Ranking microbial metabolomic and genomic links in the NPLinker framework using complementary scoring functions.

Eldj�rn, Gr�mur Hj�rleifsson; Ramsay, Andrew; van der Hooft, Justin J.J.; Duncan, Katherine R.; Soldatou, Sylvia; Rousu, Juho; Daly, R�n�n; Wandy, Joe; Rogers, Simon

Abstract

Specialised metabolites from microbial sources are well-known for their wide range of biomedical applications, particularly as antibiotics. When mining paired genomic and metabolomic data sets for novel specialised metabolites, establishing links between Biosynthetic Gene Clusters (BGCs) and metabolites represents a promising way of finding such novel chemistry. However, due to the lack of detailed biosynthetic knowledge for the majority of predicted BGCs, and the large number of possible combinations, this is not a simple task. This problem is becoming ever more pressing with the increased availability of paired omics data sets. Current tools are not effective at identifying valid links automatically, and manual verification is a considerable bottleneck in natural product research. We demonstrate that using multiple link-scoring functions together makes it easier to prioritise true links relative to others. Based on standardising a commonly used score, we introduce a new, more effective score, and introduce a novel score using an Input-Output Kernel Regression approach. Finally, we present NPLinker, a software framework to link genomic and metabolomic data. Results are verified using publicly available data sets that include validated links.

Citation

ELDJÁRN, G.H., RAMSAY, A., VAN DER HOOFT, J.J.J., DUNCAN, K.R., SOLDATOU, S., ROUSU, J., DALY, J., WANDY, J. and ROGERS, S. 2021. Ranking microbial metabolomic and genomic links in the NPLinker framework using complementary scoring functions. PLOS computational biology [online], 17(5), e1008920. Available from: https://doi.org/10.1371/journal.pcbi.1008920

• Journal Article Type: Article
• Acceptance Date: Mar 26, 2021
• Online Publication Date: May 4, 2021
• Publication Date: May 31, 2021
• Deposit Date: May 31, 2021
• Publicly Available Date: May 31, 2021
• Journal: PLOS Computational Biology
• Print ISSN: 1553-734X
• Electronic ISSN: 1553-7358
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 5
• Article Number: e1008920
• DOI: https://doi.org/10.1371/journal.pcbi.1008920
• Keywords: Ecology; Modelling and simulation; Computational theory and mathematics; Genetics; Ecology, evolution, behavior and systematics; Molecular biology; Cellular and molecular neuroscience
• Public URL: https://rgu-repository.worktribe.com/output/1347280
• Related Public URLs: https://rgu-repository.worktribe.com/output/1347302