Skin Cutaneous Melanoma: Correlation between molecular cancer subtypes and selected clinical features<BR>(NRAS_Hotspot

Skin Cutaneous Melanoma: Correlation between molecular cancer subtypes and selected clinical features
(NRAS_Hotspot_Mutants cohort)

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

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 8 different clustering approaches and 7 clinical features across 45 patients, one significant finding detected with P value < 0.05 and Q value < 0.25.

4 subtypes identified in current cancer cohort by 'Copy Number Ratio CNMF subtypes'. These subtypes do not correlate to any clinical features.
3 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 2 subtypes that do not correlate to any clinical features.
Consensus hierarchical clustering analysis on RPPA data identified 5 subtypes that do not correlate to any clinical features.
CNMF clustering analysis on sequencing-based mRNA expression data identified 3 subtypes that do not correlate to any clinical features.
Consensus hierarchical clustering analysis on sequencing-based mRNA expression data identified 3 subtypes that correlate to 'PRIMARY.SITE.OF.DISEASE'.
4 subtypes identified in current cancer cohort by 'MIRSEQ CNMF'. These subtypes do not correlate to any clinical features.
3 subtypes identified in current cancer cohort by 'MIRSEQ CHIERARCHICAL'. 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 8 different clustering approaches and 7 clinical features. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, one significant finding detected.


Clinical Features	Time to Death	AGE	PRIMARY SITE OF DISEASE	GENDER	LYMPH NODE METASTASIS	TUMOR STAGECODE	NEOPLASM DISEASESTAGE
Statistical Tests	logrank test	ANOVA	Chi-square test	Fisher's exact test	Chi-square test	ANOVA	Chi-square test
Copy Number Ratio CNMF subtypes	0.113 (1.00)	0.656 (1.00)	0.913 (1.00)	0.369 (1.00)	0.714 (1.00)		0.435 (1.00)
METHLYATION CNMF	0.297 (1.00)	0.0278 (1.00)	0.16 (1.00)	0.287 (1.00)	0.693 (1.00)		0.839 (1.00)
RPPA CNMF subtypes	0.101 (1.00)	0.149 (1.00)	0.795 (1.00)	0.466 (1.00)	0.915 (1.00)		0.673 (1.00)
RPPA cHierClus subtypes	0.0945 (1.00)	0.341 (1.00)	0.269 (1.00)	0.426 (1.00)	0.494 (1.00)		0.19 (1.00)
RNAseq CNMF subtypes	0.0145 (0.667)	0.633 (1.00)	0.0337 (1.00)	0.0833 (1.00)	0.881 (1.00)		0.629 (1.00)
RNAseq cHierClus subtypes	0.00856 (0.402)	0.83 (1.00)	0.00122 (0.0587)	0.157 (1.00)	0.905 (1.00)		0.547 (1.00)
MIRSEQ CNMF	0.838 (1.00)	0.294 (1.00)	0.423 (1.00)	0.579 (1.00)	0.144 (1.00)		0.226 (1.00)
MIRSEQ CHIERARCHICAL	0.473 (1.00)	0.242 (1.00)	0.58 (1.00)	1 (1.00)	0.151 (1.00)		0.121 (1.00)

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

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

Cluster Labels	1	2	3	4
Number of samples	12	8	12	13

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

P value = 0.113 (logrank test), Q value = 1

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

	nPatients	nDeath	Duration Range (Median), Month
ALL	45	25	2.6 - 314.5 (48.9)
subtype1	12	8	4.9 - 133.6 (33.1)
subtype2	8	6	12.6 - 203.0 (38.5)
subtype3	12	4	24.4 - 314.5 (52.2)
subtype4	13	7	2.6 - 202.6 (53.2)

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 'AGE'

P value = 0.656 (ANOVA), Q value = 1

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

	nPatients	Mean (Std.Dev)
ALL	45	57.8 (15.4)
subtype1	12	61.8 (20.7)
subtype2	8	53.1 (14.8)
subtype3	12	56.2 (11.3)
subtype4	13	58.4 (14.2)

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

'Copy Number Ratio CNMF subtypes' versus 'PRIMARY.SITE.OF.DISEASE'

P value = 0.913 (Chi-square test), Q value = 1

Table S4. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

nPatients	DISTANT METASTASIS	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	REGIONAL LYMPH NODE
ALL	8	9	28
subtype1	3	2	7
subtype2	1	2	5
subtype3	1	2	9
subtype4	3	3	7

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

'Copy Number Ratio CNMF subtypes' versus 'GENDER'

P value = 0.369 (Fisher's exact test), Q value = 1

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

nPatients	FEMALE	MALE
ALL	16	29
subtype1	6	6
subtype2	4	4
subtype3	3	9
subtype4	3	10

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 'LYMPH.NODE.METASTASIS'

P value = 0.714 (Chi-square test), Q value = 1

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

nPatients	N0	N1A	N1B	N2A	N2B	N3
ALL	27	3	4	1	2	5
subtype1	5	2	1	1	1	2
subtype2	6	0	0	0	0	1
subtype3	8	1	1	0	0	0
subtype4	8	0	2	0	1	2

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

'Copy Number Ratio CNMF subtypes' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.435 (Chi-square test), Q value = 1

Table S7. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	I OR II NOS	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE IIC	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	1	3	4	6	4	3	4	2	1	1	6	6	1
subtype1	1	0	0	1	0	1	1	1	0	1	3	3	0
subtype2	0	1	1	1	2	0	0	1	0	0	0	0	1
subtype3	0	1	0	3	1	1	2	0	0	0	2	0	0
subtype4	0	1	3	1	1	1	1	0	1	0	1	3	0

Figure S6. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #2: 'METHLYATION CNMF'

Table S8. Get Full Table Description of clustering approach #2: 'METHLYATION CNMF'

Cluster Labels	1	2	3
Number of samples	15	14	16

'METHLYATION CNMF' versus 'Time to Death'

P value = 0.297 (logrank test), Q value = 1

Table S9. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	45	25	2.6 - 314.5 (48.9)
subtype1	15	11	10.5 - 216.9 (27.1)
subtype2	14	7	21.5 - 314.5 (51.3)
subtype3	16	7	2.6 - 203.0 (52.4)

Figure S7. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

'METHLYATION CNMF' versus 'AGE'

P value = 0.0278 (ANOVA), Q value = 1

Table S10. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	45	57.8 (15.4)
subtype1	15	54.6 (15.3)
subtype2	14	52.0 (15.2)
subtype3	16	65.8 (12.9)

Figure S8. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #2: 'AGE'

'METHLYATION CNMF' versus 'PRIMARY.SITE.OF.DISEASE'

P value = 0.16 (Chi-square test), Q value = 1

Table S11. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

nPatients	DISTANT METASTASIS	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	REGIONAL LYMPH NODE
ALL	8	9	28
subtype1	4	4	7
subtype2	4	2	8
subtype3	0	3	13

Figure S9. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

'METHLYATION CNMF' versus 'GENDER'

P value = 0.287 (Fisher's exact test), Q value = 1

Table S12. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	16	29
subtype1	5	10
subtype2	3	11
subtype3	8	8

Figure S10. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #4: 'GENDER'

'METHLYATION CNMF' versus 'LYMPH.NODE.METASTASIS'

P value = 0.693 (Chi-square test), Q value = 1

Table S13. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1A	N1B	N2A	N2B	N3
ALL	27	3	4	1	2	5
subtype1	8	2	1	0	1	1
subtype2	8	1	2	1	0	1
subtype3	11	0	1	0	1	3

Figure S11. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

'METHLYATION CNMF' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.839 (Chi-square test), Q value = 1

Table S14. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	I OR II NOS	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE IIC	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	1	3	4	6	4	3	4	2	1	1	6	6	1
subtype1	0	0	1	3	1	1	1	1	0	1	2	2	0
subtype2	1	1	0	2	2	1	1	0	1	0	2	1	1
subtype3	0	2	3	1	1	1	2	1	0	0	2	3	0

Figure S12. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #3: 'RPPA CNMF subtypes'

Table S15. Get Full Table Description of clustering approach #3: 'RPPA CNMF subtypes'

