title: Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations.
abstract: Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.
authors.affiliation: Department of Medical Chemistry, Semmelweis University, P.O. Box 260, H-1444 Budapest 8, Hungary.
authors.forename: Áron R
authors.initials: ÁR
authors.lastname: Perez-Lopez
authors.affiliation: Department of Medical Chemistry, Semmelweis University, P.O. Box 260, H-1444 Budapest 8, Hungary.
authors.forename: Kristóf Z
authors.initials: KZ
authors.lastname: Szalay
authors.affiliation: Department of Genetics, Eötvös Loránd University, Pázmány P. s. 1C, H-1117 Budapest, Hungary.
authors.forename: Dénes
authors.initials: D
authors.lastname: Türei
authors.affiliation: 1] Department of Genetics, Eötvös Loránd University, Pázmány P. s. 1C, H-1117 Budapest, Hungary [2] Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Vas u. 17, H-1088 Budapest, Hungary.
authors.forename: Dezső
authors.initials: D
authors.lastname: Módos
authors.affiliation: Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Vas u. 17, H-1088 Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Lenti
authors.affiliation: 1] Department of Genetics, Eötvös Loránd University, Pázmány P. s. 1C, H-1117 Budapest, Hungary [2] TGAC, The Genome Analysis Centre, Norwich, UK [3] Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK.
authors.forename: Tamás
authors.initials: T
authors.lastname: Korcsmáros
authors.affiliation: Department of Medical Chemistry, Semmelweis University, P.O. Box 260, H-1444 Budapest 8, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Csermely
mesh_terms: D015179:Colorectal Neoplasms / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D016503:Drug Delivery Systems; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D060066:Protein Interaction Maps; D013997:Time Factors
chemical_list: D009363:Neoplasm Proteins