Correlation between gene mutation status and molecular subtypes
Uveal Melanoma (Primary solid tumor)
13 July 2018  |  None
Maintainer Information
Maintained by Broad Institute GDAC (Broad Institute of MIT & Harvard)
Overview
Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and molecular subtypes.

Summary

Testing the association between mutation status of 7 genes and 10 molecular subtypes across 80 patients, 33 significant findings detected with P value < 0.05 and Q value < 0.25.

  • EIF1AX mutation correlated to 'MRNA_CHIERARCHICAL',  'LINCRNA_CNMF',  'LINCRNA_CHIERARCHICAL',  'MIR_MATURE_CNMF',  'MIR_MATURE_CHIERARCHICAL',  'CN_CNMF',  'CN_THRESHOLDED_CNMF',  'METHYLATION_CNMF', and 'METHYLATION_CHIERARCHICAL'.

  • BAP1 mutation correlated to 'MRNA_CNMF',  'MRNA_CHIERARCHICAL',  'LINCRNA_CNMF',  'LINCRNA_CHIERARCHICAL',  'MIR_MATURE_CNMF',  'MIR_MATURE_CHIERARCHICAL',  'CN_CNMF',  'CN_THRESHOLDED_CNMF',  'METHYLATION_CNMF', and 'METHYLATION_CHIERARCHICAL'.

  • GNAQ mutation correlated to 'CN_CNMF'.

  • GNA11 mutation correlated to 'CN_CNMF'.

  • SF3B1 mutation correlated to 'MRNA_CNMF',  'MRNA_CHIERARCHICAL',  'LINCRNA_CNMF',  'LINCRNA_CHIERARCHICAL',  'MIR_MATURE_CNMF',  'MIR_MATURE_CHIERARCHICAL',  'CN_CNMF',  'CN_THRESHOLDED_CNMF',  'METHYLATION_CNMF', and 'METHYLATION_CHIERARCHICAL'.

  • SRSF2 mutation correlated to 'MRNA_CNMF'.

  • CYSLTR2 mutation correlated to 'CN_CNMF'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 7 genes and 10 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 33 significant findings detected.

Clinical
Features
MRNA
CNMF
MRNA
CHIERARCHICAL
LINCRNA
CNMF
LINCRNA
CHIERARCHICAL
MIR
MATURE
CNMF
MIR
MATURE
CHIERARCHICAL
CN
CNMF
CN
THRESHOLDED
CNMF
METHYLATION
CNMF
METHYLATION
CHIERARCHICAL
nMutated (%) nWild-Type Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
BAP1 20 (25%) 60 1e-05
(0.000117)
1e-05
(0.000117)
0.0036
(0.0133)
1e-05
(0.000117)
0.0144
(0.0348)
0.00165
(0.00877)
1e-05
(0.000117)
1e-05
(0.000117)
9e-05
(0.000787)
1e-05
(0.000117)
SF3B1 18 (22%) 62 0.0431
(0.0915)
0.00444
(0.0141)
0.00321
(0.0125)
0.0193
(0.0451)
0.00403
(0.0139)
0.0105
(0.0283)
0.00299
(0.0123)
0.00021
(0.00134)
9e-05
(0.000787)
0.00188
(0.00877)
EIF1AX 10 (12%) 70 0.068
(0.126)
0.00654
(0.0199)
0.00418
(0.0139)
0.00184
(0.00877)
0.0101
(0.0283)
0.00206
(0.00901)
0.00938
(0.0274)
0.00021
(0.00134)
0.00016
(0.00124)
0.00073
(0.00426)
GNAQ 40 (50%) 40 0.557
(0.696)
0.0851
(0.149)
0.501
(0.65)
0.0684
(0.126)
0.151
(0.24)
0.0579
(0.116)
0.0247
(0.0541)
0.154
(0.24)
0.517
(0.658)
0.0778
(0.14)
GNA11 35 (44%) 45 0.781
(0.882)
0.141
(0.231)
0.332
(0.467)
0.0672
(0.126)
0.618
(0.736)
0.334
(0.467)
0.0137
(0.0341)
0.207
(0.315)
0.592
(0.727)
0.142
(0.231)
SRSF2 3 (4%) 77 0.0234
(0.0529)
0.05
(0.103)
0.901
(0.986)
0.621
(0.736)
1
(1.00)
0.671
(0.783)
1
(1.00)
0.727
(0.834)
0.269
(0.4)
0.434
(0.574)
CYSLTR2 3 (4%) 77 0.0939
(0.16)
0.329
(0.467)
0.43
(0.574)
0.423
(0.574)
0.889
(0.986)
1
(1.00)
0.0136
(0.0341)
1
(1.00)
1
(1.00)
1
(1.00)
'EIF1AX MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.068 (Fisher's exact test), Q value = 0.13

Table S1.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 11 11 29 21 8
EIF1AX MUTATED 0 1 8 1 0
EIF1AX WILD-TYPE 11 10 21 20 8
'EIF1AX MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.00654 (Fisher's exact test), Q value = 0.02

Table S2.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 15 15 27 23
EIF1AX MUTATED 0 3 7 0
EIF1AX WILD-TYPE 15 12 20 23

Figure S1.  Get High-res Image Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

'EIF1AX MUTATION STATUS' versus 'LINCRNA_CNMF'

P value = 0.00418 (Fisher's exact test), Q value = 0.014

Table S3.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 7 28 11 16
EIF1AX MUTATED 0 4 2 1 3
EIF1AX WILD-TYPE 18 3 26 10 13

Figure S2.  Get High-res Image Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

'EIF1AX MUTATION STATUS' versus 'LINCRNA_CHIERARCHICAL'

P value = 0.00184 (Fisher's exact test), Q value = 0.0088

Table S4.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 24 20 15
EIF1AX MUTATED 0 7 0 3
EIF1AX WILD-TYPE 21 17 20 12

Figure S3.  Get High-res Image Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

'EIF1AX MUTATION STATUS' versus 'MIR_MATURE_CNMF'

P value = 0.0101 (Fisher's exact test), Q value = 0.028

Table S5.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 13 21 18 24 4
EIF1AX MUTATED 1 0 5 2 2
EIF1AX WILD-TYPE 12 21 13 22 2

Figure S4.  Get High-res Image Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

'EIF1AX MUTATION STATUS' versus 'MIR_MATURE_CHIERARCHICAL'

P value = 0.00206 (Fisher's exact test), Q value = 0.009

Table S6.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 21 20 8 17 14
EIF1AX MUTATED 0 0 3 4 3
EIF1AX WILD-TYPE 21 20 5 13 11

Figure S5.  Get High-res Image Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

'EIF1AX MUTATION STATUS' versus 'CN_CNMF'

P value = 0.00938 (Fisher's exact test), Q value = 0.027

Table S7.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 21 37 2 2
EIF1AX MUTATED 0 0 10 0 0
EIF1AX WILD-TYPE 18 21 27 2 2

Figure S6.  Get High-res Image Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

'EIF1AX MUTATION STATUS' versus 'CN_THRESHOLDED_CNMF'

P value = 0.00021 (Fisher's exact test), Q value = 0.0013

Table S8.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 16 7 22 12 2 14 5 2
EIF1AX MUTATED 0 0 10 0 0 0 0 0
EIF1AX WILD-TYPE 16 7 12 12 2 14 5 2

Figure S7.  Get High-res Image Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

'EIF1AX MUTATION STATUS' versus 'METHYLATION_CNMF'

P value = 0.00016 (Fisher's exact test), Q value = 0.0012

Table S9.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 28 13 16 23
EIF1AX MUTATED 0 6 0 4
EIF1AX WILD-TYPE 28 7 16 19

Figure S8.  Get High-res Image Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

'EIF1AX MUTATION STATUS' versus 'METHYLATION_CHIERARCHICAL'

P value = 0.00073 (Fisher's exact test), Q value = 0.0043

Table S10.  Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 40 15 25
EIF1AX MUTATED 0 4 6
EIF1AX WILD-TYPE 40 11 19

Figure S9.  Get High-res Image Gene #1: 'EIF1AX MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

'BAP1 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00012

Table S11.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 11 11 29 21 8
BAP1 MUTATED 8 1 0 8 3
BAP1 WILD-TYPE 3 10 29 13 5

Figure S10.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

'BAP1 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 1e-05 (Fisher's exact test), Q value = 0.00012

Table S12.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 15 15 27 23
BAP1 MUTATED 8 1 0 11
BAP1 WILD-TYPE 7 14 27 12

Figure S11.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

'BAP1 MUTATION STATUS' versus 'LINCRNA_CNMF'

P value = 0.0036 (Fisher's exact test), Q value = 0.013

Table S13.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 7 28 11 16
BAP1 MUTATED 9 0 8 3 0
BAP1 WILD-TYPE 9 7 20 8 16

Figure S12.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

'BAP1 MUTATION STATUS' versus 'LINCRNA_CHIERARCHICAL'

P value = 1e-05 (Fisher's exact test), Q value = 0.00012

Table S14.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 24 20 15
BAP1 MUTATED 11 0 9 0
BAP1 WILD-TYPE 10 24 11 15

Figure S13.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

'BAP1 MUTATION STATUS' versus 'MIR_MATURE_CNMF'

P value = 0.0144 (Fisher's exact test), Q value = 0.035

Table S15.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 13 21 18 24 4
BAP1 MUTATED 5 10 3 2 0
BAP1 WILD-TYPE 8 11 15 22 4

Figure S14.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

'BAP1 MUTATION STATUS' versus 'MIR_MATURE_CHIERARCHICAL'

P value = 0.00165 (Fisher's exact test), Q value = 0.0088

Table S16.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 21 20 8 17 14
BAP1 MUTATED 8 10 0 1 1
BAP1 WILD-TYPE 13 10 8 16 13

Figure S15.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

'BAP1 MUTATION STATUS' versus 'CN_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00012

Table S17.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 21 37 2 2
BAP1 MUTATED 7 11 0 1 1
BAP1 WILD-TYPE 11 10 37 1 1

Figure S16.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

'BAP1 MUTATION STATUS' versus 'CN_THRESHOLDED_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00012

Table S18.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 16 7 22 12 2 14 5 2
BAP1 MUTATED 5 5 0 0 0 9 1 0
BAP1 WILD-TYPE 11 2 22 12 2 5 4 2

Figure S17.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

'BAP1 MUTATION STATUS' versus 'METHYLATION_CNMF'

P value = 9e-05 (Fisher's exact test), Q value = 0.00079

Table S19.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 28 13 16 23
BAP1 MUTATED 13 1 6 0
BAP1 WILD-TYPE 15 12 10 23

Figure S18.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

'BAP1 MUTATION STATUS' versus 'METHYLATION_CHIERARCHICAL'

P value = 1e-05 (Fisher's exact test), Q value = 0.00012

Table S20.  Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 40 15 25
BAP1 MUTATED 20 0 0
BAP1 WILD-TYPE 20 15 25

Figure S19.  Get High-res Image Gene #2: 'BAP1 MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

'GNAQ MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.557 (Fisher's exact test), Q value = 0.7

Table S21.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 11 11 29 21 8
GNAQ MUTATED 5 4 18 10 3
GNAQ WILD-TYPE 6 7 11 11 5
'GNAQ MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.0851 (Fisher's exact test), Q value = 0.15

Table S22.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 15 15 27 23
GNAQ MUTATED 6 6 19 9
GNAQ WILD-TYPE 9 9 8 14
'GNAQ MUTATION STATUS' versus 'LINCRNA_CNMF'

P value = 0.501 (Fisher's exact test), Q value = 0.65

Table S23.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 7 28 11 16
GNAQ MUTATED 8 3 14 4 11
GNAQ WILD-TYPE 10 4 14 7 5
'GNAQ MUTATION STATUS' versus 'LINCRNA_CHIERARCHICAL'

P value = 0.0684 (Fisher's exact test), Q value = 0.13

Table S24.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 24 20 15
GNAQ MUTATED 6 15 9 10
GNAQ WILD-TYPE 15 9 11 5
'GNAQ MUTATION STATUS' versus 'MIR_MATURE_CNMF'

P value = 0.151 (Fisher's exact test), Q value = 0.24

Table S25.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 13 21 18 24 4
GNAQ MUTATED 3 9 11 15 2
GNAQ WILD-TYPE 10 12 7 9 2
'GNAQ MUTATION STATUS' versus 'MIR_MATURE_CHIERARCHICAL'

P value = 0.0579 (Fisher's exact test), Q value = 0.12

Table S26.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 21 20 8 17 14
GNAQ MUTATED 6 8 5 11 10
GNAQ WILD-TYPE 15 12 3 6 4
'GNAQ MUTATION STATUS' versus 'CN_CNMF'

P value = 0.0247 (Fisher's exact test), Q value = 0.054

Table S27.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 21 37 2 2
GNAQ MUTATED 7 7 25 1 0
GNAQ WILD-TYPE 11 14 12 1 2

Figure S20.  Get High-res Image Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

'GNAQ MUTATION STATUS' versus 'CN_THRESHOLDED_CNMF'

P value = 0.154 (Fisher's exact test), Q value = 0.24

Table S28.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 16 7 22 12 2 14 5 2
GNAQ MUTATED 6 2 15 7 1 4 3 2
GNAQ WILD-TYPE 10 5 7 5 1 10 2 0
'GNAQ MUTATION STATUS' versus 'METHYLATION_CNMF'

P value = 0.517 (Fisher's exact test), Q value = 0.66

Table S29.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 28 13 16 23
GNAQ MUTATED 11 8 8 13
GNAQ WILD-TYPE 17 5 8 10
'GNAQ MUTATION STATUS' versus 'METHYLATION_CHIERARCHICAL'

P value = 0.0778 (Fisher's exact test), Q value = 0.14

Table S30.  Gene #3: 'GNAQ MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 40 15 25
GNAQ MUTATED 15 10 15
GNAQ WILD-TYPE 25 5 10
'GNA11 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.781 (Fisher's exact test), Q value = 0.88

Table S31.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 11 11 29 21 8
GNA11 MUTATED 6 5 10 10 4
GNA11 WILD-TYPE 5 6 19 11 4
'GNA11 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.141 (Fisher's exact test), Q value = 0.23

Table S32.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 15 15 27 23
GNA11 MUTATED 8 8 7 12
GNA11 WILD-TYPE 7 7 20 11
'GNA11 MUTATION STATUS' versus 'LINCRNA_CNMF'

P value = 0.332 (Fisher's exact test), Q value = 0.47

Table S33.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 7 28 11 16
GNA11 MUTATED 10 4 11 6 4
GNA11 WILD-TYPE 8 3 17 5 12
'GNA11 MUTATION STATUS' versus 'LINCRNA_CHIERARCHICAL'

P value = 0.0672 (Fisher's exact test), Q value = 0.13

Table S34.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 24 20 15
GNA11 MUTATED 14 8 9 4
GNA11 WILD-TYPE 7 16 11 11
'GNA11 MUTATION STATUS' versus 'MIR_MATURE_CNMF'

P value = 0.618 (Fisher's exact test), Q value = 0.74

Table S35.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 13 21 18 24 4
GNA11 MUTATED 7 11 8 8 1
GNA11 WILD-TYPE 6 10 10 16 3
'GNA11 MUTATION STATUS' versus 'MIR_MATURE_CHIERARCHICAL'

P value = 0.334 (Fisher's exact test), Q value = 0.47

Table S36.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 21 20 8 17 14
GNA11 MUTATED 13 9 3 5 5
GNA11 WILD-TYPE 8 11 5 12 9
'GNA11 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.0137 (Fisher's exact test), Q value = 0.034

