The PeCan Knowledgebase is comprised of curated pediatric cancer genomics data including variants, mutational signatures, and gene expression data in addition to histological slide images from ~9000 hematological, CNS, and non-CNS solid tumor patient samples.

Variants

ONCOPRINT METHODS All oncoprint visualizations have been generated using ProteinPaint’s mutational landscape study views.

ONCOPRINT DATA Variant data represented within oncoprint visualizations are sourced from published studies from organizations including St. Jude Children’s Research Hospital, NCI-TARGET TARGET, German Cancer Research Center DKFZ, and Shanghai Children’s Medical Hospital.

A user can access associated studies that involve a subset of the data displayed in the onocprint by clicking Associated Study where applicable.

VARIANT PREVALENCE METHODS Variant Prevalence is a custom interface portraying barplots (for selected genes) conveying the prevalence of each variant types for the displayed genes (selected as described below). In addition, Variant Origin, and Total number of Mutations are displayed.

Mutation type proportion rules: Note that the gene lists provided are not curated, however, for each selected diagnosis cohort of samples, the occurrence gene among the samples therein are counted and ranked. A select number of diagnoses have curated gene pathways. If pathway information is available for the diagnosis cohort, 20 genes are listed, else we return a list of the top 50 genes.

Variant selection rules: Variant classes are found below with the definition of each.

Glossary of Classes

Mutation Class	Description
MISSENSE	a substitution variant in the coding region resulting in altered protein coding.
FRAMESHIFT	an insertion or deletion variant that alters the protein coding frame.
NONSENSE	a variant altering protein coding to produce a premature stopgain or stoploss.
PROTEINDEL	a deletion resulting in a loss of one or more codons from the product, but not altering the protein coding frame.
PROTEININS	an insertion introducing one or more codons into the product, but not altering the protein coding frame.
SPLICE	a variant near an exon edge that may affect splicing functionality.
SILENT	a substitution variant in the coding region that does not alter protein coding.
SPLICE_REGION	a variant in an intron within 10 nt of an exon boundary.
UTR_5	a variant in the 5’ untranslated region.
UTR_3	a variant in the 3’ untranslated region.
EXON	a variant in the exon of a non-coding RNA.
INTRON	an intronic variant.
CNV LOSS	a copy number loss.
CNV GAIN	a copy number gain.

Table 1. Mutation Class glossary. Definition of variant classes that are provided in Oncoprint, Variant Prevalence, and ProteinPaint views.

Variant origin count rules: If the variant origin is not recorded as germline, then it is counted as somatic, which also includes the relapse samples. When the variant origin is germline, the record is counted as germline.

Glossary of Origins

Mutation Origin	Description
Germline	a variant found in a normal sample of a cancer patient.
Somatic	a variant found only in a tumor sample.
Relapse	a variant that arose in recurrence tumor.

Table 2. Mutation Origin glossary. Definitition of origins listed.

Total # Mutations rules: This is the total number of variants for that given gene for the selected diagnosis and/or subtype divided by the gene with the largest variant total (rounded to the nearest 50) for that selected diagnosis and/or subtype.

VARIANT PREVALENCE DATA The most prevelant genes are shown based on the rules described above for variant selection and variant origin. The legend Mutation Type is the same variant classes used for the oncoprints. View Glossary of Classes above to learn more.

The variants that will be used for the Variant Prevalence page are indicated in the below table.

dataset_label	variant type
BROAD	snv, indel, sv
DKFZ	snv, indel, sv
DKTK	snv, indel
MAGIC	snv, indel
PCGP	snv, indel, sv, fusions
SCMC	snv, indel, sv, fusions
SJCRH	snv, indel, sv
TARGET	snv, indel, cnv, sv, fusions
UTSMC	snv, indel

Table 3: Variant Prevelance. The table provides the available variant information which are represented in PeCan per dataset.

GENOMEPAINT METHODS

Documentation can be found here.

GENOMEPAINT DATA

The Pediatric2 dataset expands the original Pediatric dataset by adding non-coding variants and expression data. The additional data includes Genome for Kids (PMID: 34301788), Shanghai Children’s Medical Center relapsed ALL cohort (PMID: 32632335), St Jude’s Clinical cancer genomic profiling by three-platform sequencing study (PMID: 30262806), and St Jude’s Pan-neuroblastoma analysis data study (PMID: 33056981).

Ref Genome	Dataset
hg19	Pediatric, PAN-ALL
hg38	Pediatric, SJLIFE

Table 4. GenomePaint datasets. GenomePaint supports different combinations of datasets for each reference genome (hg19/hg38).

PROTEINPAINT METHODS

Documentation can be found here.

PROTEINPAINT DATA The Pediatric dataset consists of somatic variants and tumor RNA-seq data shown in the protein view. The dataset is comprised of the GRCh37/hg19 genome as well as data from the Pediatric Cancer Genome Project (PCGP), NCI TARGET cohort, the Pan-TARGET study (PMID: 29489755), and the Shanghai Children’s Medical Center T-ALL cohort (PMID: 32632335). A liftover of genomic variants and gene internals created the GRCh/hg38 dataset. The NCI’s Genomic Data Commmons (GDC) coagulates data from NCI-supported programs, such as TCGA and TARGET. The Clinical Interpretation of Variants in Cancer (ClinVar) is “an open-source platform for crowdsourced and expert-moderated cancer variant curation.” Supported by the NIH, NHGRI, and NCI, CIViC is a richly curated oncology dataset (PMID: 28138153).

Ref Genome	Dataset
hg19	Pediatric, COSMIC, ClinVar
hg39	Pediatric, GDC, COSMIC, ClinVar

Table 5. ProteinPaint dataset. ProteinPaint supports different combinations of datasets for each reference genome (hg19/hg38).

See below for more information regarding the glossary for origins and mutation classes.

MUTATIONAL SIGNATURES (SNV) METHODS

Identification of COSMIC SBS signatures (v3.3) upon consideration of somatic variants was performed using SigProfilerExtractor (v1.1.20) on pediatric tumor samples grouped by subtype.

MUTATIONAL SIGNATURES DATA Sample data from G4K, PCGP, Clinical Pilot and Real-Time Clincal Genomics (RTCG) samples were considered for mutational signature detection analysis.

EXPRESSION

EXPRESSION METHODS RAPID RNA-Seq workflow hosted on St. Jude Cloud’s Genomics Platform was employed for the analysis of RNA-seq gene expression count data and plotted using ProteinPaint’s scatterplot.

EXPRESSION DATA The sample data used to generate the expression scatterplot maps are from the G4K, PCGP, Clinical Pilot and Real-Time Clinical Genomics studies.

Histology

HISTOLOGY METHODS All slides (with H&E staining) come off the microscope in .svs format which are then uploaded and processed in Azure. Currently, each sample is only accompanied by one slide but we plan on extending this feature for multiple slides per sample.

HISTOLOGY DATA All histological images are shared by the COMET Blue Sky Initiatve led by Dr. Mike Dyer. A large subset of COMET slides are pending publication.

Interested in collaborating with your data? Reach out to us at support@stjude.cloud.