Correlation between mRNAseq expression and clinical features
Sarcoma (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/C19W0DKD
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 18184 genes and 5 clinical features across 248 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 3 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • RNASEL|6041 ,  TICAM1|148022 ,  B3GALT4|8705 ,  GLO1|2739 ,  TARDBP|23435 ,  ...

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • KTI12|112970 ,  VASN|114990 ,  NDRG2|57447 ,  CA11|770 ,  NANS|54187 ,  ...

  • 9 genes correlated to 'GENDER'.

    • CYORF15B|84663 ,  NCRNA00183|554203 ,  CYORF15A|246126 ,  HDHD1A|8226 ,  DBF4B|80174 ,  ...

  • No genes correlated to 'RACE', 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=30 shorter survival N=10 longer survival N=20
YEARS_TO_BIRTH Spearman correlation test N=30 older N=12 younger N=18
GENDER Wilcoxon test N=9 male N=9 female N=0
RACE Kruskal-Wallis test   N=0        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

30 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) 0.1-188.2 (median=23.1)
  censored N = 165
  death N = 82
     
  Significant markers N = 30
  associated with shorter survival 10
  associated with longer survival 20
List of top 10 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
RNASEL|6041 0.55 1.986e-07 0.0036 0.336
TICAM1|148022 0.42 6.038e-07 0.0051 0.347
B3GALT4|8705 0.65 1.061e-06 0.0051 0.303
GLO1|2739 2 1.281e-06 0.0051 0.646
TARDBP|23435 8.8 1.562e-06 0.0051 0.67
TRIM21|6737 0.49 1.833e-06 0.0051 0.343
DHX58|79132 0.59 1.954e-06 0.0051 0.368
LRRC41|10489 3.3 2.614e-06 0.0055 0.676
ALDH1A1|216 0.79 2.701e-06 0.0055 0.33
VPS18|57617 0.32 3.64e-06 0.0066 0.324
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 61.19 (14)
  Significant markers N = 30
  pos. correlated 12
  neg. correlated 18
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
KTI12|112970 0.3776 8.59e-10 1.56e-05
VASN|114990 0.3541 1.047e-08 9.52e-05
NDRG2|57447 -0.3474 2.058e-08 0.000104
CA11|770 -0.3448 2.659e-08 0.000104
NANS|54187 0.3417 3.609e-08 0.000104
ZNF37B|100129482 -0.3406 3.983e-08 0.000104
MARCO|8685 0.3438 4.895e-08 0.000104
MBD5|55777 -0.3375 5.403e-08 0.000104
ALS2CR8|79800 -0.3366 5.898e-08 0.000104
MED8|112950 0.3353 6.691e-08 0.000104
Clinical variable #3: 'GENDER'

9 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 134
  MALE 114
     
  Significant markers N = 9
  Higher in MALE 9
  Higher in FEMALE 0
List of 9 genes differentially expressed by 'GENDER'

Table S6.  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
CYORF15B|84663 3184 3.965e-16 6.01e-13 0.9975
NCRNA00183|554203 3443 9.322e-14 1.21e-10 0.7746
CYORF15A|246126 2508 1.284e-13 1.56e-10 1
HDHD1A|8226 4243 1.647e-09 1.58e-06 0.7222
DBF4B|80174 4344 4.921e-09 4.26e-06 0.7156
CA5BP|340591 4462 1.698e-08 1.29e-05 0.7079
MYST2|11143 4622 8.506e-08 5.73e-05 0.6974
UNC5D|137970 1536 8.887e-08 5.77e-05 0.75
TYRO3|7301 4713 2.053e-07 0.000124 0.6915
Clinical variable #4: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  ASIAN 6
  BLACK OR AFRICAN AMERICAN 18
  WHITE 196
     
  Significant markers N = 0
Clinical variable #5: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 5
  NOT HISPANIC OR LATINO 193
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = SARC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 248

  • Number of genes = 18184

  • Number of clinical features = 5

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)