This pipeline computes the correlation between significant copy number variation (cnv) genes and molecular subtypes.
Testing the association between copy number variation of 53 peak regions and 6 molecular subtypes across 97 patients, 10 significant findings detected with Q value < 0.25.
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Amp Peak 2(1q22) cnvs correlated to 'METHLYATION_CNMF'.
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Amp Peak 11(6p21.1) cnvs correlated to 'METHLYATION_CNMF'.
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Amp Peak 14(8q13.1) cnvs correlated to 'CN_CNMF'.
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Amp Peak 15(8q24.13) cnvs correlated to 'CN_CNMF'.
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Amp Peak 18(12q23.1) cnvs correlated to 'CN_CNMF'.
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Amp Peak 24(17q25.3) cnvs correlated to 'CN_CNMF'.
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Del Peak 4(3p13) cnvs correlated to 'MRNASEQ_CHIERARCHICAL'.
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Del Peak 5(4q24) cnvs correlated to 'CN_CNMF'.
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Del Peak 10(8p23.2) cnvs correlated to 'CN_CNMF'.
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Del Peak 21(16q23.1) cnvs correlated to 'CN_CNMF'.
Table 1. Get Full Table Overview of the association between significant copy number variation of 53 regions and 6 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 10 significant findings detected.
|
Molecular subtypes |
CN CNMF |
METHLYATION CNMF |
MRNASEQ CNMF |
MRNASEQ CHIERARCHICAL |
MIRSEQ CNMF |
MIRSEQ CHIERARCHICAL |
||
| nCNV (%) | nWild-Type | Fisher's exact test | Fisher's exact test | Chi-square test | Fisher's exact test | Fisher's exact test | Fisher's exact test | |
| Amp Peak 2(1q22) | 0 (0%) | 25 |
0.00126 (0.385) |
0.000571 (0.177) |
0.131 (1.00) |
0.581 (1.00) |
0.412 (1.00) |
0.723 (1.00) |
| Amp Peak 11(6p21 1) | 0 (0%) | 54 |
0.00087 (0.268) |
7.43e-05 (0.0234) |
0.00623 (1.00) |
0.332 (1.00) |
0.346 (1.00) |
1 (1.00) |
| Amp Peak 14(8q13 1) | 0 (0%) | 48 |
4.22e-09 (1.34e-06) |
0.931 (1.00) |
0.149 (1.00) |
1 (1.00) |
0.38 (1.00) |
0.523 (1.00) |
| Amp Peak 15(8q24 13) | 0 (0%) | 37 |
1.8e-07 (5.7e-05) |
0.737 (1.00) |
0.178 (1.00) |
0.623 (1.00) |
0.4 (1.00) |
0.743 (1.00) |
| Amp Peak 18(12q23 1) | 0 (0%) | 78 |
0.00045 (0.14) |
0.0737 (1.00) |
0.668 (1.00) |
0.131 (1.00) |
0.472 (1.00) |
0.452 (1.00) |
| Amp Peak 24(17q25 3) | 0 (0%) | 53 |
0.000453 (0.141) |
0.0959 (1.00) |
0.388 (1.00) |
0.811 (1.00) |
0.929 (1.00) |
0.533 (1.00) |
| Del Peak 4(3p13) | 0 (0%) | 81 |
0.113 (1.00) |
0.292 (1.00) |
0.00238 (0.724) |
0.000163 (0.051) |
0.00806 (1.00) |
0.208 (1.00) |
