Directional integration and pathway enrichment analysis for multi-omics data

Mykhaylo Slobodyanyuk, Alexander T. Bahcheli, Zoe P. Klein, Masroor Bayati, Lisa J. Strug and Jüri Reimand ()
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Mykhaylo Slobodyanyuk: 661 University Ave Suite 510
Alexander T. Bahcheli: 661 University Ave Suite 510
Zoe P. Klein: 661 University Ave Suite 510
Masroor Bayati: 661 University Ave Suite 510
Lisa J. Strug: the Hospital for Sick Children Research Institute
Jüri Reimand: 661 University Ave Suite 510

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Omics techniques generate comprehensive profiles of biomolecules in cells and tissues. However, a holistic understanding of underlying systems requires joint analyses of multiple data modalities. We present DPM, a data fusion method for integrating omics datasets using directionality and significance estimates of genes, transcripts, or proteins. DPM allows users to define how the input datasets are expected to interact directionally given the experimental design or biological relationships between the datasets. DPM prioritises genes and pathways that change consistently across the datasets and penalises those with inconsistent directionality. To demonstrate our approach, we characterise gene and pathway regulation in IDH-mutant gliomas by jointly analysing transcriptomic, proteomic, and DNA methylation datasets. Directional integration of survival information in ovarian cancer reveals candidate biomarkers with consistent prognostic signals in transcript and protein expression. DPM is a general and adaptable framework for gene prioritisation and pathway analysis in multi-omics datasets.

Date: 2024
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DOI: 10.1038/s41467-024-49986-4

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