A gene is considered to be knocked out for a sample when there is a set of variants that disable each copy of a certain gene.

This analysis obtains the list of knocked out genes for each input sample.

A variant is considered to disable a gene depending on the biotype of the gene, and its annotated consequence type. In protein_coding genes, the consequence type must be any from the list of loss of function sequence ontology terms listed below. In genes with other biotypes, the consequence type is not checked. The variants must also match other filter quality criteria.

Loss of function consequence type:

• frameshift_variant

• inframe_deletion

• inframe_insertion

• start_lost

• stop_gained

• stop_lost

• splice_acceptor_variant

• splice_donor_variant

• transcript_ablation

• transcript_amplification

• initiator_codon_variant

• splice_region_variant

• incomplete_terminal_codon_variant

There are multiple scenarios where we can ensure that a set of variants are affecting all copies of the gene, therefore, the gene is knocked out.

1. Homozygous Alternate : The sample presents the same knock-out variant in both copies of the chromosome.
2. Multi-allelic : The sample presents two different knock-out variants in the same position.
3. Compound Heterozygous : The sample presents two different variants at a particular gene, one on each chromosome of a pair, each of them inherited from different parents.
4. Structural Variation overlap : The sample presents a large structural deletion overlapping with a knock out variant.

Implementation

Implemented at opencga#1455.

Input

Parameters

• sample : List of samples to analyse. The analysis will produce a file for each sample.
• gene : List of genes of interest.
• panel : List of panels of interest.
• biotype :

Output

Files