varcode 4.23.0

Variant annotation in Python

Varcode

Varcode is a library for working with genomic variant data in Python and predicting the impact of those variants on protein sequences.

Installation

You can install varcode using pip:

pip install varcode

You can install required reference genome data through PyEnsembl as follows:

# Downloads and installs the Ensembl releases (75 and 76)
pyensembl install --release 75 76

Example

import varcode

# Load TCGA MAF containing variants from their
variants = varcode.load_maf("tcga-ovarian-cancer-variants.maf")

print(variants)
### <VariantCollection from 'tcga-ovarian-cancer-variants.maf' with 6428 elements>
###  -- Variant(contig=1, start=69538, ref=G, alt=A, genome=GRCh37)
###  -- Variant(contig=1, start=881892, ref=T, alt=G, genome=GRCh37)
###  -- Variant(contig=1, start=3389714, ref=G, alt=A, genome=GRCh37)
###  -- Variant(contig=1, start=3624325, ref=G, alt=T, genome=GRCh37)
###  ...

# you can index into a VariantCollection and get back a Variant object
variant = variants[0]

# groupby_gene_name returns a dictionary whose keys are gene names
# and whose values are themselves VariantCollections
gene_groups = variants.groupby_gene_name()

# get variants which affect the TP53 gene
TP53_variants = gene_groups["TP53"]

# predict protein coding effect of every TP53 variant on
# each transcript of the TP53 gene
TP53_effects = TP53_variants.effects()

print(TP53_effects)
### <EffectCollection with 789 elements>
### -- PrematureStop(variant=chr17 g.7574003G>A, transcript_name=TP53-001, transcript_id=ENST00000269305, effect_description=p.R342*)
### -- ThreePrimeUTR(variant=chr17 g.7574003G>A, transcript_name=TP53-005, transcript_id=ENST00000420246)
### -- PrematureStop(variant=chr17 g.7574003G>A, transcript_name=TP53-002, transcript_id=ENST00000445888, effect_description=p.R342*)
### -- FrameShift(variant=chr17 g.7574030_7574030delG, transcript_name=TP53-001, transcript_id=ENST00000269305, effect_description=p.R333fs)
### ...

premature_stop_effect = TP53_effects[0]

print(str(premature_stop_effect.mutant_protein_sequence))
### 'MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMF'

print(premature_stop_effect.aa_mutation_start_offset)
### 341

print(premature_stop_effect.transcript)
### Transcript(id=ENST00000269305, name=TP53-001, gene_name=TP53, biotype=protein_coding, location=17:7571720-7590856)

print(premature_stop_effect.gene.name)
### 'TP53'

If you are looking for a quick start guide, you can check out this iPython book that demonstrates simple use cases of Varcode.

Further reading

Feature guides live in docs/ and on the docs site:

• Effect annotation — how variants become effects, splice outcome representations, pluggable annotators, and structural variants.
• Genotypes and sample-aware queries — per-sample zygosity on multi-sample VCFs.
• VariantCollection transforms — pair_breakends, left_align_indels, and the transform contract.
• CSV round-trip and metadata headers — to_csv / from_csv with #-prefixed provenance headers.
• Error handling — ReferenceMismatchError, GenomeBuildMismatchError, SampleNotFoundError, and raise_on_error=False.
• Germline-aware annotation — niche. Classify somatic variants against the patient's germline-applied transcript when somatic and germline share a codon.

See CHANGELOG.md for the release history.

Effect Types

Effect type	Description
AlternateStartCodon	Replace annotated start codon with alternative start codon (e.g. "ATG>CAG").
ComplexSubstitution	Insertion and deletion of multiple amino acids.
Deletion	Coding mutation which causes deletion of amino acid(s).
ExonLoss	Deletion of entire exon, significantly disrupts protein.
ExonicSpliceSite	Mutation at the beginning or end of an exon, may affect splicing.
FivePrimeUTR	Variant affects 5' untranslated region before start codon.
FrameShiftTruncation	A frameshift which leads immediately to a stop codon (no novel amino acids created).
FrameShift	Out-of-frame insertion or deletion of nucleotides, causes novel protein sequence and often premature stop codon.
IncompleteTranscript	Can't determine effect since transcript annotation is incomplete (often missing either the start or stop codon).
Insertion	Coding mutation which causes insertion of amino acid(s).
Intergenic	Occurs outside of any annotated gene.
Intragenic	Within the annotated boundaries of a gene but not in a region that's transcribed into pre-mRNA.
IntronicSpliceSite	Mutation near the beginning or end of an intron but less likely to affect splicing than donor/acceptor mutations.
Intronic	Variant occurs between exons and is unlikely to affect splicing.
NoncodingTranscript	Transcript doesn't code for a protein.
PrematureStop	Insertion of stop codon, truncates protein.
Silent	Mutation in coding sequence which does not change the amino acid sequence of the translated protein.
SpliceAcceptor	Mutation in the last two nucleotides of an intron, likely to affect splicing.
SpliceDonor	Mutation in the first two nucleotides of an intron, likely to affect splicing.
StartLoss	Mutation causes loss of start codon, likely result is that an alternate start codon will be used down-stream (possibly in a different frame).
StopLoss	Loss of stop codon, causes extension of protein by translation of nucleotides from 3' UTR.
Substitution	Coding mutation which causes simple substitution of one amino acid for another.
ThreePrimeUTR	Variant affects 3' untranslated region after stop codon of mRNA.

Coordinate System

Varcode currently uses a "base counted, one start" genomic coordinate system, to match the Ensembl annotation database. We are planning to switch over to "space counted, zero start" (interbase) coordinates, since that system allows for more uniform logic (no special cases for insertions). To learn more about genomic coordinate systems, read this blog post.