Large Numbers of New Human Paralogs Discovered.

ABSTRACT: The identification of paralogs is critical for understanding protein evolution, function, and for drug design, yet many human proteins remain unannotated and poorly classified. Sequence-based homology detection alone often fails to detect distant paralogs, especially in the "twilight zone" or beyond, regarding sequence identity. Here we present an integrated homolog detection framework that combines results from BLASTp, MMseqs2, Foldseek, and the large protein language model-based tool PROST, followed by validation based on comparison of structures and for enzymes comparison of the specific structures of the catalytic residues. Using all-versus-all exhaustive comparisons across the 20,647 human proteins, we systematically identify novel paralogs and assess their catalytic residues for two

SUBMITTER: Bk P 

PROVIDER: S-EPMC12632886 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature