Td
(ers)Tj
1.3719 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(],)Tj
2.0806 0 Td
(Segway)Tj
3.1578 0 Td
(38,922)Tj
2.8233 0 Td
(enhancers)Tj
4.2803 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(],)Tj
2.0749 0 Td
(and)Tj
1.7291 0 Td
(EpicSeg)Tj
3.3619 0 Td
(53,982)Tj
2.8233 0 Td
(enhancers)Tj
4.286 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(].)Tj
2.0749 0 Td
(Altogether,)Tj
-30.064 -1.3039 Td
(improved)Tj
4.1045 0 Td
(methods)Tj
3.685 0 Td
(and)Tj
1.7348 0 Td
(detailed)Tj
3.3675 0 Td
(benchmarking)Tj
6.0491 0 Td
(analyses)Tj
3.4866 0 Td
(are)Tj
1.4457 0 Td
(required)Tj
3.6396 0 Td
(for)Tj
1.389 0 Td
(a)Tj
0.652 0 Td
(reliable)Tj
3.1407 0 Td
(annotation)Tj
-32.6945 -1.2982 Td
(of)Tj
1.0147 0 Td
(transcriptional)Tj
6.1115 0 Td
(cis-regulatory)Tj
5.7203 0 Td
(elements.)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 356.7685 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Accurate)Tj
4.1031 0 Td
(Promoter)Tj
4.2733 0 Td
(and)Tj
1.8567 0 Td
(Enhanc)Tj
3.3307 0 Td
(er)Tj
1.0985 0 Td
(Identificati)Tj
4.415 0 Td
(on)Tj
1.311 0 Td
(with)Tj
1.963 0 Td
(GenoSTAN)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.0169)Tj
3.5434 0 Td
(249)Tj
2.6362 0 Td
(January)Tj
3.7134 0 Td
(5,)Tj
1.0417 0 Td
(2017)Tj
38.346 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(25)Tj
/F9 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(fu)Tj
0 Tc
0.3401 0 Td
()Tj
-0.025 Tc
0.3898 0 Td
(r)Tj
0.5244 0 Td
(Bildung)Tj
3.026 0 Td
(und)Tj
1.6441 0 Td
(Forschung)Tj
3.9331 0 Td
(,)Tj
0.4465 0 Td
(Juniorverbu)Tj
4.4362 0 Td
(nd)Tj
1.1693 0 Td
(in)Tj
0.8859 0 Td
(der)Tj
-16.7954 -1.3748 Td
(Systemmedi)Tj
4.6417 0 Td
(zin)Tj
1.2473 0 Td
(mitOmi)Tj
3.0898 0 Td
(cs)Tj
1.4244 0 Td
(grant)Tj
2.1543 0 Td
(FKZ)Tj
1.637 0 Td
(01ZX1405A.)Tj
-14.1945 -1.3749 Td
(PC)Tj
1.2685 0 Td
(was)Tj
1.7079 0 Td
(funded)Tj
2.785 0 Td
(by)Tj
1.1197 0 Td
(Advance)Tj
3.1536 0 Td
(d)Tj
0.6945 0 Td
(Grant)Tj
-10.7292 -1.3748 Td
(TRANSREGU)Tj
4.9323 0 Td
(LON)Tj
1.8709 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(European)Tj
3.7418 0 Td
(Researc)Tj
2.9976 0 Td
(h)Tj
-15.8599 -1.3748 Td
(Council,)Tj
3.196 0 Td
(the)Tj
1.3749 0 Td
(Deutsche)Tj
3.6921 0 Td
(Forschungs)Tj
4.3583 0 Td
(gemeinschaft,)Tj
-12.6213 -1.3748 Td
(the)Tj
1.3677 0 Td
(Volkswage)Tj
3.9898 0 Td
(n)Tj
0.6945 0 Td
(Foundation,)Tj
4.578 0 Td
(CIMED,)Tj
3.0401 0 Td
(and)Tj
-13.6701 -1.3748 Td
(SciLifeLab)Tj
3.848 0 Td
(.)Tj
0.4465 0 Td
(This)Tj
1.7858 0 Td
(work)Tj
2.0551 0 Td
(was)Tj
1.7079 0 Td
(supporte)Tj
3.2953 0 Td
(d)Tj
0.6945 0 Td
(by)Tj
1.1126 0 Td
(the)Tj
-14.9457 -1.3748 Td
(German)Tj
3.1819 0 Td
(Research)Tj
3.6992 0 Td
(Foundation)Tj
4.3512 0 Td
(\(DFG\))Tj
2.4307 0 Td
(and)Tj
1.5875 0 Td
(the)Tj
-15.2505 -1.3748 Td
(Technisch)Tj
3.7701 0 Td
(e)Tj
0.6448 0 Td
(Universita)Tj
0 Tc
3.3379 0 Td
()Tj
-0.025 Tc
0.3543 0 Td
(t)Tj
0.4748 0 Td
(Mu)Tj
0 Tc
0.8433 0 Td
()Tj
-0.025 Tc
0.3898 0 Td
(nchen)Tj
2.4803 0 Td
(within)Tj
2.4449 0 Td
(the)Tj
1.3748 0 Td
(Open)Tj
-16.115 -1.3748 Td
(Access)Tj
2.8559 0 Td
(Publishi)Tj
2.9409 0 Td
(ng)Tj
1.1693 0 Td
(Funding)Tj
3.2032 0 Td
(Programm)Tj
4.0111 0 Td
(e.)Tj
/F8 1 Tf
-14.1804 -2.1261 Td
(Competing)Tj
4.3795 0 Td
(Interests)Tj
3.3307 0 Td
(:)Tj
/F9 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
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
endstream
endobj
54 0 obj
<>stream
endstream
endobj
55 0 obj
<>stream
endstream
endobj
56 0 obj
<>stream
endstream
endobj
57 0 obj
<>stream
endstream
endobj
58 0 obj
<>stream
endstream
endobj
59 0 obj
<>stream
endstream
endobj
60 0 obj
<>stream
endstream
endobj
61 0 obj
<>stream
endstream
endobj
62 0 obj
<>stream
endstream
endobj
63 0 obj
<>stream
endstream
endobj
64 0 obj
<>stream
endstream
endobj
65 0 obj
<>stream
endstream
endobj
66 0 obj
<>stream
BT
10.3394 68.2162 Td
(exist.)Tj
ET
Q
endstream
endobj
67 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 10 0 R/Annots 81 0 R/Contents 82 0 R/TrimBox[0 0 612 792]>>
endobj
69 0 obj
<>
endobj
83 0 obj
<>
endobj
86 0 obj
<>stream
MinionPro-BoldIt 9 `abz+
YK Yd Z9 ' - 3 > H N T Z ` j q t { +2=CIU[cnz~
"(.9CIOU[elov|&-8>DPV^iuy &+/49@DGLPU[]_ahjmru|
&-4;BIPW^elsz
")07>ELSZahov} %,3:AHOV]dkry#/;JTey ! ( / 6 = D K R Y ` g n u |
$
+
2
9
@
G
N
U
\
c
j
q
x
'.5<CJQX_fmt{ #*18?FMT[bkry
"
)
0
7
>
E
J
O
W
d
q
v
$+29@GNU\cjqx '.5<CJQX_fmt{ #*18?FMT[bipw~
&-4;BIPW^elsz !(/6=DOVcpuz-B\v$<Tdy*5@Tanz!2>O_fmt{ #*18?FMT[bipw~(4@LZk{ "3EU_px!-?IUas $6BN\m
-:EQ]n}
%.7@IR[dmv!*3<ENW`ir{&/8AJS\enw ! * 3 < E N W ` i r { !!
