Biophysical Reviews

, Volume 7, Issue 1, pp 141–159

Decoding the complex genetic causes of heart diseases using systems biology

  • Djordje Djordjevic
  • Vinita Deshpande
  • Tomasz Szczesnik
  • Andrian Yang
  • David T. Humphreys
  • Eleni Giannoulatou
  • Joshua W. K. Ho
Review

DOI: 10.1007/s12551-014-0145-3

Cite this article as:
Djordjevic, D., Deshpande, V., Szczesnik, T. et al. Biophys Rev (2015) 7: 141. doi:10.1007/s12551-014-0145-3

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 non-coding regulatory regions is becoming increasingly critical in predicting the functional consequences of genetic mutations identified by genome-wide association studies and whole-genome 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-the-art 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.

Keywords

Cardiac gene regulatory network Whole-genome sequencing Epigenomics Congenital heart disease Cardiomyopathy Gene prioritisation 

Supplementary material

12551_2014_145_MOESM1_ESM.xls (369 kb)
ESM 1(XLS 369 kb)

Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Djordje Djordjevic
    • 1
    • 2
  • Vinita Deshpande
    • 1
  • Tomasz Szczesnik
    • 1
    • 2
  • Andrian Yang
    • 1
  • David T. Humphreys
    • 1
    • 2
  • Eleni Giannoulatou
    • 1
    • 2
  • Joshua W. K. Ho
    • 1
    • 2
  1. 1.Victor Chang Cardiac Research InstituteDarlinghurstAustralia
  2. 2.St. Vincent’s Clinical SchoolThe University of New South WalesDarlinghurstAustralia

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