Identifying functional metabolic shifts in heart failure with the integration of omics data and a heart-specific, genome-scale model
| Autor: | Kalyan C. Vinnakota, Glynis L. Kolling, Bonnie V. Dougherty, Kristopher D. Rawls, Jason A. Papin, Anders Wallqvist |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genome scale Metabolic network heart failure Computational biology Biology Models Biological Severity of Illness Index GENRE General Biochemistry Genetics and Molecular Biology Nitric oxide Transcriptome 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Metabolomics nitric oxide metabolic network Gene expression medicine Humans Databases Protein lcsh:QH301-705.5 Heart metabolism Myocardium medicine.disease 030104 developmental biology chemistry lcsh:Biology (General) Heart failure heart metabolism sense organs N-acetylneuraminic acid 030217 neurology & neurosurgery Metabolic Networks and Pathways |
| Zdroj: | Cell Reports, Vol 34, Iss 10, Pp 108836-(2021) |
| ISSN: | 2211-1247 |
| Popis: | Summary In diseased states, the heart can shift to use different carbon substrates, measured through changes in uptake of metabolites by imaging methods or blood metabolomics. However, it is not known whether these measured changes are a result of transcriptional changes or external factors. Here, we explore transcriptional changes in late-stage heart failure using publicly available data integrated with a model of heart metabolism. First, we present a heart-specific genome-scale metabolic network reconstruction (GENRE), iCardio. Next, we demonstrate the utility of iCardio in interpreting heart failure gene expression data by identifying tasks inferred from differential expression (TIDEs), which represent metabolic functions associated with changes in gene expression. We identify decreased gene expression for nitric oxide (NO) and N-acetylneuraminic acid (Neu5Ac) synthesis as common metabolic markers of heart failure. The methods presented here for constructing a tissue-specific model and identifying TIDEs can be extended to multiple tissues and diseases of interest. |
| Databáze: | OpenAIRE |
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