A Multimodal Omics Framework to Empower Target Discovery for Cardiovascular Regeneration

Figures

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  Fig. 1. Map of factors to consider for single-cell studies in the cardiovascular field. The heart is a complex organ, and single-cell profiling studies focusing on specific questions often only provide limited information. This road map highlights some of the primary systems and factors that are now important to consider in a holistic manner to improve our understanding of heart function, repair, and regeneration. These systems and factors include different anatomical regions in the heart (the four chambers, the three layers of the heart wall, and specialised subregions like the conduction system and valvular apparatus), major cardiac cell types (endocardial cells, epicardial cells, cardiomyocytes, endothelial cells, fibroblasts, vascular smooth muscle cells, pericytes, neuronal cells, lymphoid cells, and myeloid cells), the health status of the heart (healthy or diseased such as myocardial infarction, cardiomyopathy, heart failure, valvular disease), sex (women and men), and age (prenatal, postnatal, adult, ageing)

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  Fig. 2. Schematic of a multi-species, multi-omics, meta-analysis framework for target discovery in cardiovascular regeneration. There are four main stages in the framework: stage 1, bulk/single-cell/spatial profiling of genome, epigenome, transcriptome, and proteome data from human, large animal models like porcine, small animal models like mice and rats, highly regenerative non-mammal models like axolotl and zebrafish, will be collated and inventorised based on species and three main technologies, including bulk, single-cell, and spatial profiling; stage 2, multi-omics data (including genome, epigenome, transcriptome, and proteome profiling) are integrated vertically within each species and technology, potential targets and their regulatory networks are identified, and targets from individual integrations are pulled out and prioritised based on the factors like expression level, relevance to human pathophysiology, and novelty; stage 3, top ranked targets are tested in in vitro, ex vivo, and finally in vivo experiments; stage 4, targets with the greatest safety and efficacy recommended for further preclinical or clinical investigations. The framework will embrace new technologies/omics…