AutoPVS1

An automatic classification tool for PVS1 interpretation of null variants.

A web version for AutoPVS1 is also provided: http://autopvs1.genetics.bgi.com/

PREREQUISITE

1. Variant Effect Predictor (VEP)

autopvs1 use VEP to determine the effect of your variants (SNVs, insertions, deletions, CNVs) on genes, transcripts, and protein sequence.

To get HGVS name for the variant, homo_sapiens_refseq 97_GRCh37 cache should be used.

# VEP Installation
git clone https://github.com/Ensembl/ensembl-vep.git
cd ensembl-vep
git pull
git checkout release/97
perl INSTALL.pl

2. pyfaidx

Samtools provides a function “faidx” (FAsta InDeX), which creates a small flat index file “.fai” allowing for fast random access to any subsequence in the indexed FASTA file, while loading a minimal amount of the file in to memory. pyfaidx module implements pure Python classes for indexing, retrieval, and in-place modification of FASTA files using a samtools compatible index.

2. maxentpy

maxentpy is a python wrapper for MaxEntScan to calculate splice site strength. It contains two functions. score5 is adapt from MaxEntScan::score5ss to score 5' splice sites. score3 is adapt from MaxEntScan::score3ss to score 3' splice sites.

maxentpy is already included in the autopvs1.

3. pyhgvs

pyhgvs provides a simple Python API for parsing, formatting, and normalizing HGVS names.

But it only supports python2, I modified it to support python3 and added some other features. It is also included in the autopvs1.

4. configure file

# autopvs1/config.ini
[DEFAULT]

ref = data/hg19.fa
trans = data/refGenePlus_20191020.gpe
domain = data/PM1.domain.bed
hotspot = data/PM1.hotspot.bed
curated_region = data/PM1.expert_curated.bed
pathogenic_ref = data/clinvar_pathogenic_20200106.vcf
pvs1levels = data/PVS1.level
exon_lof_popmax = data/exon_lof_popmax.bed
gene_trans = data/clinvar_trans_stats_20200106.tsv
gene_alias = data/hgnc.symbol.previous.tsv

hg19.fa is downloaded from ucsc database and indexed with samtools faidx

USAGE

single variant

from autopvs1 import AutoPVS1
demo=AutoPVS1('22-36678800-G-A')
print(demo.consequence, demo.hgvs_c, demo.hgvs_p, demo.pvs1.strength_raw, 
      demo.pvs1.strength, demo.pvs1.criterion)

batch processing

VCF input are required

cd test
bash vep.sh pilot/pvs1.pilot.vcf >pvs1.pilot.vep
python3 vep_lof_filter.py pvs1.pilot.vep
python3 test.py pvs1.pilot.vep.lof >pvs1.pilot.vep.lof.autopvs1

FAQ

Please see http://autopvs1.genetics.bgi.com/faq/

Terms of use

Users may freely use the AutoPVS1 for non-commercial purposes as long as they properly cite it. This resource is intended for research purposes only. For clinical or medical use, please consult professionals.

yangmqglobe/autopvs1