Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases

MicrobLiver consortium, GALAXY consortium, Maja Thiele, Ida Falk Villesen, Lili Niu, Stine Johansen, Karolina Sulek, Suguru Nishijima, Lore Van Espen, Marisa Keller, Mads Israelsen, Tommi Suvitaival, Andressa de Zawadzki, Helene Bæk Juel, Maximilian Joseph Brol, Sara Elizabeth Stinson, Yun Huang, Maria Camilla Alvarez Silva, Michael Kuhn, Ema AnastasiadouDiana Julie Leeming, Morten Karsdal, Jelle Matthijnssens, Manimozhiyan Arumugam, Louise Torp Dalgaard, Cristina Legido-Quigley, Matthias Mann, Jonel Trebicka, Peer Bork, Lars Juhl Jensen, Torben Hansen, Aleksander Krag*

*Corresponding author for this work

Research output: Contribution to journalReviewpeer-review

Abstract

The rising prevalence of liver diseases related to obesity and excessive use of alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis of steatohepatitis and significant fibrosis, monitoring, prognostication and prediction of treatment efficacy. Breakthroughs in omics methodologies and the power of bioinformatics have created an excellent opportunity to apply technological advances to clinical needs, for instance in the development of precision biomarkers for personalised medicine. Via omics technologies, biological processes from the genes to circulating protein, as well as the microbiome – including bacteria, viruses and fungi, can be investigated on an axis. However, there are important barriers to omics-based biomarker discovery and validation, including the use of semi-quantitative measurements from untargeted platforms, which may exhibit high analytical, inter- and intra-individual variance. Standardising methods and the need to validate them across diverse populations presents a challenge, partly due to disease complexity and the dynamic nature of biomarker expression at different disease stages. Lack of validity causes lost opportunities when studies fail to provide the knowledge needed for regulatory approvals, all of which contributes to a delayed translation of these discoveries into clinical practice. While no omics-based biomarkers have matured to clinical implementation, the extent of data generated has enabled the hypothesis-free discovery of a plethora of candidate biomarkers that warrant further validation. To explore the many opportunities of omics technologies, hepatologists need detailed knowledge of commonalities and differences between the various omics layers, and both the barriers to and advantages of these approaches.
Original languageEnglish
JournalJournal of Hepatology
Volume81
Issue number2
Pages (from-to)345-359
Number of pages15
ISSN0168-8278
DOIs
Publication statusPublished - Aug 2024

Bibliographical note

Funding Information:
This project has received funding from the GALAXY project from the European Union's Horizon 2020 research and innovation programme under grant agreement number 668031; and from Challenge Grant \u201CMicrobLiver\u201D grant number NNF15OC0016692 from the Novo Nordisk Foundation. LVE is funded by the Fonds Wetenschappelijk Onderzoek (FWO) Vlaanderen (grant number: 1S25720N). MT is funded by a grant from the Novo Nordisk Foundation (NNF20OC0059393). KS is supported by the Novo Nordisk Foundation Excellence Emerging Investigator Grant \u2013 Endocrinology and Metabolism 2022 (grant no. NNF 0074491). LTD is funded by grants from the Novo Nordisk Foundation (NNF22OC0078203 and NNF23OC0081177). JT was supported by the German Research Foundation (DFG) project ID 403224013 \u2013 SFB 1382 (A09), by the German Federal Ministry of Education and Research (BMBF) for the DEEP-HCC project and by the Hessian Ministry of Higher Education, Research and the Arts (HMWK) for the ENABLE and ACLF-I cluster projects. The MICROB-PREDICT (project ID 825694), DECISION (project ID 847949), GALAXY (project ID 668031), LIVERHOPE (project ID 731875) and IHMCSA (project ID 964590) projects have received funding from the European Union's Horizon 2020 research and innovation programme. LJJ is funded by the Novo Nordisk Foundation (NNF14CC0001). The manuscript reflects only the authors\u2019 views, and the European Commission is not responsible for any use that may be made of the information it contains. The funders had no influence on literature used, preparation of the manuscript or where to publish.

Keywords

  • genetics
  • lipidomics
  • metabolomics
  • metagenomics
  • metatranscriptomics
  • microbiome
  • Non-invasive test
  • proteomics
  • viromics

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