Integration of Meta-Multi-Omics Data Using Probabilistic Graphs and External Knowledge

Cells. 2023 Aug 4;12(15):1998. doi: 10.3390/cells12151998.

Abstract

Multi-omics has the promise to provide a detailed molecular picture of biological systems. Although obtaining multi-omics data is relatively easy, methods that analyze such data have been lagging. In this paper, we present an algorithm that uses probabilistic graph representations and external knowledge to perform optimal structure learning and deduce a multifarious interaction network for multi-omics data from a bacterial community. Kefir grain, a microbial community that ferments milk and creates kefir, represents a self-renewing, stable, natural microbial community. Kefir has been shown to have a wide range of health benefits. We obtained a controlled bacterial community using the two most abundant and well-studied species in kefir grains: Lentilactobacillus kefiri and Lactobacillus kefiranofaciens. We applied growth temperatures of 30 °C and 37 °C and obtained transcriptomic, metabolomic, and proteomic data for the same 20 samples (10 samples per temperature). We obtained a multi-omics interaction network, which generated insights that would not have been possible with single-omics analysis. We identified interactions among transcripts, proteins, and metabolites, suggesting active toxin/antitoxin systems. We also observed multifarious interactions that involved the shikimate pathway. These observations helped explain bacterial adaptation to different stress conditions, co-aggregation, and increased activation of L. kefiranofaciens at 37 °C.

Keywords: Bayesian networks; Lactobacillus kefiranofaciens; Lentilactobacillus kefiri; kefir; multi-omics.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / genetics
  • Cultured Milk Products* / microbiology
  • Multiomics
  • Proteomics

Substances

  • shikimate

Grants and funding

This research was funded by the University of Nebraska Foundation, the Jane Robertson Layman Fund and the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) Hatch project [1015890]. The Proteomics & Metabolomics Facility (RRID:SCR_021314) and instrumentation are supported by the Nebraska Research Initiative.