Revana Analysis Report

2022-05-04

Revana was developed by
Elias Ulrich, Stefan Pfister and Natalie Jaeger

Part I: Input data

Analysed samples Input data
  • ICGC_MB107
  • ICGC_MB112
  • ICGC_MB113
  • ICGC_MB117
  • ICGC_MB122
  • ICGC_MB124
  • ICGC_MB128
  • ICGC_MB130
  • ICGC_MB140
  • ICGC_MB148
  • ICGC_MB176
  • ICGC_MB31
  • ICGC_MB46
  • ICGC_MB54
  • ICGC_MB20
  • ICGC_MB1
  • ICGC_MB101
  • ICGC_MB102
  • ICGC_MB104
  • ICGC_MB12
  • ICGC_MB132
  • ICGC_MB136
  • ICGC_MB137
  • ICGC_MB178
  • ICGC_MB179
  • ICGC_MB181
  • ICGC_MB193
  • ICGC_MB194
  • ICGC_MB204
  • ICGC_MB206
  • ICGC_MB234
  • ICGC_MB239
  • ICGC_MB243
  • ICGC_MB244
  • ICGC_MB246
  • ICGC_MB250
  • ICGC_MB28
  • ICGC_MB34
  • ICGC_MB35
  • ICGC_MB37
  • ICGC_MB53
  • ICGC_MB56
  • ICGC_MB59
  • ICGC_MB60
  • ICGC_MB61
  • ICGC_MB62
  • ICGC_MB63
  • ICGC_MB68
  • ICGC_MB88
  • ICGC_MB23
  • ICGC_MB106
  • ICGC_MB111
  • ICGC_MB131
  • ICGC_MB134
  • ICGC_MB139
  • ICGC_MB146
  • ICGC_MB16
  • ICGC_MB164
  • ICGC_MB166
  • ICGC_MB170
  • ICGC_MB18
  • ICGC_MB188
  • ICGC_MB198
  • ICGC_MB205
  • ICGC_MB226
  • ICGC_MB235
  • ICGC_MB247
  • ICGC_MB248
  • ICGC_MB39
  • ICGC_MB45
  • ICGC_MB5
  • ICGC_MB50
  • ICGC_MB57
  • ICGC_MB89
  • ICGC_MB9
  • ICGC_MB90
  • ICGC_MB95
  • ICGC_MB96
  • ICGC_MB98
  • ICGC_MB36
  • ICGC_MB108
  • ICGC_MB110
  • ICGC_MB114
  • ICGC_MB115
  • ICGC_MB118
  • ICGC_MB119
  • ICGC_MB121
  • ICGC_MB129
  • ICGC_MB15
  • ICGC_MB165
  • ICGC_MB174
  • ICGC_MB175
  • ICGC_MB177
  • ICGC_MB183
  • ICGC_MB184
  • ICGC_MB185
  • ICGC_MB19
  • ICGC_MB199
  • ICGC_MB2
  • ICGC_MB213
  • ICGC_MB224
  • ICGC_MB227
  • ICGC_MB228
  • ICGC_MB230
  • ICGC_MB232
  • ICGC_MB233
  • ICGC_MB236
  • ICGC_MB237
  • ICGC_MB24
  • ICGC_MB26
  • ICGC_MB38
  • ICGC_MB40
  • ICGC_MB49
  • ICGC_MB58
  • ICGC_MB64
  • ICGC_MB65
  • ICGC_MB7
  • ICGC_MB70
  • ICGC_MB71
  • ICGC_MB83
  • ICGC_MB84
  • ICGC_MB85
  • ICGC_MB86
  • ICGC_MB91
  • ICGC_MB92
  • ICGC_MB94
  • ICGC_MB99
  • ICGC_MB6
  • SHH - 35 samples
  • WNT - 15 samples
  • group_3 - 30 samples
  • group_4 - 48 samples
Sample Subgroup Composition Input data
SNP Markers Input data
SNP marker input contains all somatic and germline single nucleotide polymorphisms of the tumor sample. It is used to calculate allele-specific expression.
Somatic SNVs/InDels Input data
Somatic SNV input contains somatic single nucleotide variants (SNVs) and small insertion and deletions (InDels) of the tumor sample. These variants are being evaluated for being candidate regulatory variants.
SVs Input data
SV input contains somatic structural variants of the tumor sample. These variants are being evaluated for being candidate regulatory variants. They are also tested for recurrent SV TAD juxtaposition.
CNAs Input data
CNA input contains somatic copy number alterations of the tumor sample. These variants are being evaluated for being candidate regulatory variants.
Gene Expression Input data
Gene Expression input contains RNA-Seq feature counts in FPKM. Use of this input includes Outlier High Expression (OHE) detection.
Gene Expression - PCA Input data
These graphs show the principal component analysis (PCA) of gene expression of the included subgroups. They help to quickly detect batch effect distortions between subsets of the samples, and thus to assert comparability between the samples.

Part II: Results Overview

Cis-Activation Overview
  • ICGC_MB1
  • ICGC_MB101
  • ICGC_MB102
  • ICGC_MB104
  • ICGC_MB106
  • ICGC_MB107
  • ICGC_MB108
  • ICGC_MB110
  • ICGC_MB111
  • ICGC_MB112
  • ICGC_MB113
  • ICGC_MB114
  • ICGC_MB115
  • ICGC_MB117
  • ICGC_MB118
  • ICGC_MB119
  • ICGC_MB12
  • ICGC_MB121
  • ICGC_MB122
  • ICGC_MB124
  • ICGC_MB128
  • ICGC_MB129
  • ICGC_MB130
  • ICGC_MB131
  • ICGC_MB132
  • ICGC_MB134
  • ICGC_MB136
  • ICGC_MB137
  • ICGC_MB139
  • ICGC_MB140
  • ICGC_MB146
  • ICGC_MB148
  • ICGC_MB15
  • ICGC_MB16
  • ICGC_MB164
  • ICGC_MB165
  • ICGC_MB166
  • ICGC_MB170
  • ICGC_MB174
  • ICGC_MB175
  • ICGC_MB176
  • ICGC_MB177
  • ICGC_MB178
  • ICGC_MB179
  • ICGC_MB18
  • ICGC_MB181
  • ICGC_MB183
  • ICGC_MB184
  • ICGC_MB185
  • ICGC_MB188
  • ICGC_MB19
  • ICGC_MB193
  • ICGC_MB194
  • ICGC_MB198
  • ICGC_MB199
  • ICGC_MB2
  • ICGC_MB20
  • ICGC_MB204
  • ICGC_MB205
  • ICGC_MB206
  • ICGC_MB213
  • ICGC_MB224
  • ICGC_MB226
  • ICGC_MB227
  • ICGC_MB228
  • ICGC_MB23
  • ICGC_MB230
  • ICGC_MB232
  • ICGC_MB233
  • ICGC_MB234
  • ICGC_MB235
  • ICGC_MB236
  • ICGC_MB237
  • ICGC_MB239
  • ICGC_MB24
  • ICGC_MB243
  • ICGC_MB244
  • ICGC_MB246
  • ICGC_MB247
  • ICGC_MB248
  • ICGC_MB250
  • ICGC_MB26
  • ICGC_MB28
  • ICGC_MB31
  • ICGC_MB34
  • ICGC_MB35
  • ICGC_MB36
  • ICGC_MB37
  • ICGC_MB38
  • ICGC_MB39
  • ICGC_MB40
  • ICGC_MB45
  • ICGC_MB46
  • ICGC_MB49
  • ICGC_MB5
  • ICGC_MB50
  • ICGC_MB53
  • ICGC_MB54
  • ICGC_MB56
  • ICGC_MB57
  • ICGC_MB58
  • ICGC_MB59
  • ICGC_MB6
  • ICGC_MB60
  • ICGC_MB61
  • ICGC_MB62
  • ICGC_MB63
  • ICGC_MB64
  • ICGC_MB65
  • ICGC_MB68
  • ICGC_MB7
  • ICGC_MB70
  • ICGC_MB71
  • ICGC_MB83
  • ICGC_MB84
  • ICGC_MB85
  • ICGC_MB86
  • ICGC_MB88
  • ICGC_MB89
  • ICGC_MB9
  • ICGC_MB90
  • ICGC_MB91
  • ICGC_MB92
  • ICGC_MB94
  • ICGC_MB95
  • ICGC_MB96
  • ICGC_MB98
  • ICGC_MB99
Cis-activated genes

3952

Unique cis-activated genes

2803

Average cis-activated genes per sample

30.875

Algorithm insights Results
Detected Cis-Activated Samples Per Gene
Mutations highlighted Input data

Applied Outlier High Expression

Mutations matched via

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Detected Cis-Activated Samples Per Gene
SVs highlighted Input data

Applied Outlier High Expression

Mutations matched via

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Detected Cis-Activated Samples Per Gene
CNAs highlighted Input data

Applied Outlier High Expression

Mutations matched via

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Detected Cis-Activated Samples Per Gene
somatic SNVs highlighted Input data

Applied Outlier High Expression

Mutations matched via

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Detected Cis-Activated Samples Per Gene
somatic SNVs with relevant TF binding site highlighted Input data

Applied Outlier High Expression

Mutations matched via

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SVs: Recurrent SV TAD juxtaposition Results
TADs N of samples Samples N of samples with cis-activated genes affected cis-activated genes
chr8:126800001-127840000 <-> chr8:128800001-129600000 3 ICGC_MB198, ICGC_MB248, ICGC_MB50 2 ICGC_MB198: PVT1; ICGC_MB248: PVT1
chr8:127880001-128760000 <-> chr8:128800001-129600000 4 ICGC_MB198, ICGC_MB248, ICGC_MB50, ICGC_MB94 2 ICGC_MB198: PVT1, RP11-382A18.2; ICGC_MB248: PVT1
chr12:11680001-12280000 <-> chr12:4920001-6160000 2 ICGC_MB137, ICGC_MB243 1 ICGC_MB137: RP11-1038A11.2
chr12:4040001-4880000 <-> chr12:4920001-6160000 2 ICGC_MB137, ICGC_MB34 1 ICGC_MB137: RP11-1038A11.2
chr12:4920001-6160000 <-> chr12:6200001-7240000 2 ICGC_MB137, ICGC_MB243 1 ICGC_MB137: RP11-1038A11.2
chr17:71400001-72880000 <-> chr17:77760001-79080000 3 ICGC_MB224, ICGC_MB243, ICGC_MB91 1 ICGC_MB243: TBC1D16
chr2:121040001-122600000 <-> chr2:123320001-124720000 2 ICGC_MB250, ICGC_MB50 1 ICGC_MB50: INHBB
chr2:121040001-122600000 <-> chr2:125400001-126400000 2 ICGC_MB243, ICGC_MB250 1 ICGC_MB243: CLASP1, CNTNAP5
chr2:122640001-123280000 <-> chr2:124760001-125360000 2 ICGC_MB243, ICGC_MB250 1 ICGC_MB243: CNTNAP5
chr2:13240001-15120000 <-> chr2:15800001-16800000 2 ICGC_MB165, ICGC_MB183 1 ICGC_MB183: AC092635.1
chr2:15160001-15760000 <-> chr2:15800001-16800000 4 ICGC_MB177, ICGC_MB183, ICGC_MB36, ICGC_MB6 1 ICGC_MB36: AC008278.3
chr2:15800001-16800000 <-> chr2:16840001-17920000 2 ICGC_MB36, ICGC_MB6 1 ICGC_MB36: AC008278.3
chr2:222880001-223600000 <-> chr2:223640001-224760000 2 ICGC_MB106, ICGC_MB250 1 ICGC_MB250: ACSL3
chr5:86760001-88040000 <-> chr5:88080001-89000000 2 ICGC_MB19, ICGC_MB199 1 ICGC_MB199: MEF2C
chr11:84400001-85320000 <-> chr20:54960001-56040000 2 ICGC_MB65, ICGC_MB68 0
chr12:1840001-2920000 <-> chr12:29280001-30960000 2 ICGC_MB137, ICGC_MB34 0
chr12:1840001-2920000 <-> chr12:31480001-32920000 2 ICGC_MB137, ICGC_MB34 0
chr12:1840001-2920000 <-> chr12:4040001-4880000 2 ICGC_MB137, ICGC_MB34 0
chr17:36480001-36880000 <-> chr2:15800001-16800000 2 ICGC_MB137, ICGC_MB6 0
chr1:196000001-196760000 <-> chr1:196800001-197360000 2 ICGC_MB65, ICGC_MB68 0
chr1:32640001-33600000 <-> chr1:57280001-59120000 2 ICGC_MB65, ICGC_MB68 0
chr21:17120001-17880000 <-> chr21:17920001-18760000 2 ICGC_MB19, ICGC_MB89 0
chr2:117840001-118560000 <-> chr2:123320001-124720000 2 ICGC_MB102, ICGC_MB250 0
chr2:120200001-121000000 <-> chr2:129560001-130760000 2 ICGC_MB243, ICGC_MB250 0
chr2:122640001-123280000 <-> chr2:123320001-124720000 2 ICGC_MB102, ICGC_MB250 0
chr2:126440001-127760000 <-> chr2:128840001-129520000 2 ICGC_MB243, ICGC_MB250 0
chr2:15160001-15760000 <-> chr2:16840001-17920000 4 ICGC_MB165, ICGC_MB183, ICGC_MB36, ICGC_MB6 0
chr2:16840001-17920000 <-> chr2:17960001-18600000 2 ICGC_MB165, ICGC_MB6 0
chr3:37000001-37360000 <-> chr3:38520001-39440000 2 ICGC_MB1, ICGC_MB174 0
chr3:38040001-38480000 <-> chr3:38520001-39440000 2 ICGC_MB131, ICGC_MB247 0
chr3:38520001-39440000 <-> chr3:39480001-40400000 2 ICGC_MB247, ICGC_MB85 0
chr4:90080001-91240000 <-> chr4:92120001-93280000 2 ICGC_MB110, ICGC_MB86 0
chr5:134240001-134800000 <-> chr5:134840001-135560000 2 ICGC_MB121, ICGC_MB64 0
chr5:18440001-19600000 <-> chr5:19640001-20680000 2 ICGC_MB137, ICGC_MB34 0
chr7:65200001-66760000 <-> chr7:71280001-72480000 3 ICGC_MB65, ICGC_MB68, ICGC_MB71 0
chr8:128800001-129600000 <-> chr8:82720001-84080000 2 ICGC_MB205, ICGC_MB89 0
chr8:82720001-84080000 <-> chr8:84120001-84840000 2 ICGC_MB6, ICGC_MB89 0
chr9:19480001-20320000 <-> chr9:20360001-21200000 2 ICGC_MB110, ICGC_MB83 0

Part III: Analysis of mutation types

Relation between mutations and cis activation Mutation Type

All

Overview
no mutation any mutation
gene NOT cis activated 4650473 2483495
gene cis activated 2450 1502
cis activation frequency 0.000526550729509171 0.000604427289047029

ODDS RATIO: 1.14798889139569

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 17.6132420723284, df = 1, p-value = 2.70696875780571e-05

Genehancer

no mutation (via genehancer) any mutation (via genehancer)
gene NOT cis activated 7030355 103613
gene cis activated 3761 191
cis activation frequency 0.000534679837523294 0.00184000616546569

ODDS RATIO: 3.44582359787565

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 312.627241863826, df = 1, p-value = 5.84662710554429e-70

Gene

no mutation (via gene TAD) any mutation (via gene TAD)
gene NOT cis activated 4658380 2475588
gene cis activated 2470 1482
cis activation frequency 0.000529946254438568 0.000598287492884739

ODDS RATIO: 1.12903601083864

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 13.5286629473679, df = 1, p-value = 0.000234947372916894

ChIP-Seq

no mutation (with affected ChIP-Seq region) any mutation (with affected ChIP-Seq region)
gene NOT cis activated 6931720 202248
gene cis activated 3749 203
cis activation frequency 0.000540554647421825 0.00100271176729184

ODDS RATIO: 1.85582650633447

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 75.0945270634014, df = 1, p-value = 4.48708413872907e-18

Relation between SVs and cis activation Mutation Type

All

Overview
no SV any SV
gene NOT cis activated 7060676 73292
gene cis activated 3862 90
cis activation frequency 0.000546674106643633 0.00122645880461149

ODDS RATIO: 2.24501863434368

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 59.4289815433565, df = 1, p-value = 1.26788049288852e-14

Genehancer

no SV (via genehancer) any SV (via genehancer)
gene NOT cis activated 7104174 29794
gene cis activated 3889 63
cis activation frequency 0.000547125145064134 0.00211005794286097

ODDS RATIO: 3.86266800954106

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 128.441434790913, df = 1, p-value = 8.98600075965905e-30

Gene

no SV (via gene TAD) any SV (via gene TAD)
gene NOT cis activated 7063396 70572
gene cis activated 3866 86
cis activation frequency 0.000547029387052581 0.00121713040278525

ODDS RATIO: 2.2264745292176

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 55.5651909586256, df = 1, p-value = 9.04104638855294e-14

ChIP-Seq

no SV (with affected ChIP-Seq region) any SV (with affected ChIP-Seq region)
gene NOT cis activated 7079354 54614
gene cis activated 3872 80
cis activation frequency 0.00054664357737562 0.00146268329250009

ODDS RATIO: 2.67820787029149

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 80.6572839409651, df = 1, p-value = 2.68463131145813e-19

Relation between CNAs and cis activation Mutation Type

All

Overview
no CNA any CNA
gene NOT cis activated 6991542 142426
gene cis activated 3783 169
cis activation frequency 0.000540789741720363 0.0011851747957502

ODDS RATIO: 2.19297689912693

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 103.702796066654, df = 1, p-value = 2.35059261729545e-24

Genehancer

no CNA (via genehancer) any CNA (via genehancer)
gene NOT cis activated 7081007 52961
gene cis activated 3830 122
cis activation frequency 0.000540591124397075 0.00229828758736319

ODDS RATIO: 4.25892413171858

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 291.000982510995, df = 1, p-value = 3.00921044587203e-65

Gene

no CNA (via gene TAD) any CNA (via gene TAD)
gene NOT cis activated 6997006 136962
gene cis activated 3802 150
cis activation frequency 0.000543080170174643 0.00109399614913355

ODDS RATIO: 2.01553945306931

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 72.767267652562, df = 1, p-value = 1.45876293284383e-17

ChIP-Seq

no CNA (with affected ChIP-Seq region) any CNA (with affected ChIP-Seq region)
gene NOT cis activated 7022824 111144
gene cis activated 3835 117
cis activation frequency 0.000545778584103768 0.00105158141666891

ODDS RATIO: 1.92773021897383

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 49.728223186276, df = 1, p-value = 1.7658734518754e-12

Relation between somatic SNVs and cis activation Mutation Type

All

Overview
no somatic_SNV any somatic_SNV
gene NOT cis activated 4744141 2389827
gene cis activated 2531 1421
cis activation frequency 0.000533215693016075 0.000594250366335905

ODDS RATIO: 1.11453332218632

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 10.5950837036705, df = 1, p-value = 0.00113388765565416

Genehancer

no somatic_SNV (via genehancer) any somatic_SNV (via genehancer)
gene NOT cis activated 7099238 34730
gene cis activated 3896 56
cis activation frequency 0.000548490286118775 0.00160984304030357

ODDS RATIO: 2.93816398843292

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 68.5639381718932, df = 1, p-value = 1.22829844173787e-16

Gene

no somatic_SNV (via gene TAD) any somatic_SNV (via gene TAD)
gene NOT cis activated 4747175 2386793
gene cis activated 2538 1414
cis activation frequency 0.000534348075346868 0.000592075980013458

ODDS RATIO: 1.10809827317813

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 9.46645840442032, df = 1, p-value = 0.00209262994962569

ChIP-Seq

no somatic_SNV (with affected ChIP-Seq region) any somatic_SNV (with affected ChIP-Seq region)
gene NOT cis activated 7071487 62481
gene cis activated 3890 62
cis activation frequency 0.000534348075346868 0.000592075980013458

ODDS RATIO: 1.80386845415916

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 21.0497764564183, df = 1, p-value = 4.47505058614993e-06

Relation between "relevant" somatic SNVs and cis activation Mutation Type
"Relevant" somatic SNVs/InDels in this context describe SNVs, that introduce new significant transcription factor binding sites to transcription factors with a minimum gene expression of > 5 FPKM in the same tumor sample.

All

Overview
no relevant somatic SNV any relevant somatic SNV
gene NOT cis activated 4983903 2150065
gene cis activated 2671 1281
cis activation frequency 0.000535638295952291 0.000595441179614994

ODDS RATIO: 1.11171440584111

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 9.60583094458175, df = 1, p-value = 0.00193960488908808

Genehancer

no relevant somatic SNV (via genehancer) any relevant somatic SNV (via genehancer)
gene NOT cis activated 7102917 31051
gene cis activated 3901 51
cis activation frequency 0.000548909511964426 0.00163976593145135

ODDS RATIO: 2.99057965440769

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 64.6352771894726, df = 1, p-value = 9.01272182482257e-16

TF binding site analysis ROC

Gene

no relevant somatic SNV (via gene TAD) any relevant somatic SNV (via gene TAD)
gene NOT cis activated 4986639 2147329
gene cis activated 2678 1274
cis activation frequency 0.000536746813241171 0.000592943414860726

ODDS RATIO: 1.10476064581419

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 8.46993179365657, df = 1, p-value = 0.00361064969537433

TF binding site analysis ROC

ChIP-Seq

no relevant somatic SNV (with affected ChIP-Seq region) any relevant somatic SNV (with affected ChIP-Seq region)
gene NOT cis activated 7079927 54041
gene cis activated 3900 52
cis activation frequency 0.000536746813241171 0.000592943414860726

ODDS RATIO: 1.74680384646225

Chi-Square Test

Pearson's Chi-squared test with Yates' continuity correction

X-squared = 15.6344155837162, df = 1, p-value = 7.68432345259015e-05

TF binding site analysis ROC

Part IV: Analysis by gene

GFI1B
protein_coding

chr9 : 135 820 932 - 135 867 083

4 cis-activated samples
4 cis-activated samples with SVs
3 cis-activated samples with CNAs
2 cis-activated samples with somatic SNVs
PRDM6
protein_coding

chr5 : 122 424 816 - 122 529 960

7 cis-activated samples
7 cis-activated samples with SVs
7 cis-activated samples with CNAs
6 cis-activated samples with somatic SNVs
PVT1
processed_transcript

chr8 : 128 806 779 - 129 113 499

2 cis-activated samples
2 cis-activated samples with SVs
2 cis-activated samples with CNAs
2 cis-activated samples with somatic SNVs
MYC
protein_coding

chr8 : 128 747 680 - 128 753 674

1 cis-activated samples
1 cis-activated samples with SVs
0 cis-activated samples with CNAs
0 cis-activated samples with somatic SNVs