Correlation between aggregated molecular cancer subtypes and selected clinical features

Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (Primary solid tumor)

28 January 2016 | analyses__2016_01_28

Maintainer Information

Citation Information

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between aggregated molecular cancer subtypes and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1KP81JV

Overview

Introduction

This pipeline computes the correlation between cancer subtypes identified by different molecular patterns and selected clinical features.

Summary

Testing the association between subtypes identified by 10 different clustering approaches and 8 clinical features across 48 patients, no significant finding detected with P value < 0.05 and Q value < 0.25.

3 subtypes identified in current cancer cohort by 'Copy Number Ratio CNMF subtypes'. These subtypes do not correlate to any clinical features.
4 subtypes identified in current cancer cohort by 'METHLYATION CNMF'. These subtypes do not correlate to any clinical features.
CNMF clustering analysis on RPPA data identified 6 subtypes that do not correlate to any clinical features.
Consensus hierarchical clustering analysis on RPPA data identified 3 subtypes that do not correlate to any clinical features.
CNMF clustering analysis on sequencing-based mRNA expression data identified 6 subtypes that do not correlate to any clinical features.
Consensus hierarchical clustering analysis on sequencing-based mRNA expression data identified 4 subtypes that do not correlate to any clinical features.
3 subtypes identified in current cancer cohort by 'MIRSEQ CNMF'. These subtypes do not correlate to any clinical features.
5 subtypes identified in current cancer cohort by 'MIRSEQ CHIERARCHICAL'. These subtypes do not correlate to any clinical features.
4 subtypes identified in current cancer cohort by 'MIRseq Mature CNMF subtypes'. These subtypes do not correlate to any clinical features.
4 subtypes identified in current cancer cohort by 'MIRseq Mature cHierClus subtypes'. These subtypes do not correlate to any clinical features.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between subtypes identified by 10 different clustering approaches and 8 clinical features. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, no significant finding detected.


Clinical Features	Time to Death	YEARS TO BIRTH	TUMOR TISSUE SITE	GENDER	RADIATION THERAPY	HISTOLOGICAL TYPE	RACE	ETHNICITY
Statistical Tests	logrank test	Kruskal-Wallis (anova)	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
Copy Number Ratio CNMF subtypes	0.515 (0.777)	0.654 (0.894)	0.428 (0.713)	0.387 (0.709)	1 (1.00)	0.256 (0.571)	0.0713 (0.408)	0.59 (0.842)
METHLYATION CNMF	0.93 (1.00)	0.654 (0.894)	0.151 (0.483)	0.975 (1.00)	0.127 (0.46)	0.0415 (0.332)	0.257 (0.571)	0.339 (0.66)
RPPA CNMF subtypes	0.346 (0.66)	0.933 (1.00)	0.457 (0.717)	0.746 (0.947)	0.322 (0.645)	0.183 (0.523)	0.19 (0.523)	0.399 (0.709)
RPPA cHierClus subtypes	0.306 (0.628)	0.572 (0.842)	0.393 (0.709)	0.902 (1.00)	0.83 (1.00)	0.427 (0.713)	0.277 (0.599)	1 (1.00)
RNAseq CNMF subtypes	0.917 (1.00)	0.437 (0.713)	0.0405 (0.332)	0.446 (0.714)	0.226 (0.547)	0.0365 (0.332)	0.21 (0.542)	0.083 (0.415)
RNAseq cHierClus subtypes	0.302 (0.628)	0.682 (0.897)	0.0603 (0.402)	0.974 (1.00)	0.0886 (0.415)	0.0795 (0.415)	0.854 (1.00)	0.209 (0.542)
MIRSEQ CNMF	0.684 (0.897)	0.855 (1.00)	0.103 (0.424)	0.581 (0.842)	0.0671 (0.408)	0.233 (0.549)	0.73 (0.942)	0.0365 (0.332)
MIRSEQ CHIERARCHICAL	0.511 (0.777)	0.888 (1.00)	0.901 (1.00)	0.171 (0.523)	0.138 (0.481)	0.0401 (0.332)	0.982 (1.00)	0.0177 (0.332)
MIRseq Mature CNMF subtypes	0.986 (1.00)	0.798 (0.997)	0.411 (0.713)	0.186 (0.523)	0.0398 (0.332)	0.0197 (0.332)	0.145 (0.483)	0.0189 (0.332)
MIRseq Mature cHierClus subtypes	0.969 (1.00)	0.223 (0.547)	0.0472 (0.343)	0.659 (0.894)	0.0934 (0.415)	0.125 (0.46)	0.106 (0.424)	0.0272 (0.332)

Clustering Approach #1: 'Copy Number Ratio CNMF subtypes'

Table S1. Description of clustering approach #1: 'Copy Number Ratio CNMF subtypes'

Cluster Labels	1	2	3
Number of samples	20	7	21

'Copy Number Ratio CNMF subtypes' versus 'Time to Death'

P value = 0.515 (logrank test), Q value = 0.78

Table S2. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	47	9	0.0 - 211.2 (27.4)
subtype1	19	5	0.0 - 211.2 (32.0)
subtype2	7	2	1.9 - 196.6 (24.0)
subtype3	21	2	4.1 - 128.1 (27.4)

Figure S1. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'Copy Number Ratio CNMF subtypes' versus 'YEARS_TO_BIRTH'

P value = 0.654 (Kruskal-Wallis (anova)), Q value = 0.89

Table S3. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	48	56.3 (13.9)
subtype1	20	53.9 (14.7)
subtype2	7	56.0 (14.2)
subtype3	21	58.7 (13.4)

Figure S2. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'Copy Number Ratio CNMF subtypes' versus 'TUMOR_TISSUE_SITE'

P value = 0.428 (Fisher's exact test), Q value = 0.71

Table S4. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	SOFT TISSUE (MUSCLE LIGAMENTS SUBCUTANEOUS)	STOMACH	THYROID
ALL	2	2	4	3	1	2	1	1	1	3	1	2	2
subtype1	1	1	2	1	0	1	0	1	0	0	1	2	2
subtype2	0	1	0	0	0	0	1	0	0	0	0	0	0
subtype3	1	0	2	2	1	1	0	0	1	3	0	0	0

Figure S3. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'Copy Number Ratio CNMF subtypes' versus 'GENDER'

P value = 0.387 (Fisher's exact test), Q value = 0.71

Table S5. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	26	22
subtype1	12	8
subtype2	2	5
subtype3	12	9

Figure S4. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #4: 'GENDER'

'Copy Number Ratio CNMF subtypes' versus 'RADIATION_THERAPY'

P value = 1 (Fisher's exact test), Q value = 1

Table S6. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	40	7
subtype1	16	3
subtype2	6	1
subtype3	18	3

Figure S5. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

'Copy Number Ratio CNMF subtypes' versus 'HISTOLOGICAL_TYPE'

P value = 0.256 (Fisher's exact test), Q value = 0.57

Table S7. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	41	3	4
subtype1	15	2	3
subtype2	6	0	1
subtype3	20	1	0

Figure S6. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'Copy Number Ratio CNMF subtypes' versus 'RACE'

P value = 0.0713 (Fisher's exact test), Q value = 0.41

Table S8. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	18	1	29
subtype1	5	1	14
subtype2	1	0	6
subtype3	12	0	9

Figure S7. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #7: 'RACE'

'Copy Number Ratio CNMF subtypes' versus 'ETHNICITY'

P value = 0.59 (Fisher's exact test), Q value = 0.84

Table S9. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	12	36
subtype1	4	16
subtype2	1	6
subtype3	7	14

Figure S8. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #8: 'ETHNICITY'

Clustering Approach #2: 'METHLYATION CNMF'

Table S10. Description of clustering approach #2: 'METHLYATION CNMF'

Cluster Labels	1	2	3	4
Number of samples	9	13	19	7

'METHLYATION CNMF' versus 'Time to Death'

P value = 0.93 (logrank test), Q value = 1

Table S11. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	47	9	0.0 - 211.2 (27.4)
subtype1	9	2	1.9 - 150.5 (35.5)
subtype2	13	2	4.3 - 128.1 (41.2)
subtype3	18	4	0.0 - 211.2 (23.5)
subtype4	7	1	19.6 - 196.6 (31.7)

Figure S9. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

'METHLYATION CNMF' versus 'YEARS_TO_BIRTH'

P value = 0.654 (Kruskal-Wallis (anova)), Q value = 0.89

Table S12. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	48	56.3 (13.9)
subtype1	9	52.1 (19.2)
subtype2	13	53.6 (15.4)
subtype3	19	59.8 (11.3)
subtype4	7	56.9 (9.5)

Figure S10. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'METHLYATION CNMF' versus 'TUMOR_TISSUE_SITE'

P value = 0.151 (Fisher's exact test), Q value = 0.48

Table S13. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	SOFT TISSUE (MUSCLE LIGAMENTS SUBCUTANEOUS)	STOMACH	THYROID
ALL	2	2	4	3	1	2	1	1	1	3	1	2	2
subtype1	0	0	0	0	0	0	0	0	0	0	0	1	2
subtype2	0	2	1	0	0	0	1	0	1	0	0	0	0
subtype3	2	0	2	3	1	1	0	1	0	2	1	1	0
subtype4	0	0	1	0	0	1	0	0	0	1	0	0	0

Figure S11. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'METHLYATION CNMF' versus 'GENDER'

P value = 0.975 (Fisher's exact test), Q value = 1

Table S14. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	26	22
subtype1	4	5
subtype2	7	6
subtype3	11	8
subtype4	4	3

Figure S12. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #4: 'GENDER'

'METHLYATION CNMF' versus 'RADIATION_THERAPY'

P value = 0.127 (Fisher's exact test), Q value = 0.46

Table S15. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	40	7
subtype1	6	3
subtype2	10	3
subtype3	17	1
subtype4	7	0

Figure S13. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #5: 'RADIATION_THERAPY'

'METHLYATION CNMF' versus 'HISTOLOGICAL_TYPE'

P value = 0.0415 (Fisher's exact test), Q value = 0.33

Table S16. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	41	3	4
subtype1	6	0	3
subtype2	12	0	1
subtype3	16	3	0
subtype4	7	0	0

Figure S14. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'METHLYATION CNMF' versus 'RACE'

P value = 0.257 (Fisher's exact test), Q value = 0.57

Table S17. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	18	1	29
subtype1	3	0	6
subtype2	2	1	10
subtype3	9	0	10
subtype4	4	0	3

Figure S15. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #7: 'RACE'

'METHLYATION CNMF' versus 'ETHNICITY'

P value = 0.339 (Fisher's exact test), Q value = 0.66

Table S18. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	12	36
subtype1	2	7
subtype2	5	8
subtype3	5	14
subtype4	0	7

Figure S16. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #8: 'ETHNICITY'

Clustering Approach #3: 'RPPA CNMF subtypes'

Table S19. Description of clustering approach #3: 'RPPA CNMF subtypes'

Cluster Labels	1	2	3	4	5	6
Number of samples	6	5	5	6	6	5

'RPPA CNMF subtypes' versus 'Time to Death'

P value = 0.346 (logrank test), Q value = 0.66

Table S20. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	32	6	0.0 - 211.2 (24.7)
subtype1	5	1	4.3 - 31.7 (14.0)
subtype2	5	2	1.9 - 45.1 (18.2)
subtype3	5	1	4.1 - 26.0 (22.3)
subtype4	6	0	23.6 - 196.6 (34.7)
subtype5	6	1	25.1 - 211.2 (33.8)
subtype6	5	1	0.0 - 70.1 (12.8)

Figure S17. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'RPPA CNMF subtypes' versus 'YEARS_TO_BIRTH'

P value = 0.933 (Kruskal-Wallis (anova)), Q value = 1

Table S21. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	33	54.8 (14.2)
subtype1	6	59.2 (13.7)
subtype2	5	55.0 (15.7)
subtype3	5	57.8 (12.3)
subtype4	6	53.7 (16.8)
subtype5	6	53.0 (16.2)
subtype6	5	50.0 (14.7)

Figure S18. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'RPPA CNMF subtypes' versus 'TUMOR_TISSUE_SITE'

P value = 0.457 (Fisher's exact test), Q value = 0.72

Table S22. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	STOMACH	THYROID
ALL	1	1	2	2	1	2	1	1	1	3	2	1
subtype1	0	0	0	0	0	1	1	0	0	2	2	0
subtype2	0	0	0	1	0	0	0	0	0	0	0	0
subtype3	0	0	0	0	0	0	0	0	1	0	0	1
subtype4	0	0	1	0	1	0	0	0	0	0	0	0
subtype5	0	0	0	0	0	1	0	1	0	1	0	0
subtype6	1	1	1	1	0	0	0	0	0	0	0	0

Figure S19. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'RPPA CNMF subtypes' versus 'GENDER'

P value = 0.746 (Fisher's exact test), Q value = 0.95

Table S23. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	15	18
subtype1	2	4
subtype2	2	3
subtype3	4	1
subtype4	3	3
subtype5	2	4
subtype6	2	3

Figure S20. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #4: 'GENDER'

'RPPA CNMF subtypes' versus 'RADIATION_THERAPY'

P value = 0.322 (Fisher's exact test), Q value = 0.64

Table S24. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	27	5
subtype1	6	0
subtype2	3	2
subtype3	5	0
subtype4	4	2
subtype5	5	1
subtype6	4	0

Figure S21. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

'RPPA CNMF subtypes' versus 'HISTOLOGICAL_TYPE'

P value = 0.183 (Fisher's exact test), Q value = 0.52

Table S25. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	27	2	4
subtype1	6	0	0
subtype2	4	0	1
subtype3	5	0	0
subtype4	5	0	1
subtype5	4	0	2
subtype6	3	2	0

Figure S22. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'RPPA CNMF subtypes' versus 'RACE'

P value = 0.19 (Fisher's exact test), Q value = 0.52

Table S26. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	WHITE
ALL	16	17
subtype1	3	3
subtype2	2	3
subtype3	5	0
subtype4	3	3
subtype5	2	4
subtype6	1	4

Figure S23. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #7: 'RACE'

'RPPA CNMF subtypes' versus 'ETHNICITY'

P value = 0.399 (Fisher's exact test), Q value = 0.71

Table S27. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	7	26
subtype1	0	6
subtype2	2	3
subtype3	0	5
subtype4	2	4
subtype5	1	5
subtype6	2	3

Figure S24. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #8: 'ETHNICITY'

Clustering Approach #4: 'RPPA cHierClus subtypes'

Table S28. Description of clustering approach #4: 'RPPA cHierClus subtypes'

Cluster Labels	1	2	3
Number of samples	6	15	12

'RPPA cHierClus subtypes' versus 'Time to Death'

P value = 0.306 (logrank test), Q value = 0.63

Table S29. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	32	6	0.0 - 211.2 (24.7)
subtype1	6	1	0.0 - 70.1 (8.6)
subtype2	14	2	12.7 - 211.2 (31.4)
subtype3	12	3	1.9 - 196.6 (23.2)

Figure S25. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'RPPA cHierClus subtypes' versus 'YEARS_TO_BIRTH'

P value = 0.572 (Kruskal-Wallis (anova)), Q value = 0.84

Table S30. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	33	54.8 (14.2)
subtype1	6	55.2 (16.9)
subtype2	15	52.3 (14.7)
subtype3	12	57.8 (12.6)

Figure S26. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'RPPA cHierClus subtypes' versus 'TUMOR_TISSUE_SITE'

P value = 0.393 (Fisher's exact test), Q value = 0.71

Table S31. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	STOMACH	THYROID
ALL	1	1	2	2	1	2	1	1	1	3	2	1
subtype1	0	1	1	0	0	0	1	0	0	1	1	0
subtype2	1	0	1	0	1	2	0	1	0	2	1	0
subtype3	0	0	0	2	0	0	0	0	1	0	0	1

Figure S27. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'RPPA cHierClus subtypes' versus 'GENDER'

P value = 0.902 (Fisher's exact test), Q value = 1

Table S32. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	15	18
subtype1	3	3
subtype2	6	9
subtype3	6	6

Figure S28. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

'RPPA cHierClus subtypes' versus 'RADIATION_THERAPY'

P value = 0.83 (Fisher's exact test), Q value = 1

Table S33. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	27	5
subtype1	5	0
subtype2	12	3
subtype3	10	2

Figure S29. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

'RPPA cHierClus subtypes' versus 'HISTOLOGICAL_TYPE'

P value = 0.427 (Fisher's exact test), Q value = 0.71

Table S34. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	27	2	4
subtype1	5	1	0
subtype2	12	0	3
subtype3	10	1	1

Figure S30. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'RPPA cHierClus subtypes' versus 'RACE'

P value = 0.277 (Fisher's exact test), Q value = 0.6

Table S35. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	WHITE
ALL	16	17
subtype1	1	5
subtype2	8	7
subtype3	7	5

Figure S31. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #7: 'RACE'

'RPPA cHierClus subtypes' versus 'ETHNICITY'

P value = 1 (Fisher's exact test), Q value = 1

Table S36. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	7	26
subtype1	1	5
subtype2	3	12
subtype3	3	9

Figure S32. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #8: 'ETHNICITY'

Clustering Approach #5: 'RNAseq CNMF subtypes'

Table S37. Description of clustering approach #5: 'RNAseq CNMF subtypes'

Cluster Labels	1	2	3	4	5	6
Number of samples	10	12	9	3	8	6

'RNAseq CNMF subtypes' versus 'Time to Death'

P value = 0.917 (logrank test), Q value = 1

Table S38. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	47	9	0.0 - 211.2 (27.4)
subtype1	9	2	0.0 - 211.2 (27.4)
subtype2	12	2	1.9 - 128.1 (33.6)
subtype3	9	1	4.1 - 57.2 (14.0)
subtype4	3	1	8.2 - 52.0 (32.3)
subtype5	8	2	0.6 - 116.8 (33.8)
subtype6	6	1	12.8 - 70.1 (38.6)

Figure S33. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'RNAseq CNMF subtypes' versus 'YEARS_TO_BIRTH'

P value = 0.437 (Kruskal-Wallis (anova)), Q value = 0.71

Table S39. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	48	56.3 (13.9)
subtype1	10	57.2 (10.4)
subtype2	12	57.2 (13.3)
subtype3	9	57.8 (12.0)
subtype4	3	62.3 (6.1)
subtype5	8	59.1 (18.3)
subtype6	6	43.7 (17.2)

Figure S34. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'RNAseq CNMF subtypes' versus 'TUMOR_TISSUE_SITE'

P value = 0.0405 (Fisher's exact test), Q value = 0.33

Table S40. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	SOFT TISSUE (MUSCLE LIGAMENTS SUBCUTANEOUS)	STOMACH	THYROID
ALL	2	2	4	3	1	2	1	1	1	3	1	2	2
subtype1	0	0	1	0	0	0	0	1	0	2	0	2	2
subtype2	0	1	1	0	0	0	1	0	1	0	0	0	0
subtype3	2	0	1	2	1	0	0	0	0	1	1	0	0
subtype4	0	0	1	0	0	0	0	0	0	0	0	0	0
subtype5	0	0	0	1	0	2	0	0	0	0	0	0	0
subtype6	0	1	0	0	0	0	0	0	0	0	0	0	0

Figure S35. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'RNAseq CNMF subtypes' versus 'GENDER'

P value = 0.446 (Fisher's exact test), Q value = 0.71

Table S41. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	26	22
subtype1	4	6
subtype2	6	6
subtype3	4	5
subtype4	3	0
subtype5	6	2
subtype6	3	3

Figure S36. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #4: 'GENDER'

'RNAseq CNMF subtypes' versus 'RADIATION_THERAPY'

P value = 0.226 (Fisher's exact test), Q value = 0.55

Table S42. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	40	7
subtype1	8	1
subtype2	10	2
subtype3	8	1
subtype4	3	0
subtype5	8	0
subtype6	3	3

Figure S37. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

'RNAseq CNMF subtypes' versus 'HISTOLOGICAL_TYPE'

P value = 0.0365 (Fisher's exact test), Q value = 0.33

Table S43. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	41	3	4
subtype1	9	1	0
subtype2	12	0	0
subtype3	8	1	0
subtype4	3	0	0
subtype5	6	1	1
subtype6	3	0	3

Figure S38. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'RNAseq CNMF subtypes' versus 'RACE'

P value = 0.21 (Fisher's exact test), Q value = 0.54

Table S44. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	18	1	29
subtype1	4	0	6
subtype2	5	1	6
subtype3	6	0	3
subtype4	1	0	2
subtype5	2	0	6
subtype6	0	0	6

Figure S39. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #7: 'RACE'

'RNAseq CNMF subtypes' versus 'ETHNICITY'

P value = 0.083 (Fisher's exact test), Q value = 0.42

Table S45. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	12	36
subtype1	0	10
subtype2	3	9
subtype3	2	7
subtype4	1	2
subtype5	2	6
subtype6	4	2

Figure S40. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #8: 'ETHNICITY'

Clustering Approach #6: 'RNAseq cHierClus subtypes'

Table S46. Description of clustering approach #6: 'RNAseq cHierClus subtypes'

Cluster Labels	1	2	3	4
Number of samples	22	11	7	8

'RNAseq cHierClus subtypes' versus 'Time to Death'

P value = 0.302 (logrank test), Q value = 0.63

Table S47. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	47	9	0.0 - 211.2 (27.4)
subtype1	21	3	0.6 - 211.2 (31.7)
subtype2	11	2	1.9 - 128.1 (41.2)
subtype3	7	2	0.0 - 52.0 (23.3)
subtype4	8	2	9.8 - 57.2 (23.8)

Figure S41. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'RNAseq cHierClus subtypes' versus 'YEARS_TO_BIRTH'

P value = 0.682 (Kruskal-Wallis (anova)), Q value = 0.9

Table S48. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	48	56.3 (13.9)
subtype1	22	57.5 (13.3)
subtype2	11	57.8 (13.8)
subtype3	7	57.9 (11.2)
subtype4	8	49.5 (18.2)

Figure S42. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'RNAseq cHierClus subtypes' versus 'TUMOR_TISSUE_SITE'

P value = 0.0603 (Fisher's exact test), Q value = 0.4

Table S49. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	SOFT TISSUE (MUSCLE LIGAMENTS SUBCUTANEOUS)	STOMACH	THYROID
ALL	2	2	4	3	1	2	1	1	1	3	1	2	2
subtype1	0	1	0	2	0	2	0	1	0	2	0	2	2
subtype2	0	1	1	0	0	0	1	0	1	0	0	0	0
subtype3	1	0	3	0	0	0	0	0	0	1	0	0	0
subtype4	1	0	0	1	1	0	0	0	0	0	1	0	0

Figure S43. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'RNAseq cHierClus subtypes' versus 'GENDER'

P value = 0.974 (Fisher's exact test), Q value = 1

Table S50. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	26	22
subtype1	11	11
subtype2	6	5
subtype3	4	3
subtype4	5	3

Figure S44. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

'RNAseq cHierClus subtypes' versus 'RADIATION_THERAPY'

P value = 0.0886 (Fisher's exact test), Q value = 0.42

Table S51. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	40	7
subtype1	21	1
subtype2	9	2
subtype3	5	1
subtype4	5	3

Figure S45. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

'RNAseq cHierClus subtypes' versus 'HISTOLOGICAL_TYPE'

P value = 0.0795 (Fisher's exact test), Q value = 0.42

Table S52. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	41	3	4
subtype1	19	2	1
subtype2	11	0	0
subtype3	6	1	0
subtype4	5	0	3

Figure S46. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'RNAseq cHierClus subtypes' versus 'RACE'

P value = 0.854 (Fisher's exact test), Q value = 1

Table S53. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	18	1	29
subtype1	8	0	14
subtype2	4	1	6
subtype3	3	0	4
subtype4	3	0	5

Figure S47. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #7: 'RACE'

'RNAseq cHierClus subtypes' versus 'ETHNICITY'

P value = 0.209 (Fisher's exact test), Q value = 0.54

Table S54. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	12	36
subtype1	3	19
subtype2	3	8
subtype3	2	5
subtype4	4	4

Figure S48. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #8: 'ETHNICITY'

Clustering Approach #7: 'MIRSEQ CNMF'

Table S55. Description of clustering approach #7: 'MIRSEQ CNMF'

Cluster Labels	1	2	3
Number of samples	16	16	15

'MIRSEQ CNMF' versus 'Time to Death'

P value = 0.684 (logrank test), Q value = 0.9

Table S56. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	46	9	0.0 - 211.2 (26.7)
subtype1	15	3	0.0 - 211.2 (27.4)
subtype2	16	4	1.9 - 116.8 (33.8)
subtype3	15	2	9.8 - 128.1 (24.6)

Figure S49. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #1: 'Time to Death'

'MIRSEQ CNMF' versus 'YEARS_TO_BIRTH'

P value = 0.855 (Kruskal-Wallis (anova)), Q value = 1

Table S57. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	47	56.3 (14.1)
subtype1	16	56.4 (13.1)
subtype2	16	57.6 (15.2)
subtype3	15	54.7 (14.8)

Figure S50. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'MIRSEQ CNMF' versus 'TUMOR_TISSUE_SITE'

P value = 0.103 (Fisher's exact test), Q value = 0.42

Table S58. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	SOFT TISSUE (MUSCLE LIGAMENTS SUBCUTANEOUS)	STOMACH	THYROID
ALL	2	2	4	3	1	2	1	1	1	3	1	2	1
subtype1	0	1	2	2	0	0	0	1	0	3	1	2	0
subtype2	0	1	1	0	0	2	1	0	0	0	0	0	1
subtype3	2	0	1	1	1	0	0	0	1	0	0	0	0

Figure S51. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'MIRSEQ CNMF' versus 'GENDER'

P value = 0.581 (Fisher's exact test), Q value = 0.84

Table S59. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	25	22
subtype1	7	9
subtype2	10	6
subtype3	8	7

Figure S52. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #4: 'GENDER'

'MIRSEQ CNMF' versus 'RADIATION_THERAPY'

P value = 0.0671 (Fisher's exact test), Q value = 0.41

Table S60. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	40	6
subtype1	13	2
subtype2	16	0
subtype3	11	4

Figure S53. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #5: 'RADIATION_THERAPY'

'MIRSEQ CNMF' versus 'HISTOLOGICAL_TYPE'

P value = 0.233 (Fisher's exact test), Q value = 0.55

Table S61. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	40	3	4
subtype1	12	3	1
subtype2	15	0	1
subtype3	13	0	2

Figure S54. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'MIRSEQ CNMF' versus 'RACE'

P value = 0.73 (Fisher's exact test), Q value = 0.94

Table S62. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	18	1	28
subtype1	5	0	11
subtype2	7	1	8
subtype3	6	0	9

Figure S55. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #7: 'RACE'

'MIRSEQ CNMF' versus 'ETHNICITY'

P value = 0.0365 (Fisher's exact test), Q value = 0.33

Table S63. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	12	35
subtype1	4	12
subtype2	1	15
subtype3	7	8

Figure S56. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #8: 'ETHNICITY'

Clustering Approach #8: 'MIRSEQ CHIERARCHICAL'

Table S64. Description of clustering approach #8: 'MIRSEQ CHIERARCHICAL'

Cluster Labels	1	2	3	4	5
Number of samples	9	12	8	12	6

'MIRSEQ CHIERARCHICAL' versus 'Time to Death'

P value = 0.511 (logrank test), Q value = 0.78

Table S65. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	46	9	0.0 - 211.2 (26.7)
subtype1	9	1	4.3 - 211.2 (31.1)
subtype2	12	3	1.9 - 116.8 (24.9)
subtype3	7	2	0.0 - 196.6 (14.0)
subtype4	12	2	9.8 - 128.1 (35.3)
subtype5	6	1	4.1 - 98.1 (31.8)

Figure S57. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #1: 'Time to Death'

'MIRSEQ CHIERARCHICAL' versus 'YEARS_TO_BIRTH'

P value = 0.888 (Kruskal-Wallis (anova)), Q value = 1

Table S66. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	47	56.3 (14.1)
subtype1	9	56.3 (10.4)
subtype2	12	58.8 (12.6)
subtype3	8	57.4 (9.1)
subtype4	12	56.2 (18.9)
subtype5	6	49.8 (18.3)

Figure S58. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'MIRSEQ CHIERARCHICAL' versus 'TUMOR_TISSUE_SITE'

P value = 0.901 (Fisher's exact test), Q value = 1

Table S67. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	SOFT TISSUE (MUSCLE LIGAMENTS SUBCUTANEOUS)	STOMACH	THYROID
ALL	2	2	4	3	1	2	1	1	1	3	1	2	1
subtype1	1	1	1	0	0	0	0	1	0	1	0	1	0
subtype2	0	1	1	0	0	0	1	0	0	0	0	0	1
subtype3	0	0	1	2	0	0	0	0	0	2	0	1	0
subtype4	1	0	1	1	1	0	0	0	1	0	1	0	0
subtype5	0	0	0	0	0	2	0	0	0	0	0	0	0

Figure S59. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'MIRSEQ CHIERARCHICAL' versus 'GENDER'

P value = 0.171 (Fisher's exact test), Q value = 0.52

Table S68. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	25	22
subtype1	2	7
subtype2	8	4
subtype3	4	4
subtype4	6	6
subtype5	5	1

Figure S60. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #4: 'GENDER'

'MIRSEQ CHIERARCHICAL' versus 'RADIATION_THERAPY'

P value = 0.138 (Fisher's exact test), Q value = 0.48

Table S69. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	40	6
subtype1	9	0
subtype2	10	2
subtype3	7	0
subtype4	8	4
subtype5	6	0

Figure S61. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #5: 'RADIATION_THERAPY'

'MIRSEQ CHIERARCHICAL' versus 'HISTOLOGICAL_TYPE'

P value = 0.0401 (Fisher's exact test), Q value = 0.33

Table S70. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	40	3	4
subtype1	9	0	0
subtype2	10	0	2
subtype3	5	3	0
subtype4	11	0	1
subtype5	5	0	1

Figure S62. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'MIRSEQ CHIERARCHICAL' versus 'RACE'

P value = 0.982 (Fisher's exact test), Q value = 1

Table S71. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	18	1	28
subtype1	4	0	5
subtype2	4	1	7
subtype3	3	0	5
subtype4	4	0	8
subtype5	3	0	3

Figure S63. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #7: 'RACE'

'MIRSEQ CHIERARCHICAL' versus 'ETHNICITY'

P value = 0.0177 (Fisher's exact test), Q value = 0.33

Table S72. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	12	35
subtype1	0	9
subtype2	3	9
subtype3	2	6
subtype4	7	5
subtype5	0	6

Figure S64. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #8: 'ETHNICITY'

Clustering Approach #9: 'MIRseq Mature CNMF subtypes'

Table S73. Description of clustering approach #9: 'MIRseq Mature CNMF subtypes'

Cluster Labels	1	2	3	4
Number of samples	9	10	9	14

'MIRseq Mature CNMF subtypes' versus 'Time to Death'

P value = 0.986 (logrank test), Q value = 1

Table S74. Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	41	9	0.0 - 211.2 (27.4)
subtype1	8	1	0.0 - 196.6 (18.7)
subtype2	10	2	1.9 - 111.6 (33.4)
subtype3	9	2	8.2 - 128.1 (26.0)
subtype4	14	4	4.1 - 211.2 (33.8)

Figure S65. Get High-res Image Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'MIRseq Mature CNMF subtypes' versus 'YEARS_TO_BIRTH'

P value = 0.798 (Kruskal-Wallis (anova)), Q value = 1

Table S75. Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	42	55.1 (14.0)
subtype1	9	58.2 (10.7)
subtype2	10	53.8 (19.3)
subtype3	9	57.2 (12.5)
subtype4	14	52.6 (13.2)

Figure S66. Get High-res Image Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'MIRseq Mature CNMF subtypes' versus 'TUMOR_TISSUE_SITE'

P value = 0.411 (Fisher's exact test), Q value = 0.71

Table S76. Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	STOMACH	THYROID
ALL	1	2	4	3	1	2	1	1	1	3	2	1
subtype1	0	0	1	2	0	0	0	0	0	2	2	0
subtype2	0	1	1	0	0	0	1	0	0	0	0	0
subtype3	1	0	1	1	1	0	0	0	1	0	0	0
subtype4	0	1	1	0	0	2	0	1	0	1	0	1

Figure S67. Get High-res Image Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'MIRseq Mature CNMF subtypes' versus 'GENDER'

P value = 0.186 (Fisher's exact test), Q value = 0.52

Table S77. Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	22	20
subtype1	3	6
subtype2	6	4
subtype3	3	6
subtype4	10	4

Figure S68. Get High-res Image Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #4: 'GENDER'

'MIRseq Mature CNMF subtypes' versus 'RADIATION_THERAPY'

P value = 0.0398 (Fisher's exact test), Q value = 0.33

Table S78. Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	36	5
subtype1	8	0
subtype2	8	2
subtype3	6	3
subtype4	14	0

Figure S69. Get High-res Image Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

'MIRseq Mature CNMF subtypes' versus 'HISTOLOGICAL_TYPE'

P value = 0.0197 (Fisher's exact test), Q value = 0.33

Table S79. Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	36	3	3
subtype1	6	3	0
subtype2	8	0	2
subtype3	9	0	0
subtype4	13	0	1

Figure S70. Get High-res Image Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'MIRseq Mature CNMF subtypes' versus 'RACE'

P value = 0.145 (Fisher's exact test), Q value = 0.48

Table S80. Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	16	1	25
subtype1	3	0	6
subtype2	1	0	9
subtype3	5	0	4
subtype4	7	1	6

Figure S71. Get High-res Image Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #7: 'RACE'

'MIRseq Mature CNMF subtypes' versus 'ETHNICITY'

P value = 0.0189 (Fisher's exact test), Q value = 0.33

Table S81. Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	10	32
subtype1	2	7
subtype2	4	6
subtype3	4	5
subtype4	0	14

Figure S72. Get High-res Image Clustering Approach #9: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #8: 'ETHNICITY'

Clustering Approach #10: 'MIRseq Mature cHierClus subtypes'

Table S82. Description of clustering approach #10: 'MIRseq Mature cHierClus subtypes'

Cluster Labels	1	2	3	4
Number of samples	8	15	5	14

'MIRseq Mature cHierClus subtypes' versus 'Time to Death'

P value = 0.969 (logrank test), Q value = 1

Table S83. Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	41	9	0.0 - 211.2 (27.4)
subtype1	7	1	0.6 - 196.6 (22.3)
subtype2	15	4	1.9 - 128.1 (42.7)
subtype3	5	1	10.3 - 38.2 (26.0)
subtype4	14	3	0.0 - 211.2 (29.2)

Figure S73. Get High-res Image Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'MIRseq Mature cHierClus subtypes' versus 'YEARS_TO_BIRTH'

P value = 0.223 (Kruskal-Wallis (anova)), Q value = 0.55

Table S84. Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	42	55.1 (14.0)
subtype1	8	58.9 (11.0)
subtype2	15	50.5 (17.9)
subtype3	5	65.2 (7.5)
subtype4	14	54.2 (10.6)

Figure S74. Get High-res Image Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'MIRseq Mature cHierClus subtypes' versus 'TUMOR_TISSUE_SITE'

P value = 0.0472 (Fisher's exact test), Q value = 0.34

Table S85. Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

nPatients	ADRENAL	ASCITES/PERITONEUM	BONE	BRAIN	BREAST	COLON	LIVER	OTHER EXTRANODAL SITE	PAROTID GLAND	SMALL INTESTINE	STOMACH	THYROID
ALL	1	2	4	3	1	2	1	1	1	3	2	1
subtype1	0	0	0	2	0	0	0	0	0	2	2	1
subtype2	0	2	1	0	0	0	1	0	0	0	0	0
subtype3	0	0	1	1	1	0	0	0	1	0	0	0
subtype4	1	0	2	0	0	2	0	1	0	1	0	0

Figure S75. Get High-res Image Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #3: 'TUMOR_TISSUE_SITE'

'MIRseq Mature cHierClus subtypes' versus 'GENDER'

P value = 0.659 (Fisher's exact test), Q value = 0.89

Table S86. Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	22	20
subtype1	3	5
subtype2	8	7
subtype3	2	3
subtype4	9	5

Figure S76. Get High-res Image Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

'MIRseq Mature cHierClus subtypes' versus 'RADIATION_THERAPY'

P value = 0.0934 (Fisher's exact test), Q value = 0.42

Table S87. Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients	NO	YES
ALL	36	5
subtype1	8	0
subtype2	11	4
subtype3	4	1
subtype4	13	0

Figure S77. Get High-res Image Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #5: 'RADIATION_THERAPY'

'MIRseq Mature cHierClus subtypes' versus 'HISTOLOGICAL_TYPE'

P value = 0.125 (Fisher's exact test), Q value = 0.46

Table S88. Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOS (ANY ANATOMIC SITE NODAL OR EXTRANODAL)	PRIMARY DLBCL OF THE CNS	PRIMARY MEDIASTINAL (THYMIC) DLBCL
ALL	36	3	3
subtype1	6	2	0
subtype2	12	0	3
subtype3	5	0	0
subtype4	13	1	0

Figure S78. Get High-res Image Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'MIRseq Mature cHierClus subtypes' versus 'RACE'

P value = 0.106 (Fisher's exact test), Q value = 0.42

Table S89. Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #7: 'RACE'

nPatients	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	16	1	25
subtype1	3	0	5
subtype2	2	1	12
subtype3	3	0	2
subtype4	8	0	6

Figure S79. Get High-res Image Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #7: 'RACE'

'MIRseq Mature cHierClus subtypes' versus 'ETHNICITY'

P value = 0.0272 (Fisher's exact test), Q value = 0.33

Table S90. Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #8: 'ETHNICITY'

nPatients	HISPANIC OR LATINO	NOT HISPANIC OR LATINO
ALL	10	32
subtype1	2	6
subtype2	6	9
subtype3	2	3
subtype4	0	14

Figure S80. Get High-res Image Clustering Approach #10: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #8: 'ETHNICITY'

Methods & Data

Input

Cluster data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_mergedClustering/DLBC-TP/22541055/DLBC-TP.mergedcluster.txt
Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/DLBC-TP/22506396/DLBC-TP.merged_data.txt
Number of patients = 48
Number of clustering approaches = 10
Number of selected clinical features = 8
Exclude small clusters that include fewer than K patients, K = 3

Clustering approaches

CNMF clustering

consensus non-negative matrix factorization clustering approach (Brunet et al. 2004)

Consensus hierarchical clustering

Resampling-based clustering method (Monti et al. 2003)

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

Fisher's exact test

For binary clinical features, two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.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

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] Brunet et al., Metagenes and molecular pattern discovery using matrix factorization, PNAS 101(12):4164-9 (2004)

[2] Monti et al., Consensus Clustering: A Resampling-Based Method for Class Discovery and Visualization of Gene Expression Microarray Data, Machine Learning 52(1):91-118 (2003)

[3] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)

[4] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)

[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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