Acute Myeloid Leukemia: Correlation between mRNAseq expression and clinical features

Maintained by Juok Cho (Broad Institute)

Overview

Introduction

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

Summary

Testing the association between 17799 genes and 3 clinical features across 179 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

4 genes correlated to 'Time to Death'.

IL2RA|3559_CALCULATED , C2ORF67|151050_CALCULATED , TREML2|79865_CALCULATED , MYB|4602_CALCULATED

19 genes correlated to 'AGE'.

GBP2|2634_CALCULATED , PI4K2A|55361_CALCULATED , STK16|8576|2OF2_CALCULATED , SLC22A16|85413_CALCULATED , HK2|3099_CALCULATED , ...

26 genes correlated to 'GENDER'.

DDX3Y|8653_CALCULATED , XIST|7503_CALCULATED , TSIX|9383_CALCULATED , ZFY|7544_CALCULATED , EIF1AY|9086_CALCULATED , ...

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 Q value < 0.05.

Clinical feature	Statistical test	Significant genes	Associated with		Associated with
Time to Death	Cox regression test	N=4	shorter survival	N=2	longer survival	N=2
AGE	Spearman correlation test	N=19	older	N=14	younger	N=5
GENDER	t test	N=26	male	N=13	female	N=13

Clinical variable #1: 'Time to Death'

4 genes related to 'Time to Death'.

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


Time to Death	Duration (Months)	0.9-94.1 (median=12)
	censored	N = 60
	death	N = 95

	Significant markers	N = 4
	associated with shorter survival	2
	associated with longer survival	2

List of 4 genes significantly associated with 'Time to Death' by Cox regression test

Table S2. Get Full Table List of 4 genes significantly associated with 'Time to Death' by Cox regression test

	HazardRatio	Wald_P	Q	C_index
IL2RA\|3559_CALCULATED	1.25	1.685e-06	0.03	0.638
C2ORF67\|151050_CALCULATED	0.46	1.739e-06	0.031	0.342
TREML2\|79865_CALCULATED	1.56	2.37e-06	0.042	0.657
MYB\|4602_CALCULATED	0.57	2.773e-06	0.049	0.35

Figure S1. Get High-res Image As an example, this figure shows the association of IL2RA|3559_CALCULATED to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 1.69e-06 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

19 genes related to 'AGE'.

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


AGE	Mean (SD)	55.02 (16)
	Significant markers	N = 19
	pos. correlated	14
	neg. correlated	5

List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

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

	SpearmanCorr	corrP	Q
GBP2\|2634_CALCULATED	0.4064	1.651e-08	0.000294
PI4K2A\|55361_CALCULATED	0.39	6.801e-08	0.00121
STK16\|8576\|2OF2_CALCULATED	0.3766	2.034e-07	0.00362
SLC22A16\|85413_CALCULATED	-0.3601	7.399e-07	0.0132
HK2\|3099_CALCULATED	-0.3595	7.71e-07	0.0137
ITPKA\|3706_CALCULATED	-0.356	1.076e-06	0.0191
C6ORF105\|84830_CALCULATED	0.3586	1.104e-06	0.0196
C7ORF58\|79974_CALCULATED	0.3551	1.156e-06	0.0206
PLXNA1\|5361_CALCULATED	0.3517	1.379e-06	0.0245
BDH1\|622_CALCULATED	-0.3503	1.537e-06	0.0273

Figure S2. Get High-res Image As an example, this figure shows the association of GBP2|2634_CALCULATED to 'AGE'. P value = 1.65e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

26 genes related to 'GENDER'.

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


GENDER	Labels	N
	FEMALE	84
	MALE	95

	Significant markers	N = 26
	Higher in MALE	13
	Higher in FEMALE	13

List of top 10 genes differentially expressed by 'GENDER'

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

	T(pos if higher in 'MALE')	ttestP	Q	AUC
DDX3Y\|8653_CALCULATED	79.24	8.103e-105	1.44e-100	1
XIST\|7503_CALCULATED	-47.03	1.56e-91	2.77e-87	0.9996
TSIX\|9383_CALCULATED	-45.22	1.205e-88	2.14e-84	0.9996
ZFY\|7544_CALCULATED	49.96	3.073e-79	5.47e-75	1
EIF1AY\|9086_CALCULATED	48.48	8.026e-62	1.43e-57	1
PRKY\|5616_CALCULATED	37.28	9.451e-49	1.68e-44	1
BCORP1\|286554_CALCULATED	36.82	2.503e-48	4.45e-44	1
PRKX\|5613_CALCULATED	-12.94	2.137e-27	3.8e-23	0.9145
USP9Y\|8287_CALCULATED	43.12	3.196e-26	5.68e-22	1
TMSB4Y\|9087_CALCULATED	28.93	1.063e-24	1.89e-20	0.9995

Figure S3. Get High-res Image As an example, this figure shows the association of DDX3Y|8653_CALCULATED to 'GENDER'. P value = 8.1e-105 with T-test analysis.

Methods & Data

Input

Expresson data file = LAML.mRNAseq_RPKM_log2.txt
Clinical data file = LAML.clin.merged.picked.txt
Number of patients = 179
Number of genes = 17799
Number of clinical features = 3

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

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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] 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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