Extracting Complementary Insights from Molecular Phenotypes for Prioritization of Disease-Associated Mutations.

ABSTRACT: Rapid advances in next-generation sequencing technology have resulted in an explosion of whole-exome/genome sequencing data, providing an unprecedented opportunity to identify disease- and trait-associated variants in humans on a large scale. To date, the long-standing paradigm has leveraged fitness-based approximations to translate this ever-expanding sequencing data into causal insights in disease. However, while this approach robustly identifies variants under evolutionary constraint, it fails to provide molecular insights. Moreover, complex disease phenomena often violate standard assumptions of a direct organismal phenotype to overall fitness effect relationship. Here we discuss the potential of a molecular phenotype-oriented paradigm to uniquely identify candidate disease-causing mut

SUBMITTER: Wierbowski SD 

PROVIDER: S-EPMC6510504 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature