Correlation between mRNAseq expression and clinical features
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features. The input file "CPTAC3-LUAD-TP.mRNA_RPKM_log2_norm_protein_coding.txt" is generated in the pipeline mRNAseq_Preprocess in the stddata run.

Summary

Testing the association between 18099 genes and 17 clinical features across 111 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 13 clinical features related to at least one genes.

- 2 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

- FAM217B|ENSG00000196227.10 , CCDC102A|ENSG00000135736.5

- 30 genes correlated to 'HISTOLOGICAL_TYPE'.

- PCNX3|ENSG00000197136.4 , ANXA4|ENSG00000196975.15 , MGP|ENSG00000111341.9 , CDT1|ENSG00000167513.8 , GINS2|ENSG00000131153.8 , ...

- 30 genes correlated to 'HISTOLOGIC_GRADE'.

- ANKRD29|ENSG00000154065.16 , VEGFD|ENSG00000165197.4 , NOSTRIN|ENSG00000163072.15 , MGST3|ENSG00000143198.12 , PNPLA2|ENSG00000177666.16 , ...

- 30 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

- PRR33|ENSG00000283787.1 , HIST1H4J|ENSG00000197238.4 , SLC25A30|ENSG00000174032.16 , PTBP1|ENSG00000011304.19 , CALCOCO2|ENSG00000136436.14 , ...

- 30 genes correlated to 'PATHOLOGY_T_STAGE'.

- TSC22D3|ENSG00000157514.16 , POU5F1|ENSG00000204531.17 , CITED2|ENSG00000164442.9 , HK2|ENSG00000159399.9 , GAPDH|ENSG00000111640.14 , ...

- 30 genes correlated to 'PATHOLOGIC_STAGE'.

- PPIF|ENSG00000108179.13 , CDC20|ENSG00000117399.13 , CLUL1|ENSG00000079101.16 , CUL2|ENSG00000108094.14 , CDC25A|ENSG00000164045.11 , ...

- 30 genes correlated to 'YEARS_TO_BIRTH'.

- RHBDD1|ENSG00000144468.16 , LY75|ENSG00000054219.10 , ABCA9|ENSG00000154258.16 , CCL19|ENSG00000172724.11 , OXNAD1|ENSG00000154814.13 , ...

- 9 genes correlated to 'GENDER'.

- PRMT2|ENSG00000160310.17 , RNASE1|ENSG00000129538.13 , ZNF8|ENSG00000278129.1 , C16ORF89|ENSG00000153446.15 , TMEM9B|ENSG00000175348.10 , ...

- 30 genes correlated to 'BMI'.

- AK9|ENSG00000155085.15 , GINM1|ENSG00000055211.12 , KPNA5|ENSG00000196911.10 , SPATC1L|ENSG00000160284.14 , PNISR|ENSG00000132424.14 , ...

- 1 gene correlated to 'NUMBER_PACK_YEARS_SMOKED'.

- ALDH1A3|ENSG00000184254.16

- 30 genes correlated to 'SMOKER'.

- CH507-42P11.8|ENSG00000275993.2 , GPR15|ENSG00000154165.4 , PM20D1|ENSG00000162877.12 , CST1|ENSG00000170373.8 , ADCYAP1|ENSG00000141433.12 , ...

- 30 genes correlated to 'COUNTRY_OF_ORIGIN'.

- PM20D1|ENSG00000162877.12 , PTBP1|ENSG00000011304.19 , CCDC144A|ENSG00000170160.17 , MAZ|ENSG00000103495.13 , ABCD1|ENSG00000101986.11 , ...

- 30 genes correlated to 'ORIGIN_ASIA'.

- PM20D1|ENSG00000162877.12 , CCDC144A|ENSG00000170160.17 , ASPA|ENSG00000108381.10 , SIGLEC12|ENSG00000254521.6 , CASS4|ENSG00000087589.16 , ...

- No genes correlated to 'PATHOLOGY_N_STAGE', 'ETHNICITY', 'RACE', and 'RADIATION_THERAPY'.

Results
Overview of the results

Complete statistical result table is provided in Supplement Table 1

Table 1. Get Full Table This table shows the clinical features, statistical methods used, and the number of genes that are significantly associated with each clinical feature at P value < 0.05 and Q value < 0.3.

Clinical feature | Statistical test | Significant genes | Associated with |  | Associated with |
--- | --- | --- | --- | --- | --- | ---
DAYS_TO_DEATH_OR_LAST_FUP | Cox regression test | N=2 |  | N=NA |  | N=NA
HISTOLOGICAL_TYPE | Kruskal-Wallis test | N=30 |  |  |  |
HISTOLOGIC_GRADE | Kruskal-Wallis test | N=30 |  |  |  |
KARNOFSKY_PERFORMANCE_SCORE | Spearman correlation test | N=30 | higher score | N=20 | lower score | N=10
PATHOLOGY_T_STAGE | Spearman correlation test | N=30 | higher stage | N=9 | lower stage | N=21
PATHOLOGY_N_STAGE | Spearman correlation test | N=0 |  |  |  |
PATHOLOGIC_STAGE | Kruskal-Wallis test | N=30 |  |  |  |
YEARS_TO_BIRTH | Spearman correlation test | N=30 | older | N=30 | younger | N=0
ETHNICITY | Wilcoxon test | N=0 |  |  |  |
GENDER | Wilcoxon test | N=9 | male | N=9 | female | N=0
RACE | Kruskal-Wallis test | N=0 |  |  |  |
RADIATION_THERAPY | Wilcoxon test | N=0 |  |  |  |
BMI | Kruskal-Wallis test | N=30 |  |  |  |
NUMBER_PACK_YEARS_SMOKED | Spearman correlation test | N=1 | higher number_pack_years_smoked | N=1 | lower number_pack_years_smoked | N=0
SMOKER | Wilcoxon test | N=30 | smoker | N=30 | non-smoker | N=0
COUNTRY_OF_ORIGIN | Kruskal-Wallis test | N=30 |  |  |  |
ORIGIN_ASIA | Wilcoxon test | N=30 | western | N=30 | asian | N=0

Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

2 genes related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1. Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'

DAYS_TO_DEATH_OR_LAST_FUP | Duration (Months) | 0.2-35 (median=13.1)
| censored | N = 92
| death | N = 12
| Significant markers | N = 2
| associated with shorter survival | NA
| associated with longer survival | NA

List of 2 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2. Get Full Table List of 2 genes significantly associated with 'Time to Death' by Cox regression test. For the survival curves, it compared quantile intervals at c(0, 0.25, 0.50, 0.75, 1) and did not try survival analysis if there is only one interval.

| logrank_P | Q | C_index
--- | --- | --- | ---
FAM217B|ENSG00000196227.10 | 3.73e-06 | 0.067 | 0.162
CCDC102A|ENSG00000135736.5 | 2.91e-05 | 0.26 | 0.234

Clinical variable #2: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

Table S3. Basic characteristics of clinical feature: 'HISTOLOGICAL_TYPE'

HISTOLOGICAL_TYPE | Labels | N
| ACINAR ADENOCARCINOMA | 13
| ADENOCARCINOMA | 68
| BASALOID SQUAMOUS CELL CARCINOMA | 1
| INVASIVE MUCINOUS ADENOCARCINOMA | 3
| LEPIDIC ADENOCARCINOMA | 2
| MICROPAPILLARY ADENOCARCINOMA | 2
| OTHER | 7
| PAPILLARY ADENOCARCINOMA | 5
| SOLID ADENOCARCINOMA | 8
| SQUAMOUS CELL CARCINOMA | 2
| Significant markers | N = 30

List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S4. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

| kruskal_wallis_P | Q
--- | --- | ---
PCNX3|ENSG00000197136.4 | 5.11e-06 | 0.0925
ANXA4|ENSG00000196975.15 | 2.232e-05 | 0.144
MGP|ENSG00000111341.9 | 2.388e-05 | 0.144
CDT1|ENSG00000167513.8 | 7.964e-05 | 0.21
GINS2|ENSG00000131153.8 | 8.036e-05 | 0.21
ACRV1|ENSG00000134940.13 | 0.0001215 | 0.21
PRRC2A|ENSG00000204469.12 | 0.0001364 | 0.21
RECQL4|ENSG00000160957.12 | 0.0001375 | 0.21
UBE2C|ENSG00000175063.16 | 0.0001438 | 0.21
MEOX2|ENSG00000106511.5 | 0.0001493 | 0.21

Clinical variable #3: 'HISTOLOGIC_GRADE'

30 genes related to 'HISTOLOGIC_GRADE'.

Table S5. Basic characteristics of clinical feature: 'HISTOLOGIC_GRADE'

HISTOLOGIC_GRADE | Labels | N
| G1 | 8
| G2 | 65
| G3 | 31
| G4 | 1
| GX | 6
| Significant markers | N = 30

List of top 10 genes differentially expressed by 'HISTOLOGIC_GRADE'

Table S6. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGIC_GRADE'

| kruskal_wallis_P | Q
--- | --- | ---
ANKRD29|ENSG00000154065.16 | 8.75e-06 | 0.128
VEGFD|ENSG00000165197.4 | 1.688e-05 | 0.128
NOSTRIN|ENSG00000163072.15 | 2.288e-05 | 0.128
MGST3|ENSG00000143198.12 | 3.893e-05 | 0.128
PNPLA2|ENSG00000177666.16 | 3.953e-05 | 0.128
FBLN5|ENSG00000140092.14 | 4.785e-05 | 0.128
CDO1|ENSG00000129596.4 | 5.127e-05 | 0.128
ADH1B|ENSG00000196616.13 | 6.429e-05 | 0.128
RSPO2|ENSG00000147655.10 | 7.648e-05 | 0.128
MYL3|ENSG00000160808.9 | 9.197e-05 | 0.128

Clinical variable #4: 'KARNOFSKY_PERFORMANCE_SCORE'

30 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

Table S7. Basic characteristics of clinical feature: 'KARNOFSKY_PERFORMANCE_SCORE'

KARNOFSKY_PERFORMANCE_SCORE | Mean (SD) | 81.71 (9)
| Score | N
| 70 | 18
| 80 | 27
| 90 | 20
| 100 | 5
| Significant markers | N = 30
| pos. correlated | 20
| neg. correlated | 10

List of top 10 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S8. Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
PRR33|ENSG00000283787.1 | 0.5814 | 1.306e-07 | 0.00236
HIST1H4J|ENSG00000197238.4 | -0.5312 | 2.228e-06 | 0.0185
SLC25A30|ENSG00000174032.16 | 0.5251 | 3.059e-06 | 0.0185
PTBP1|ENSG00000011304.19 | -0.5103 | 6.389e-06 | 0.0279
CALCOCO2|ENSG00000136436.14 | 0.5065 | 7.705e-06 | 0.0279
OSTN|ENSG00000188729.6 | 0.5454 | 9.555e-06 | 0.0288
CT62|ENSG00000225362.8 | 0.4948 | 1.796e-05 | 0.0464
FAM180B|ENSG00000196666.4 | 0.5082 | 2.114e-05 | 0.0478
NABP2|ENSG00000139579.12 | -0.4796 | 2.66e-05 | 0.0497
HIST2H2BF|ENSG00000203814.6 | -0.4789 | 2.747e-05 | 0.0497

Clinical variable #5: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S9. Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE | Mean (SD) | 1.86 (0.6)
|  | N
| T1 | 28
| T2 | 70
| T3 | 13
| Significant markers | N = 30
| pos. correlated | 9
| neg. correlated | 21

List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S10. Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
TSC22D3|ENSG00000157514.16 | -0.4381 | 1.523e-06 | 0.0253
POU5F1|ENSG00000204531.17 | -0.4257 | 3.204e-06 | 0.0253
CITED2|ENSG00000164442.9 | -0.421 | 4.196e-06 | 0.0253
HK2|ENSG00000159399.9 | 0.4083 | 8.659e-06 | 0.0392
GAPDH|ENSG00000111640.14 | 0.3927 | 2.02e-05 | 0.0721
C1ORF186|ENSG00000263961.6 | -0.3895 | 2.391e-05 | 0.0721
DAPK2|ENSG00000035664.11 | -0.3854 | 2.955e-05 | 0.0764
ZFAND5|ENSG00000107372.12 | -0.3787 | 4.164e-05 | 0.0847
SLC15A2|ENSG00000163406.10 | -0.3775 | 4.42e-05 | 0.0847
C7|ENSG00000112936.18 | -0.3764 | 4.681e-05 | 0.0847

Clinical variable #6: 'PATHOLOGY_N_STAGE'

No gene related to 'PATHOLOGY_N_STAGE'.

Table S11. Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE | Mean (SD) | 0.5 (0.78)
|  | N
| N0 | 74
| N1 | 17
| N2 | 19
| Significant markers | N = 0

Clinical variable #7: 'PATHOLOGIC_STAGE'

30 genes related to 'PATHOLOGIC_STAGE'.

Table S12. Basic characteristics of clinical feature: 'PATHOLOGIC_STAGE'

PATHOLOGIC_STAGE | Labels | N
| STAGE I | 2
| STAGE IA | 23
| STAGE IB | 34
| STAGE IIA | 17
| STAGE IIB | 13
| STAGE III | 1
| STAGE IIIA | 20
| STAGE IV | 1
| Significant markers | N = 30

List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

Table S13. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

| kruskal_wallis_P | Q
--- | --- | ---
PPIF|ENSG00000108179.13 | 3.456e-05 | 0.253
CDC20|ENSG00000117399.13 | 3.98e-05 | 0.253
CLUL1|ENSG00000079101.16 | 5.174e-05 | 0.253
CUL2|ENSG00000108094.14 | 5.592e-05 | 0.253
CDC25A|ENSG00000164045.11 | 0.0001046 | 0.266
AURKA|ENSG00000087586.17 | 0.0001132 | 0.266
RALA|ENSG00000006451.7 | 0.0001333 | 0.266
TLR5|ENSG00000187554.11 | 0.0001454 | 0.266
MAPK10|ENSG00000109339.19 | 0.0001783 | 0.266
C1QTNF7|ENSG00000163145.12 | 0.0002186 | 0.266

Clinical variable #8: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

Table S14. Basic characteristics of clinical feature: 'YEARS_TO_BIRTH'

YEARS_TO_BIRTH | Mean (SD) | 62.57 (9.6)
| Significant markers | N = 30
| pos. correlated | 30
| neg. correlated | 0

List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S15. Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
RHBDD1|ENSG00000144468.16 | 0.4631 | 3.08e-07 | 0.0053
LY75|ENSG00000054219.10 | 0.4478 | 8.322e-07 | 0.0053
ABCA9|ENSG00000154258.16 | 0.4469 | 8.79e-07 | 0.0053
CCL19|ENSG00000172724.11 | 0.434 | 1.948e-06 | 0.0067
OXNAD1|ENSG00000154814.13 | 0.4339 | 1.956e-06 | 0.0067
PTGDS|ENSG00000107317.12 | 0.4284 | 2.729e-06 | 0.0067
LY9|ENSG00000122224.17 | 0.4267 | 3.005e-06 | 0.0067
EPS15|ENSG00000085832.16 | 0.4236 | 3.609e-06 | 0.0067
PZP|ENSG00000126838.9 | 0.4214 | 4.117e-06 | 0.0067
ANGPTL1|ENSG00000116194.12 | 0.4197 | 4.537e-06 | 0.0067

Clinical variable #9: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S16. Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY | Labels | N
| HISPANIC OR LATINO | 3
| NOT HISPANIC OR LATINO | 35
| Significant markers | N = 0

Clinical variable #10: 'GENDER'

9 genes related to 'GENDER'.

Table S17. Basic characteristics of clinical feature: 'GENDER'

GENDER | Labels | N
| FEMALE | 38
| MALE | 73
| Significant markers | N = 9
| Higher in MALE | 9
| Higher in FEMALE | 0

List of 9 genes differentially expressed by 'GENDER'

Table S18. Get Full Table List of 9 genes differentially expressed by 'GENDER'. 21 significant gene(s) located in sex chromosomes is(are) filtered out.

| W(pos if higher in 'MALE') | wilcoxontestP | Q | AUC
--- | --- | --- | --- | ---
PRMT2|ENSG00000160310.17 | 607 | 1.27e-06 | 0.00104 | 0.7812
RNASE1|ENSG00000129538.13 | 609 | 1.352e-06 | 0.00105 | 0.7805
ZNF8|ENSG00000278129.1 | 2164 | 1.394e-06 | 0.00105 | 0.7801
C16ORF89|ENSG00000153446.15 | 623 | 2.085e-06 | 0.00151 | 0.7754
TMEM9B|ENSG00000175348.10 | 627.5 | 2.393e-06 | 0.00167 | 0.7738
HAUS6|ENSG00000147874.10 | 2143.5 | 2.622e-06 | 0.00175 | 0.7727
TMEM116|ENSG00000198270.12 | 631.5 | 2.703e-06 | 0.00175 | 0.7724
HPDL|ENSG00000186603.5 | 2137 | 3.193e-06 | 0.00199 | 0.7704
SMAD5|ENSG00000113658.16 | 641 | 3.601e-06 | 0.00217 | 0.7689

Clinical variable #11: 'RACE'

No gene related to 'RACE'.

Table S19. Basic characteristics of clinical feature: 'RACE'

RACE | Labels | N
| AMERICAN INDIAN OR ALASKA NATIVE | 1
| ASIAN | 1
| BLACK OR AFRICAN AMERICAN | 1
| WHITE | 34
| Significant markers | N = 0

Clinical variable #12: 'RADIATION_THERAPY'

No gene related to 'RADIATION_THERAPY'.

Table S20. Basic characteristics of clinical feature: 'RADIATION_THERAPY'

RADIATION_THERAPY | Labels | N
| NO | 72
| YES | 22
| Significant markers | N = 0

Clinical variable #13: 'BMI'

30 genes related to 'BMI'.

Table S21. Basic characteristics of clinical feature: 'BMI'

BMI | Labels | N
| NORMAL | 54
| OBESE | 10
| OVERWEIGHT | 28
| SEVERELY OBESE | 3
| UNDERWEIGHT | 16
| Significant markers | N = 30

List of top 10 genes differentially expressed by 'BMI'

Table S22. Get Full Table List of top 10 genes differentially expressed by 'BMI'

| kruskal_wallis_P | Q
--- | --- | ---
AK9|ENSG00000155085.15 | 3.892e-07 | 0.00704
GINM1|ENSG00000055211.12 | 2.208e-06 | 0.0196
KPNA5|ENSG00000196911.10 | 3.251e-06 | 0.0196
SPATC1L|ENSG00000160284.14 | 5.239e-06 | 0.0237
PNISR|ENSG00000132424.14 | 1.137e-05 | 0.0312
ASPA|ENSG00000108381.10 | 1.314e-05 | 0.0312
RAD23A|ENSG00000179262.9 | 1.428e-05 | 0.0312
PIK3C3|ENSG00000078142.12 | 1.432e-05 | 0.0312
ITIH5|ENSG00000123243.14 | 2.075e-05 | 0.0312
CDC34|ENSG00000099804.8 | 2.078e-05 | 0.0312

Clinical variable #14: 'NUMBER_PACK_YEARS_SMOKED'

One gene related to 'NUMBER_PACK_YEARS_SMOKED'.

Table S23. Basic characteristics of clinical feature: 'NUMBER_PACK_YEARS_SMOKED'

NUMBER_PACK_YEARS_SMOKED | Mean (SD) | 27.41 (23)
| Significant markers | N = 1
| pos. correlated | 1
| neg. correlated | 0

List of one gene differentially expressed by 'NUMBER_PACK_YEARS_SMOKED'

Table S24. Get Full Table List of one gene significantly correlated to 'NUMBER_PACK_YEARS_SMOKED' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
ALDH1A3|ENSG00000184254.16 | 0.5559 | 1.053e-05 | 0.191

Clinical variable #15: 'SMOKER'

30 genes related to 'SMOKER'.

Table S25. Basic characteristics of clinical feature: 'SMOKER'

SMOKER | Labels | N
| NON-SMOKER | 46
| SMOKER | 62
| Significant markers | N = 30
| Higher in SMOKER | 30
| Higher in NON-SMOKER | 0

List of top 10 genes differentially expressed by 'SMOKER'

Table S26. Get Full Table List of top 10 genes differentially expressed by 'SMOKER'

| W(pos if higher in 'SMOKER') | wilcoxontestP | Q | AUC
--- | --- | --- | --- | ---
CH507-42P11.8|ENSG00000275993.2 | 2179 | 2.935e-06 | 0.0531 | 0.764
GPR15|ENSG00000154165.4 | 2145 | 8.042e-06 | 0.0601 | 0.7521
PM20D1|ENSG00000162877.12 | 2126 | 1.386e-05 | 0.0601 | 0.7454
CST1|ENSG00000170373.8 | 731 | 1.596e-05 | 0.0601 | 0.7437
ADCYAP1|ENSG00000141433.12 | 1975 | 1.66e-05 | 0.0601 | 0.7481
PTP4A1|ENSG00000112245.10 | 2059 | 8.504e-05 | 0.229 | 0.7219
NR1H4|ENSG00000012504.13 | 1323 | 8.937e-05 | 0.229 | 0.75
NLGN4X|ENSG00000146938.14 | 2049 | 0.0001099 | 0.229 | 0.7184
TTLL8|ENSG00000138892.11 | 833 | 0.0001312 | 0.229 | 0.7763
GEM|ENSG00000164949.7 | 2041 | 0.0001346 | 0.229 | 0.7156

Clinical variable #16: 'COUNTRY_OF_ORIGIN'

30 genes related to 'COUNTRY_OF_ORIGIN'.

Table S27. Basic characteristics of clinical feature: 'COUNTRY_OF_ORIGIN'

COUNTRY_OF_ORIGIN | Labels | N
| BULGARIA | 2
| CANADA | 1
| CHINA | 18
| JAMAICA | 1
| MEXICO | 2
| POLAND | 2
| RUSSIA | 1
| UKRAINE | 3
| UNITED STATES | 34
| VIETNAM | 45
| Significant markers | N = 30

List of top 10 genes differentially expressed by 'COUNTRY_OF_ORIGIN'

Table S28. Get Full Table List of top 10 genes differentially expressed by 'COUNTRY_OF_ORIGIN'

| kruskal_wallis_P | Q
--- | --- | ---
PM20D1|ENSG00000162877.12 | 1.687e-08 | 0.000305
PTBP1|ENSG00000011304.19 | 1.04e-07 | 0.000664
CCDC144A|ENSG00000170160.17 | 1.101e-07 | 0.000664
MAZ|ENSG00000103495.13 | 4.329e-07 | 0.00196
ABCD1|ENSG00000101986.11 | 1.046e-06 | 0.00379
ITIH5|ENSG00000123243.14 | 1.859e-06 | 0.00503
CASS4|ENSG00000087589.16 | 2.001e-06 | 0.00503
NABP2|ENSG00000139579.12 | 2.224e-06 | 0.00503
ASPA|ENSG00000108381.10 | 3.129e-06 | 0.00564
CDC34|ENSG00000099804.8 | 3.331e-06 | 0.00564

