A heuristic gene regulatory networks model for cardiac function and pathology

Genome-wide association studies (GWAS) and next-generation sequencing (NGS) has led to an increase in information about the human genome and cardiovascular disease. Understanding the role of genes in cardiac function and pathology requires modeling gene interactions and identification of regulatory genes as part of a gene regulatory network (GRN). Feature selection and data reduction not sufficient and require domain knowledge to deal with large data. We propose three novel innovations in constructing a GRN based on heuristics. A 2D Visualised Co-regulation function. Post-processing to identify gene-gene interactions. Finally a threshold algorithm is applied to identify the hub genes that provide the backbone of the GRN. The 2D Visualized Co-regulation function performed significantly better compared to the Pearson's correlation for measuring pairwise associations (t=3.46, df=5, p=0.018). The F-measure, improved from 0.11 to 0.12. The hub network provided a 60% improvement to that reported in the literature. The performance of the hub network was then also compared against ARACNe and performed significantly better (p=0.024). We conclude that a heuristics approach in developing GRNs has potential to improve our understanding of gene regulation and interaction in diverse biological function and disease.