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Systems analysis of dilated cardiomyopathy in the next generation sequencing era

Harakalova, M; Asselbergs, FW; (2018) Systems analysis of dilated cardiomyopathy in the next generation sequencing era. Wiley Interdisciplinary Reviews: Systems Biology and Medicine , 10 (4) , Article e1419. 10.1002/wsbm.1419. Green open access

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Abstract

Dilated cardiomyopathy (DCM) is a form of severe failure of cardiac muscle caused by a long list of etiologies ranging from myocardial infarction, DNA mutations in cardiac genes, to toxics. Systems analysis integrating next‐generation sequencing (NGS)‐based omics approaches, such as the sequencing of DNA, RNA, and chromatin, provide valuable insights into DCM mechanisms. The outcome and interpretation of NGS methods can be affected by the localization of cardiac biopsy, level of tissue degradation, and variable ratios of different cell populations, especially in the presence of fibrosis. Heart tissue composition may even differ between sexes, or siblings carrying the same disease causing mutation. Therefore, before planning any experiments, it is important to fully appreciate the complexities of DCM, and the selection of samples suitable for given research question should be an interdisciplinary effort involving clinicians and biologists. The list of NGS omics datasets in DCM to date is short. More studies have to be performed to contribute to public data repositories and facilitate systems analysis. In addition, proper data integration is a difficult task requiring complex computational approaches. Despite these complications, there are multiple promising implications of systems analysis in DCM. By combining various types of datasets, for example, RNA‐seq, ChIP‐seq, or 4C, deep insights into cardiac biology, and possible biomarkers and treatment targets, can be gained. Systems analysis can also facilitate the annotation of noncoding mutations in cardiac‐specific DNA regulatory regions that play a substantial role in maintaining the tissue‐ and cell‐specific transcriptional programs in the heart.

Type: Article
Title: Systems analysis of dilated cardiomyopathy in the next generation sequencing era
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/wsbm.1419
Publisher version: http://doi.org/10.1002/wsbm.1419
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: chromatin, dilated cardiomyopathy, DNA, next generation sequencing, omics, RNA, systems analysis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
URI: https://discovery.ucl.ac.uk/id/eprint/10068123
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