GOing Forward With the Cardiac Conduction System Using Gene Ontology

Abstract

The cardiac conduction system (CCS) comprises critical components responsible for the initiation, propagation, and coordination of the action potential. Aberrant CCS development can cause conduction abnormalities, including sick sinus syndrome, accessory pathways, and atrioventricular and bundle branch blocks. Gene Ontology (GO; http://geneontology.org/) is an invaluable global bioinformatics resource which provides structured, computable knowledge describing the functions of gene products. Many gene products are known to be involved in CCS development; however, this information is not comprehensively captured by GO. To address the needs of the heart development research community, this study aimed to describe the specific roles of proteins reported in the literature to be involved with CCS development and/or function. 14 proteins were prioritized for GO annotation which led to the curation of 15 peer-reviewed primary experimental articles using carefully selected GO terms. 152 descriptive GO annotations, including those describing sinoatrial node and atrioventricular node development were created and submitted to the GO Consortium database. A functional enrichment analysis of 35 key CCS development proteins confirmed that this work has improved the in-silico interpretation of this CCS dataset. This work may improve future investigations of the CCS with application of high-throughput methods such as genome-wide association studies analysis, proteomics, and transcriptomics.

Keywords: annotation; biocuration; cardiac conduction; gene ontology (GO); heart development.

FIGURE 1

Ontology relevant to cardiac conduction system development. QuickGO graph of the part of the heart development ontology (www.ebi.ac.uk/QuickGO). Six GO terms used as GO slims are highlighted in yellow: GO:0003161 cardiac conduction system development, GO:0003162 atrioventricular node development, GO:0003163 sinoatrial node development, GO:0003164 His-Purkinje system development, GO:0036302 atrioventricular canal development and GO:0007507 heart development. The is_a relations between the GO term are indicated by black arrows, the part_of relations as blue arrows ((Ashburner et al., 2000), (The Gene Ontology Consortium et al., 2021)).