Cluster Labels	1	2
Number of samples	16	14

'RPPA CNMF subtypes' versus 'Time to Death'

P value = 0.101 (logrank test), Q value = 1

Table S16. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	30	20	2.6 - 216.9 (48.2)
subtype1	16	9	12.6 - 216.9 (51.0)
subtype2	14	11	2.6 - 203.0 (38.5)

Figure S13. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'RPPA CNMF subtypes' versus 'AGE'

P value = 0.149 (t-test), Q value = 1

Table S17. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	30	57.5 (16.7)
subtype1	16	53.3 (14.4)
subtype2	14	62.4 (18.3)

Figure S14. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #2: 'AGE'

'RPPA CNMF subtypes' versus 'PRIMARY.SITE.OF.DISEASE'

P value = 0.795 (Chi-square test), Q value = 1

Table S18. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

nPatients	DISTANT METASTASIS	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	REGIONAL LYMPH NODE
ALL	5	2	23
subtype1	2	1	13
subtype2	3	1	10

Figure S15. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

'RPPA CNMF subtypes' versus 'GENDER'

P value = 0.466 (Fisher's exact test), Q value = 1

Table S19. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	11	19
subtype1	7	9
subtype2	4	10

Figure S16. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #4: 'GENDER'

'RPPA CNMF subtypes' versus 'LYMPH.NODE.METASTASIS'

P value = 0.915 (Chi-square test), Q value = 1

Table S20. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1A	N1B	N2B	N3
ALL	16	2	4	1	4
subtype1	8	1	2	1	2
subtype2	8	1	2	0	2

Figure S17. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

'RPPA CNMF subtypes' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.673 (Chi-square test), Q value = 1

Table S21. Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	I OR II NOS	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	1	3	3	3	3	2	1	1	1	3	5	1
subtype1	0	2	2	2	1	1	0	1	1	2	1	1
subtype2	1	1	1	1	2	1	1	0	0	1	4	0

Figure S18. Get High-res Image Clustering Approach #3: 'RPPA CNMF subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #4: 'RPPA cHierClus subtypes'

Table S22. Get Full Table Description of clustering approach #4: 'RPPA cHierClus subtypes'

Cluster Labels	1	2	3	4	5	6
Number of samples	3	4	1	5	7	10

'RPPA cHierClus subtypes' versus 'Time to Death'

P value = 0.0945 (logrank test), Q value = 1

Table S23. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	29	19	2.6 - 216.9 (47.5)
subtype1	3	1	55.0 - 74.7 (55.9)
subtype2	4	4	13.9 - 65.5 (43.7)
subtype4	5	4	12.6 - 64.4 (16.6)
subtype5	7	2	24.4 - 167.9 (47.5)
subtype6	10	8	2.6 - 216.9 (50.2)

Figure S19. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'RPPA cHierClus subtypes' versus 'AGE'

P value = 0.341 (ANOVA), Q value = 1

Table S24. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	29	58.4 (16.3)
subtype1	3	57.0 (20.0)
subtype2	4	71.5 (16.4)
subtype4	5	48.8 (17.9)
subtype5	7	60.9 (10.9)
subtype6	10	56.7 (16.9)

Figure S20. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #2: 'AGE'

'RPPA cHierClus subtypes' versus 'PRIMARY.SITE.OF.DISEASE'

P value = 0.269 (Chi-square test), Q value = 1

Table S25. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

nPatients	DISTANT METASTASIS	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	REGIONAL LYMPH NODE
ALL	4	2	23
subtype1	0	0	3
subtype2	1	1	2
subtype4	0	1	4
subtype5	0	0	7
subtype6	3	0	7

Figure S21. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

'RPPA cHierClus subtypes' versus 'GENDER'

P value = 0.426 (Chi-square test), Q value = 1

Table S26. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	10	19
subtype1	1	2
subtype2	0	4
subtype4	3	2
subtype5	3	4
subtype6	3	7

Figure S22. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

'RPPA cHierClus subtypes' versus 'LYMPH.NODE.METASTASIS'

P value = 0.494 (Chi-square test), Q value = 1

Table S27. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1A	N1B	N2B	N3
ALL	15	2	4	1	4
subtype1	3	0	0	0	0
subtype2	2	1	1	0	0
subtype4	1	1	1	0	2
subtype5	3	0	1	1	0
subtype6	6	0	1	0	2

Figure S23. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

'RPPA cHierClus subtypes' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.19 (Chi-square test), Q value = 1

Table S28. Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	I OR II NOS	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	1	3	2	3	3	2	1	1	1	3	5	1
subtype1	0	0	0	0	1	2	0	0	0	0	0	0
subtype2	0	1	0	1	0	0	0	0	0	1	1	0
subtype4	0	0	0	1	0	0	0	0	1	0	2	1
subtype5	0	2	1	0	0	0	0	0	0	2	0	0
subtype6	1	0	1	1	2	0	1	1	0	0	2	0

Figure S24. Get High-res Image Clustering Approach #4: 'RPPA cHierClus subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #5: 'RNAseq CNMF subtypes'

Table S29. Get Full Table Description of clustering approach #5: 'RNAseq CNMF subtypes'

Cluster Labels	1	2	3
Number of samples	18	15	12

'RNAseq CNMF subtypes' versus 'Time to Death'

P value = 0.0145 (logrank test), Q value = 0.67

Table S30. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	45	25	2.6 - 314.5 (48.9)
subtype1	18	13	10.5 - 314.5 (33.7)
subtype2	15	3	24.4 - 203.0 (55.0)
subtype3	12	9	2.6 - 133.6 (38.8)

Figure S25. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'RNAseq CNMF subtypes' versus 'AGE'

P value = 0.633 (ANOVA), Q value = 1

Table S31. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	45	57.8 (15.4)
subtype1	18	55.2 (15.5)
subtype2	15	58.5 (15.0)
subtype3	12	60.7 (16.5)

Figure S26. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

'RNAseq CNMF subtypes' versus 'PRIMARY.SITE.OF.DISEASE'

P value = 0.0337 (Chi-square test), Q value = 1

Table S32. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

nPatients	DISTANT METASTASIS	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	REGIONAL LYMPH NODE
ALL	8	9	28
subtype1	3	7	8
subtype2	1	1	13
subtype3	4	1	7

Figure S27. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

'RNAseq CNMF subtypes' versus 'GENDER'

P value = 0.0833 (Fisher's exact test), Q value = 1

Table S33. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	16	29
subtype1	9	9
subtype2	2	13
subtype3	5	7

Figure S28. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #4: 'GENDER'

'RNAseq CNMF subtypes' versus 'LYMPH.NODE.METASTASIS'

P value = 0.881 (Chi-square test), Q value = 1

Table S34. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1A	N1B	N2A	N2B	N3
ALL	27	3	4	1	2	5
subtype1	10	2	1	1	1	2
subtype2	8	1	2	0	1	1
subtype3	9	0	1	0	0	2

Figure S29. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

'RNAseq CNMF subtypes' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.629 (Chi-square test), Q value = 1

Table S35. Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	I OR II NOS	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE IIC	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	1	3	4	6	4	3	4	2	1	1	6	6	1
subtype1	0	1	1	3	1	1	2	1	0	1	3	2	1
subtype2	0	2	1	2	1	2	0	0	1	0	3	1	0
subtype3	1	0	2	1	2	0	2	1	0	0	0	3	0

Figure S30. Get High-res Image Clustering Approach #5: 'RNAseq CNMF subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #6: 'RNAseq cHierClus subtypes'

Table S36. Get Full Table Description of clustering approach #6: 'RNAseq cHierClus subtypes'

Cluster Labels	1	2	3
Number of samples	9	16	20

'RNAseq cHierClus subtypes' versus 'Time to Death'

P value = 0.00856 (logrank test), Q value = 0.4

Table S37. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	45	25	2.6 - 314.5 (48.9)
subtype1	9	8	2.6 - 133.6 (29.8)
subtype2	16	5	24.4 - 203.0 (55.4)
subtype3	20	12	10.5 - 314.5 (38.3)

Figure S31. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'RNAseq cHierClus subtypes' versus 'AGE'

P value = 0.83 (ANOVA), Q value = 1

Table S38. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	45	57.8 (15.4)
subtype1	9	60.1 (18.7)
subtype2	16	58.2 (15.2)
subtype3	20	56.4 (14.6)

Figure S32. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

'RNAseq cHierClus subtypes' versus 'PRIMARY.SITE.OF.DISEASE'

P value = 0.00122 (Chi-square test), Q value = 0.059

Table S39. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

nPatients	DISTANT METASTASIS	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	REGIONAL LYMPH NODE
ALL	8	9	28
subtype1	4	0	5
subtype2	0	1	15
subtype3	4	8	8

Figure S33. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

'RNAseq cHierClus subtypes' versus 'GENDER'

P value = 0.157 (Fisher's exact test), Q value = 1

Table S40. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	16	29
subtype1	3	6
subtype2	3	13
subtype3	10	10

Figure S34. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #4: 'GENDER'

'RNAseq cHierClus subtypes' versus 'LYMPH.NODE.METASTASIS'

P value = 0.905 (Chi-square test), Q value = 1

Table S41. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1A	N1B	N2A	N2B	N3
ALL	27	3	4	1	2	5
subtype1	6	0	1	0	0	2
subtype2	9	2	1	0	1	1
subtype3	12	1	2	1	1	2

Figure S35. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

'RNAseq cHierClus subtypes' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.547 (Chi-square test), Q value = 1

Table S42. Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	I OR II NOS	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE IIC	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	1	3	4	6	4	3	4	2	1	1	6	6	1
subtype1	1	0	1	1	1	0	1	1	0	0	0	3	0
subtype2	0	2	2	1	2	2	0	0	0	1	3	1	0
subtype3	0	1	1	4	1	1	3	1	1	0	3	2	1

Figure S36. Get High-res Image Clustering Approach #6: 'RNAseq cHierClus subtypes' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #7: 'MIRSEQ CNMF'

Table S43. Get Full Table Description of clustering approach #7: 'MIRSEQ CNMF'

Cluster Labels	1	2	3	4
Number of samples	9	6	15	15

'MIRSEQ CNMF' versus 'Time to Death'

P value = 0.838 (logrank test), Q value = 1

Table S44. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	45	25	2.6 - 314.5 (48.9)
subtype1	9	7	16.6 - 202.6 (47.5)
subtype2	6	2	21.5 - 203.0 (37.7)
subtype3	15	7	12.6 - 314.5 (44.0)
subtype4	15	9	2.6 - 216.9 (55.0)

Figure S37. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #1: 'Time to Death'

'MIRSEQ CNMF' versus 'AGE'

P value = 0.294 (ANOVA), Q value = 1

Table S45. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	45	57.8 (15.4)
subtype1	9	54.7 (16.0)
subtype2	6	49.0 (16.3)
subtype3	15	58.3 (15.1)
subtype4	15	62.5 (14.6)

Figure S38. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #2: 'AGE'

'MIRSEQ CNMF' versus 'PRIMARY.SITE.OF.DISEASE'

P value = 0.423 (Chi-square test), Q value = 1

Table S46. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

nPatients	DISTANT METASTASIS	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	REGIONAL LYMPH NODE
ALL	8	9	28
subtype1	2	1	6
subtype2	0	1	5
subtype3	4	5	6
subtype4	2	2	11

Figure S39. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

'MIRSEQ CNMF' versus 'GENDER'

P value = 0.579 (Fisher's exact test), Q value = 1

Table S47. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	16	29
subtype1	5	4
subtype2	2	4
subtype3	4	11
subtype4	5	10

Figure S40. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #4: 'GENDER'

'MIRSEQ CNMF' versus 'LYMPH.NODE.METASTASIS'

P value = 0.144 (Chi-square test), Q value = 1

Table S48. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1A	N1B	N2A	N2B	N3
ALL	27	3	4	1	2	5
subtype1	7	0	0	0	0	1
subtype2	3	0	1	1	0	1
subtype3	10	1	3	0	0	0
subtype4	7	2	0	0	2	3

Figure S41. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

'MIRSEQ CNMF' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.226 (Chi-square test), Q value = 1

