Matching whole genomes to rare genetic disorders: Identification of potential causative variants using phenotype-weighted knowledge in the CAGI SickKids5 clinical genomes challenge.

ABSTRACT: Precise identification of causative variants from whole-genome sequencing data, including both coding and noncoding variants, is challenging. The Critical Assessment of Genome Interpretation 5 SickKids clinical genome challenge provided an opportunity to assess our ability to extract such information. Participants in the challenge were required to match each of the 24 whole-genome sequences to the correct phenotypic profile and to identify the disease class of each genome. These are all rare disease cases that have resisted genetic diagnosis in a state-of-the-art pipeline. The patients have a range of eye, neurological, and connective-tissue disorders. We used a gene-centric approach to address this problem, assigning each gene a multiphenotype-matching score. Mutations in the top-scoring

SUBMITTER: Pal LR 

PROVIDER: S-EPMC7182498 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature