A computational framework to explore large-scale biosynthetic diversity
| Autor: | Anthony W. Goering, Marley Yeong, Michael W. Mullowney, William W. Metcalf, Pablo Cruz-Morales, Regan J. Thomson, James H. Tryon, Arne Roeters, Neil L. Kelleher, Nelly Selem-Mojica, Satria A. Kautsar, Antonio Fernandez-Guerra, Emmanuel L. C. de los Santos, Wouter Lokhorst, Jorge C. Navarro-Muñoz, Elizabeth I. Parkinson, Marnix H. Medema, Sahar Abubucker, Francisco Barona-Gómez, Luciana Teresa Dias Cappelini |
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| Přispěvatelé: | Westerdijk Fungal Biodiversity Institute |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Bioinformatics
Computer science Computational biology Article 03 medical and health sciences Similarity (network science) Bioinformatica Gene cluster Life Science Cluster Analysis Data Mining Metabolomics Cluster analysis Molecular Biology Gene Phylogeny 030304 developmental biology Synteny Biological Products 0303 health sciences Phylogenetic tree Microbiota Strain (biology) 030302 biochemistry & molecular biology Computational Biology Reproducibility of Results Genomics Cell Biology Biosystematiek Biosynthetic Pathways Actinobacteria Workflow Multigene Family Biosystematics EPS Algorithms Genome Bacterial Software |
| Zdroj: | Nature chemical biology Nature Chemical Biology, 16(1), 60-+. Nature Publishing Group Nature Chemical Biology 16 (2019) Nature Chemical Biology, 16, 60-68 |
| ISSN: | 1552-4450 |
| Popis: | Genome mining has become a key technology to exploit natural product diversity. Although initially performed on a single-genome basis, the process is now being scaled up to mine entire genera, strain collections and microbiomes. However, no bioinformatic framework is currently available for effectively analyzing datasets of this size and complexity. In the present study, a streamlined computational workflow is provided, consisting of two new software tools: the ‘biosynthetic gene similarity clustering and prospecting engine’ (BiG-SCAPE), which facilitates fast and interactive sequence similarity network analysis of biosynthetic gene clusters and gene cluster families; and the ‘core analysis of syntenic orthologues to prioritize natural product gene clusters’ (CORASON), which elucidates phylogenetic relationships within and across these families. BiG-SCAPE is validated by correlating its output to metabolomic data across 363 actinobacterial strains and the discovery potential of CORASON is demonstrated by comprehensively mapping biosynthetic diversity across a range of detoxin/rimosamide-related gene cluster families, culminating in the characterization of seven detoxin analogues. Two bioinformatic tools, BiG-SCAPE and CORASON, enable sequence similarity network and phylogenetic analysis of gene clusters and their families across hundreds of strains and in large datasets, leading to the discovery of new natural products. |
| Databáze: | OpenAIRE |
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