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Prioritization of whole-exome data by random-walk analysis of protein-protein interactions

Exome Filtering

The Exome Walker server allows users to specify the parameters used for filtering variants from the VCF file.

In general, there are no single "correct" exome filter settings, rather, they depend on the clinical setting. Many articles have been written on this topic, including Strategies for exome and genome sequence data analysis in disease-gene discovery projects.

The following table contains basic explanations of the settings and recommendations for default values that should work reasonably well in most Mendelian disease-gene discovery projects.

ParameterMeaningRecommended default value
Mode of inheritance This parameter can be used to restrict candidate genes to one of the following modes of inheritance:
  • autosomal dominant: only consider genes with at least one heterozygous variant
  • autosomal recessive: only consider genes with homozygous or compound heterozygous variants
  • X chromosomal: only consider X chromosomal genes with variants
none
FrequencyFilter out variants with minor allele frequency equal to or above a certain thresholdMAF < 0.1%
QualityFilter out variants with PHRED variant call quality equal to less than a certain threshold. Note that different variant callers have different methods for estimating the quality, so that this number does not have any absolute meaning.qualtiy > 30
PathogenicityFilter out variants deemed to be nonpathogenic. The Exome Walker uses predictions from MutationTaster, polyphen2, and SIFT; if all of these programs predict non-pathogenicity, or if a variant belongs to a class such as synonymous substitution that is predicted to be (in general) non-pathogenic, the variant is removed from further consideration.Use filter