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bioRxiv · 10.1101/2022.11.24.517862

pLM-BLAST - distant homology detection based on direct comparison of sequence representations from protein language models

Kaminski, K.·Ludwiczak, J.·Alva, V.·Dunin-Horkawicz, S.
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Abstract

MotivationThe detection of homology through sequence comparison is a typical first step in the study of protein function and evolution. In this work, we explore the applicability of protein language models to this task. ResultsWe introduce pLM-BLAST, a tool inspired by BLAST, that detects distant homology by comparing single-sequence representations (embeddings) derived from a protein language model, ProtT5. Our benchmarks reveal that pLM-BLAST maintains a level of accuracy on par with HHsearch for both highly similar sequences (with over 50% identity) and markedly divergent sequences (with less than 30% identity), while being significantly faster. Additionally, pLM-BLAST stands out among other embedding-based tools due to its ability to compute local alignments. We show that these local alignments, produced by pLM-BLAST, often connect highly divergent proteins, thereby highlighting its potential to uncover previously undiscovered homologous relationships and improve protein annotation. Availability and ImplementationpLM-BLAST is accessible via the MPI Bioinformatics Toolkit as a web server for searching precomputed databases (https://toolkit.tuebingen.mpg.de/tools/plmblast). It is also available as a standalone tool for building custom databases and performing batch searches (https://github.com/labstructbioinf/pLM-BLAST).

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Kaminski, K., Ludwiczak, J., Alva, V., Dunin-Horkawicz, S.. 2022-11-25. pLM-BLAST - distant homology detection based on direct comparison of sequence representations from protein language models. https://doi.org/10.1101/2022.11.24.517862

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