PURPLE

require(gpgr)
require(devtools)
require(dplyr)
require(knitr)

Introduction

PURPLE: Purity Ploidy Estimator (https://github.com/hartwigmedical/hmftools/tree/master/purple).

PURPLE combines B-allele frequency, read depth ratios, small variants and structural variants to estimate the purity and copy number profile of a tumor sample.

It outputs several files, some of which are displayed below.

Data Munging

Somatic CNVs (per chromosome)

cnv_som <- system.file("extdata/purple/purple.cnv.somatic.tsv", package = "gpgr") |>
  gpgr::purple_cnv_som_process()

Description

cnv_som$descr |>
  knitr::kable(caption = "PURPLE Somatic CNVs (per chromosome) Columns.")

PURPLE Somatic CNVs (per chromosome) Columns.
Column	Description
Chr/Start/End	Coordinates of copy number segment
CN	Fitted absolute copy number of segment adjusted for purity and ploidy
CN Min+Maj	CopyNumber of minor + major allele adjusted for purity
Start/End SegSupport	Type of SV support for the CN breakpoint at start/end of region. Allowed values: CENTROMERE, TELOMERE, INV, DEL, DUP, BND (translocation), SGL (single breakend SV support), NONE (no SV support for CN breakpoint), MULT (multiple SV support at exact breakpoint)
Method	Method used to determine the CN of the region. Allowed values: BAF_WEIGHTED (avg of all depth windows for the region), STRUCTURAL_VARIANT (inferred using ploidy of flanking SVs), LONG_ARM (inferred from the long arm), GERMLINE_AMPLIFICATION (inferred using special logic to handle regions of germline amplification)
BAF (count)	Tumor BAF after adjusted for purity and ploidy (Count of AMBER baf points covered by this segment)
GC (windowCount)	Proportion of segment that is G or C (Count of COBALT windows covered by this segment)

cnv_som$tab |>
  dplyr::slice(1:10) |>
  knitr::kable(caption = "PURPLE Somatic CNVs (per chromosome) Summary Table.")

PURPLE Somatic CNVs (per chromosome) Summary Table.
Chr	Start	End	CN	CN Min+Maj	Start/End SegSupport	Method	BAF (count)	GC (windowCount)
chr1	1	123605522	1.0	0+1	TELOMERE-CENTROMERE	BAF_WEIGHTED	0.98 (20830)	0.42 (107822)
chr1	123605523	200044314	2.0	1+1	CENTROMERE-DUP	BAF_WEIGHTED	0.5 (10239)	0.4 (47332)
chr1	200044315	200044570	2.8	1+1.8	DUP-DUP	STRUCTURAL_VARIANT	0.65 (0)	0 (0)
chr1	200044571	248956422	2.0	1+1	DUP-TELOMERE	BAF_WEIGHTED	0.5 (10341)	0.42 (43373)
chr2	1	93139350	2.0	1+1	TELOMERE-CENTROMERE	BAF_WEIGHTED	0.51 (19339)	0.41 (81949)
chr2	93139351	219955359	2.0	1+1	CENTROMERE-BND	BAF_WEIGHTED	0.5 (19047)	0.39 (112493)
chr2	219955360	225225069	1.0	0+1	BND-BND	BAF_WEIGHTED	0.98 (1284)	0.4 (5069)
chr2	225225070	242193529	2.0	1+1	BND-TELOMERE	BAF_WEIGHTED	0.51 (4236)	0.44 (15099)
chr3	1	92214015	1.0	0+1	TELOMERE-CENTROMERE	BAF_WEIGHTED	0.98 (18629)	0.4 (83984)
chr3	92214016	198295559	2.0	1+1	CENTROMERE-TELOMERE	BAF_WEIGHTED	0.5 (21114)	0.39 (95873)

Somatic CNVs (per gene)

umccr_key_genes <- system.file("extdata/ref/somatic_panel-v24.03.0.tsv", package = "gpgr")
cnv_som_gene <- system.file("extdata/purple/purple.cnv.gene.tsv", package = "gpgr") |>
  gpgr::purple_cnv_som_gene_process(g = umccr_key_genes)

Description

cnv_som_gene$descr |>
  knitr::kable(caption = "PURPLE Somatic CNVs (per gene) Columns.")

