PaintOmics 4: new tools for the integrative analysis of multi-omics datasets supported by multiple pathway databases

PaintOmics is a web server for the integrative analysis and visualisation of multi-omics datasets using biological pathway maps. PaintOmics 4 has several notable updates that improve and extend analyses. Three pathway databases are now supported: KEGG, Reactome and MapMan, providing more comprehensive pathway knowledge for animals and plants. New metabolite analysis methods fill gaps in traditional pathway-based enrichment methods. The metabolite hub analysis selects compounds with a high number of significant genes in their neighbouring network, suggesting regulation by gene expression changes. The metabolite class activity analysis tests the hypothesis that a metabolic class has a higher-than-expected proportion of significant elements, indicating that these compounds are regulated in the experiment. Finally, PaintOmics 4 includes a regulatory omics module to analyse the contribution of trans-regulatory layers (microRNA and transcription factors, RNA-binding proteins) to regulate pathways. We show the performance of PaintOmics 4 on both mouse and plant data to highlight how these new analysis features provide novel insights into regulatory biology. PaintOmics 4 is available at https://paintomics.org/.Spanish Ministry of Science and Innovation [BIO2015-1658-R and PID2020-119537RB-100 to A.C. and S.T.]; National Institutes of Health [R03 CA222444 to A.C. and L.M.M.]; Slovene Research Agency Program [P4-0165]; European Union’s Horizon 2020 [GA 2020 862-858]; COST Action CA15110 STSM travel grant supported by European Cooperation in Science and Technology; Generalitat Valenciana [ACIF2019/081 to P.S.]. Spanish Ministry of Science and Innovation.Funding for open access charge: Spanish Ministry of Science and Innovation [PID2020-119537RB-100].Peer reviewe