An automatic classification tool for PVS1 interpretation of null variants.

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

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 100_GRCh37 cache should be used.

# VEP Installation
git clone https://github.com/Ensembl/ensembl-vep.git
cd ensembl-vep
git pull
git checkout release/100
perl INSTALL.pl

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.

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.

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.

# autopvs1/config.ini
[DEFAULT]

ref = data/hg19.fa
trans = data/refGenePlus_20200301.gpe
domain = data/PM1.domain.bed
hotspot = data/PM1.hotspot.bed
curated_region = data/PM1.expert_curated.bed
pathogenic_ref = data/clinvar_pathogenic_20200629.vcf
pvs1levels = data/PVS1.level
exon_lof_popmax = data/exon_lof_popmax.bed
gene_trans = data/clinvar_trans_stats_20200629.tsv
gene_alias = data/hgnc.symbol.previous.tsv
vep_cache = $HOME/.vep

hg19.fa is downloaded from ucsc database and indexed with samtools faidx. You can specify the vep cache directory to use, default is "$HOME/.vep/".

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)

The batch processing mode is deprecated and no longer maintained.

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

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.