Table S49. Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	I OR II NOS	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE IIC	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	1	3	4	6	4	3	4	2	1	1	6	6	1
subtype1	1	2	2	1	0	0	0	1	0	0	0	1	0
subtype2	0	0	1	0	2	0	0	0	0	0	2	0	1
subtype3	0	1	0	4	1	1	2	1	1	0	1	2	0
subtype4	0	0	1	1	1	2	2	0	0	1	3	3	0

Figure S42. Get High-res Image Clustering Approach #7: 'MIRSEQ CNMF' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #8: 'MIRSEQ CHIERARCHICAL'

Table S50. Get Full Table Description of clustering approach #8: 'MIRSEQ CHIERARCHICAL'

Cluster Labels	1	2	3
Number of samples	5	9	31

'MIRSEQ CHIERARCHICAL' versus 'Time to Death'

P value = 0.473 (logrank test), Q value = 1

Table S51. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	45	25	2.6 - 314.5 (48.9)
subtype1	5	1	21.5 - 203.0 (28.1)
subtype2	9	4	12.6 - 78.9 (44.0)
subtype3	31	20	2.6 - 314.5 (48.9)

Figure S43. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #1: 'Time to Death'

'MIRSEQ CHIERARCHICAL' versus 'AGE'

P value = 0.242 (ANOVA), Q value = 1

Table S52. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	45	57.8 (15.4)
subtype1	5	48.4 (18.1)
subtype2	9	54.9 (12.6)
subtype3	31	60.1 (15.5)

Figure S44. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #2: 'AGE'

'MIRSEQ CHIERARCHICAL' versus 'PRIMARY.SITE.OF.DISEASE'

P value = 0.58 (Chi-square test), Q value = 1

Table S53. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

nPatients	DISTANT METASTASIS	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	REGIONAL LYMPH NODE
ALL	8	9	28
subtype1	0	1	4
subtype2	1	3	5
subtype3	7	5	19

Figure S45. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #3: 'PRIMARY.SITE.OF.DISEASE'

'MIRSEQ CHIERARCHICAL' versus 'GENDER'

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

Table S54. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #4: 'GENDER'

nPatients	FEMALE	MALE
ALL	16	29
subtype1	2	3
subtype2	3	6
subtype3	11	20

Figure S46. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #4: 'GENDER'

'MIRSEQ CHIERARCHICAL' versus 'LYMPH.NODE.METASTASIS'

P value = 0.151 (Chi-square test), Q value = 1

Table S55. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1A	N1B	N2A	N2B	N3
ALL	27	3	4	1	2	5
subtype1	2	0	1	1	0	1
subtype2	8	0	0	0	0	0
subtype3	17	3	3	0	2	4

Figure S47. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #5: 'LYMPH.NODE.METASTASIS'

'MIRSEQ CHIERARCHICAL' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.121 (Chi-square test), Q value = 1

Table S56. Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

nPatients	I OR II NOS	STAGE I	STAGE IA	STAGE IB	STAGE II	STAGE IIA	STAGE IIB	STAGE IIC	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV
ALL	1	3	4	6	4	3	4	2	1	1	6	6	1
subtype1	0	0	1	0	1	0	0	0	0	0	2	0	1
subtype2	0	1	1	3	0	0	1	2	0	0	0	0	0
subtype3	1	2	2	3	3	3	3	0	1	1	4	6	0

Figure S48. Get High-res Image Clustering Approach #8: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #7: 'NEOPLASM.DISEASESTAGE'

Methods & Data

Input

Cluster data file = SKCM-NRAS_Hotspot_Mutants.mergedcluster.txt
Clinical data file = SKCM-NRAS_Hotspot_Mutants.clin.merged.picked.txt
Number of patients = 45
Number of clustering approaches = 8
Number of selected clinical features = 7
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

ANOVA analysis

For continuous numerical clinical features, one-way analysis of variance (Howell 2002) was applied to compare the clinical values between tumor subtypes using 'anova' function in R

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.test' 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

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between two tumor subtypes 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] 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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)

[5] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)

[6] 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)

[7] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)

[8] 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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