PURPLE Somatic CNVs (per gene) Columns.
Column	Description
gene	Name of gene
minCN/maxCN	Min/Max copy number found in gene exons
chrom/start/end	Chromosome/start/end location of gene transcript
chrBand	Chromosome band of the gene
onco_or_ts	oncogene (‘oncogene’), tumor suppressor (‘tsgene’), or both (‘onco+ts’), as reported by Cancermine
transcriptID	Ensembl transcript ID (dot version)
minMinorAlleleCN	Minimum allele ploidy found over the gene exons - useful for identifying LOH events
somReg (somaticRegions)	Count of somatic copy number regions this gene spans
minReg (minRegions)	Number of somatic regions inside the gene that share the min copy number
minRegStartEnd	Start/End base of the copy number region overlapping the gene with the minimum copy number
minRegSupportStartEndMethod	Start/end support of the CN region overlapping the gene with the min CN (plus determination method)

cnv_som_gene$tab |>
  dplyr::slice(1:10) |>
  knitr::kable(caption = "PURPLE Somatic CNVs (per gene) Summary Table.")

PURPLE Somatic CNVs (per gene) Summary Table.
gene	minCN	maxCN	chrom	start	end	chrBand	onco_or_ts	transcriptID	minMinorAlleleCN	somReg	minReg	minRegStartEnd	minRegSupportStartEndMethod
SDHA	5.6640	5.6640	chr5	218303	257082	p15.33	tsgene	ENST00000264932	1.8901	1	1	89179-297781	DEL-DEL (BAF_WEIGHTED)
DUSP22	4.6638	4.6638	chr6	291630	351355	p25.3	tsgene	ENST00000419235	1.6754	1	1	1-834611	TELOMERE-DEL (BAF_WEIGHTED)
IRF4	4.6638	4.6638	chr6	391752	411443	p25.3	oncogene	ENST00000380956	1.6754	1	1	1-834611	TELOMERE-DEL (BAF_WEIGHTED)
KDM5A	4.2953	4.2953	chr12	280057	389320	p13.33	oncogene	ENST00000399788	0.0000	1	1	1-1210023	TELOMERE-DEL (BAF_WEIGHTED)
CRLF2	3.7271	3.7271	chrX	1187549	1212723	p22.33	oncogene	ENST00000400841	0.0000	1	1	924013-2677577	DUP-DUP (BAF_WEIGHTED)

Purity

purity <- system.file("extdata/purple/purple.purity.tsv", package = "gpgr") |>
  gpgr::purple_purity_read()

purity$summary |>
  knitr::kable(caption = "PURPLE Purity Summary Table.")

PURPLE Purity Summary Table.
n	variable	value	details
2	Purity	0.99 (0.98-1)	Purity of tumor in the sample (and min-max with score within 10% of best).
3	Ploidy	2.86 (2.78-2.94)	Average ploidy of tumor sample after adjusting for purity (and min-max with score within 10% of best).
4	Gender	MALE	Gender as inferred by AMBER/COBALT.
7	WGD	TRUE	Whole genome duplication (more than 10 autosomes have average major allele ploidy > 1.5).
8	MSI (indels/Mb)	MSS (0.19)	MSI status (MSI, MSS or UNKNOWN if somatic variants not supplied) & MS Indels per Mb.
9	PolyclonalProp	0.13	Proportion of CN regions that are more than 0.25 from a whole CN
10	DiploidyProp	0.03 (0.02-0.04)	Proportion of CN regions that have 1 (+- 0.2) minor and major allele.
11	TMB	15.13 (HIGH)	Tumor mutational burden (# PASS variants per Megabase) (Status: ‘HIGH’ (>10 PASS per Mb), ‘LOW’ or ‘UNKNOWN’).
12	TML	349 (HIGH)	Tumor mutational load (# of missense variants) (Status: ‘HIGH’, ‘LOW’ or ‘UNKNOWN’).
13	TMB-SV	1267	# of non inferred, non single passing SVs.

Kataegis

kat <- system.file("extdata/purple/purple.somatic.vcf.gz", package = "gpgr") |>
  purple_kataegis()
kat$data |>
  dplyr::slice(1:10) |>
  knitr::kable(caption = "PURPLE Kataegis Table.")

PURPLE Kataegis Table.
CHROM	POS	KT	PURPLE_AF	PURPLE_CN	PURPLE_MACN	PURPLE_VCN	SUBCL	MH	TNC
chr2	45006212	REV_1	0.2601	1.52	0.000	0.396	1	NA	GGA
chr2	45007103	REV_1	0.2399	1.52	0.000	0.365	1	NA	AGA
chr2	45007598	REV_1	0.2913	1.52	0.000	0.444	1	NA	TGA
chr2	45007709	REV_1	0.2759	1.52	0.000	0.420	1	NA	TGA
chr3	71010245	REV_2	0.4054	1.16	0.461	0.469	1	NA	AGA
chr3	71010553	REV_2	0.2387	1.16	0.461	0.276	1	NA	AGA
chr3	71011404	REV_2	0.3640	1.16	0.461	0.421	1	NA	GGA
chr3	71011410	REV_2	0.3494	1.16	0.461	0.405	1	NA	AGA
chr3	71011474	REV_2	0.3302	1.16	0.461	0.382	1	NA	AGA
chr3	71327944	FWD_1	0.2494	1.26	0.438	0.314	1	NA	TCC

Description

knitr::kable(kat$description, caption = "Kataegis column description.")

Kataegis column description.
ID	Description
KT	Forward/reverse kataegis id
MH	Microhomology
PURPLE_AF	Purity adjusted allelic frequency of variant
PURPLE_CN	Purity adjusted copy number surrounding variant location
PURPLE_MACN	Purity adjusted minor allele ploidy surrounding variant location
PURPLE_VCN	Purity adjusted ploidy of variant
SUBCL	Non-zero subclonal likelihood
TNC	Tri-nucleotide context

QC

qc <- system.file("extdata/purple/purple.qc", package = "gpgr") |>
  gpgr::purple_qc_read()

qc$summary |>
  knitr::kable(caption = "PURPLE QC Summary Table.")

PURPLE QC Summary Table.
n	variable	value	details
1	QC_Status	FAIL_CONTAMINATION	See ‘Description’.
13	Method	NORMAL	Fit method (NORMAL, HIGHLY_DIPLOID, SOMATIC or NO_TUMOR).
14	CopyNumberSegments	1428 (Unsupported: 2)	# of CN segments.
2	Purity	0.8600
17	Gender	Amber: MALE; Cobalt: MALE
14	DeletedGenes	150	# of homozygously deleted genes.
15	Contamination	0.807	Rate of contamination in tumor sample as determined by AMBER.
16	GermlineAberrations	NONE	Can be one or more of: KLINEFELTER, TRISOMY_X/21/13/18/15, XYY, MOSAIC_X.
18	AmberMeanDepth	128	Mean depth as determined by AMBER.

Session Info

Main packages used in this vignette.
package	version	datestamp	source
base	4.2.3	2024-06-16	local
gpgr	2.1.1	2024-08-20	local

Platform information.
name	value
version	R version 4.2.3 (2023-03-15)
os	Ubuntu 22.04.4 LTS
system	x86_64, linux-gnu
ui	X11
language	en
collate	C.UTF-8
ctype	C.UTF-8
tz	Etc/UTC
date	2024-08-20
pandoc	3.3 @ /home/runner/micromamba/envs/pkgdownenv/bin/ (via rmarkdown)

2024-08-20

Introduction

Data Munging

Somatic CNVs (per chromosome)

Somatic CNVs (per gene)

Purity

Kataegis

QC

Session Info