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Linkage-based ortholog refinement in bacterial pangenomes with CLARC

Title: Linkage-based ortholog refinement in bacterial pangenomes with CLARC
Authors: González Ojeda, Indra; Palace, Samantha G; Martinez, Pamela P; Azarian, Taj; Grant, Lindsay R; Hammitt, Laura L; Hanage, William P; Lipsitch, Marc
Contributors: National Institutes of Health; National Science Foundation Graduate Research Fellowship
Source: Nucleic Acids Research ; volume 53, issue 12 ; ISSN 0305-1048 1362-4962
Publisher Information: Oxford University Press (OUP)
Publication Year: 2025
Description: Bacterial genomes exhibit significant variation in gene content and sequence identity. Pangenome analyses explore this diversity by classifying genes into core and accessory clusters of orthologous groups (COGs). However, strict sequence identity cutoffs can misclassify divergent alleles as different genes, inflating accessory gene counts. CLARC (Connected Linkage and Alignment Redefinition of COGs) (https://github.com/IndraGonz/CLARC) improves pangenome analyses by condensing accessory COGs using functional annotation and linkage information. Through this approach, orthologous groups are consolidated into more practical units of selection. Analyzing 8000+ Streptococcus pneumoniae genomes, CLARC reduced accessory gene estimates by >30% and improved evolutionary predictions based on accessory gene frequencies. CLARC is effective across different bacterial species, making it a broadly applicable tool for comparative genomics. By refining COG definitions, CLARC offers critical insights into bacterial evolution, aiding genetic studies across diverse populations.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1093/nar/gkaf488
Availability: https://doi.org/10.1093/nar/gkaf488; https://academic.oup.com/nar/article-pdf/53/12/gkaf488/63535514/gkaf488.pdf
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.B37B55AC
Database: BASE