!""commaaccentAbreveAmacronAogonekAEacuteCacuteCcaronCcircumflexCdotaccentDcaronDcroatEbreveEcaronEdotaccentEmacronEngEogonekGbreveGcircumflexGcommaaccentGdotaccentHbarHcircumflexIbreveIJImacronIogonekItildeJcircumflexKcommaaccentLacuteLcaronLcommaaccentLdotNacuteNcaronNcommaaccentObreveOhungarumlautOmacronOslashacuteRacuteRcaronRcommaaccentSacuteScedillaScircumflexScommaaccentTbarTcaronTcommaaccentUbreveUhungarumlautUmacronUogonekUringUtildeWacuteWcircumflexWdieresisWgraveYcircumflexYgraveZacuteZdotaccentIdotaccentabreveamacronaogonekaeacutecacuteccaronccircumflexcdotaccentdcarondcroatebreveecaronedotaccentemacronengeogonekgbrevegcircumflexgcommaaccentgdotaccenthbarhcircumflexibreveijimacroniogonekitildejcircumflexkcommaaccentlacutelcaronlcommaaccentldotnacutencaronncommaaccentobreveohungarumlautomacronoslashacuteracutercaronrcommaaccentsacutescedillascircumflexscommaaccenttbartcarontcommaaccentubreveuhungarumlautumacronuogonekuringutildewacutewcircumflexwdieresiswgraveycircumflexygravezacutezdotaccentkgreenlandiclongsnapostrophetonosdieresistonosAlphaBetaGammaDeltaEpsilonZetaEtaThetaIotaKappaLambdaMuNuXiOmicronPiRhoSigmaTauUpsilonPhiChiPsiOmegaAlphatonosEpsilontonosEtatonosIotatonosIotadieresisOmicrontonosUpsilontonosUpsilondieresisOmegatonosuni1FBBuni1F09uni1F0Duni1F0Buni1F0Funi1FB8uni1FBAuni1FBCuni1F89uni1F8Duni1F8Buni1F8Funi1F88uni1F8Cuni1F8Auni1F8Euni1F08uni1F0Cuni1F0Auni1F0Euni1FB9uni1FC9uni1F19uni1F1Duni1F1Buni1FC8uni1F18uni1F1Cuni1F1Auni1FCBuni1F29uni1F2Duni1F2Buni1F2Funi1FCAuni1FCCuni1F99uni1F9Duni1F9Buni1F9Funi1F98uni1F9Cuni1F9Auni1F9Euni1F28uni1F2Cuni1F2Auni1F2Euni1FDBuni1F39uni1F3Duni1F3Buni1F3Funi1FD8uni1FDAuni1F38uni1F3Cuni1F3Auni1F3Euni1FD9uni1FFBuni1F69uni1F6Duni1F6Buni1F6Funi1FFAuni1FFCuni1FA9uni1FADuni1FABuni1FAFuni1FA8uni1FACuni1FAAuni1FAEuni1F68uni1F6Cuni1F6Auni1F6Euni1FF9uni1F49uni1F4Duni1F4Buni1FF8uni1F48uni1F4Cuni1F4Auni1FECuni1FEBuni1F59uni1F5Duni1F5Buni1F5Funi1FE8uni1FEAuni1FE9alphabetagammadeltaepsilonzetaetathetaiotakappalambdanuxiomicronpirhosigmatauupsilonphichipsiomegaalphatonosepsilontonosetatonosiotatonosiotadieresisomicrontonosupsilontonosupsilondieresisomegatonosiotadieresistonosupsilondieresistonosuni03C2uni0374uni0375uni037Euni03D0uni03DAuni03DEuni03E0uni03F0uni1FBDuni1FBEuni1FC1uni1FCDuni1FCEuni1FCFuni1FDDuni1FDEuni1FDFuni1FEDuni1FEEuni1FFEuni1F00uni1F01uni1F02uni1F03uni1F04uni1F05uni1F06uni1F07uni1F10uni1F11uni1F12uni1F13uni1F14uni1F15uni1F20uni1F21uni1F22uni1F23uni1F24uni1F25uni1F26uni1F27uni1F30uni1F31uni1F32uni1F33uni1F34uni1F35uni1F36uni1F37uni1F40uni1F41uni1F42uni1F43uni1F44uni1F45uni1F50uni1F51uni1F52uni1F53uni1F54uni1F55uni1F56uni1F57uni1F60uni1F61uni1F62uni1F63uni1F64uni1F65uni1F66uni1F67uni1F70uni1F71uni1F72uni1F73uni1F74uni1F75uni1F76uni1F77uni1F78uni1F79uni1F7Auni1F7Buni1F7Cuni1F7Duni1F80uni1F81uni1F82uni1F83uni1F84uni1F85uni1F86uni1F87uni1F90uni1F91uni1F92uni1F93uni1F94uni1F95uni1F96uni1F97uni1FA0uni1FA1uni1FA2uni1FA3uni1FA4uni1FA5uni1FA6uni1FA7uni1FB0uni1FB1uni1FB2uni1FB3uni1FB6uni1FB7uni1FC2uni1FC3uni1FC4uni1FC6uni1FC7uni1FD0uni1FD1uni1FD2uni1FD3uni1FD6uni1FD7uni1FE0uni1FE1uni1FE2uni1FE3uni1FE4uni1FE5uni1FE6uni1FF2uni1FF3uni1FF4uni1FF6uni1FF7uni1FB4uni1FE7uniEFD5anoteleiauni03D1uni03D5uni03D6franclirapesetaEuroafii61289estimatedpartialdiffproductsummationuni2219radicalinfinityintegralapproxequalnotequallessequalgreaterequallozengeuni02C9uniEFEDuniEFEEuniEFF1uniEFF2uniEFF3uniEFF5uniEFF7AcuteCaronDieresisDieresisAcuteDieresisGraveGraveHungarumlautMacroncyrBrevecyrFlexdblGravecyrbrevecyrflexdblgravedieresisacutedieresisgraveuniF635uniF637uniF638uniF639uniF6DCuniF63AuniF63BuniF63CuniF63DuniF63EuniF63FuniF640uniF641uniF642uniF628uniF643uniF644uniF645uniF646uniF647uniF648uniF649uniF64AuniF64BuniF64CuniF64DuniF64EuniF64FuniF650uniF651uniF652uniF653uniF654uniF655uniF656uniF657uniF658uniF659uniF65AuniF65BuniF65CuniF65DuniF65EuniF65FuniF660uniF629uniF62AuniF62BuniF62CuniF62DuniF661uniF662uniF663uniF664uniF665uniF666uniF667uniF668uniF669uniF66AuniF66BuniF66CuniF62EuniF62FuniF630uniF631uniF632uniF66DuniF66EuniF66FuniF670uniF671uniF672uniF673uniF674uniF675uniF676uniF677uniF678uniF679uniF67AuniF67BuniF67CuniF67DuniF67EuniF67FuniF680uniF681uniF682uniF683uniF684uniF685uniF686uniF687uniF688uniF689uniF68AuniF68BuniF68CuniF68DuniF68EuniF68FuniF690uniF691uniF692uniF693uniF694uniF695uniF696uniF697uniF698uniF699uniF69AuniF69BuniF69CuniF69DuniF69EuniF69FuniF6A0uniF6A1uniF6A2uniF6A3uniF6A4uniF6A5uniF6A6uniF6A7uniF6A8uniF6A9uniF6AAuniF6ABuniF6ACuniF6ADuniF6AEuniF6AFuniF6B0uniF6B1uniF6B2uniF6B3uniF6B4uniF6B5uniF6B6uniF6B7uniF6B8uniF6B9uniF6BAuniF6BBuniF6BCuniF6BDuniF633c_hc_kc_tf_bf_f_bf_f_hf_f_kf_f_tf_hf_jf_f_jf_kf_ts_puniFB06T_hlongs_blongs_hlongs_ilongs_klongs_llongs_longsuniFB05longs_longs_ilongs_longs_la.ende.endm.endn.endr.endK.altR.altk.altcaron.altcommaaccent.altpeseta.altAlphaiotasub.altAlphaiotasubasper.altAlphaiotasubasperacute.altAlphaiotasubaspergrave.altAlphaiotasubaspertilde.altAlphaiotasublenis.altAlphaiotasublenisacute.altAlphaiotasublenisgrave.altAlphaiotasublenistilde.altEtaiotasub.altEtaiotasubasper.altEtaiotasubasperacute.altEtaiotasubaspergrave.altEtaiotasubaspertilde.altEtaiotasublenis.altEtaiotasublenisacute.altEtaiotasublenisgrave.altEtaiotasublenistilde.altOmegaiotasub.altOmegaiotasubasper.altOmegaiotasubasperacute.altOmegaiotasubaspergrave.altOmegaiotasubaspertilde.altOmegaiotasublenis.altOmegaiotasublenisacute.altOmegaiotasublenisgrave.altOmegaiotasublenistilde.altEuro.fittedcent.fittedcolonmonetary.fitteddollar.fittedflorin.fittedfranc.fittedlira.fittednumbersign.fittedsterling.fittedyen.fittedEuro.oldstylecolonmonetary.oldstyleestimated.oldstyleflorin.oldstylefranc.oldstylelira.oldstylenumbersign.oldstylesterling.oldstyleyen.oldstylefranc.taboldstylelira.taboldstyleorn.001orn.002orn.003orn.004orn.005orn.006orn.007orn.008orn.009orn.010orn.011orn.012orn.013orn.014orn.015orn.016orn.017orn.018orn.019orn.020orn.021orn.022orn.023A.swashB.swashC.swashD.swashE.swashF.swashG.swashH.swashI.swashJ.swashK.swashL.swashM.swashN.swashO.swashP.swashQ.swashR.swashS.swashT.swashU.swashV.swashW.swashX.swashY.swashZ.swashT_h.swashAacute.swashAbreve.swashAcircumflex