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<p>Deciphering the evolutionary history of genes is foundational for biomedical research, enabling the identification of compensatory mutations in disease-associated genes and the selection of evolutionarily relevant model organisms. However, challenges of multi-isoform handling, the presence of incomplete genomes/proteomes initial datasets, and problems of evolutionary history representation are still present. To address these issues, we introduce a novel framework based on the Clusters of Orthologous Groups (COG) method, primarily designed for improving phylogenetic tree clustering in studying evolutionary history of eukaryotes, P-COGs (Pavlov’s COGs). It encourages the use of a single sequence dataset for both constructing phylogenetic trees and inferring COGs. We demonstrate the tool’s utility through an evolutionary study of the voltage-dependent chloride channel genes family (CLCN). Moreover, P-COGs allowed us to observe multiple clusters of orthologous genes in CLCN that were not identified by other COG-based tools. Additionally, we resolved the evolutionary history of hundreds of cancer-associated genes with P-COGs to support accurate evolution-based variant effect prediction. The resulting COG graphs are accessible via our interactive web application (<a href="https://epicenter.1spbgmu.ru/shiny/pavlovscogs/">https://epicenter.1spbgmu.ru/shiny/pavlovscogs/</a>). P-COGs is openly available at <a href="https://github.com/bugds/Pavlovs_COGs">https://github.com/bugds/Pavlovs_COGs</a>.</p>

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Discovering New Orthologous Groups with P-COGs

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Dmitrii Sergeevich Bug,
  • Dariia Andreevna Kuzovenkova,
  • Artem Valerievich Tishkov,
  • Natalia Olegovna Porozova,
  • Natalia Vitalievna Petukhova

摘要

Deciphering the evolutionary history of genes is foundational for biomedical research, enabling the identification of compensatory mutations in disease-associated genes and the selection of evolutionarily relevant model organisms. However, challenges of multi-isoform handling, the presence of incomplete genomes/proteomes initial datasets, and problems of evolutionary history representation are still present. To address these issues, we introduce a novel framework based on the Clusters of Orthologous Groups (COG) method, primarily designed for improving phylogenetic tree clustering in studying evolutionary history of eukaryotes, P-COGs (Pavlov’s COGs). It encourages the use of a single sequence dataset for both constructing phylogenetic trees and inferring COGs. We demonstrate the tool’s utility through an evolutionary study of the voltage-dependent chloride channel genes family (CLCN). Moreover, P-COGs allowed us to observe multiple clusters of orthologous genes in CLCN that were not identified by other COG-based tools. Additionally, we resolved the evolutionary history of hundreds of cancer-associated genes with P-COGs to support accurate evolution-based variant effect prediction. The resulting COG graphs are accessible via our interactive web application (https://epicenter.1spbgmu.ru/shiny/pavlovscogs/). P-COGs is openly available at https://github.com/bugds/Pavlovs_COGs.