moonso
commented
8 years ago We have reasoned that the inheritance patterns should be used as just another way of filtering the variants. If they are already annotated with deleteriousness and/or frequency it should be rather easy to filter on these variables at once? I agree that the AR_comp model is weak when there is only one individual but there is no obvious way of handling this.
There is a --strict flag that will only annotate models if they have "proof", this will reduce the number significantly in for example a trio.
But I will be happy to discuss this in more detail, pleas elaborate on how your idea should be done.
dnil
The AR_comp model is very inclusive, and so renders much of filtering on this model difficult. It would be useful to be able to tune it to a more stringent approach, akin to what the combined rank score models tries to achieve - or a manual assessment gives. Several solutions would be possible.
Perhaps introducing a different model AR_comp_strict that would be valid only for rare- or high ranking deleterious variants? Neither a manual operator, nor eg ASMG guidelines would consider a common variant valid as disease causing under an AR compound model except when experimental evidence warrants it (e.g. as in Bardet-Biedel or in a select few other disorders).