.swashAdieresis.swashAgrave.swashAmacron.swashAogonek.swashAring.swashAtilde.swashCacute.swashCcaron.swashCcedilla.swashCcircumflex.swashCdotaccent.swashDcaron.swashDcroat.swashEacute.swashEbreve.swashEcaron.swashEcircumflex.swashEdieresis.swashEdotaccent.swashEgrave.swashEmacron.swashEng.swashEogonek.swashGbreve.swashGcircumflex.swashGcommaaccent.swashGdotaccent.swashHbar.swashHcircumflex.swashIJ.swashIacute.swashIbreve.swashIcircumflex.swashIdieresis.swashIdotaccent.swashIgrave.swashImacron.swashIogonek.swashItilde.swashJcircumflex.swashKcommaaccent.swashLacute.swashLcaron.swashLcommaaccent.swashLdot.swashNacute.swashNcaron.swashNcommaaccent.swashNtilde.swashOacute.swashObreve.swashOcircumflex.swashOdieresis.swashOgrave.swashOhungarumlaut.swashOmacron.swashOslash.swashOslashacute.swashOtilde.swashRacute.swashRcaron.swashRcommaaccent.swashSacute.swashScaron.swashScedilla.swashScircumflex.swashScommaaccent.swashTbar.swashTcaron.swashTcommaaccent.swashT_h.caronswashT_h.commaaccentswashUacute.swashUbreve.swashUcircumflex.swashUdieresis.swashUgrave.swashUhungarumlaut.swashUmacron.swashUogonek.swashUring.swashUtilde.swashWacute.swashWcircumflex.swashWdieresis.swashWgrave.swashYacute.swashYcircumflex.swashYdieresis.swashYgrave.swashZacute.swashZcaron.swashZdotaccent.swashafii10056T_h.caronT_h.commaaccentafii10048afii10074afii10075afii10082afii10192afii10062afii10194afii10193afii10102afii10071afii10041afii10076afii10085afii10103afii10051afii10039afii10037afii10079afii10061afii10059afii10047afii10067afii10049afii10148afii10033afii10094afii10080afii10022afii10145afii10063afii10027afii10070afii10054afii10109afii10036afii10065afii10055afii10068afii10086afii10064afii10096afii10050afii10146afii10077afii10097afii10069afii10107afii10101afii10043afii10078afii10024afii10073afii10089afii10092afii10147afii10087afii10081afii10029afii10083afii10026afii10019afii10032afii10046afii10072afii10021afii10030afii10098afii10038afii10017afii10040afii10042afii10105afii10052afii10057afii10025afii10034afii10053afii10832afii10058afii10018afii10044afii10110afii10020afii10095Rholenisafii10104afii10106afii10090afii10091afii10060afii10028afii10045afii10099afii10066afii10084afii10031afii10196afii10035afii10088afii10093Eth.swashafii10100uni0394afii10023afii10195uni2215uni021Aafii10108uni03BCuni00ADuni00A0uni03A9uni021Bafii10846afii61352afii10831Copyright 2000 Adobe Systems Incorporated. All Rights Reserved. U.S. Patents Des. 338,907 and 371,799.Minion is either a registered trademark or a trademark of Adobe Systems Incorporated in the United States and/or other countries.Minion Pro Bold ItalicMinion Prof e *xd7X{(oj=);N\ ' T
\%s
$
2
(Ywd1<vK_$(t #6"-3x?v&CQl)TLc O T Y e p { ! !!!!4!;!t!!!!!!!""
">"Q"x"|""""""##0#X#####$
$$$7$=$I$U$\$a$$$$$$$%%!%A%L%k%r%%%%%%%& &&&&>&Y&r&w&&&&&&&&''/'G'N'\'e'n'v'~''''''''''((
(!(5(I(U(](e(m(s({((((((((((())))')8)B)S)X)h)x)))))))))))))*
***-*;*I*W*d*r*************+++ +++2+9+@+G+M+R+W+c+o+{++++++++++++++++,,,,),4,?,J,O,T
{>n,,ؒёiۅ|<>{3̦ȭY)e`j=!^"d{mm8ঘG,o-MhA9q,Bo= <a/@3a)dTP
^rblguygs)v%zrZХ%- porkvni·}_i[}:{7