| Del Peak 5(4q24) | 0 (0%) | 56 |
8.47e-05 (0.0266) |
0.131 (1.00) |
0.412 (1.00) |
0.809 (1.00) |
0.141 (1.00) |
1 (1.00) |
| Del Peak 10(8p23 2) | 0 (0%) | 37 |
3.6e-07 (0.000114) |
0.467 (1.00) |
0.234 (1.00) |
0.46 (1.00) |
0.492 (1.00) |
0.195 (1.00) |
| Del Peak 21(16q23 1) | 0 (0%) | 55 |
0.00075 (0.232) |
0.00819 (1.00) |
0.0114 (1.00) |
0.0538 (1.00) |
0.305 (1.00) |
0.338 (1.00) |
| Amp Peak 1(1p22 3) | 0 (0%) | 73 |
0.0686 (1.00) |
0.363 (1.00) |
0.218 (1.00) |
0.112 (1.00) |
0.206 (1.00) |
0.279 (1.00) |
| Amp Peak 3(1q42 3) | 0 (0%) | 32 |
0.00359 (1.00) |
0.0103 (1.00) |
0.0429 (1.00) |
0.802 (1.00) |
0.532 (1.00) |
0.496 (1.00) |
| Amp Peak 4(2p24 1) | 0 (0%) | 75 |
0.244 (1.00) |
0.387 (1.00) |
0.702 (1.00) |
0.25 (1.00) |
0.164 (1.00) |
0.705 (1.00) |
| Amp Peak 5(2q33 1) | 0 (0%) | 77 |
0.263 (1.00) |
0.576 (1.00) |
0.491 (1.00) |
0.771 (1.00) |
0.633 (1.00) |
1 (1.00) |
| Amp Peak 6(3q26 31) | 0 (0%) | 77 |
0.00568 (1.00) |
0.328 (1.00) |
0.126 (1.00) |
1 (1.00) |
0.378 (1.00) |
0.224 (1.00) |
| Amp Peak 7(4q31 3) | 0 (0%) | 89 |
0.524 (1.00) |
1 (1.00) |
0.465 (1.00) |
0.122 (1.00) |
0.0467 (1.00) |
0.235 (1.00) |
| Amp Peak 8(5p15 33) | 0 (0%) | 49 |
0.00278 (0.842) |
0.522 (1.00) |
0.165 (1.00) |
0.0938 (1.00) |
0.3 (1.00) |
0.523 (1.00) |
| Amp Peak 9(5q35 3) | 0 (0%) | 60 |
0.0315 (1.00) |
0.416 (1.00) |
0.358 (1.00) |
0.443 (1.00) |
1 (1.00) |
1 (1.00) |
| Amp Peak 10(6p25 2) | 0 (0%) | 55 |
0.0102 (1.00) |
0.00334 (1.00) |
0.118 (1.00) |
0.0938 (1.00) |
0.766 (1.00) |
0.754 (1.00) |
| Amp Peak 12(6q12) | 0 (0%) | 65 |
0.0651 (1.00) |
0.0286 (1.00) |
0.101 (1.00) |
1 (1.00) |
0.0695 (1.00) |
0.322 (1.00) |
| Amp Peak 13(7q21 2) | 0 (0%) | 61 |
0.253 (1.00) |
0.0438 (1.00) |
0.397 (1.00) |
0.2 (1.00) |
0.665 (1.00) |
0.317 (1.00) |
| Amp Peak 16(10p15 1) | 0 (0%) | 78 |
0.168 (1.00) |
0.256 (1.00) |
0.273 (1.00) |
0.0167 (1.00) |
0.447 (1.00) |
0.689 (1.00) |
| Amp Peak 17(11q13 3) | 0 (0%) | 80 |
0.396 (1.00) |
0.486 (1.00) |
0.16 (1.00) |
0.732 (1.00) |
0.116 (1.00) |
0.108 (1.00) |
| Amp Peak 19(13q32 3) | 0 (0%) | 75 |
0.0011 (0.339) |
0.128 (1.00) |
0.372 (1.00) |
0.144 (1.00) |
0.536 (1.00) |
0.121 (1.00) |
| Amp Peak 20(15q21 3) | 0 (0%) | 82 |
0.013 (1.00) |
0.365 (1.00) |
0.153 (1.00) |
0.542 (1.00) |
0.932 (1.00) |
1 (1.00) |
| Amp Peak 21(15q26 3) | 0 (0%) | 82 |
0.036 (1.00) |
0.81 (1.00) |
0.61 (1.00) |
0.542 (1.00) |
0.932 (1.00) |
1 (1.00) |
| Amp Peak 22(17p11 2) | 0 (0%) | 82 |
0.00313 (0.945) |
0.755 (1.00) |
0.256 (1.00) |
0.302 (1.00) |
0.82 (1.00) |
0.202 (1.00) |
| Amp Peak 23(17q23 1) | 0 (0%) | 57 |
0.023 (1.00) |
0.513 (1.00) |
0.301 (1.00) |
0.22 (1.00) |
0.892 (1.00) |
0.754 (1.00) |
| Amp Peak 25(19q13 11) | 0 (0%) | 66 |
0.0411 (1.00) |
0.283 (1.00) |
