Analysis and Research of Key Genes in Gene Expression Network Based on Complex Network

Gene expression network is also a type of complex network. It is challenging to analyze the gene expression network through relevant knowledge and algorithms of a complex network. In this paper, the existing characteristics of genes are analyzed from various indexes of the gene expression network to analyze key genes and TOP genes. Firstly, gene chip data are screened, gene data with obvious characteristics are selected, and relevant clustering characteristics are analyzed. Then, the complex gene network structure is established, and gene networks with different threshold shapes and different sizes are selected. Finally, the relevant indexes and PR values after the PageRank algorithm are analyzed for complex networks under different thresholds, thus establishing the TOP gene and PR sequence.

Abstract MP115: Transcriptional Patterning of the Ventricular Cardiac Conduction System

The heart beats 2 billion times over the average human lifespan and is the manifestation of a pattern of cardiomyocyte depolarization organized by a specialized network of cardiomyocytes, the cardiac conduction system (CCS). Patterning of the CCS into atrial node versus ventricular conduction system (VCS) components with distinct physiology is essential for the normal heartbeat and has been recognized for more than a century. However molecular basis of this regional patterning is not well understood. Using mouse genetics, we found that the ratio between T-box transcriptional activator, Tbx5 , and T-box transcriptional repressor, Tbx3 , determines the molecular and functional output of VCS myocytes. Adult VCS-specific removal of Tbx5 or overexpression of Tbx3 re-patterned the fast VCS into slow, nodal-like cells based on molecular, cellular and functional criteria. Specifically, the ventricular fast conduction gene expression network was lost whereas the slow conduction nodal gene expression network was retained. Action potentials (APs) of Tbx5 -deficient VCS myocytes adopted nodal-specific characteristics, including increased AP duration and cellular automaticity. Removal of Tbx5 in-vivo precipitated inappropriate depolarizations in the His-bundle that initiated lethal ventricular arrhythmias. A T-box rheostat mechanism for CCS patterning was confirmed by Tbx5/Tbx3 genetic interaction studies. TBX5 bound and directly activated cis -regulatory elements at fast conduction loci genome-wide, defining the identity of the adult VCS. Furthermore, TBX5 bound and activated cis-regulatory elements at Tbx5 itself, describing a multi-tiered T-box-dependent fast conduction gene regulatory network (GRN). The hierarchical GRN established a bi-stable network in mathematical modeling, with only high or low fast conduction gene expression states, suggesting a genomic mechanism for the establishment of VCS versus nodal states in-vivo . Thus, the CCS is patterned entirely as a slow, nodal ground state, with a T-box dependent, physiologically dominant, fast conduction network driven specifically in the VCS. Disruption of the fast VCS GRN allowed nodal physiology to emerge, providing a molecular mechanism for some lethal ventricular arrhythmias.