Abstract
AbstractBy utilizing functional genetic variation within the participants of the UK Biobank project for a largescale PheWAS study we attempted to get a better understanding of how the set of human proteases and their endogenous inhibitors are involved in common diseases. Focusing on known human proteases, their inhibitors, and known substrates, we computed their ranked-biased similarity from phenome-wide association results. Putative regulatory networks were constructed from 250 high-scoring pairs of proteases and related genes. This analysis suggested thirteen network modules, five diagnosis-based and eight biomarker-based. Through genetic associations and published literature on module members, the modules could be classified into different disease modalities including cholesterol homeostasis and high blood pressure.
Publisher
Cold Spring Harbor Laboratory
Reference33 articles.
1. Proteases: History, discovery, and roles in health and disease
2. The mammalian degradome database, human hereditary diseases of proteolysis. http://degradome.uniovi.es/diseases.html.
3. MEROPS: the database of proteolytic enzymes, their substrates and inhibitors;Nucleic Acids Research,2013
4. Protease-inhibitor interaction predictions: Lessons on the complexity of protein-Protein interactions;Molecular and Cellular Proteomics,2017
5. The Genotype-Tissue Expression (GTEx) project