caa a22 4500 606242775 CHVBK 20210128101320.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s12551-014-0145-3 doi (NATIONALLICENCE)springer-10.1007/s12551-014-0145-3 Decoding the complex genetic causes of heart diseases using systems biology [Elektronische Daten] [Djordje Djordjevic, Vinita Deshpande, Tomasz Szczesnik, Andrian Yang, David Humphreys, Eleni Giannoulatou, Joshua Ho] 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. International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg, 2014 Cardiac gene regulatory network nationallicence Whole-genome sequencing nationallicence Epigenomics nationallicence Congenital heart disease nationallicence Cardiomyopathy nationallicence Gene prioritisation nationallicence Djordjevic Djordje Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut Deshpande Vinita Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut Szczesnik Tomasz Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut Yang Andrian Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut Humphreys David Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut Giannoulatou Eleni Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut Ho Joshua Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut Biophysical Reviews Springer Berlin Heidelberg 7/1(2015-03-01), 141-159 1867-2450 7:1<141 2015 7 12551 https://doi.org/10.1007/s12551-014-0145-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s12551-014-0145-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Djordjevic Djordje Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut NATIONALLICENCE 700 1- Deshpande Vinita Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut NATIONALLICENCE 700 1- Szczesnik Tomasz Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut NATIONALLICENCE 700 1- Yang Andrian Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut NATIONALLICENCE 700 1- Humphreys David Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut NATIONALLICENCE 700 1- Giannoulatou Eleni Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut NATIONALLICENCE 700 1- Ho Joshua Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia aut NATIONALLICENCE 773 0- Biophysical Reviews Springer Berlin Heidelberg 7/1(2015-03-01), 141-159 1867-2450 7:1<141 2015 7 12551