Network Medicine: A Clinical Approach for Precision Medicine and Personalized Therapy in Coronary Heart Disease

Abstract

The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Review Early identification of coronary atherosclerotic pathogenic mechanisms is useful for predicting the risk of coronary heart disease (CHD) and future cardiac events. Epigenome changes may clarify a significant fraction of this "missing hereditability", thus offering novel potential biomarkers for prevention and care of CHD. The rapidly growing disciplines of systems biology and network science are now poised to meet the fields of precision medicine and personalized therapy. Network medicine integrates standard clinical recording and non-invasive, advanced cardiac imaging tools with epigenetics into deep learning for in-depth CHD molecular phenotyping. This approach could potentially explore developing novel drugs from natural compounds (i.e. polyphenols, folic acid) and repurposing current drugs, such as statins and metformin. Several clinical trials have exploited epigenetic tags and epigenetic sensitive drugs both in primary and secondary prevention. Due to their stability in plasma and easiness of detection, many ongoing clinical trials are focused on the evaluation of circulating miRNAs (e.g. miR-8059 and miR-320a) in blood, in association with imaging parameters such as coronary calcifications and stenosis degree detected by coronary computed tomography angiography (CCTA), or functional parameters provided by FFR/CT and PET/CT. Although epigenetic modifications have also been prioritized through network based approaches, the whole set of molecular interactions (interactome) in CHD is still under investigation for primary prevention strategies. events 10, 11). In the era of next generation sequencing, the development of a plethora of high-throughput platforms has provided significant impact concerning the knowledge of CHD molecular characterization generating big "omics" data sets 12-14). Furthermore, several non-invasive imaging techniques have been developed over the last few years to detect CHD with the aim to guide optimal patient management, such as coronary computed tomography angiography (CCTA), cardiac magnetic resonance (CMR), and nuclear medicine technique positron emission tomography (PET) 15). These advances have raised challenges Copyright©2020 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

Molecular networks in Network Medicine: Development and applications

“…Application of potent network‐based algorithms represents the most fruitful way to reach useful clinical platforms for precision medicine and personalized therapy in complex diseases (Barabasi, 2007; Barabasi et al, 2011; Benincasa, Marfella, Della Mura, Schiano, & Napoli, 2020, Infante et al, 2020; Menche et al, 2015). In this section, we will review several examples in which the application of network‐based methods has provided pathobiological insights into conventionally defined complex diseases.…”

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside

“…The historically limited success in the discovery of epigenetic biomarkers and epi-drugs using a reductionist approach calls for a paradigm shift toward network medicine (NM), which combines big data, advanced bioinformatic tools, network science, systems biology, artificial intelligence, and clinical biometric data to investigate the pathogenesis of complex diseases such as cancer and CVDs. By considering the molecular perturbations of integrated biological pathways rather than a single molecular defect ([ 15 , 75 , 92 , 64 , 120 , 123 ]), NM can leverage molecular interaction networks for advancing diagnosis, prognosis, and treatment Fig. 1 [ 15 , 75 , 120 , 123 ].…”

Epigenetic-sensitive liquid biomarkers and personalised therapy in advanced heart failure: a focus on cell-free DNA and microRNAs

“…1 Indeed, discriminating HFpEF from HFmEF and HFrEF would be clinically relevant but it it is not provided by the current established biomarkers. 20…”

“…19 20 The gadolinium and other contrast agents are used to evaluate fibrosis and therefore provide additional information on myocardial tissue quality. 20 The delayed gadolinium enhancement may also reflect features beyond fibrosis including oedema and inflammatory infiltrate and is a predictor of all-cause mortality; specifically, delayed enhancement is associated with increased risk for ventricular arrhythmias. 19 Endomyocardial biopsy (EMB) has been used to confirm specific and definite forms of DCM, but the complication rate with tissue biopsy ranges from 1% to 3% including serious complications such as perforation and tamponade occurring at 0.5%.…”