Vep : MNP phased genotype

Question

[quentin54520]

Hello all,

I would like to know what is the best way to annotate a vcf taking into account the mnp. I specify that it is about a vcf with phased genotype.

For annotations i used ensembl vep. I saw that there is in the vep package, haplosaurus which annotates according to mnp, but how to combine vep and haplosaurus? I mean to have all the info provided by vep (including plugins) but in addition the mnp info?

I take this opportunity to ask another question about vep: to annotate a genome, so that it doesn't take too long, I don't want to put all the annotations on all the variants. in particular the slowest info to calculate such as the splicing I would like to put it only on the variants present in the genes and with a sufficiently low frequency in gnomad. I therefore thought of making a first annotations then filtering to obtain two vcf one with the variants of which I want more info and the other not. Then add the new annotations and finally merge the two vcf. Is this the right method? Merge two vcf which will not wear exactly the same fields in csq is not likely to pose a problem?

Thanks in advance.

Answer 1

[Ben Moore]

Hi quentin54520,

As you noted, the Haplosaurus tool takes phased genotypes from a VCF and constructs a pair of haplotype sequences by considering the combined change contributed by all the variant alleles across a transcript:

https://github.com/Ensembl/ensembl-vep#haplo

However, the range of variant annotation available through the Variant effect Predictor (VEP) is not available through the Haplosaurus, so you would need to combine the output of these tools by running them sequentially.

When using the VEP, there are a range of filters that you can use to filter your results before they are written to your output file, which may help to speed up the running speed of your query. You can see that you can filter based on a number of parameters including frequency data or whether the variants have coding or intergenic consequence predictions: https://www.ensembl.org/info/docs/tools/vep/script/vep_filter.html#filter_run

There are a number of other ways that you can speed up the VEP's runtime, which are summarised on the following documentation page: https://www.ensembl.org/info/docs/tools/vep/script/vep_other.html#faster