Computational Platform for Mechanistic Study of Chinese Herb Dr. Zhiwei Cao College of life science and biotechnology, Tongji University; Shanghai Center for Bioinformation Technology
Overview • Introduction of Mechanistic Study of Chinese Herb • Computational Platform: Resources and Technologies • Case Study • Ongoing and future development
1. Introduction: Mechanism of HerbsMultiple Ingredients, Multiple Targets, Network Pharmacology & Therapeutics 2000, 86:191-198
Questions about Herb Mechanism • What ingredients are active compounds? • What are their potential targets? • What are their targeted pathways? • How can we analyze the network? • …..
2. Platform: Resources and Technologies 1. China patent filed: • Identification of main active ingredients of herbs based on database technology (SCBIT) 2. US patent obtained: • INVDOCK to identify potential drug targets (BIDD) 3. Software license obtained: • Human intergrated PPI database (SCBIT) 4. China patent filed: • Computational platform and methodologies to support herbal mechanistic study (SCBIT)
2.1 Herbal Ingredient and Content database（HICD) • Above 30 related journals ; • >3200 literatures being curated; • Herbs from 39 countries; • >15,000 ingredient with Content information; • Including all potential factors affecting ingredient content • Collecting time, site • herbal part… • Processing methods • Method to measure the content • Therapeutic effects • Diseases…
2.2. Computational Method to Identify Potential Targets (INVDOCK) • US patent authorized: 6,519,611 B1 (Feb.11.2003 ) • German Merck testing in 2006 • Getting improved both in BIDD and SCBIT • Getting Co-developed with Bridgeway high-computing company ( www.bridgeway.com.cn) in Oct, 2007
2.3 Target network construction based on （ISHIP） • Experimental and predicted PPI > 610,000 pairs； • > 29,000 with experimental evidence； • Covering whole human genome, with confidence scoring system； • Linking to genetic disease database (OMIM）； • Software licensed: 2006SR05464。
1.3 Integrated Source of Human interacting proteins（ISHIP）
Supporting various queries • 支持多种检索方式 • Protein accession • Gene symbol • GeneID • IPI accession • Keyword • BLAST Gene symbol search
2.4 Network analysis: System biology Pajek bioverse PIN
Network Decomposition Technology Complex networks theory for analyzing metabolic networks Chinese Science Bulletin 2006 vol. 51 No. 13， 1529-1537
E.Coli代谢网络12个功能模块的GSC部分的连接图.此图的每个强连通子图对应一个蝴蝶结结构E.Coli代谢网络12个功能模块的GSC部分的连接图.此图的每个强连通子图对应一个蝴蝶结结构 Zhao J, …, Cao ZW, Li YX. Hierarchical modularity of nested bow-ties in metabolic networks. BMC Bioinformatics. 2006 Aug 18;7:386.
Identifying topological modules and their functions Modular co-evolution of metabolic networks. BMC Bioinformatics 2007，8:311.
3. Case study: ganoderic acid D • Main ingredient of tri-terpenoids in Ganoderma lucidum (灵芝）. • Inhibit hela cell proliferation apoptosis • Target: 2-DE: 21 proteins • Question: what’s the target & pathway?
Minimization :21 proteins (steiner) Proteomic characterization of the cytotoxic mechanism of ganoderic acid D and computer automated estimation of the possible drug-target networkMolecular Cell Proteomics： 2007.12.31
4. Future development • Improvement of target-searching technology ( with BIDD, NUS) • Clustering and similarity search of active ingredients (with BIDD and Tongji) • Herbal toxicity study ( with Shanghai TCM university) • Formula validation…. ( with ….? )
Collaborative Opportunities • Experts on Chinese Herb • Experts on computational chemistry and physics • Experts on biologists • …
Funding from Shanghai Commission of Science and Technology 863 funding from China Ministry of Science and Technology Prof. Chen yuzong BIDD group, NUS Prof. Li Yixue, SCBIT Shanghai TCM Modernizations Center Acknowledgements “Whether from the East or the West, we share the same goal of improving human health.”
“If there is any technology that could lead to a breakthrough in traditional Chinese medicine, it will be systems biology,” – NATURE|Vol 448|12 July 2007