Annotations¶

VEP¶

VIP uses the Ensamble Effect Predictor to annotate all variants with their consequences. We use VEP with the refseq option for the transcripts, and with the flags for sift and polyphen annotations enabled.

Plugins¶

Below we describe the other sources which we annotate using the VEP plugin framework.

CAPICE¶

CAPICE is a computational method for predicting the pathogenicity of SNVs and InDels. It is a gradient boosting tree model trained using a variety of genomic annotations used by CADD score and trained on the clinical significance. CAPICE performs consistently across diverse independent synthetic, and real clinical data sets. It ourperforms the current best method in pathogenicity estimation for variants of different molecular consequences and allele frequency.

We run the CAPICE application in the VIP pipeline and use a VEP plugin to annotate the VEP output with the scores from the CAPICE output file.

VKGL¶

The datashare workgroup of VKGL has set up a central database to enable mutual sharing of variant classifications through a partly automatic process. An additional goal is the public sharing of these data. The currently publicly available part of the database consists of DNA variant classifications established based on (former) diagnostic questions.

We add the classifications from an export of the database and use a VEP plugin to annotate the VEP output with the classifications from the this file.

SpliceAI¶

SpliceAI is an open-source deep learning splicing prediction algorithm that has demonstrated in the past few years its high ability to predict splicing defects caused by DNA variations.

We add the scores from the available precomputed scores of SpliceAI and use a copy of the available VEP plugin to annotate the VEP output with the classifications from the this file.

AnnotSV¶

AnnotSV is a program for annotating and ranking structural variations from genomes of several organisms.

We run the AnnotSV application in the VIP pipeline and use a VEP plugin to annotate the VEP output with the scores from the AnnotSV output file.

HPO¶

A file based on the HPO phenotype_to_genes.txt is used to annotate VEP consequences with the inheritance modes associated with the gene of this consequence.

Inheritance¶

A file based on the CGD database is used to annotate VEP consequences with the inheritance modes associated with the gene of this consequence.

Grantham¶

The Grantham score attempts to predict the distance between two amino acids, in an evolutionary sense. A lower Grantham score reflects less evolutionary distance. A higher Grantham score reflects a greater evolutionary distance.

We use a copy of the VEP plugin by Duarte Molha to annotate the VEP output with Grantham scores.