ECAM Evidence-Based Complementary and Alternative Medicine 1741-4288 1741-427X Hindawi Publishing Corporation 10.1155/2016/2106465 2106465 Research Article Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Sub)classes Mohamad Zobir Siti Zuraidah szm23@cam.ac.uk 1,2 2 Mohd Fauzi Fazlin fazlin205@gmail.com 3 Liggi Sonia sonia.liggi@cantab.net 4 Drakakis Georgios gdrakakis356@gmail.com 5 Fu Xianjun xianxiu@hotmail.com 6 Fan Tai-Ping tpf1000@cam.ac.uk 7 Bender Andreas ab454@cam.ac.uk 1 Cho Jae Youl 1 Centre for Molecular Science Informatics Department of Chemistry University of Cambridge Lensfield Road Cambridge CB2 1EW UK cam.ac.uk 2 Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm) Ministry of Science Technology and Innovation 11800 Penang Malaysia 3 Department of Pharmacology and Chemistry Faculty of Pharmacy Universiti Teknologi MARA Puncak Alam Campus 42300 Bandar Puncak Alam Selangor Malaysia uitm.edu.my 4 Department of Biomedical Sciences University of Cagliari Cittadella Universitaria di Monserrato SP 8 09042 Monserrato Italy unica.it 5 School of Chemical Engineering National Technical University of Athens Zografou Campus 9 Heroon Polytechniou Street 15780 Athens Greece ntua.gr 6 School of Information Management Shandong University of Traditional Chinese Medicine Jinan 250355 China sdutcm.edu.cn 7 Department of Pharmacology University of Cambridge Tennis Court Road Cambridge CB2 1PD UK cam.ac.uk 2016 1822016 2016 14 09 2015 03 12 2015 1822016 2016 Copyright © 2016 Siti Zuraidah Mohamad Zobir et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.