Correlation between mRNAseq expression and clinical features
Brain Lower Grade Glioma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1TX3DD9
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features.

Summary

Testing the association between 18334 genes and 8 clinical features across 475 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 6 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • SYT6|148281 ,  PRSS35|167681 ,  ABI1|10006 ,  CTBP2|1488 ,  CNTN3|5067 ,  ...

  • 4 genes correlated to 'GENDER'.

    • NCRNA00183|554203 ,  HDHD1A|8226 ,  CYORF15A|246126 ,  CYORF15B|84663

  • 30 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • EEF1A1|1915 ,  ZBTB47|92999 ,  EEF2|1938 ,  UGP2|7360 ,  BDKRB2|624 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • AK2|204 ,  TXNDC12|51060 ,  TRAPPC3|27095 ,  STK40|83931 ,  HDAC1|3065 ,  ...

  • 30 genes correlated to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

    • CSAD|51380 ,  RHOT2|89941 ,  NCRNA00105|80161 ,  NSUN5P2|260294 ,  MAN2C1|4123 ,  ...

  • 15 genes correlated to 'RACE'.

    • ARMC10|83787 ,  LRRC37A2|474170 ,  C21ORF56|84221 ,  LRRC37A|9884 ,  KIAA1908|114796 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', and 'ETHNICITY'.

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=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=11 younger N=19
GENDER Wilcoxon test N=4 male N=4 female N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=30 higher score N=21 lower score N=9
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test N=30 yes N=30 no N=0
RACE Kruskal-Wallis test N=15        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No gene 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) 0-211.2 (median=18.7)
  censored N = 380
  death N = 94
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

Table S2.  Basic characteristics of clinical feature: 'YEARS_TO_BIRTH'

YEARS_TO_BIRTH Mean (SD) 42.99 (13)
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
SYT6|148281 -0.4295 1.066e-22 1.95e-18
PRSS35|167681 -0.4007 1.055e-19 7.92e-16
ABI1|10006 -0.3998 1.295e-19 7.92e-16
CTBP2|1488 -0.3806 8.661e-18 3.97e-14
CNTN3|5067 -0.3768 2.082e-17 7.63e-14
RIN1|9610 0.3741 3.446e-17 1.05e-13
NOL3|8996 0.3732 4.119e-17 1.08e-13
TCTA|6988 0.3707 6.931e-17 1.5e-13
GLUD1|2746 -0.3702 7.596e-17 1.5e-13
IL17RC|84818 0.3699 8.179e-17 1.5e-13
Clinical variable #3: 'GENDER'

4 genes related to 'GENDER'.

Table S4.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 208
  MALE 267
     
  Significant markers N = 4
  Higher in MALE 4
  Higher in FEMALE 0
List of 4 genes differentially expressed by 'GENDER'

Table S5.  Get Full Table List of 4 genes differentially expressed by 'GENDER'. 26 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
NCRNA00183|554203 6072 2.176e-48 4.43e-45 0.8907
HDHD1A|8226 11638 1.651e-27 1.78e-24 0.7904
CYORF15A|246126 12273 2.898e-27 2.95e-24 0.9993
CYORF15B|84663 8265 1.032e-19 8.6e-17 0.9986
Clinical variable #4: 'KARNOFSKY_PERFORMANCE_SCORE'

30 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

Table S6.  Basic characteristics of clinical feature: 'KARNOFSKY_PERFORMANCE_SCORE'

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 87.7 (12)
  Significant markers N = 30
  pos. correlated 21
  neg. correlated 9
List of top 10 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S7.  Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
EEF1A1|1915 0.3417 8.226e-09 0.000151
ZBTB47|92999 0.3274 3.626e-08 0.000262
EEF2|1938 0.3258 4.292e-08 0.000262
UGP2|7360 -0.317 1.021e-07 0.000272
BDKRB2|624 -0.3169 1.092e-07 0.000272
VAV3|10451 -0.3162 1.101e-07 0.000272
RPS6|6194 0.3156 1.176e-07 0.000272
HNRNPA1|3178 0.3148 1.266e-07 0.000272
RPL3|6122 0.3142 1.337e-07 0.000272
ARSK|153642 -0.3126 1.572e-07 0.000275
Clinical variable #5: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

Table S8.  Basic characteristics of clinical feature: 'HISTOLOGICAL_TYPE'

HISTOLOGICAL_TYPE Labels N
  ASTROCYTOMA 176
  OLIGOASTROCYTOMA 119
  OLIGODENDROGLIOMA 180
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S9.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
AK2|204 1.038e-36 1.9e-32
TXNDC12|51060 5.678e-35 5.21e-31
TRAPPC3|27095 1.022e-34 6.25e-31
STK40|83931 8.517e-34 3.25e-30
HDAC1|3065 8.919e-34 3.25e-30
TXLNA|200081 1.063e-33 3.25e-30
ASAP3|55616 1.269e-33 3.32e-30
WDR77|79084 3.344e-33 7.23e-30
FAM155A|728215 3.574e-33 7.23e-30
NADK|65220 3.942e-33 7.23e-30
Clinical variable #6: 'RADIATIONS_RADIATION_REGIMENINDICATION'

30 genes related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

Table S10.  Basic characteristics of clinical feature: 'RADIATIONS_RADIATION_REGIMENINDICATION'

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 92
  YES 383
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
CSAD|51380 27991 1.731e-18 3.17e-14 0.7944
RHOT2|89941 27811 6.618e-18 6.07e-14 0.7893
NCRNA00105|80161 27705 1.442e-17 8.82e-14 0.7863
NSUN5P2|260294 27615 2.778e-17 1.04e-13 0.7837
MAN2C1|4123 27612 2.839e-17 1.04e-13 0.7836
CENPT|80152 27577 3.657e-17 1.1e-13 0.7826
HOOK2|29911 27558 4.194e-17 1.1e-13 0.7821
MAMDC4|158056 27539 4.809e-17 1.1e-13 0.7816
CDK10|8558 27336 2.043e-16 3.73e-13 0.7758
SULT1A3|6818 27328 2.161e-16 3.73e-13 0.7756
Clinical variable #7: 'RACE'

15 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 8
  BLACK OR AFRICAN AMERICAN 15
  WHITE 440
     
  Significant markers N = 15
List of top 10 genes differentially expressed by 'RACE'

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

kruskal_wallis_P Q
ARMC10|83787 1.011e-06 0.0185
LRRC37A2|474170 1.858e-05 0.0922
C21ORF56|84221 2.066e-05 0.0922
LRRC37A|9884 2.196e-05 0.0922
KIAA1908|114796 2.515e-05 0.0922
SEC1|653677 3.063e-05 0.0936
PWP2|5822 5.139e-05 0.128
LIMK2|3985 5.722e-05 0.128
LOC441455|441455 6.749e-05 0.128
LRRIQ3|127255 6.96e-05 0.128
Clinical variable #8: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 18
  NOT HISPANIC OR LATINO 422
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = LGG-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

  • Clinical data file = LGG-TP.merged_data.txt

  • Number of patients = 475

  • Number of genes = 18334

  • Number of clinical features = 8

Selected clinical features
  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • 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, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels

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.

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

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)