Changelog:

06/20/2024 -

Updated cohort size 497 samples > 1,566 samples.
New tsv file offers SURVIVOR merged SV data as an optional input.
Apps now have option to select data file for query (ie merged or unmerged).
Command line tool has additional option flags (see below).
Cohort information has been updated.

05/03/2024 -

Amended end coordinate of insertion calls and overlapping gene IDs.

04/04/2024 -

Re-uploaded raw data tsv.
Included homozygote count.
Updated cohort allele frequency (cohort_af) accuracy for observed genotypes.
Removed frequencies for european (eur) and admixed american (amr) ancestries based on somalier probabilities.

04/01/2024 -

We identified some issues with calculations in the tsv file and have removed the file until fixed. We will update with the corrected file soon.

GA4K SV Finder

GA4K SV Finder is a tool to search for structural variants (SV) and associated genes from 1,566 individuals in the Genomics Answers for Kids (GA4K) cohort (2024) with HiFi long read genomes processed with PBSV (v2.6.2). Whether you're interested in specific genes, SV coordinates, variant frequencies, or a mix (query file), GA4K SV Finder provides a look into the GA4K rare disease cohort.

File contents

Column Names

Chr - Chromosome location of the SV
Start - Start coordinate of the SV
End - End coordinate of the SV
Length - Length of the SV
Type - Type of the SV (DEL, DUP, INS, INV)
CohortAlleleFreq - Allele frequency of SV in cohort population
Homozygotes - Number of homozygotes for SV
VariantCount - Count of individuals with SV
CohortVariantFreq - Population frequency of SV (VariantCount / Cohort)
GeneID - Ensemble gene ID for SV intersected genes
GeneName - Gene name for SV intersected genes

Additional information

This data reflects long read HiFi WGS for 1,566 individuals in the Genomic Answers for Kids (GA4K) study.
All Structural variants were called with PBSV (v2.6.2) using reference genome GRCh38.
Gene intersects were tested against all 19,291 protein coding genes from Gencode release v26 (GRCh38).
The unmerged tsv only collapses identically called variants across individuals.
The merged tsv data comes from a single merged VCF from all individuals using SURVIVOR (v1.0.7) merge options 1000 1 1 1 0 50 (max dist, callers, type specific, strand specific, disabled, min bp).

Dependencies

• Python 3.7 or higher
• Tkinter (usually comes with Python)
• Pandas

Installation

Python Installation

For Linux (Debian/Ubuntu)

sudo apt update
sudo apt install python3

For Linux (CentOS/Red Hat)

sudo dnf install python3

For MacOS

brew install python

Pandas Installation

After installing Python, you can install Pandas using pip:

pip install pandas

Application Usage

Navigate the command line to the directory where you have downloaded the raw data tsv and ga4ksvf-app.py (cd path/to/your/download)

Execute the following command: python3 ga4ksvf-app.py

Command Line Usage

GA4K SV Finder supports three modes of operation. Navigate the command line to the directory where you have downloaded the raw data tsv and ga4ksvf-cmd.py (cd path/to/your/download)

Genes

To search for a specific gene, use:

python3 ga4ksvf-cmd.py GENENAME

Coordinates

To search by genomic coordinates:

python3 ga4ksvf-cmd.py chr3:179121491-179374301

Query Files (Both)

To run multiple queries from a file:

Example queries.txt content

chr3:179121491-179374301
chr16:53841057-53841060
chr9:121275764-121307053
MFN1
FTO
GSN

Options

python3 ga4ksvf-cmd.py [options]

• -f FILE, --file FILE: Process queries from a specified file.
• -q, --query: Query string. Either coordinate (chr:star-end), gene name (GENE1), or Ensembl gene ID (ENSG000).
• -qf, --query-file: File containing queries, one per line (see example in README).
• -e, --export: Export accumulated query results to a specified filename.ext.