0.686 (1.00) |
0.302 (1.00) |
0.462 (1.00) |
0.32 (1.00) |
| Amp Peak 26(20q13 13) | 0 (0%) | 62 |
0.0418 (1.00) |
0.556 (1.00) |
0.00449 (1.00) |
0.461 (1.00) |
0.885 (1.00) |
0.519 (1.00) |
| Del Peak 1(1p36 32) | 0 (0%) | 52 |
0.0159 (1.00) |
0.0145 (1.00) |
0.276 (1.00) |
0.631 (1.00) |
0.661 (1.00) |
0.218 (1.00) |
| Del Peak 2(2q22 1) | 0 (0%) | 87 |
0.489 (1.00) |
0.392 (1.00) |
0.751 (1.00) |
0.69 (1.00) |
0.0432 (1.00) |
0.0911 (1.00) |
| Del Peak 3(2q37 3) | 0 (0%) | 81 |
0.357 (1.00) |
0.563 (1.00) |
0.442 (1.00) |
0.75 (1.00) |
0.0724 (1.00) |
0.0886 (1.00) |
| Del Peak 6(4q35 1) | 0 (0%) | 55 |
0.00205 (0.624) |
0.0465 (1.00) |
0.116 (1.00) |
0.337 (1.00) |
0.181 (1.00) |
0.532 (1.00) |
| Del Peak 7(5q23 1) | 0 (0%) | 83 |
0.156 (1.00) |
0.228 (1.00) |
0.335 (1.00) |
0.152 (1.00) |
0.266 (1.00) |
0.208 (1.00) |
| Del Peak 8(6q16 3) | 0 (0%) | 61 |
0.304 (1.00) |
0.707 (1.00) |
0.419 (1.00) |
0.127 (1.00) |
0.64 (1.00) |
1 (1.00) |
| Del Peak 9(6q26) | 0 (0%) | 58 |
0.165 (1.00) |
0.714 (1.00) |
0.669 (1.00) |
0.127 (1.00) |
0.294 (1.00) |
0.747 (1.00) |
| Del Peak 11(9p21 3) | 0 (0%) | 58 |
0.155 (1.00) |
0.772 (1.00) |
0.781 (1.00) |
0.337 (1.00) |
0.365 (1.00) |
0.342 (1.00) |
| Del Peak 12(10p15 3) | 0 (0%) | 89 |
0.731 (1.00) |
0.893 (1.00) |
0.42 (1.00) |
0.634 (1.00) |
0.317 (1.00) |
0.235 (1.00) |
| Del Peak 13(10q23 31) | 0 (0%) | 66 |
0.0337 (1.00) |
0.637 (1.00) |
0.00548 (1.00) |
0.0722 (1.00) |
0.082 (1.00) |
0.169 (1.00) |
| Del Peak 14(10q24 33) | 0 (0%) | 68 |
0.051 (1.00) |
0.577 (1.00) |
0.0056 (1.00) |
0.0647 (1.00) |
0.0152 (1.00) |
0.0881 (1.00) |
| Del Peak 15(11q14 1) | 0 (0%) | 79 |
0.576 (1.00) |
0.751 (1.00) |
0.429 (1.00) |
0.554 (1.00) |
0.94 (1.00) |
1 (1.00) |
| Del Peak 16(12p12 1) | 0 (0%) | 74 |
0.184 (1.00) |
0.863 (1.00) |
0.248 (1.00) |
0.177 (1.00) |
0.12 (1.00) |
0.018 (1.00) |
| Del Peak 17(12q24 33) | 0 (0%) | 81 |
0.484 (1.00) |
1 (1.00) |
0.593 (1.00) |
0.75 (1.00) |
0.153 (1.00) |
0.391 (1.00) |
| Del Peak 18(13q14 2) | 0 (0%) | 54 |
0.00682 (1.00) |
0.148 (1.00) |
0.0528 (1.00) |
0.0538 (1.00) |
0.0294 (1.00) |
0.532 (1.00) |
| Del Peak 19(14q23 3) | 0 (0%) | 61 |
0.022 (1.00) |
0.292 (1.00) |
0.401 (1.00) |
0.0482 (1.00) |
0.726 (1.00) |
0.017 (1.00) |
| Del Peak 20(15q15 1) | 0 (0%) | 79 |
0.00375 (1.00) |
0.591 (1.00) |
0.364 (1.00) |
0.0341 (1.00) |
0.73 (1.00) |
1 (1.00) |
| Del Peak 22(17p12) | 0 (0%) | 40 |
0.0921 (1.00) |
0.515 (1.00) |
0.121 (1.00) |
0.139 (1.00) |
0.00447 (1.00) |
0.0258 (1.00) |
| Del Peak 23(18q21 2) | 0 (0%) | 79 |
0.118 (1.00) |
0.126 (1.00) |
0.132 (1.00) |
1 (1.00) |
0.506 (1.00) |
1 (1.00) |
| Del Peak 24(19p13 3) | 0 (0%) | 77 |
0.0516 (1.00) |
0.101 (1.00) |
0.503 (1.00) |
0.267 (1.00) |
0.146 (1.00) |
0.0521 (1.00) |
