Correlation between mRNA expression and clinical features
PANCANCER cohort with 12 disease types (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1Q52MPG
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between mRNA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1Q52MPG
Overview
Introduction

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

Summary

Testing the association between 17814 genes and 15 clinical features across 1593 samples, statistically thresholded by Q value < 0.05, 12 clinical features related to at least one genes.

  • 3048 genes correlated to 'Time to Death'.

    • KLHL14 ,  ASS1 ,  IGSF11 ,  UPK1B ,  C4ORF32 ,  ...

  • 3682 genes correlated to 'AGE'.

    • GREB1 ,  COL18A1 ,  DUOX2 ,  LDOC1 ,  GALNTL1 ,  ...

  • 17229 genes correlated to 'PRIMARY.SITE.OF.DISEASE'.

    • KLHL14 ,  ZG16 ,  SLC22A2 ,  FOXE1 ,  PDZD3 ,  ...

  • 8979 genes correlated to 'GENDER'.

    • ESR1 ,  DDX3Y ,  RSPO1 ,  RPS4Y1 ,  EIF1AY ,  ...

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

    • PPP1R9A ,  VASN ,  METTL8 ,  MARCH7 ,  ZNF503 ,  ...

  • 17150 genes correlated to 'HISTOLOGICAL.TYPE'.

    • KLHL14 ,  ZG16 ,  SLC22A2 ,  FOXE1 ,  PDZD3 ,  ...

  • 5806 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • CYP3A5 ,  CYP3A4 ,  CYP3A7 ,  MAP2K7 ,  TCF21 ,  ...

  • 2 genes correlated to 'YEAROFTOBACCOSMOKINGONSET'.

    • MMP10 ,  ALS2CR4

  • 576 genes correlated to 'DISTANT.METASTASIS'.

    • VIL1 ,  MUC13 ,  FABP1 ,  SPACA3 ,  ACF ,  ...

  • 9839 genes correlated to 'LYMPH.NODE.METASTASIS'.

    • FXYD2 ,  EFHD1 ,  GATA3 ,  OVOL2 ,  TRPS1 ,  ...

  • 2084 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • NPR1 ,  WIT1 ,  THRSP ,  KLHL14 ,  S100A1 ,  ...

  • 10650 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • SCGB3A2 ,  MUPCDH ,  HNF1A ,  PDZD3 ,  CLRN3 ,  ...

  • No genes correlated to 'TUMOR.STAGE', 'NUMBERPACKYEARSSMOKED', and 'NUMBER.OF.LYMPH.NODES'.

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=3048 shorter survival N=1442 longer survival N=1606
AGE Spearman correlation test N=3682 older N=1744 younger N=1938
PRIMARY SITE OF DISEASE ANOVA test N=17229        
GENDER t test N=8979 male N=4341 female N=4638
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=196 higher score N=92 lower score N=104
HISTOLOGICAL TYPE ANOVA test N=17150        
TUMOR STAGE Spearman correlation test   N=0        
RADIATIONS RADIATION REGIMENINDICATION t test N=5806 yes N=2804 no N=3002
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
YEAROFTOBACCOSMOKINGONSET Spearman correlation test N=2 higher yearoftobaccosmokingonset N=0 lower yearoftobaccosmokingonset N=2
DISTANT METASTASIS ANOVA test N=576        
LYMPH NODE METASTASIS ANOVA test N=9839        
COMPLETENESS OF RESECTION ANOVA test N=2084        
NUMBER OF LYMPH NODES Spearman correlation test   N=0        
NEOPLASM DISEASESTAGE ANOVA test N=10650        
Clinical variable #1: 'Time to Death'

3048 genes related to 'Time to Death'.

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

Time to Death Duration (Months) 0.1-223.4 (median=22.7)
  censored N = 1006
  death N = 438
     
  Significant markers N = 3048
  associated with shorter survival 1442
  associated with longer survival 1606
List of top 10 genes significantly associated with 'Time to Death' by Cox regression test

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
KLHL14 1.27 0 0 0.605
ASS1 1.33 0 0 0.623
IGSF11 1.36 0 0 0.644
UPK1B 1.21 0 0 0.637
C4ORF32 0.78 0 0 0.38
ZRSR1 0.55 0 0 0.349
MDS1 1.38 0 0 0.625
GALNT12 1.32 0 0 0.616
NUBP1 0.47 0 0 0.356
DAPL1 1.14 0 0 0.624

Figure S1.  Get High-res Image As an example, this figure shows the association of KLHL14 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 0 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

3682 genes related to 'AGE'.

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

AGE Mean (SD) 61.39 (13)
  Significant markers N = 3682
  pos. correlated 1744
  neg. correlated 1938
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
GREB1 -0.2892 9.188e-32 1.64e-27
COL18A1 -0.2758 6.342e-29 1.13e-24
DUOX2 0.2752 8.485e-29 1.51e-24
LDOC1 -0.2683 2.09e-27 3.72e-23
GALNTL1 -0.267 3.747e-27 6.67e-23
OBSL1 -0.2642 1.335e-26 2.38e-22
FOXF1 0.2611 5.404e-26 9.62e-22
CYP2C18 0.2585 1.69e-25 3.01e-21
NOTCH2 -0.2559 5.25e-25 9.35e-21
BBOX1 -0.2557 5.714e-25 1.02e-20

Figure S2.  Get High-res Image As an example, this figure shows the association of GREB1 to 'AGE'. P value = 9.19e-32 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

17229 genes related to 'PRIMARY.SITE.OF.DISEASE'.

Table S5.  Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'

PRIMARY.SITE.OF.DISEASE Labels N
  BREAST 526
  COLON 152
  ENDOMETRIAL 54
  KIDNEY 72
  LUNG 186
  OMENTUM 2
  OVARY 529
  PERITONEUM OVARY 2
  RECTUM 68
     
  Significant markers N = 17229
List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

ANOVA_P Q
KLHL14 0 0
ZG16 0 0
SLC22A2 0 0
FOXE1 0 0
PDZD3 0 0
EMX2 0 0
NPR1 0 0
FUT4 0 0
ACF 0 0
FXYD2 0 0

Figure S3.  Get High-res Image As an example, this figure shows the association of KLHL14 to 'PRIMARY.SITE.OF.DISEASE'. P value = 0 with ANOVA analysis.

Clinical variable #4: 'GENDER'

8979 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 1304
  MALE 289
     
  Significant markers N = 8979
  Higher in MALE 4341
  Higher in FEMALE 4638
List of top 10 genes differentially expressed by 'GENDER'

Table S8.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
ESR1 -35.87 9.367e-164 1.67e-159 0.8775
DDX3Y 53.23 5.05e-163 9e-159 0.9837
RSPO1 -31.07 4.803e-162 8.56e-158 0.8428
RPS4Y1 51.71 2.642e-155 4.71e-151 0.9711
EIF1AY 49.21 1.083e-151 1.93e-147 0.9842
RPS4Y2 48.53 1.689e-147 3.01e-143 0.9814
ERBB4 -32.57 2.549e-147 4.54e-143 0.8586
JARID1D 44.6 2.007e-146 3.57e-142 0.9767
SCGB2A2 -29.39 1.805e-145 3.21e-141 0.8531
CYORF15A 43.7 2.34e-139 4.17e-135 0.981

Figure S4.  Get High-res Image As an example, this figure shows the association of ESR1 to 'GENDER'. P value = 9.37e-164 with T-test analysis.

Clinical variable #5: 'KARNOFSKY.PERFORMANCE.SCORE'

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

Table S9.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 60.22 (34)
  Significant markers N = 196
  pos. correlated 92
  neg. correlated 104
List of top 10 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

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

SpearmanCorr corrP Q
PPP1R9A 0.591 4.461e-10 7.95e-06
VASN 0.5685 2.77e-09 4.93e-05
METTL8 -0.5495 1.168e-08 0.000208
MARCH7 -0.5488 1.234e-08 0.00022
ZNF503 0.5415 2.087e-08 0.000372
ADK -0.5406 2.225e-08 0.000396
PCYT1A -0.5405 2.235e-08 0.000398
INSIG2 -0.5394 2.423e-08 0.000432
ARHGEF17 0.5392 2.453e-08 0.000437
POGZ 0.5364 2.984e-08 0.000531

Figure S5.  Get High-res Image As an example, this figure shows the association of PPP1R9A to 'KARNOFSKY.PERFORMANCE.SCORE'. P value = 4.46e-10 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #6: 'HISTOLOGICAL.TYPE'

17150 genes related to 'HISTOLOGICAL.TYPE'.

