Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Koh HWL

PROVIDER: S-EPMC6616462 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

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

Koh Hiromi W L HWL Fermin Damian D Vogel Christine C Choi Kwok Pui KP Ewing Rob M RM Choi Hyungwon H

NPJ systems biology and applications 20190709

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 ...[more]

PMID: 31312515

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Project description:Untargeted mass spectrometry (MS)-based proteomics provides a powerful platform for protein biomarker discovery, but clinical translation depends on the selection of a small number of proteins for downstream verification and validation. Due to the small sample size of typical discovery studies, protein markers identified from discovery data may not be generalizable to independent datasets. In addition, a good protein marker identified using a discovery platform may be difficult to implement in verification and validation platforms. Moreover, although multiomics characterization is being increasingly used in discovery cohort studies, there is no existing method for multiomics-facilitated protein biomarker selection. Here, we present ProMS, a computational algorithm for protein marker selection. The algorithm is based on the hypothesis that a phenotype is characterized by a few underlying biological functions, each manifested by a group of coexpressed proteins. A weighted k-medoids clustering algorithm is applied to all univariately informative proteins to identify both coexpressed protein clusters and a representative protein for each cluster as markers. In two clinically important classification problems, ProMS shows superior performance compared with existing feature selection methods. ProMS can be extended to the multiomics setting (ProMS_mo) through a constrained weighted k-medoids clustering algorithm, and the protein panels selected by ProMS_mo show improved performance on independent test data compared with ProMS. In addition to superior performance, ProMS and ProMS_mo also have two unique strengths. First, the feature clusters enable functional interpretation of the selected protein markers. Second, the feature clusters provide an opportunity to select replacement protein markers, facilitating a robust transition to the verification and validation platforms. In summary, this study provides a unified and effective computational framework for selecting protein biomarkers using proteomics or multiomics data. The software implementation is publicly available at https://github.com/bzhanglab/proms.

Dataset Information

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

Publications

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

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