| Del Peak 25(22q12 1) | 0 (0%) | 79 |
0.0318 (1.00) |
0.239 (1.00) |
0.123 (1.00) |
0.235 (1.00) |
0.943 (1.00) |
0.435 (1.00) |
| Del Peak 26(22q13 32) | 0 (0%) | 73 |
0.0206 (1.00) |
0.381 (1.00) |
0.0415 (1.00) |
1 (1.00) |
0.455 (1.00) |
0.463 (1.00) |
| Del Peak 27(Xq27 3) | 0 (0%) | 83 |
0.00774 (1.00) |
0.126 (1.00) |
0.216 (1.00) |
0.336 (1.00) |
0.601 (1.00) |
0.36 (1.00) |
P value = 0.000571 (Fisher's exact test), Q value = 0.18
Table S1. Gene #2: 'Amp Peak 2(1q22)' versus Molecular Subtype #2: 'METHLYATION_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 23 | 28 | 45 |
| AMP PEAK 2(1Q22) CNV | 10 | 23 | 39 |
| AMP PEAK 2(1Q22) WILD-TYPE | 13 | 5 | 6 |
Figure S1. Get High-res Image Gene #2: 'Amp Peak 2(1q22)' versus Molecular Subtype #2: 'METHLYATION_CNMF'
P value = 7.43e-05 (Fisher's exact test), Q value = 0.023
Table S2. Gene #11: 'Amp Peak 11(6p21.1)' versus Molecular Subtype #2: 'METHLYATION_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 23 | 28 | 45 |
| AMP PEAK 11(6P21.1) CNV | 2 | 12 | 28 |
| AMP PEAK 11(6P21.1) WILD-TYPE | 21 | 16 | 17 |
Figure S2. Get High-res Image Gene #11: 'Amp Peak 11(6p21.1)' versus Molecular Subtype #2: 'METHLYATION_CNMF'
P value = 4.22e-09 (Fisher's exact test), Q value = 1.3e-06
Table S3. Gene #14: 'Amp Peak 14(8q13.1)' versus Molecular Subtype #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 28 | 36 | 33 |
| AMP PEAK 14(8Q13.1) CNV | 27 | 10 | 12 |
| AMP PEAK 14(8Q13.1) WILD-TYPE | 1 | 26 | 21 |
Figure S3. Get High-res Image Gene #14: 'Amp Peak 14(8q13.1)' versus Molecular Subtype #1: 'CN_CNMF'
P value = 1.8e-07 (Fisher's exact test), Q value = 5.7e-05
Table S4. Gene #15: 'Amp Peak 15(8q24.13)' versus Molecular Subtype #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 28 | 36 | 33 |
| AMP PEAK 15(8Q24.13) CNV | 28 | 15 | 17 |
| AMP PEAK 15(8Q24.13) WILD-TYPE | 0 | 21 | 16 |
Figure S4. Get High-res Image Gene #15: 'Amp Peak 15(8q24.13)' versus Molecular Subtype #1: 'CN_CNMF'
P value = 0.00045 (Fisher's exact test), Q value = 0.14
Table S5. Gene #18: 'Amp Peak 18(12q23.1)' versus Molecular Subtype #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 28 | 36 | 33 |
| AMP PEAK 18(12Q23.1) CNV | 5 | 1 | 13 |
| AMP PEAK 18(12Q23.1) WILD-TYPE | 23 | 35 | 20 |
Figure S5. Get High-res Image Gene #18: 'Amp Peak 18(12q23.1)' versus Molecular Subtype #1: 'CN_CNMF'
P value = 0.000453 (Fisher's exact test), Q value = 0.14
Table S6. Gene #24: 'Amp Peak 24(17q25.3)' versus Molecular Subtype #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 28 | 36 | 33 |
| AMP PEAK 24(17Q25.3) CNV | 10 | 10 | 24 |
| AMP PEAK 24(17Q25.3) WILD-TYPE | 18 | 26 | 9 |
Figure S6. Get High-res Image Gene #24: 'Amp Peak 24(17q25.3)' versus Molecular Subtype #1: 'CN_CNMF'
