Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach
Abstract Heart failure is a heterogeneous disease with multiple risk factors and various pathophysiological types, which makes it difficult to understand the molecular mechanisms involved. In this study, we proposed a trans-omics approach for predicting molecular pathological mechanisms of heart fai...
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2021-04-01
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doaj-a8044467d1be4acda25dd41642b4d56d2021-04-18T11:35:44ZengNature Publishing GroupScientific Reports2045-23222021-04-0111111710.1038/s41598-021-86821-yPrediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approachMomoko Hamano0Seitaro Nomura1Midori Iida2Issei Komuro3Yoshihiro Yamanishi4Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of TechnologyDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of TokyoDepartment of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of TechnologyDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of TokyoDepartment of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of TechnologyAbstract Heart failure is a heterogeneous disease with multiple risk factors and various pathophysiological types, which makes it difficult to understand the molecular mechanisms involved. In this study, we proposed a trans-omics approach for predicting molecular pathological mechanisms of heart failure and identifying marker genes to distinguish heterogeneous phenotypes, by integrating multiple omics data including single-cell RNA-seq, ChIP-seq, and gene interactome data. We detected a significant increase in the expression level of natriuretic peptide A (Nppa), after stress loading with transverse aortic constriction (TAC), and showed that cardiomyocytes with high Nppa expression displayed specific gene expression patterns. Multiple NADH ubiquinone complex family, which are associated with the mitochondrial electron transport system, were negatively correlated with Nppa expression during the early stages of cardiac hypertrophy. Large-scale ChIP-seq data analysis showed that Nkx2-5 and Gtf2b were transcription factors characteristic of high-Nppa-expressing cardiomyocytes. Nppa expression levels may, therefore, represent a useful diagnostic marker for heart failure.https://doi.org/10.1038/s41598-021-86821-y |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Momoko Hamano Seitaro Nomura Midori Iida Issei Komuro Yoshihiro Yamanishi |
spellingShingle |
Momoko Hamano Seitaro Nomura Midori Iida Issei Komuro Yoshihiro Yamanishi Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach Scientific Reports |
author_facet |
Momoko Hamano Seitaro Nomura Midori Iida Issei Komuro Yoshihiro Yamanishi |
author_sort |
Momoko Hamano |
title |
Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach |
title_short |
Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach |
title_full |
Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach |
title_fullStr |
Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach |
title_full_unstemmed |
Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach |
title_sort |
prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-04-01 |
description |
Abstract Heart failure is a heterogeneous disease with multiple risk factors and various pathophysiological types, which makes it difficult to understand the molecular mechanisms involved. In this study, we proposed a trans-omics approach for predicting molecular pathological mechanisms of heart failure and identifying marker genes to distinguish heterogeneous phenotypes, by integrating multiple omics data including single-cell RNA-seq, ChIP-seq, and gene interactome data. We detected a significant increase in the expression level of natriuretic peptide A (Nppa), after stress loading with transverse aortic constriction (TAC), and showed that cardiomyocytes with high Nppa expression displayed specific gene expression patterns. Multiple NADH ubiquinone complex family, which are associated with the mitochondrial electron transport system, were negatively correlated with Nppa expression during the early stages of cardiac hypertrophy. Large-scale ChIP-seq data analysis showed that Nkx2-5 and Gtf2b were transcription factors characteristic of high-Nppa-expressing cardiomyocytes. Nppa expression levels may, therefore, represent a useful diagnostic marker for heart failure. |
url |
https://doi.org/10.1038/s41598-021-86821-y |
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