Clinical variable #17: 'ORIGIN_ASIA'

30 genes related to 'ORIGIN_ASIA'.

Table S29. Basic characteristics of clinical feature: 'ORIGIN_ASIA'

ORIGIN_ASIA | Labels | N
| ASIAN | 63
| WESTERN | 46
| Significant markers | N = 30
| Higher in WESTERN | 30
| Higher in ASIAN | 0

List of top 10 genes differentially expressed by 'ORIGIN_ASIA'

Table S30. Get Full Table List of top 10 genes differentially expressed by 'ORIGIN_ASIA'

| W(pos if higher in 'WESTERN') | wilcoxontestP | Q | AUC
--- | --- | --- | --- | ---
PM20D1|ENSG00000162877.12 | 2557 | 1.083e-11 | 1.96e-07 | 0.8823
CCDC144A|ENSG00000170160.17 | 2480 | 2.573e-10 | 2.33e-06 | 0.8558
ASPA|ENSG00000108381.10 | 2454 | 7.136e-10 | 4.31e-06 | 0.8468
SIGLEC12|ENSG00000254521.6 | 456 | 1.133e-09 | 5.13e-06 | 0.8427
CASS4|ENSG00000087589.16 | 2393 | 7.09e-09 | 2.57e-05 | 0.8257
CLPB|ENSG00000162129.12 | 518.5 | 1.157e-08 | 3.08e-05 | 0.8211
MAZ|ENSG00000103495.13 | 523 | 1.36e-08 | 3.08e-05 | 0.8195
ITIH5|ENSG00000123243.14 | 2375 | 1.36e-08 | 3.08e-05 | 0.8195
NPIPB15|ENSG00000196436.8 | 535 | 2.086e-08 | 4.1e-05 | 0.8154
THOC3|ENSG00000051596.9 | 539 | 2.403e-08 | 4.1e-05 | 0.814

Methods & Data
Input

- Expresson data file = CPTAC3-LUAD-TP.mRNA_RPKM_log2_norm_protein_coding.txt

- Clinical data file = CPTAC3-LUAD-TP.clin.merged.picked.txt

- Number of patients = 111

- Number of genes = 18099

- Number of clinical features = 17

Selected clinical features

- Further details on clinical features selected for this analysis, please find a documentation on selected CDEs (Clinical Data Elements). The first column of the file is a formula to convert values and the second column is a clinical parameter name.

- There are also useful links about clinical features.

- CDE Browser

- Data dictionary for clinical data

- NCI wiki - Biospecimen and Clinical XSD Files Specification

- Survival time data

- Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

- if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

- if 'vital_status'==0(alive),

- if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

- if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

- if 'vital_status'==NA,excludes this case in survival analysis and report the case.

- cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

- This analysis excluded clinical variables that has only NA values.

Survival analysis

For survival clinical features, logrank test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values comparing quantile intervals using the 'coxph' function in R. Kaplan-Meier survival curves were plotted using quantile intervals at c(0, 0.25, 0.50, 0.75, 1). If there is only one interval group, it will not try survival analysis.

Correlation analysis

For continuous numerical clinical features, Spearman's rank correlation coefficients (Spearman 1904) and two-tailed P values were estimated using 'cor.test' function in R

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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] Andersen and Gill, Cox's regression model for counting processes, a large sample study, Annals of Statistics 10(4):1100-1120 (1982)
[2] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[3] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[4] 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)
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