Systems Biology–Derived Genetic Signatures of Mastitis in Dairy Cattle: A New Avenue for Drug Repurposing

SIMPLE SUMMARY: Therapeutic success of bovine mastitis depends mainly on accurately diagnosing the type of pathogen involved. Despite the development prospects for bovine mastitis diagnosis, including new biomarker discovery to target specific pathogens with high sensitivity and specificity, treatment studies have shown controversial results, and the most efficient, safe, and economical treatments for mastitis are still topics of scientific debate. The goal of this research is the integration of different levels of systems biology data to predict candidate drugs for the control and management of E. coli mastitis. We propose that the novel drugs could be used by pharmaceutical scientists or veterinarians to find commercially efficacious medicines. ABSTRACT: Mastitis, a disease with high incidence worldwide, is the most prevalent and costly disease in the dairy industry. Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among the leading agents causing acute severe infection with clinical signs. E. Coli, environmental mastitis pathogens, are the primary etiological agents of bovine mastitis in well-managed dairy farms. Response to E. Coli infection has a complex pattern affected by genetic and environmental parameters. On the other hand, the efficacy of antibiotics and/or anti-inflammatory treatment in E. coli mastitis is still a topic of scientific debate, and studies on the treatment of clinical cases show conflicting results. Unraveling the bio-signature of mastitis in dairy cattle can open new avenues for drug repurposing. In the current research, a novel, semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local and global network features for data integration, was used to potentially identify novel therapeutic avenues for the treatment of E. coli mastitis. Online data repositories relevant to known diseases, drugs, and gene targets, along with other specialized biological information for E. coli mastitis, including critical genes with robust bio-signatures, drugs, and related disorders, were used as input data for analysis with the Heter-LP algorithm. Our research identified novel drugs such as Glibenclamide, Ipratropium, Salbutamol, and Carbidopa as possible therapeutics that could be used against E. coli mastitis. Predicted relationships can be used by pharmaceutical scientists or veterinarians to find commercially efficacious medicines or a combination of two or more active compounds to treat this infectious disease.