Defining NASH from a Multi-Omics Systems Biology Perspective

Abstract

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease affecting up to 6.5% of the general population. There is no simple definition of NASH, and the molecular mechanism underlying disease pathogenesis remains elusive. Studies applying single omics technologies have enabled a better understanding of the molecular profiles associated with steatosis and hepatic inflammation—the commonly accepted histologic features for diagnosing NASH, as well as the discovery of novel candidate biomarkers. Multi-omics analysis holds great potential to uncover new insights into disease mechanism through integrating multiple layers of molecular information. Despite the technical and computational challenges associated with such efforts, a few pioneering studies have successfully applied multi-omics technologies to investigate NASH. Here, we review the most recent technological developments in mass spectrometry (MS)-based proteomics, metabolomics, and lipidomics. We summarize multi-omics studies and emerging omics biomarkers in NASH and highlight the biological insights gained through these integrated analyses.

Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches

“…In the era of non-invasive biomarker discovery, omics is a promising revolutionary approach, as it provides the benefit of a large-scale analysis of patients’ samples [ 317 ]. The advancement in omics technology has allowed the identification of promising novel biomarkers in a hypothesis-free approach [ 134 ].…”

“…In addition, machine-learning-based-methodologies are constantly evolving to discover multi-omics marker panels and explore their diagnostic accuracy [ 134 ]. Pioneering studies are now investigating the integration of multi-omics data with clinical characteristics to build multi-component classifiers for diagnosing NAFLD [ 317 , 318 ]. Zhou et al developed the NASH ClinLipMet Score, including PNPLA3 genotype, metabolomics and lipidomics data, as well as clinical variables [ 318 ].…”

Screening Potential Drugs for the Development of NAFLD Based on Drug Perturbation Gene Set

“…The current research is only for the known signal pathways and the ways and technical means that can be intervened. The development of multiple omics technology, genetics, proteomics, genomics, and metabolomics will help us have a better understanding of the development of NAFLD [ 32 ].…”

Opportunities for Systems Biology and Quantitative Systems Pharmacology to Address Knowledge Gaps for Drug Development in Pregnancy

“…Examples of how these advances have made a difference include identification of new targets in the field of cancer immunotherapy and identification of targets to overcome resistance against tuberculosis drug combinations. 34 Systems biology platforms are now actively applied in the search for new therapeutics for nonalcoholic steatohepatitis and long COVID (following infection with the COVID-19 virus, some people continue to experience health problems long after having COVID-19) and are expected to play an important role in the advancement of novel medicines for neurodegenerative diseases 35,36 given the neurologic component of both disease trajectories. In a similar way, computational and systems biology has the potential to advance our understanding of the tissue-and cell-specific changes that occur during different stages of pregnancy, for example, providing a broader and more in-depth understanding of lipid and metabolic changes, and predicting how these underlying changes in metabolism can impact drug efficacy or drug metabolism.…”