iOmicsPASS: network-based integration of multiomics data for predictive subnetwork discovery

• Published in: NPJ systems biology and applications Vol. 5; no. 1; pp. 22 - 10
• Main Authors: Koh, Hiromi W. L., Fermin, Damian, Vogel, Christine, Choi, Kwok Pui, Ewing, Rob M., Choi, Hyungwon
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.07.2019; Nature Publishing Group
• Subjects: 631/114; 631/553; Algorithms; Bioinformatics; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - genetics; Computational Biology - methods; Computational Biology/Bioinformatics; Computer Appl. in Life Sciences; Computer applications; Datasets; Gene Expression Profiling - methods; Gene Expression Regulation - genetics; Gene Regulatory Networks - genetics; Genomes; Genomics - methods; Humans; Integration; Life Sciences; Mathematical models; Models, Statistical; Models, Theoretical; Phenotypic variations; Protein Interaction Mapping - methods; Proteomics - methods; Software; Systems Biology; Technology Feature; Transcription; Systems biology; Computational biology and bioinformatics
• DOI: 10.1038/s41540-019-0099-y
• ISSN: 2056-7189

Computational tools for multiomics data integration have usually been designed for unsupervised detection of multiomics features explaining large phenotypic variations. To achieve this, some approaches extract latent signals in heterogeneous data sets from a joint statistical error model, while others use biological networks to propagate differential expression signals and find consensus signatures. However, few approaches directly consider molecular interaction as a data feature, the essential linker between different omics data sets. The increasing availability of genome-scale interactome data connecting different molecular levels motivates a new class of methods to extract interactive signals from multiomics data. Here we developed iOmicsPASS, a tool to search for predictive subnetworks consisting of molecular interactions within and between related omics data types in a supervised analysis setting. Based on user-provided network data and relevant omics data sets, iOmicsPASS computes a score for each molecular interaction, and applies a modified nearest shrunken centroid algorithm to the scores to select densely connected subnetworks that can accurately predict each phenotypic group. iOmicsPASS detects a sparse set of predictive molecular interactions without loss of prediction accuracy compared to alternative methods, and the selected network signature immediately provides mechanistic interpretation of the multiomics profile representing each sample group. Extensive simulation studies demonstrate clear benefit of interaction-level modeling. iOmicsPASS analysis of TCGA/CPTAC breast cancer data also highlights new transcriptional regulatory network underlying the basal-like subtype as positive protein markers, a result not seen through analysis of individual omics data.