Djordjevic, Djordje and Deshpande, Vinita and Szczesnik, Tomasz and Yang, Andrian and Humphreys, David T and Giannoulatou, Eleni and Ho, Joshua W K (2015) Decoding the complex genetic causes of heart diseases using systems biology. Biophys Rev, 7. pp.141-159. ISSN (PP OA)
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Abstract
The pace of disease gene discovery is still much
slower than expected, even with the use of cost-effective DNA
sequencing and genotyping technologies. It is increasingly
clear that many inherited heart diseases have a more complex
polygenic aetiology than previously thought. Understanding
the role of gene–gene interactions, epigenetics, and noncoding
regulatory regions is becoming increasingly critical
in predicting the functional consequences of genetic mutations
identified by genome-wide association studies and wholegenome
or exome sequencing. A systems biology approach
is now being widely employed to systematically discover
genes that are involved in heart diseases in humans or relevant
animal models through bioinformatics. The overarching premise
is that the integration of high-quality causal gene regulatory
networks (GRNs), genomics, epigenomics, transcriptomics
and other genome-wide data will greatly accelerate the
discovery of the complex genetic causes of congenital and
complex heart diseases. This review summarises state-of-theart
genomic and bioinformatics techniques that are used in
accelerating the pace of disease gene discovery in heart diseases.
Accompanying this review, we provide an interactive
web-resource for systems biology analysis of mammalian
heart development and diseases, CardiacCode (http://
CardiacCode.victorchang.edu.au/). CardiacCode features a
dataset of over 700 pieces of manually curated genetic or
molecular perturbation data, which enables the inference of a
cardiac-specific GRN of 280 regulatory relationships between
33 regulator genes and 129 target genes. We believe this
growing resource will fill an urgent unmet need to fully realise
the true potential of predictive and personalised genomic
medicine in tackling human heart disease.
(Human Frontier Science Program grant RGY0084/2014).
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 19 Jan 2016 05:04 |
| Last Modified: | 28 Sep 2016 05:34 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/195 |
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