Table S11.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 127
  COLON MUCINOUS ADENOCARCINOMA 24
  ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA 41
  INFILTRATING DUCTAL CARCINOMA 449
  INFILTRATING LOBULAR CARCINOMA 41
  KIDNEY CLEAR CELL RENAL CARCINOMA 72
  LUNG ADENOCARCINOMA MIXED SUBTYPE 1
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 30
  LUNG BASALOID SQUAMOUS CELL CARCINOMA 5
  LUNG CLEAR CELL ADENOCARCINOMA 1
  LUNG PAPILLARY SQUAMOUS CELL CARICNOMA 1
  LUNG SQUAMOUS CELL CARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 148
  MEDULLARY CARCINOMA 1
  MIXED HISTOLOGY (PLEASE SPECIFY) 11
  MIXED SEROUS AND ENDOMETRIOID 1
  MUCINOUS CARCINOMA 2
  OTHER SPECIFY 22
  RECTAL ADENOCARCINOMA 58
  RECTAL MUCINOUS ADENOCARCINOMA 7
  SEROUS CYSTADENOCARCINOMA 533
  SEROUS ENDOMETRIAL ADENOCARCINOMA 12
     
  Significant markers N = 17150
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
KLHL14 0 0
ZG16 0 0
SLC22A2 0 0
FOXE1 0 0
PDZD3 0 0
EMX2 0 0
NPR1 0 0
FUT4 0 0
ACF 0 0
FXYD2 0 0

Figure S6.  Get High-res Image As an example, this figure shows the association of KLHL14 to 'HISTOLOGICAL.TYPE'. P value = 0 with ANOVA analysis.

Clinical variable #7: 'TUMOR.STAGE'

No gene related to 'TUMOR.STAGE'.

Table S13.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 3.17 (0.48)
  N
  Stage 1 2
  Stage 2 2
  Stage 3 133
  Stage 4 35
     
  Significant markers N = 0
Clinical variable #8: 'RADIATIONS.RADIATION.REGIMENINDICATION'

5806 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S14.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 180
  YES 1413
     
  Significant markers N = 5806
  Higher in YES 2804
  Higher in NO 3002
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
CYP3A5 22.2 5.34e-77 9.51e-73 0.7876
CYP3A4 20.43 4.757e-69 8.47e-65 0.7735
CYP3A7 20.48 6.735e-69 1.2e-64 0.765
MAP2K7 21.46 1.143e-65 2.04e-61 0.8093
TCF21 20.88 5.069e-65 9.03e-61 0.7933
AADAC 19.82 6.153e-62 1.1e-57 0.7706
CCDC71 21.07 9.49e-62 1.69e-57 0.8196
PDZD3 17.37 3.482e-59 6.2e-55 0.6903
REG1A 19.03 1.149e-58 2.05e-54 0.7743
CHMP4B 19.79 2.297e-56 4.09e-52 0.809

Figure S7.  Get High-res Image As an example, this figure shows the association of CYP3A5 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 5.34e-77 with T-test analysis.

Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 53.05 (35)
  Significant markers N = 0
Clinical variable #10: 'YEAROFTOBACCOSMOKINGONSET'

2 genes related to 'YEAROFTOBACCOSMOKINGONSET'.

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

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1959.74 (11)
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
List of 2 genes significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

Table S18.  Get Full Table List of 2 genes significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

SpearmanCorr corrP Q
MMP10 -0.4479 4.625e-07 0.00824
ALS2CR4 -0.4273 1.724e-06 0.0307

Figure S8.  Get High-res Image As an example, this figure shows the association of MMP10 to 'YEAROFTOBACCOSMOKINGONSET'. P value = 4.63e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #11: 'DISTANT.METASTASIS'

576 genes related to 'DISTANT.METASTASIS'.

Table S19.  Basic characteristics of clinical feature: 'DISTANT.METASTASIS'

DISTANT.METASTASIS Labels N
  CM0 (I+) 2
  M0 925
  M1 58
  M1A 1
  MX 14
     
  Significant markers N = 576
List of top 10 genes differentially expressed by 'DISTANT.METASTASIS'

Table S20.  Get Full Table List of top 10 genes differentially expressed by 'DISTANT.METASTASIS'

ANOVA_P Q
VIL1 8.478e-13 1.51e-08
MUC13 2.841e-12 5.06e-08
FABP1 4.306e-12 7.67e-08
SPACA3 4.683e-12 8.34e-08
ACF 7.447e-12 1.33e-07
CALML4 7.796e-12 1.39e-07
TMEM25 8.062e-12 1.44e-07
IL22RA1 8.786e-12 1.56e-07
PCLKC 1.225e-11 2.18e-07
PDZD3 1.317e-11 2.35e-07

Figure S9.  Get High-res Image As an example, this figure shows the association of VIL1 to 'DISTANT.METASTASIS'. P value = 8.48e-13 with ANOVA analysis.

Clinical variable #12: 'LYMPH.NODE.METASTASIS'

9839 genes related to 'LYMPH.NODE.METASTASIS'.

Table S21.  Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS Labels N
  N0 428
  N0 (I+) 16
  N0 (I-) 101
  N1 146
  N1A 78
  N1B 21
  N1C 2
  N1MI 13
  N2 91
  N2A 30
  N3 15
  N3A 18
  N3C 1
  NX 46
     
  Significant markers N = 9839
List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S22.  Get Full Table List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

ANOVA_P Q
FXYD2 2.922e-72 5.21e-68
EFHD1 2.266e-70 4.04e-66
GATA3 7.001e-68 1.25e-63
OVOL2 1.062e-66 1.89e-62
TRPS1 1.272e-66 2.27e-62
GALNTL1 3.045e-62 5.42e-58
CDH16 7.022e-62 1.25e-57
SCGB2A2 1.407e-61 2.51e-57
C14ORF105 1.311e-60 2.33e-56
N4BP3 3.338e-60 5.94e-56

Figure S10.  Get High-res Image As an example, this figure shows the association of FXYD2 to 'LYMPH.NODE.METASTASIS'. P value = 2.92e-72 with ANOVA analysis.

Clinical variable #13: 'COMPLETENESS.OF.RESECTION'

2084 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S23.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 403
  R1 38
  R2 36
  RX 7
     
  Significant markers N = 2084
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S24.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
NPR1 2.763e-36 4.92e-32
WIT1 5.858e-35 1.04e-30
THRSP 2.077e-34 3.7e-30
KLHL14 1.748e-32 3.11e-28
S100A1 8.042e-32 1.43e-27
WT1 1.283e-31 2.28e-27
DOK5 7.471e-31 1.33e-26
LYPD1 7.893e-28 1.41e-23
SCGB1D2 6.032e-27 1.07e-22
SCGB1C1 1.615e-26 2.88e-22

Figure S11.  Get High-res Image As an example, this figure shows the association of NPR1 to 'COMPLETENESS.OF.RESECTION'. P value = 2.76e-36 with ANOVA analysis.

Clinical variable #14: 'NUMBER.OF.LYMPH.NODES'

No gene related to 'NUMBER.OF.LYMPH.NODES'.

Table S25.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 1.94 (4)
  Significant markers N = 0
Clinical variable #15: 'NEOPLASM.DISEASESTAGE'

10650 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S26.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 129
  STAGE IA 73
  STAGE IB 78
  STAGE II 28
  STAGE IIA 258
  STAGE IIB 145
  STAGE III 24
  STAGE IIIA 102
  STAGE IIIB 52
  STAGE IIIC 39
  STAGE IV 57
  STAGE IVA 1
  STAGE TIS 1
  STAGE X 16
     
  Significant markers N = 10650
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S27.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
SCGB3A2 1.701e-87 3.03e-83
MUPCDH 5.802e-85 1.03e-80
HNF1A 7.145e-84 1.27e-79
PDZD3 9.868e-84 1.76e-79
CLRN3 1.743e-83 3.1e-79
LRRC19 5.968e-82 1.06e-77
USH1C 6.653e-82 1.18e-77
NR1H4 1.731e-81 3.08e-77
GAL3ST1 2.38e-81 4.24e-77
SCGB1A1 2.215e-80 3.94e-76

Figure S12.  Get High-res Image As an example, this figure shows the association of SCGB3A2 to 'NEOPLASM.DISEASESTAGE'. P value = 1.7e-87 with ANOVA analysis.

Methods & Data
Input

  • Expresson data file = PANCAN12-TP.medianexp.txt

  • Clinical data file = PANCAN12-TP.clin.merged.picked.txt

  • Number of patients = 1593

  • Number of genes = 17814

  • Number of clinical features = 15

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

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

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