Correlation between gene mutation status and molecular subtypes
Overview
Introduction
This pipeline computes the correlation between significantly recurrent gene mutations and molecular subtypes.
Summary
Testing the association between mutation status of 74 genes and 8 molecular subtypes across 105 patients, no significant finding detected with P value < 0.05 and Q value < 0.25.
-
No gene mutations related to molecuar subtypes.
Results
Overview of the results
Table 1. Get Full Table Overview of the association between mutation status of 74 genes and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, no significant finding detected.
|
Clinical Features |
CN CNMF |
METHLYATION CNMF |
RPPA CNMF |
RPPA CHIERARCHICAL |
MRNASEQ CNMF |
MRNASEQ CHIERARCHICAL |
MIRSEQ CNMF |
MIRSEQ CHIERARCHICAL |
||
| nMutated (%) | 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 | Fisher's exact test | Fisher's exact test | |
| BRAF | 59 (56%) | 46 |
0.0383 (1.00) |
0.242 (1.00) |
0.0794 (1.00) |
0.417 (1.00) |
0.274 (1.00) |
0.139 (1.00) |
0.117 (1.00) |
0.494 (1.00) |
| CDKN2A | 16 (15%) | 89 |
0.31 (1.00) |
0.979 (1.00) |
0.874 (1.00) |
0.04 (1.00) |
0.331 (1.00) |
0.46 (1.00) |
0.157 (1.00) |
0.31 (1.00) |
| NRAS | 29 (28%) | 76 |
0.0228 (1.00) |
0.0502 (1.00) |
0.072 (1.00) |
0.505 (1.00) |
0.574 (1.00) |
0.495 (1.00) |
0.444 (1.00) |
0.71 (1.00) |
| STK19 | 7 (7%) | 98 |
0.437 (1.00) |
0.534 (1.00) |
0.129 (1.00) |
0.358 (1.00) |
0.145 (1.00) |
0.0576 (1.00) |
0.0319 (1.00) |
0.713 (1.00) |
| TTN | 83 (79%) | 22 |
0.973 (1.00) |
0.803 (1.00) |
0.344 (1.00) |
0.236 (1.00) |
0.719 (1.00) |
0.738 (1.00) |
0.276 (1.00) |
0.571 (1.00) |
| TP53 | 18 (17%) | 87 |
0.128 (1.00) |
0.0813 (1.00) |
0.489 (1.00) |
0.699 (1.00) |
0.103 (1.00) |
0.0421 (1.00) |
0.00436 (1.00) |
0.077 (1.00) |
| PTEN | 11 (10%) | 94 |
0.459 (1.00) |
0.175 (1.00) |
0.387 (1.00) |
0.105 (1.00) |
0.559 (1.00) |
0.136 (1.00) |
0.25 (1.00) |
0.701 (1.00) |
| TPTE | 29 (28%) | 76 |
0.481 (1.00) |
0.587 (1.00) |
0.822 (1.00) |
0.206 (1.00) |
0.492 (1.00) |
0.952 (1.00) |
0.481 (1.00) |
1 (1.00) |
| PRB4 | 15 (14%) | 90 |
0.139 (1.00) |
0.922 (1.00) |
0.249 (1.00) |
0.154 (1.00) |
0.409 (1.00) |
0.689 (1.00) |
0.522 (1.00) |
0.47 (1.00) |
| CDH9 | 22 (21%) | 83 |
0.688 (1.00) |
0.24 (1.00) |
0.919 (1.00) |
0.667 (1.00) |
0.368 (1.00) |
0.525 (1.00) |
0.0811 (1.00) |
0.705 (1.00) |
| SERPINB4 | 17 (16%) | 88 |
0.724 (1.00) |
0.634 (1.00) |
0.0886 (1.00) |
0.0163 (1.00) |
0.795 (1.00) |
0.81 (1.00) |
0.491 (1.00) |
0.504 (1.00) |
| PRB2 | 19 (18%) | 86 |
0.788 (1.00) |
0.763 (1.00) |
0.36 (1.00) |
0.943 (1.00) |
0.855 (1.00) |
0.21 (1.00) |
0.0312 (1.00) |
0.0609 (1.00) |
| TCEB3C | 14 (13%) | 91 |
0.184 (1.00) |
0.0621 (1.00) |
0.898 (1.00) |
0.472 (1.00) |
0.255 (1.00) |
0.596 (1.00) |
0.574 (1.00) |
0.14 (1.00) |
| ADH1C | 17 (16%) | 88 |
0.861 (1.00) |
0.761 (1.00) |
0.103 (1.00) |
0.607 (1.00) |
0.0191 (1.00) |
0.0241 (1.00) |
0.788 (1.00) |
0.187 (1.00) |
| C15ORF23 | 7 (7%) | 98 |
0.261 (1.00) |
0.587 (1.00) |
0.869 (1.00) |
0.763 (1.00) |
0.478 (1.00) |
0.3 (1.00) |
0.786 (1.00) |
0.575 (1.00) |
| CCNE2 | 10 (10%) | 95 |
1 (1.00) |
0.314 (1.00) |
0.171 (1.00) |
0.0854 (1.00) |
0.84 (1.00) |
0.648 (1.00) |
0.399 (1.00) |
0.773 (1.00) |
| SDR16C5 | 16 (15%) | 89 |
0.895 (1.00) |
0.0422 (1.00) |
0.0534 (1.00) |
0.406 (1.00) |
0.0515 (1.00) |
0.00901 (1.00) |
0.504 (1.00) |
0.919 (1.00) |
| PDE1A | 19 (18%) | 86 |
0.901 (1.00) |
0.54 (1.00) |
0.641 (1.00) |
0.852 (1.00) |
0.855 (1.00) |
0.413 (1.00) |
0.444 (1.00) |
0.41 (1.00) |
| TLL1 | 24 (23%) | 81 |
0.584 (1.00) |
0.733 (1.00) |
0.462 (1.00) |
0.0468 (1.00) |
0.298 (1.00) |
0.336 (1.00) |
0.576 (1.00) |
0.1 (1.00) |
| RAC1 | 7 (7%) | 98 |
0.95 (1.00) |
0.857 (1.00) |
0.857 (1.00) |
0.858 (1.00) |
1 (1.00) |
0.869 (1.00) |
1 (1.00) |
0.452 (1.00) |
| RERG | 8 (8%) | 97 |
1 (1.00) |
1 (1.00) |
0.025 (1.00) |
0.721 (1.00) |
0.335 (1.00) |
0.467 (1.00) |
0.356 (1.00) |
0.161 (1.00) |
| OR52L1 | 12 (11%) | 93 |
0.528 (1.00) |
0.343 (1.00) |
0.078 (1.00) |
0.165 (1.00) |
0.316 (1.00) |
0.121 (1.00) |
0.857 (1.00) |
0.349 (1.00) |
| HBD | 8 (8%) | 97 |
0.0565 (1.00) |
1 (1.00) |
0.26 (1.00) |
0.315 (1.00) |
0.238 (1.00) |
0.142 (1.00) |
0.23 (1.00) |
0.161 (1.00) |
| VEGFC | 12 (11%) | 93 |
0.394 (1.00) |
0.527 (1.00) |
0.0865 (1.00) |
0.141 (1.00) |
0.16 (1.00) |
0.0144 (1.00) |
0.0816 (1.00) |
0.0334 (1.00) |
| BAGE2 | 7 (7%) | 98 |
0.354 (1.00) |
0.264 (1.00) |
0.661 (1.00) |
0.927 (1.00) |
0.253 (1.00) |
0.229 (1.00) |
0.524 (1.00) |
0.575 (1.00) |
| OR1N2 | 13 (12%) | 92 |
0.548 (1.00) |
0.337 (1.00) |
0.254 (1.00) |
0.353 (1.00) |
0.651 (1.00) |
0.741 (1.00) |
1 (1.00) |
0.207 (1.00) |
| PPP6C | 10 (10%) | 95 |
0.521 (1.00) |
0.85 (1.00) |
0.323 (1.00) |
0.507 (1.00) |
0.54 (1.00) |
0.966 (1.00) |
0.121 (1.00) |
0.237 (1.00) |
| HNF4G | 12 (11%) | 93 |
0.859 (1.00) |
1 (1.00) |
0.744 (1.00) |
0.504 (1.00) |
1 (1.00) |
0.926 (1.00) |
1 (1.00) |
0.454 (1.00) |
| TRAT1 | 6 (6%) | 99 |
0.429 (1.00) |
0.492 (1.00) |
0.7 (1.00) |
0.727 (1.00) |
0.103 (1.00) |
0.222 (1.00) |
0.373 (1.00) |
0.326 (1.00) |
| AREG | 5 (5%) | 100 |
0.864 (1.00) |
0.644 (1.00) |
0.496 (1.00) |
1 (1.00) |
0.365 (1.00) |
0.529 (1.00) |
0.84 (1.00) |
1 (1.00) |
| ST18 | 24 (23%) | 81 |
1 (1.00) |
0.815 (1.00) |
0.559 (1.00) |
0.327 (1.00) |
0.408 (1.00) |
0.863 (1.00) |
0.437 (1.00) |
0.554 (1.00) |
| TAF1A | 8 (8%) | 97 |
0.284 (1.00) |
0.375 (1.00) |
0.319 (1.00) |
0.487 (1.00) |
0.41 (1.00) |
0.579 (1.00) |
0.64 (1.00) |
0.868 (1.00) |
| GRXCR2 | 9 (9%) | 96 |
0.0843 (1.00) |
0.168 (1.00) |
0.447 (1.00) |
1 (1.00) |
0.103 (1.00) |
0.261 (1.00) |
0.136 (1.00) |
0.338 (1.00) |
| OR9K2 | 11 (10%) | 94 |
0.663 (1.00) |
0.305 (1.00) |
0.414 (1.00) |
0.0221 (1.00) |
0.723 (1.00) |
0.606 (1.00) |
0.208 (1.00) |
1 (1.00) |
| OXA1L | 4 (4%) | 101 |
0.328 (1.00) |
0.306 (1.00) |
0.833 (1.00) |
0.913 (1.00) |
0.834 (1.00) |
0.261 (1.00) |
||
| A2BP1 | 14 (13%) | 91 |
0.729 (1.00) |
0.845 (1.00) |
0.0228 (1.00) |
0.723 (1.00) |
0.273 (1.00) |
0.28 (1.00) |
0.0675 (1.00) |
0.496 (1.00) |
| HIST1H2AA | 5 (5%) | 100 |
0.612 (1.00) |
0.644 (1.00) |
0.638 (1.00) |
0.453 (1.00) |
0.437 (1.00) |
0.935 (1.00) |
0.731 (1.00) |
0.616 (1.00) |
| LILRA1 | 21 (20%) | 84 |
0.264 (1.00) |
0.49 (1.00) |
0.759 (1.00) |
0.31 (1.00) |
0.413 (1.00) |
0.769 (1.00) |
0.739 (1.00) |
0.808 (1.00) |
| LIN7A | 8 (8%) | 97 |
0.424 (1.00) |
0.0151 (1.00) |
0.476 (1.00) |
0.664 (1.00) |
0.238 (1.00) |
0.336 (1.00) |
0.64 (1.00) |
0.738 (1.00) |
| VGLL1 | 3 (3%) | 102 |
1 (1.00) |
0.668 (1.00) |
1 (1.00) |
1 (1.00) |
0.794 (1.00) |
1 (1.00) |
||
| GALNTL5 | 10 (10%) | 95 |
0.125 (1.00) |
0.195 (1.00) |
0.289 (1.00) |
0.104 (1.00) |
0.131 (1.00) |
0.372 (1.00) |
0.215 (1.00) |
0.773 (1.00) |
| HSD11B1 | 6 (6%) | 99 |
0.712 (1.00) |
0.602 (1.00) |
0.234 (1.00) |
0.28 (1.00) |
0.764 (1.00) |
1 (1.00) |
0.12 (1.00) |
0.662 (1.00) |
| ANKRD20A4 | 4 (4%) | 101 |
0.361 (1.00) |
0.901 (1.00) |
0.0982 (1.00) |
0.296 (1.00) |
0.833 (1.00) |
0.415 (1.00) |
0.677 (1.00) |
0.725 (1.00) |
| GPR141 | 8 (8%) | 97 |
0.384 (1.00) |
0.473 (1.00) |
0.00297 (1.00) |
0.0173 (1.00) |
0.301 (1.00) |
0.348 (1.00) |
0.512 (1.00) |
1 (1.00) |
| NAP1L2 | 10 (10%) | 95 |
0.386 (1.00) |
1 (1.00) |
0.402 (1.00) |
0.139 (1.00) |
0.84 (1.00) |
0.783 (1.00) |
0.638 (1.00) |
1 (1.00) |
| C18ORF26 | 13 (12%) | 92 |
0.181 (1.00) |
0.642 (1.00) |
0.622 (1.00) |
0.0587 (1.00) |
1 (1.00) |
0.419 (1.00) |
0.278 (1.00) |
0.428 (1.00) |
| DEFB110 | 5 (5%) | 100 |
0.702 (1.00) |
0.744 (1.00) |
0.103 (1.00) |
0.131 (1.00) |
0.365 (1.00) |
0.288 (1.00) |
0.632 (1.00) |
1 (1.00) |
| IDH1 | 6 (6%) | 99 |
0.313 (1.00) |
0.602 (1.00) |
0.121 (1.00) |
0.405 (1.00) |
0.764 (1.00) |
0.551 (1.00) |
0.502 (1.00) |
0.0972 (1.00) |
| SNAP91 | 15 (14%) | 90 |
0.59 (1.00) |
0.00172 (1.00) |
0.933 (1.00) |
1 (1.00) |
0.162 (1.00) |
0.268 (1.00) |
1 (1.00) |
0.47 (1.00) |
| CA1 | 6 (6%) | 99 |
0.00987 (1.00) |
0.142 (1.00) |
0.751 (1.00) |
0.733 (1.00) |
0.386 (1.00) |
0.271 (1.00) |
0.046 (1.00) |
0.176 (1.00) |
| SERPINB11 | 12 (11%) | 93 |
0.129 (1.00) |
0.478 (1.00) |
0.872 (1.00) |
0.947 (1.00) |
0.292 (1.00) |
0.0606 (1.00) |
0.79 (1.00) |
0.51 (1.00) |
| UGT2B15 | 13 (12%) | 92 |
0.89 (1.00) |
0.284 (1.00) |
0.924 (1.00) |
0.407 (1.00) |
1 (1.00) |
0.852 (1.00) |
0.596 (1.00) |
0.0892 (1.00) |
| ACSM2B | 21 (20%) | 84 |
0.769 (1.00) |
0.0497 (1.00) |
0.236 (1.00) |
0.166 (1.00) |
0.556 (1.00) |
0.207 (1.00) |
0.00697 (1.00) |
0.155 (1.00) |
| C16ORF78 | 8 (8%) | 97 |
0.0199 (1.00) |
0.49 (1.00) |
0.87 (1.00) |
0.27 (1.00) |
0.814 (1.00) |
0.79 (1.00) |
0.23 (1.00) |
0.614 (1.00) |
| TFEC | 10 (10%) | 95 |
0.828 (1.00) |
0.559 (1.00) |
0.154 (1.00) |
0.206 (1.00) |
0.918 (1.00) |
0.275 (1.00) |
0.576 (1.00) |
0.19 (1.00) |
| TRHDE | 24 (23%) | 81 |
0.788 (1.00) |
0.00627 (1.00) |
0.798 (1.00) |
0.058 (1.00) |
0.536 (1.00) |
0.6 (1.00) |
0.797 (1.00) |
0.144 (1.00) |
| OR5AC2 | 13 (12%) | 92 |
0.742 (1.00) |
0.869 (1.00) |
0.647 (1.00) |
0.624 (1.00) |
0.205 (1.00) |
0.0246 (1.00) |
1 (1.00) |
0.896 (1.00) |
| CCDC102B | 11 (10%) | 94 |
0.056 (1.00) |
0.629 (1.00) |
0.722 (1.00) |
0.18 (1.00) |
0.262 (1.00) |
0.606 (1.00) |
0.228 (1.00) |
0.316 (1.00) |
| GRXCR1 | 12 (11%) | 93 |
0.311 (1.00) |
0.202 (1.00) |
0.949 (1.00) |
0.485 (1.00) |
1 (1.00) |
0.926 (1.00) |
0.538 (1.00) |
0.791 (1.00) |
| OR4M2 | 13 (12%) | 92 |
0.726 (1.00) |
0.125 (1.00) |
0.779 (1.00) |
0.666 (1.00) |
0.526 (1.00) |
0.601 (1.00) |
0.185 (1.00) |
0.896 (1.00) |
| PLAC8L1 | 3 (3%) | 102 |
0.187 (1.00) |
0.863 (1.00) |
0.171 (1.00) |
1 (1.00) |
0.259 (1.00) |
0.183 (1.00) |
0.794 (1.00) |
1 (1.00) |
| POM121 | 10 (10%) | 95 |
0.758 (1.00) |
0.366 (1.00) |
0.517 (1.00) |
0.272 (1.00) |
0.766 (1.00) |
0.738 (1.00) |
0.399 (1.00) |
0.388 (1.00) |
| RBM11 | 9 (9%) | 96 |
0.895 (1.00) |
0.378 (1.00) |
0.715 (1.00) |
0.629 (1.00) |
1 (1.00) |
0.835 (1.00) |
0.673 (1.00) |
0.562 (1.00) |
| RUNX1T1 | 16 (15%) | 89 |
0.168 (1.00) |
0.533 (1.00) |
0.0103 (1.00) |
0.0403 (1.00) |
1 (1.00) |
0.46 (1.00) |
0.575 (1.00) |
0.842 (1.00) |
| RGS7 | 17 (16%) | 88 |
0.65 (1.00) |
0.544 (1.00) |
0.795 (1.00) |
0.701 (1.00) |
0.376 (1.00) |
0.314 (1.00) |
0.385 (1.00) |
0.923 (1.00) |
| CLVS2 | 11 (10%) | 94 |
0.386 (1.00) |
0.685 (1.00) |
0.319 (1.00) |
0.629 (1.00) |
0.216 (1.00) |
0.263 (1.00) |
1 (1.00) |
0.701 (1.00) |
| DEFB118 | 6 (6%) | 99 |
0.0237 (1.00) |
0.492 (1.00) |
0.44 (1.00) |
0.604 (1.00) |
0.386 (1.00) |
0.791 (1.00) |
0.645 (1.00) |
1 (1.00) |
| OR52A5 | 12 (11%) | 93 |
0.647 (1.00) |
0.00302 (1.00) |
0.0805 (1.00) |
0.575 (1.00) |
0.0886 (1.00) |
0.0104 (1.00) |
0.927 (1.00) |
0.454 (1.00) |
| SPTLC3 | 13 (12%) | 92 |
0.539 (1.00) |
0.573 (1.00) |
0.787 (1.00) |
0.935 (1.00) |
0.0359 (1.00) |
0.601 (1.00) |
0.414 (1.00) |
0.896 (1.00) |
| ACTL7B | 7 (7%) | 98 |
0.203 (1.00) |
1 (1.00) |
0.712 (1.00) |
0.682 (1.00) |
0.693 (1.00) |
0.454 (1.00) |
0.885 (1.00) |
0.853 (1.00) |
| PHGDH | 7 (7%) | 98 |
0.698 (1.00) |
0.613 (1.00) |
0.708 (1.00) |
0.682 (1.00) |
0.376 (1.00) |
1 (1.00) |
0.471 (1.00) |
0.452 (1.00) |
| RGPD3 | 18 (17%) | 87 |
0.156 (1.00) |
0.321 (1.00) |
0.565 (1.00) |
0.564 (1.00) |
0.458 (1.00) |
0.166 (1.00) |
0.428 (1.00) |
0.561 (1.00) |
| WDR12 | 7 (7%) | 98 |
0.698 (1.00) |
0.951 (1.00) |
0.712 (1.00) |
0.415 (1.00) |
0.693 (1.00) |
0.108 (1.00) |
0.055 (1.00) |
0.0567 (1.00) |
| MPP7 | 13 (12%) | 92 |
0.487 (1.00) |
0.36 (1.00) |
0.622 (1.00) |
0.506 (1.00) |
0.334 (1.00) |
0.149 (1.00) |
0.929 (1.00) |
1 (1.00) |
Methods & Data
Input
-
Mutation data file = SKCM-Regional_LN.mutsig.cluster.txt
-
Molecular subtypes file = SKCM-Regional_LN.transferedmergedcluster.txt
-
Number of patients = 105
-
Number of significantly mutated genes = 74
-
Number of Molecular subtypes = 8
-
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
Chi-square test
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
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] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[3] 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)