2024/11/15 by Sean R. Johnson, Peter Weigele, Alexey Fomenkov +5 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Influenza Virus Research Studies #RNA and protein synthesis mechanisms #interferon and immune responses
paper · pdf · doi:10.1093/nar/gkae1175
openalex publication_date 2024/11/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
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, identify an abundant variant of Lamassu defense systems and demonstrate its in vivo activity against several T-even phages. Third, we integrate a protein language model into Domainator and use it to identify restriction endonucleases with low similarity 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.