Drug contraindications in comorbid diseases: a protein interactome perspective

AbstractAdverse drug reactions (ADRs) are leading causes of death and drug withdrawals and frequently co-occur with comorbidities. However, systematic studies on the effects of drugs on comorbidities are lacking. Drug interactions with the cellular protein –protein interaction (PPI) network give rise to ADRs. We selected 6 comorbid disease pairs, identified the drugs used in the treatment of the individual diseases ‘A’ and ‘B’– 44 drugs in anxiety and depression, 128 in asthma and hypertension, 48 in chronic obstructive pulmonary disease a nd heart failure, 58 in type 2 diabetes and obesity, 58 in Parkinson’s disease and schizophrenia, and 84 in rheumatoid arthritis and osteoporosis—and categorized them based on whether they aggravate the comorbid condition. We constructed drug target networks (DTNs) and examined their enrichment among genes in disease A/B PPI networks, expressed across 53 tissues and involved in ~ 1000 pathways. To characterize the biological features of the DTNs, we performed principal component analysis and computed the Euclidean distance between DTN component scores and feature loading values. DTNs o f disease A drugs not contraindicated in B were affiliated with proteins common to A/B networks or uniquely found in the B network, similarly regulated common pathways, and disease-B specific pathways and tissues. DTNs of disease A drugs contraindicated in B were affiliated with common proteins or t hose uniquely found in the A network, di...
Source: Network Modeling Analysis in Health Informatics and Bioinformatics - Category: Bioinformatics Source Type: research