Soldatou, S. | bioRxiv Science

bioRxiv2022

FERMO: a Dashboard for Streamlined Rationalized Prioritization of Molecular Features from Mass Spectrometry Data

Small molecules shape phenotypic variation by modulating biological processes, yet linking specific molecules to observed traits remains challenging due to the complexity of biological samples. Liquid chromatography-tandem mass spectrometry routinely detects hundreds of molecules per sample, and computational tools aid in the selection of the biologically relevant subset by organizing, annotating, and integrating orthogonal data. Existing tools typically focus on facilitating data-driven exploration to support manual interpretation, rather than more objective, data-driven prioritization and hypothesis-generation. Here, we introduce FERMO, a free online dashboard interface for prioritization of molecular features and samples associated with phenotypes of interest. FERMOs modular framework automates data processing, annotation, and integration of standardized phenotypic and other metadata. FERMO supports both exploratory and targeted analysis through efficient interactive visualization, reproducible prioritization, and data filtering. We demonstrate FERMOs utility in benchmarking studies prioritizing bioactive compounds from complex biological matrices. FERMO is freely available at https://fermo.bioinformatics.nl/.

bioinformatics↗

bioRxiv2020

Ranking microbial metabolomic and genomic links using correlation-based and feature-based scoring functions

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. Author summaryIn this article, we introduce NPLinker, a software framework to link genomic and metabolomic data, to link microbial secondary metabolites to their producing genomic regions. Two of the major approaches for such linking are analysis of the correlation between sets of strains, and analysis of predicted features of the molecules. While these methods are usually used separately, we demonstrate that they are in fact complementary, and show a way to combine them to improve their performance. We begin by demonstrating a weakness in the most common method of strain correlation analysis, and suggest an improvement. We then introduce a new feature-based analysis method which, unlike most such methods, does not directly depend on the natural prodcut compound class. Finally, we demonstrate that the two are complementary and proceed to combine them into a single scoring function for genomic and metabolomic links, which shows improved performance over either of the individual approaches. Verification is done using curated databases of genomic and metabolomic data, as well as public data sets of microbial data including verified links.

systems biology↗