TitleCascade PSI-BLAST 2.0: a fast-searching parallelized remote homology detection tool and development of Cascade web server 2.0
Publication TypeJournal Article
Year of Publication2026
AuthorsNayak S, Regati DReddy, Pavalam M, Sowdhamini R.
JournalSpringer Nature Link
Date Published18 February 2026
KeywordsCascade PSI_BLAST, GNU parallel, Parallel processing, PSI BLAST, Remote homology search, Webserver
Abstract

Remote homology detection is critical for inferring evolutionary and functional relationships among proteins, but divergence below 30% identity often hinders standard sequence-based searches. Profile-based methods and HMMs improve sensitivity, yet many distant homologues remain undetected. Cascade PSI-BLAST uses efficient, iterative, multi-generation searches of intermediate hits to bridge sequence gaps, constructing successive PSSMs that reveal remote relationships without structural information. However, its application to ultra-large databases such as NR and UniProt is computationally intensive. We address this limitation by optimizing intermediate selection and enabling distributed execution across multiple CPUs or servers, significantly enhancing throughput and resource utilization while preserving detection sensitivity.

URLhttps://link.springer.com/article/10.1186/s12859-026-06366-7
DOI10.1186/s12859-026-06366-7