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bioRxiv · 10.1101/2024.04.23.590562

Domainator, a flexible software suite for domain-based annotation and neighborhood analysis, identifies proteins involved in antiviral systems

Johnson, S. R.·Weigele, P.·Fomenkov, A.·Ge, A.·Vincze, A.·Roberts, R. J.·Sun, Z.
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Abstract

The availability of large databases of biological sequences presents an opportunity for in-depth exploration of gene diversity and function. Bacterial defense systems are a rich source of diverse, but difficult to annotate genes with biotechnological applications. In this work, we present Domainator, a flexible and modular software suite for domain-based gene neighborhood and protein search, extraction, and clustering. We demonstrate the utility of Domainator through three examples related to bacterial defense systems. First, we cluster CRISPR-associated Rossman fold (CARF) containing proteins with difficult to annotate effector domains, classifying most of them as likely transcriptional regulators and a subset as likely RNAses. Second, we extract and cluster P4-like phage satellite defense hotspots and identify an abundant system related to Lamassu phage defense systems. Third, we integrate a protein language model into Domainator and use it to identify restriction enzymes with low homology to known reference sequences, validating the activity of one example in-vitro. Domainator is made available as an open-source package with detailed documentation and usage examples.

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Johnson, S. R., Weigele, P., Fomenkov, A., Ge, A., Vincze, A., Roberts, R. J., Sun, Z.. 2024-04-26. Domainator, a flexible software suite for domain-based annotation and neighborhood analysis, identifies proteins involved in antiviral systems. https://doi.org/10.1101/2024.04.23.590562

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