P value = 0.000163 (Fisher's exact test), Q value = 0.051
Table S7. Gene #30: 'Del Peak 4(3p13)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'
| nPatients | CLUS_1 | CLUS_2 |
|---|---|---|
| ALL | 29 | 40 |
| DEL PEAK 4(3P13) CNV | 11 | 1 |
| DEL PEAK 4(3P13) WILD-TYPE | 18 | 39 |
Figure S7. Get High-res Image Gene #30: 'Del Peak 4(3p13)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'
P value = 8.47e-05 (Fisher's exact test), Q value = 0.027
Table S8. Gene #31: 'Del Peak 5(4q24)' versus Molecular Subtype #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 28 | 36 | 33 |
| DEL PEAK 5(4Q24) CNV | 13 | 6 | 22 |
| DEL PEAK 5(4Q24) WILD-TYPE | 15 | 30 | 11 |
Figure S8. Get High-res Image Gene #31: 'Del Peak 5(4q24)' versus Molecular Subtype #1: 'CN_CNMF'
P value = 3.6e-07 (Fisher's exact test), Q value = 0.00011
Table S9. Gene #36: 'Del Peak 10(8p23.2)' versus Molecular Subtype #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 28 | 36 | 33 |
| DEL PEAK 10(8P23.2) CNV | 27 | 12 | 21 |
| DEL PEAK 10(8P23.2) WILD-TYPE | 1 | 24 | 12 |
Figure S9. Get High-res Image Gene #36: 'Del Peak 10(8p23.2)' versus Molecular Subtype #1: 'CN_CNMF'
P value = 0.00075 (Fisher's exact test), Q value = 0.23
Table S10. Gene #47: 'Del Peak 21(16q23.1)' versus Molecular Subtype #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 28 | 36 | 33 |
| DEL PEAK 21(16Q23.1) CNV | 9 | 10 | 23 |
| DEL PEAK 21(16Q23.1) WILD-TYPE | 19 | 26 | 10 |
Figure S10. Get High-res Image Gene #47: 'Del Peak 21(16q23.1)' versus Molecular Subtype #1: 'CN_CNMF'
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Copy number data file = All Lesions File (all_lesions.conf_##.txt, where ## is the confidence level). The all lesions file is from GISTIC pipeline and summarizes the results from the GISTIC run. It contains data about the significant regions of amplification and deletion as well as which samples are amplified or deleted in each of these regions. The identified regions are listed down the first column, and the samples are listed across the first row, starting in column 10.
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Molecular subtype file = LIHC-TP.transferedmergedcluster.txt
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Number of patients = 97
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Number of copy number variation regions = 53
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Number of molecular subtypes = 6
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Exclude regions that fewer than K tumors have alterations, K = 3
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
For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.test' function in R
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.