SHARK enables sensitive detection of evolutionary homologs and functional analogs in unalignable and disordered sequences.

ABSTRACT: Intrinsically disordered regions (IDRs) are structurally flexible protein segments with regulatory functions in multiple contexts, such as in the assembly of biomolecular condensates. Since IDRs undergo more rapid evolution than ordered regions, identifying homology of such poorly conserved regions remains challenging for state-of-the-art alignment-based methods that rely on position-specific conservation of residues. Thus, systematic functional annotation and evolutionary analysis of IDRs have been limited, despite them comprising ~21% of proteins. To accurately assess homology between unalignable sequences, we developed an alignment-free sequence comparison algorithm, SHARK (Similarity/Homology Assessment by Relating K-mers). We trained SHARK-dive, a machine learning homology classifier,

SUBMITTER: Chow CFW 

PROVIDER: S-EPMC11494347 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature