Display options
Cite
Esmaili S, Langfelder P, Belgard TG, et al. Core liver homeostatic co-expression networks are preserved but respond to perturbations in an organism- and disease-specific manner. Cell Syst. 2021;12(5):432-445.e7doi: 10.1016/j.cels.2021.04.004.
Esmaili, S., Langfelder, P., Belgard, T. G., Vitale, D., Azardaryany, M. K., Alipour Talesh, G., Ramezani-Moghadam, M., Ho, V., Dvorkin, D., Dervish, S., Gloss, B. S., Grønbæk, H., Liddle, C., & George, J. (2021). Core liver homeostatic co-expression networks are preserved but respond to perturbations in an organism- and disease-specific manner. Cell systems, 12(5), 432-445.e7. https://doi.org/10.1016/j.cels.2021.04.004
Esmaili, Saeed, et al. "Core liver homeostatic co-expression networks are preserved but respond to perturbations in an organism- and disease-specific manner." Cell systems vol. 12,5 (2021): 432-445.e7. doi: https://doi.org/10.1016/j.cels.2021.04.004
Esmaili S, Langfelder P, Belgard TG, Vitale D, Azardaryany MK, Alipour Talesh G, Ramezani-Moghadam M, Ho V, Dvorkin D, Dervish S, Gloss BS, Grønbæk H, Liddle C, George J. Core liver homeostatic co-expression networks are preserved but respond to perturbations in an organism- and disease-specific manner. Cell Syst. 2021 May 19;12(5):432-445.e7. doi: 10.1016/j.cels.2021.04.004. Epub 2021 May 05. PMID: 33957084.
Copy Download .nbib Format: NLM
Share it on

Cell Syst. 2021 May 19;12(5):432-445.e7. doi: 10.1016/j.cels.2021.04.004. Epub 2021 May 05.

Core liver homeostatic co-expression networks are preserved but respond to perturbations in an organism- and disease-specific manner.

Cell systems

Saeed Esmaili, Peter Langfelder, T Grant Belgard, Daniele Vitale, Mahmoud Karimi Azardaryany, Ghazal Alipour Talesh, Mehdi Ramezani-Moghadam, Vikki Ho, Daniel Dvorkin, Suat Dervish, Brian S Gloss, Henning Grønbæk, Christopher Liddle, Jacob George

Affiliations

  1. Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia; Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
  2. The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA.
  3. The Bioinformatics CRO, Niceville, FL, USA.
  4. Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.
  5. Westmead Research Hub, Westmead Institute for Medical Research, Sydney, NSW, Australia.
  6. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
  7. Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia. Electronic address: [email protected].

PMID: 33957084 DOI: 10.1016/j.cels.2021.04.004

Abstract

Findings about chronic complex diseases are difficult to extrapolate from animal models to humans. We reason that organs may have core network modules that are preserved between species and are predictably altered when homeostasis is disrupted. To test this idea, we perturbed hepatic homeostasis in mice by dietary challenge and compared the liver transcriptome with that in human fatty liver disease and liver cancer. Co-expression module preservation analysis pointed to alterations in immune responses and metabolism (core modules) in both human and mouse datasets. The extent of derailment in core modules was predictive of survival in the cancer genome atlas (TCGA) liver cancer dataset. We identified module eigengene quantitative trait loci (module-eQTL) for these predictive co-expression modules, targeting of which may resolve homeostatic perturbations and improve patient outcomes. The framework presented can be used to understand homeostasis at systems levels in pre-clinical models and in humans. A record of this paper's transparent peer review process is included in the supplemental information.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: MAFLD; WGCNA; core modules; homeostatic networks; human fatty liver; liver cancer; metabolic (dysfunction) associated fatty liver disease; module_eQTL; weighted gene co-expression network analysis

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Publication Types