Table S37.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 21 37 2 2
GNA11 MUTATED 8 14 11 0 2
GNA11 WILD-TYPE 10 7 26 2 0

Figure S21.  Get High-res Image Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

'GNA11 MUTATION STATUS' versus 'CN_THRESHOLDED_CNMF'

P value = 0.207 (Fisher's exact test), Q value = 0.32

Table S38.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 16 7 22 12 2 14 5 2
GNA11 MUTATED 8 5 6 4 1 9 2 0
GNA11 WILD-TYPE 8 2 16 8 1 5 3 2
'GNA11 MUTATION STATUS' versus 'METHYLATION_CNMF'

P value = 0.592 (Fisher's exact test), Q value = 0.73

Table S39.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 28 13 16 23
GNA11 MUTATED 15 5 7 8
GNA11 WILD-TYPE 13 8 9 15
'GNA11 MUTATION STATUS' versus 'METHYLATION_CHIERARCHICAL'

P value = 0.142 (Fisher's exact test), Q value = 0.23

Table S40.  Gene #4: 'GNA11 MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 40 15 25
GNA11 MUTATED 22 5 8
GNA11 WILD-TYPE 18 10 17
'SF3B1 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.0431 (Fisher's exact test), Q value = 0.092

Table S41.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 11 11 29 21 8
SF3B1 MUTATED 2 0 11 5 0
SF3B1 WILD-TYPE 9 11 18 16 8

Figure S22.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

'SF3B1 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.00444 (Fisher's exact test), Q value = 0.014

Table S42.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 15 15 27 23
SF3B1 MUTATED 0 3 12 3
SF3B1 WILD-TYPE 15 12 15 20

Figure S23.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

'SF3B1 MUTATION STATUS' versus 'LINCRNA_CNMF'

P value = 0.00321 (Fisher's exact test), Q value = 0.012

Table S43.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 7 28 11 16
SF3B1 MUTATED 0 0 7 3 8
SF3B1 WILD-TYPE 18 7 21 8 8

Figure S24.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

'SF3B1 MUTATION STATUS' versus 'LINCRNA_CHIERARCHICAL'

P value = 0.0193 (Fisher's exact test), Q value = 0.045

Table S44.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 24 20 15
SF3B1 MUTATED 3 7 1 7
SF3B1 WILD-TYPE 18 17 19 8

Figure S25.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

'SF3B1 MUTATION STATUS' versus 'MIR_MATURE_CNMF'

P value = 0.00403 (Fisher's exact test), Q value = 0.014

Table S45.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 13 21 18 24 4
SF3B1 MUTATED 0 1 6 10 1
SF3B1 WILD-TYPE 13 20 12 14 3

Figure S26.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

'SF3B1 MUTATION STATUS' versus 'MIR_MATURE_CHIERARCHICAL'

P value = 0.0105 (Fisher's exact test), Q value = 0.028

Table S46.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 21 20 8 17 14
SF3B1 MUTATED 2 1 2 7 6
SF3B1 WILD-TYPE 19 19 6 10 8

Figure S27.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

'SF3B1 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.00299 (Fisher's exact test), Q value = 0.012

Table S47.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 21 37 2 2
SF3B1 MUTATED 3 0 14 0 1
SF3B1 WILD-TYPE 15 21 23 2 1

Figure S28.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

'SF3B1 MUTATION STATUS' versus 'CN_THRESHOLDED_CNMF'

P value = 0.00021 (Fisher's exact test), Q value = 0.0013

Table S48.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 16 7 22 12 2 14 5 2
SF3B1 MUTATED 4 0 2 8 1 1 0 2
SF3B1 WILD-TYPE 12 7 20 4 1 13 5 0

Figure S29.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

'SF3B1 MUTATION STATUS' versus 'METHYLATION_CNMF'

P value = 9e-05 (Fisher's exact test), Q value = 0.00079

Table S49.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 28 13 16 23
SF3B1 MUTATED 0 2 5 11
SF3B1 WILD-TYPE 28 11 11 12

