title: Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Sub)classes.
abstract: Traditional Chinese medicine (TCM) still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs) of 45 TCM therapeutic action (sub)classes from in silico target prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (sub)class. The MOA of a (sub)class was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2) and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR), and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, "the foundation of acquired constitution" that includes spleen and stomach. In short, the TCM (sub)classes, in many cases share similar targets/pathways despite having different indications.
authors.affiliation: Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), Ministry of Science, Technology and Innovation, 11800 Penang, Malaysia.
authors.forename: Siti Zuraidah
authors.initials: SZ
authors.lastname: Mohamad Zobir
authors.affiliation: Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia.
authors.forename: Fazlin
authors.initials: F
authors.lastname: Mohd Fauzi
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SP 8, 09042 Monserrato, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Liggi
authors.affiliation: School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 9 Heroon Polytechniou Street, 15780 Athens, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Drakakis
authors.affiliation: School of Information Management, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
authors.forename: Tai-Ping
authors.initials: TP
authors.lastname: Fan
authors.affiliation: Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender