Correlation guided Network Integration (CoNI) reveals novel genes affecting hepatic metabolism

Abstract

Objective Technological advances have brought a steady increase in the availability of various types of omics data, from genomics to metabolomics. Integrating these multi-omics data is a chance and challenge for systems biology; yet, tools to fully tap their potential remain scarce. Methods We present here a fully unsupervised and versatile correlation-based method – termed Correlation guided Network Integration (CoNI) – to integrate multi-omics data into a hypergraph structure that allows for the identification of effective modulators of metabolism. Our approach yields single transcripts of potential relevance that map to specific, densely connected, metabolic subgraphs or pathways. Results By applying our method on transcriptomics and metabolomics data from murine livers under standard Chow or high-fat diet, we identified eleven genes with potential regulatory effects on hepatic metabolism. Five candidates, including the hepatokine INHBE, were validated in human liver biopsies to correlate with diabetes-related traits such as overweight, hepatic fat content, and insulin resistance (HOMA-IR). Conclusion Our method's successful application to an independent omics dataset confirmed that the novel CoNI framework is a transferable, entirely data-driven, flexible, and versatile tool for multiple omics data integration and interpretation.

Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity

“…10 ). While we cannot exclude the possibility that the differences in the age of the monkeys contribute to expression differences, our observations are consistent with previous reports of elevated INHBE expression in conditions of insulin resistance 34 , 35 .…”

“…Notably, several non-genetic studies implicate INHBE in metabolic dysfunction. Two studies report a correlation between increased expression of INHBE and insulin resistance in both humans and mice 34 , 35 . Here, we observed higher expression of INHBE in the livers of obese monkeys compared to lean monkeys providing further support for this.…”

Discussion on Redundant Processing Algorithm of Association Rules Based on Hypergraph in Data Mining

“…e Internet, the Internet of ings, cloud computing, and other information technologies are constantly updated, and they are constantly integrated with the human world in various fields such as economy, politics, military, scientific research, and life [6]. Information visualization is the use of images to express information clearly and effectively.…”

Correlation-guided Network Integration (CoNI), an R package for integrating numerical omics data that allows multiform graph representations to study molecular interaction networks

“…Next, we perform significance testing comparing the difference between and applying Steiger test ( Steiger, 1980 ). When we have a significant difference between and , we consider a confounder for the vertex pairs ( Klaus et al , 2021 ). Finally, we construct a network with nodes as the correlated features of and the edges as the identified confounding variables from .…”

“…To this end, we developed Correlation-guided Network Integration (CoNI) ( Klaus et al , 2021 ), an unsupervised data-driven correlation-based tool to uncover potential interactions between features and how they are regulated between different molecular regimes. The inferred interactions and estimated regulatory variables are represented in a graph structure that allows for multiform representation.…”