Inferencing Bulk Tumor and Single-Cell Multi-Omics Regulatory Networks for Discovery of Biomarkers and Therapeutic Targets

Cells. 2022 Dec 26;12(1):101. doi: 10.3390/cells12010101.

Abstract

There are insufficient accurate biomarkers and effective therapeutic targets in current cancer treatment. Multi-omics regulatory networks in patient bulk tumors and single cells can shed light on molecular disease mechanisms. Integration of multi-omics data with large-scale patient electronic medical records (EMRs) can lead to the discovery of biomarkers and therapeutic targets. In this review, multi-omics data harmonization methods were introduced, and common approaches to molecular network inference were summarized. Our Prediction Logic Boolean Implication Networks (PLBINs) have advantages over other methods in constructing genome-scale multi-omics networks in bulk tumors and single cells in terms of computational efficiency, scalability, and accuracy. Based on the constructed multi-modal regulatory networks, graph theory network centrality metrics can be used in the prioritization of candidates for discovering biomarkers and therapeutic targets. Our approach to integrating multi-omics profiles in a patient cohort with large-scale patient EMRs such as the SEER-Medicare cancer registry combined with extensive external validation can identify potential biomarkers applicable in large patient populations. These methodologies form a conceptually innovative framework to analyze various available information from research laboratories and healthcare systems, accelerating the discovery of biomarkers and therapeutic targets to ultimately improve cancer patient survival outcomes.

Keywords: Prediction Logic Boolean Implication Networks (PLBINs); SEER-Medicare; biomarkers; electronic medical records (EMRs); multi-omics regulatory networks; network centrality; single cells; therapeutic targets.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers
  • Genome
  • Humans
  • Medicare
  • Multiomics*
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • United States

Substances

  • Biomarkers