Filter sites such that gene-specific de novo enrichment analyses are not contaminated with dodgy genes/sites. Further specificity will be achieved through downstream experimental validation of sites in putative 'hit' genes.

The filtering is based on a combination of site-specific strand bias and three parental alt metrics. A site fails if it fails either the strand bias filter, or any two of the three parental alt metrics. These rules have been set so as to allow us to pass:

• good sites in dodgy genes
• sites that are mosaic in one parent
• high depth sites that have a very small number of alt reads in both parents by chance (typically 1 alt read in each parent)

Reject site: If strand-bias p-value < 1e-3 (SNVs only)

OR

If any two of the following conditions are met:

1. alt reads present in both parents
2. site-specific parental alt p-value <1e-3
3. gene-wide parental alt p-value < 1e-3 (only if >1 sites called per gene after strand bias filter applied, otherwise it is redundant with the site specific parental alt p-value)

Clone the repository and install with:

git clone https://github.com/jeremymcrae/denovoFilter.git
cd denovoFilter
python setup.py install --user

A script is included (scripts/filter_de_novos.py) which can be used as:

python scripts/filter_de_novos.py \
  --de-novos DE_NOVO_PATH \
  --families FAMILIES_PATH \
  --output OUTPUT_PATH

You can also use other optional flags:

• --de-novos-indels MISSING_INDELS_PATH to filter a set of candidate indels that were missed by denovogear.
• --sample-fails SAMPLE_FAILS_PATH to exclude a set of probands who we know have problems with de novo calling.
• --sample-fails-indels SAMPLE_FAILS_INDELS_PATH to exclude a set of probands from the missing indels candidates, due to those problems showing problems in the missing indels dataset.
• --annotate-only to add an extra column ('pass') which has True/False values for whether the variants pass rather than filtering to a smaller subset. By default the script will exclude site which fail the filtering.
• --include-noncoding to include noncoding sites in the filtered output.
• --include-recurrent to skip screening out sites which occur multiple times in a family, or multiple sites in a gene in a single individual.

These sites have been filtered for sites that are present in the child, but not in the parents, and not examined by denovogear.