Figure S30.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

'SF3B1 MUTATION STATUS' versus 'METHYLATION_CHIERARCHICAL'

P value = 0.00188 (Fisher's exact test), Q value = 0.0088

Table S50.  Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 40 15 25
SF3B1 MUTATED 3 4 11
SF3B1 WILD-TYPE 37 11 14

Figure S31.  Get High-res Image Gene #5: 'SF3B1 MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

'SRSF2 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.0234 (Fisher's exact test), Q value = 0.053

Table S51.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 11 11 29 21 8
SRSF2 MUTATED 0 2 0 0 1
SRSF2 WILD-TYPE 11 9 29 21 7

Figure S32.  Get High-res Image Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

'SRSF2 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.05 (Fisher's exact test), Q value = 0.1

Table S52.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 15 15 27 23
SRSF2 MUTATED 1 2 0 0
SRSF2 WILD-TYPE 14 13 27 23
'SRSF2 MUTATION STATUS' versus 'LINCRNA_CNMF'

P value = 0.901 (Fisher's exact test), Q value = 0.99

Table S53.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 7 28 11 16
SRSF2 MUTATED 1 0 2 0 0
SRSF2 WILD-TYPE 17 7 26 11 16
'SRSF2 MUTATION STATUS' versus 'LINCRNA_CHIERARCHICAL'

P value = 0.621 (Fisher's exact test), Q value = 0.74

Table S54.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 24 20 15
SRSF2 MUTATED 1 2 0 0
SRSF2 WILD-TYPE 20 22 20 15
'SRSF2 MUTATION STATUS' versus 'MIR_MATURE_CNMF'

P value = 1 (Fisher's exact test), Q value = 1

Table S55.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 13 21 18 24 4
SRSF2 MUTATED 0 1 1 1 0
SRSF2 WILD-TYPE 13 20 17 23 4
'SRSF2 MUTATION STATUS' versus 'MIR_MATURE_CHIERARCHICAL'

P value = 0.671 (Fisher's exact test), Q value = 0.78

Table S56.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 21 20 8 17 14
SRSF2 MUTATED 1 2 0 0 0
SRSF2 WILD-TYPE 20 18 8 17 14
'SRSF2 MUTATION STATUS' versus 'CN_CNMF'

P value = 1 (Fisher's exact test), Q value = 1

Table S57.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 21 37 2 2
SRSF2 MUTATED 1 1 1 0 0
SRSF2 WILD-TYPE 17 20 36 2 2
'SRSF2 MUTATION STATUS' versus 'CN_THRESHOLDED_CNMF'

P value = 0.727 (Fisher's exact test), Q value = 0.83

Table S58.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 16 7 22 12 2 14 5 2
SRSF2 MUTATED 1 0 0 1 0 1 0 0
SRSF2 WILD-TYPE 15 7 22 11 2 13 5 2
'SRSF2 MUTATION STATUS' versus 'METHYLATION_CNMF'

P value = 0.269 (Fisher's exact test), Q value = 0.4

Table S59.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 28 13 16 23
SRSF2 MUTATED 1 0 2 0
SRSF2 WILD-TYPE 27 13 14 23
'SRSF2 MUTATION STATUS' versus 'METHYLATION_CHIERARCHICAL'

P value = 0.434 (Fisher's exact test), Q value = 0.57

Table S60.  Gene #6: 'SRSF2 MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 40 15 25
SRSF2 MUTATED 2 1 0
SRSF2 WILD-TYPE 38 14 25
'CYSLTR2 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.0939 (Fisher's exact test), Q value = 0.16

Table S61.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 11 11 29 21 8
CYSLTR2 MUTATED 0 2 0 1 0
CYSLTR2 WILD-TYPE 11 9 29 20 8
'CYSLTR2 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.329 (Fisher's exact test), Q value = 0.47

Table S62.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 15 15 27 23
CYSLTR2 MUTATED 0 1 0 2
CYSLTR2 WILD-TYPE 15 14 27 21
'CYSLTR2 MUTATION STATUS' versus 'LINCRNA_CNMF'

P value = 0.43 (Fisher's exact test), Q value = 0.57

Table S63.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #3: 'LINCRNA_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 7 28 11 16
CYSLTR2 MUTATED 0 0 3 0 0
CYSLTR2 WILD-TYPE 18 7 25 11 16
'CYSLTR2 MUTATION STATUS' versus 'LINCRNA_CHIERARCHICAL'

P value = 0.423 (Fisher's exact test), Q value = 0.57

Table S64.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #4: 'LINCRNA_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 24 20 15
CYSLTR2 MUTATED 0 1 2 0
CYSLTR2 WILD-TYPE 21 23 18 15
'CYSLTR2 MUTATION STATUS' versus 'MIR_MATURE_CNMF'

P value = 0.889 (Fisher's exact test), Q value = 0.99

Table S65.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #5: 'MIR_MATURE_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 13 21 18 24 4
CYSLTR2 MUTATED 1 1 0 1 0
CYSLTR2 WILD-TYPE 12 20 18 23 4
'CYSLTR2 MUTATION STATUS' versus 'MIR_MATURE_CHIERARCHICAL'

P value = 1 (Fisher's exact test), Q value = 1

Table S66.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #6: 'MIR_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 21 20 8 17 14
CYSLTR2 MUTATED 1 1 0 1 0
CYSLTR2 WILD-TYPE 20 19 8 16 14
'CYSLTR2 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.0136 (Fisher's exact test), Q value = 0.034

Table S67.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 18 21 37 2 2
CYSLTR2 MUTATED 2 0 0 1 0
CYSLTR2 WILD-TYPE 16 21 37 1 2

Figure S33.  Get High-res Image Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #7: 'CN_CNMF'

'CYSLTR2 MUTATION STATUS' versus 'CN_THRESHOLDED_CNMF'

P value = 1 (Fisher's exact test), Q value = 1

Table S68.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #8: 'CN_THRESHOLDED_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 16 7 22 12 2 14 5 2
CYSLTR2 MUTATED 1 0 1 0 0 1 0 0
CYSLTR2 WILD-TYPE 15 7 21 12 2 13 5 2
'CYSLTR2 MUTATION STATUS' versus 'METHYLATION_CNMF'

P value = 1 (Fisher's exact test), Q value = 1

Table S69.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #9: 'METHYLATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 28 13 16 23
CYSLTR2 MUTATED 1 0 1 1
CYSLTR2 WILD-TYPE 27 13 15 22
'CYSLTR2 MUTATION STATUS' versus 'METHYLATION_CHIERARCHICAL'

P value = 1 (Fisher's exact test), Q value = 1

Table S70.  Gene #7: 'CYSLTR2 MUTATION STATUS' versus Molecular Subtype #10: 'METHYLATION_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 40 15 25
CYSLTR2 MUTATED 2 0 1
CYSLTR2 WILD-TYPE 38 15 24
Methods & Data
Input
  • Mutation data file = sample_sig_gene_table.txt from Mutsig_2CV pipeline

  • Processed Mutation data file = /cromwell_root/fc-f5144117-2d5a-42c2-8998-5b38e52db5d9/5947d552-214f-400c-a2a3-61737bb767b7/correlate_genomic_events_all/4e4e215a-e17e-44fb-bf9c-509dde44b76c/call-preprocess_genomic_event/transformed.cor.cli.txt

  • Molecular subtypes file = /cromwell_root/fc-f5144117-2d5a-42c2-8998-5b38e52db5d9/9d897bdb-7a9a-423a-ad17-06f28ae98803/aggregate_clusters_workflow/1d8bac82-5a1d-4cd2-aeb1-8ddd0e1e7a20/call-aggregate_clusters/TCGA-UVM-TP.transposedmergedcluster.txt

  • Number of patients = 80

  • Number of significantly mutated genes = 7

  • Number of Molecular subtypes = 10

  • Exclude genes that fewer than K tumors have mutations, K = 3

Fisher's exact test

For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

References
[1] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)
[2] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)