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Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions

Biodiversity within the animal kingdom is associated with extensive molecular diversity. The expansion of genomic, transcriptomic and proteomic data sets for invertebrate groups and species with unique biological traits necessitates reliable in silico tools for the accurate identification and annota...

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Autores principales: Zheng, Yuanting, Young, Neil D., Song, Jiangning, Gasser, Robin B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418638/
https://www.ncbi.nlm.nih.gov/pubmed/37569696
http://dx.doi.org/10.3390/ijms241512320
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author Zheng, Yuanting
Young, Neil D.
Song, Jiangning
Gasser, Robin B.
author_facet Zheng, Yuanting
Young, Neil D.
Song, Jiangning
Gasser, Robin B.
author_sort Zheng, Yuanting
collection PubMed
description Biodiversity within the animal kingdom is associated with extensive molecular diversity. The expansion of genomic, transcriptomic and proteomic data sets for invertebrate groups and species with unique biological traits necessitates reliable in silico tools for the accurate identification and annotation of molecules and molecular groups. However, conventional tools are inadequate for lesser-known organismal groups, such as eukaryotic pathogens (parasites), so that improved approaches are urgently needed. Here, we established a combined sequence- and structure-based workflow system to harness well-curated publicly available data sets and resources to identify, classify and annotate proteases and protease inhibitors of a highly pathogenic parasitic roundworm (nematode) of global relevance, called Haemonchus contortus (barber’s pole worm). This workflow performed markedly better than conventional, sequence-based classification and annotation alone and allowed the first genome-wide characterisation of protease and protease inhibitor genes and gene products in this worm. In total, we identified 790 genes encoding 860 proteases and protease inhibitors representing 83 gene families. The proteins inferred included 280 metallo-, 145 cysteine, 142 serine, 121 aspartic and 81 “mixed” proteases as well as 91 protease inhibitors, all of which had marked physicochemical diversity and inferred involvements in >400 biological processes or pathways. A detailed investigation revealed a remarkable expansion of some protease or inhibitor gene families, which are likely linked to parasitism (e.g., host–parasite interactions, immunomodulation and blood-feeding) and exhibit stage- or sex-specific transcription profiles. This investigation provides a solid foundation for detailed explorations of the structures and functions of proteases and protease inhibitors of H. contortus and related nematodes, and it could assist in the discovery of new drug or vaccine targets against infections or diseases.
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spelling pubmed-104186382023-08-12 Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions Zheng, Yuanting Young, Neil D. Song, Jiangning Gasser, Robin B. Int J Mol Sci Article Biodiversity within the animal kingdom is associated with extensive molecular diversity. The expansion of genomic, transcriptomic and proteomic data sets for invertebrate groups and species with unique biological traits necessitates reliable in silico tools for the accurate identification and annotation of molecules and molecular groups. However, conventional tools are inadequate for lesser-known organismal groups, such as eukaryotic pathogens (parasites), so that improved approaches are urgently needed. Here, we established a combined sequence- and structure-based workflow system to harness well-curated publicly available data sets and resources to identify, classify and annotate proteases and protease inhibitors of a highly pathogenic parasitic roundworm (nematode) of global relevance, called Haemonchus contortus (barber’s pole worm). This workflow performed markedly better than conventional, sequence-based classification and annotation alone and allowed the first genome-wide characterisation of protease and protease inhibitor genes and gene products in this worm. In total, we identified 790 genes encoding 860 proteases and protease inhibitors representing 83 gene families. The proteins inferred included 280 metallo-, 145 cysteine, 142 serine, 121 aspartic and 81 “mixed” proteases as well as 91 protease inhibitors, all of which had marked physicochemical diversity and inferred involvements in >400 biological processes or pathways. A detailed investigation revealed a remarkable expansion of some protease or inhibitor gene families, which are likely linked to parasitism (e.g., host–parasite interactions, immunomodulation and blood-feeding) and exhibit stage- or sex-specific transcription profiles. This investigation provides a solid foundation for detailed explorations of the structures and functions of proteases and protease inhibitors of H. contortus and related nematodes, and it could assist in the discovery of new drug or vaccine targets against infections or diseases. MDPI 2023-08-01 /pmc/articles/PMC10418638/ /pubmed/37569696 http://dx.doi.org/10.3390/ijms241512320 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zheng, Yuanting
Young, Neil D.
Song, Jiangning
Gasser, Robin B.
Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions
title Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions
title_full Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions
title_fullStr Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions
title_full_unstemmed Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions
title_short Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions
title_sort genome-wide analysis of haemonchus contortus proteases and protease inhibitors using advanced informatics provides insights into parasite biology and host–parasite interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418638/
https://www.ncbi.nlm.nih.gov/pubmed/37569696
http://dx.doi.org/10.3390/ijms241512320
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