# Prior and pop\_frequency\_prior in de\_novo **URL:** \ **Category:** Hail Query & hailctl\ **Created:** [October 1, 2020, 6:59am UTC](https://discuss.hail.is/t/prior-and-pop-frequency-prior-in-de-novo/1718 "2020-10-01T06:59:02Z")\ **Posts on this page:** 7\ **Page:** 1
**Author:** ![olszewskip](https://avatars.discourse-cdn.com/v4/letter/o/f1d935/32.png) [@olszewskip](https://discuss.hail.is/u/olszewskip)\ **Post date:** [October 1, 2020, 6:59am UTC](https://discuss.hail.is/t/prior-and-pop-frequency-prior-in-de-novo/1718/1 "2020-10-01T06:59:02Z")
Hello! I want to use the `de_novo` function but I’m not sure if I understand the documentation correctly, and if so, then I’d like to ask for help 🙂 It’s about the `prior` parameter: `It is the maximum of: the computed dataset alternate allele frequency, the pop_frequency_prior parameter, and the global prior 1 / 3e7`. Do I understand correctly that ths value, reported back as `prior`, is what is denoted as `AF` in the formula for `P(m)` down in the documentation? I have a single family to analyze without a larger set of samples from the same population and so it doesn’t seem to make sense to rely on the computed dataset alternate allele frequency as the `AF`. I think it would be seriously skewed due to presence of only related samples, large fraction of whom are the sick “probands”. And so I think I need to ensure that the `pop_frequency_prior` is used as the `AF` instead of the computed frequency. As if I had an infinity of homref samples in my vcf, next to the family. Would You agree? Is that possible? ---
**Author:** ![tpoterba](https://yyz2.discourse-cdn.com/flex036/user_avatar/discuss.hail.is/tpoterba/32/61_2.png) [@tpoterba](https://discuss.hail.is/u/tpoterba)\ **Post date:** [October 1, 2020, 3:31pm UTC](https://discuss.hail.is/t/prior-and-pop-frequency-prior-in-de-novo/1718/2 "2020-10-01T15:31:01Z")
This is a good question. I think your concern is valid, but fortunately the algorithm is designed to handle this case – the definition of `computed dataset alternate allele frequency` is the AAF _without_ the putative de novo allele in the individual of interest. This means that if you have a single trio, and your genotype configuration is (0/0 - 0/0) =\> (0/1), then the `computed dataset alternate allele frequency` is 0%. Here’s where the code implements these rules: > ---
**Author:** ![olszewskip](https://avatars.discourse-cdn.com/v4/letter/o/f1d935/32.png) [@olszewskip](https://discuss.hail.is/u/olszewskip)\ **Post date:** [October 1, 2020, 3:40pm UTC](https://discuss.hail.is/t/prior-and-pop-frequency-prior-in-de-novo/1718/3 "2020-10-01T15:40:35Z")
I see. So, in case I have more trios, I should probably just externally loop over those trios, each time filtering the columns down to the three samples and calling (something like) `hl.de_novo(mt_trio, hl.Pedigree([trio]), pop_frequency_prior = mt_trio.AF)`. ---
**Author:** ![tpoterba](https://yyz2.discourse-cdn.com/flex036/user_avatar/discuss.hail.is/tpoterba/32/61_2.png) [@tpoterba](https://discuss.hail.is/u/tpoterba)\ **Post date:** [October 2, 2020, 3:24pm UTC](https://discuss.hail.is/t/prior-and-pop-frequency-prior-in-de-novo/1718/4 "2020-10-02T15:24:29Z")
Ack, that’s going to be pretty inefficient. Are you worried that you have the same de novo mutation in many families for the same disease, leading to an inflated estimate of in-sample allele frequency due to the ascertainment? If so, it isn’t actually hard to add a flag to `hl.de_novo` to just remove the in-sample AF from the calculatino. ---
**Author:** ![olszewskip](https://avatars.discourse-cdn.com/v4/letter/o/f1d935/32.png) [@olszewskip](https://discuss.hail.is/u/olszewskip)\ **Post date:** [October 2, 2020, 4:17pm UTC](https://discuss.hail.is/t/prior-and-pop-frequency-prior-in-de-novo/1718/5 "2020-10-02T16:17:50Z")
Yup. Assuming I understand correctly, in case when I have, say, grandparents -\> father, and (father, mother) -\> (child1, child2), and I’m interested in de\_novos in father and child1; and I don’t want to have the AAF of fathers de\_novo computed from these 6-persons-population: I should run the de\_novo function separately for father and child1? ---
**Author:** ![tpoterba](https://yyz2.discourse-cdn.com/flex036/user_avatar/discuss.hail.is/tpoterba/32/61_2.png) [@tpoterba](https://discuss.hail.is/u/tpoterba)\ **Post date:** [October 2, 2020, 5:00pm UTC](https://discuss.hail.is/t/prior-and-pop-frequency-prior-in-de-novo/1718/6 "2020-10-02T17:00:25Z")
This pull request adds a mode that essentially treats each trio as the only one in the dataset: > ---
**Author:** ![olszewskip](https://avatars.discourse-cdn.com/v4/letter/o/f1d935/32.png) [@olszewskip](https://discuss.hail.is/u/olszewskip)\ **Post date:** [October 7, 2020, 12:21pm UTC](https://discuss.hail.is/t/prior-and-pop-frequency-prior-in-de-novo/1718/7 "2020-10-07T12:21:43Z")
Many thanks.