Estimates of gene ensemble noise highlight critical pathways and predict disease severity in H1N1, COVID-19 and mortality in sepsis patients

Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expressi...

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Bibliographic Details
Published in:Scientific reports 2021-05, Vol.11 (1), p.10793-10793, Article 10793
Main Authors: de Jong, Tristan V., Guryev, Victor, Moshkin, Yuri M.
Format: Article
Language:English
Subjects:
631/1647/2017
631/1647/48
631/1647/767/2201
692/53/2422
692/53/2423
Coronaviruses
COVID-19
Electron transport chain
Gene expression
Humanities and Social Sciences
Mitochondria
Molecular modelling
Mortality
multidisciplinary
Oxidative stress
Pathology
Peroxisomes
Science
Science (multidisciplinary)
Sepsis
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Summary:Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative approach that could be applied to dissect the disease-associated molecular changes. We define gene ensemble noise as a measure that represents a variance for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes and calculated within an individual. The gene ensemble noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. By comparing gene expression data from COVID-19, H1N1, and sepsis patients we identified common disturbances in a number of pathways and protein complexes relevant to the sepsis pathology. Among others, these include the mitochondrial respiratory chain complex I and peroxisomes. This suggests a Warburg effect and oxidative stress as common hallmarks of the immune host–pathogen response. Finally, we showed that gene ensemble noise could successfully be applied for the prediction of clinical outcome namely, the mortality of patients. Thus, we conclude that gene ensemble noise represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of alterations in the coherent expression of gene circuits.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-90192-9