Correlation between mRNAseq expression and clinical features
Brain Lower Grade Glioma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1MG7NDC
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1MG7NDC
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 18333 genes and 8 clinical features across 430 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 6 clinical features related to at least one genes.

  • 1140 genes correlated to 'AGE'.

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

  • 7 genes correlated to 'GENDER'.

    • NCRNA00183|554203 ,  HDHD1A|8226 ,  CYORF15A|246126 ,  CYORF15B|84663 ,  GZF1|64412 ,  ...

  • 160 genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • EEF1A1|1915 ,  UGP2|7360 ,  EEF2|1938 ,  HNRNPA1|3178 ,  RPL3|6122 ,  ...

  • 5679 genes correlated to 'HISTOLOGICAL.TYPE'.

    • AK2|204 ,  STK40|83931 ,  TXLNA|200081 ,  ASAP3|55616 ,  NADK|65220 ,  ...

  • 915 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • CSAD|51380 ,  MAMDC4|158056 ,  RHOT2|89941 ,  MAN2C1|4123 ,  NSUN5P2|260294 ,  ...

  • 1 gene correlated to 'RACE'.

    • ARMC10|83787

  • No genes correlated to 'Time to Death', 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
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=1140 older N=610 younger N=530
GENDER Wilcoxon test N=7 male N=7 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=160 higher score N=105 lower score N=55
HISTOLOGICAL TYPE Kruskal-Wallis test N=5679        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=915 yes N=915 no N=0
RACE Kruskal-Wallis test N=1        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0-211.2 (median=15.9)
  censored N = 352
  death N = 75
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

1140 genes related to 'AGE'.

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

AGE Mean (SD) 42.96 (13)
  Significant markers N = 1140
  pos. correlated 610
  neg. correlated 530
List of top 10 genes differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
SYT6|148281 -0.4291 1.213e-20 2.22e-16
ABI1|10006 -0.3959 1.51e-17 2.77e-13
PRSS35|167681 -0.385 1.321e-16 2.42e-12
CTBP2|1488 -0.377 6.126e-16 1.12e-11
CNTN3|5067 -0.3746 9.799e-16 1.8e-11
NOL3|8996 0.3689 2.838e-15 5.2e-11
RIN1|9610 0.3654 5.406e-15 9.91e-11
PPP2R5A|5525 -0.3649 5.916e-15 1.08e-10
RBM17|84991 -0.3645 6.338e-15 1.16e-10
SFRP2|6423 -0.3642 6.62e-15 1.21e-10
Clinical variable #3: 'GENDER'

7 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 190
  MALE 240
     
  Significant markers N = 7
  Higher in MALE 7
  Higher in FEMALE 0
List of 7 genes differentially expressed by 'GENDER'

Table S5.  Get Full Table List of 7 genes differentially expressed by 'GENDER'. 30 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
NCRNA00183|554203 4434 1.055e-46 1.93e-42 0.9028
HDHD1A|8226 9481 2.304e-25 4.22e-21 0.7921
CYORF15A|246126 10078 5.052e-25 9.25e-21 0.9998
CYORF15B|84663 6233 6.645e-17 1.22e-12 0.9989
GZF1|64412 29027 1.143e-06 0.0209 0.6366
NLRP2|55655 16103 2.769e-06 0.0507 0.6328
SPESP1|246777 28360 1.398e-05 0.256 0.6219
Clinical variable #4: 'KARNOFSKY.PERFORMANCE.SCORE'

160 genes related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S6.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 87.77 (12)
  Significant markers N = 160
  pos. correlated 105
  neg. correlated 55
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 0.3676 2.561e-09 4.7e-05
UGP2|7360 -0.3536 1.096e-08 0.000201
EEF2|1938 0.3531 1.16e-08 0.000213
HNRNPA1|3178 0.3503 1.531e-08 0.000281
RPL3|6122 0.3419 3.512e-08 0.000644
OPN3|23596 -0.3401 4.197e-08 0.000769
VAV3|10451 -0.34 4.236e-08 0.000776
RPL15|6138 0.3391 4.616e-08 0.000846
RPL13|6137 0.3326 8.6e-08 0.00158
RPS23|6228 0.3269 1.472e-07 0.0027
Clinical variable #5: 'HISTOLOGICAL.TYPE'

5679 genes related to 'HISTOLOGICAL.TYPE'.

Table S8.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  ASTROCYTOMA 158
  OLIGOASTROCYTOMA 108
  OLIGODENDROGLIOMA 164
     
  Significant markers N = 5679
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'

ANOVA_P Q
AK2|204 4.18e-34 7.66e-30
STK40|83931 3.954e-33 7.25e-29
TXLNA|200081 2.604e-32 4.77e-28
ASAP3|55616 8.143e-32 1.49e-27
NADK|65220 8.282e-32 1.52e-27
WDR77|79084 2.513e-31 4.61e-27
TXNDC12|51060 7.249e-31 1.33e-26
HDAC1|3065 8.136e-31 1.49e-26
TRAPPC3|27095 1.276e-30 2.34e-26
VIM|7431 1.828e-30 3.35e-26
Clinical variable #6: 'RADIATIONS.RADIATION.REGIMENINDICATION'

915 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S10.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 89
  YES 341
     
  Significant markers N = 915
  Higher in YES 915
  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 23669 4.097e-16 7.51e-12 0.7799
MAMDC4|158056 23555 1.003e-15 1.84e-11 0.7761
RHOT2|89941 23490 1.663e-15 3.05e-11 0.774
MAN2C1|4123 23467 1.987e-15 3.64e-11 0.7732
NSUN5P2|260294 23342 5.181e-15 9.5e-11 0.7691
NCRNA00105|80161 23312 6.507e-15 1.19e-10 0.7681
HOOK2|29911 23247 1.063e-14 1.95e-10 0.766
GOLGA6L9|440295 23186 1.68e-14 3.08e-10 0.764
CDK10|8558 23156 2.101e-14 3.85e-10 0.763
CCDC154|645811 22956.5 3.502e-14 6.42e-10 0.7609
Clinical variable #7: 'RACE'

One gene related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 6
  BLACK OR AFRICAN AMERICAN 14
  WHITE 400
     
  Significant markers N = 1
List of one gene differentially expressed by 'RACE'

Table S13.  Get Full Table List of one gene differentially expressed by 'RACE'

ANOVA_P Q
ARMC10|83787 4.71e-06 0.0863
Clinical variable #8: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 16
  NOT HISPANIC OR LATINO 387
     
  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 = 430

  • Number of genes = 18333

  • Number of clinical features = 8

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

Student's t-test analysis

For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R

ANOVA analysis

For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' 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.

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] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[5] 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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