Filtering on ref/alt depths within built-in analysis tools

[phillip.a...@gmail.com]

Hello Gemini gurus,

I have a question about GEMINI built-in commands, for example de_novo:

Is it possible to use a genotype filter alongside these tools? Specifically, I want to filter on the alt depth for the proband (index, child, etc.) to reduce my set of de novo candidates. Ideally, I would also be able to set a limit on the ref depth at a locus as well.

Seeing as how this is trivial with gemini query, I was wondering if the syntax is available within the de_novo script. Since this information is stored within the DB, I guess what I'm wondering is how to format the --filter option to mimic the --genotype-filter option.

Right now, my de_novo command looks like this:

gemini de_novo \

        --columns "$COLUMNS" \

        --filter "(aaf_gnomad_genome_all <= 0.01) and (confidentregion = 1) and (inhousedb_ac <= 3 or inhousedb_ac is NULL) and (impact_severity == 'HIGH' or impact_severity=='MED')" \

        -d 20 \

        --min-gq 30 \

        $GEMINIDB > $DENOVO_OUT

python $TableAnnotator -i $DENOVO_OUT -o ${DENOVO_OUT}_annotated.txt

And I'm wondering if there is some sort of additional argument to --filter which I can add, perhaps something like:

gt_alt_depth > 10

Alternatively, if this is not possible, then perhaps it is something that I should be applying beforehand (e.g. to my VCF before creating a DB) with bcftools filter:

bcftools view  -i  'MIN(FMT/DP)>10 & MIN(FMT/GQ)>15'   my.vcf.gz

Thoughts/recommendations are appreciated.

Cheers,

Phil

[phillip.a...@gmail.com]

Hi, this is not possible directly, but you can output gt_alt_depths in
the result and filter on that.
-Brent

Thanks Brent,

My solution is to add bcftools filter (v1.8) command, to create a filter which then I parse through GEMINI with (filter is NULL):

NORMFILTERVCF=$WORKING_DIR${FAMILY_ID}.merged.hc.norm.filter.vcf.gz

/opt/tools/bcftools-1.8/bin/bcftools filter \
         --include 'FORMAT/AD[0:1]>=3 && FORMAT/DP[0] < 300' \
         -m + \
         -s + \
         -O z \
         --output $NORMFILTERVCF \
         $NORMVCF

Cheers,

Phil