中藥作用機理的生物信息學平臺搭建課件

1、Dr. Zhiwei CaoCollege of life science and biotechnology, Tongji University;Shanghai Center for Bioinformation TechnologyComputational Platform for Mechanistic Study of Chinese Herb第1頁，共24頁。OverviewIntroduction of Mechanistic Study of Chinese HerbComputational Platform: Resources and Technologies Cas

2、e StudyOngoing and future development第2頁，共24頁。第3頁，共24頁。1. Introduction: Mechanism of Herbs Multiple Ingredients, Multiple Targets, Network Pharmacology & Therapeutics 2000, 86:191-198第4頁，共24頁。Questions about Herb MechanismWhat ingredients are active compounds?What are their potential targets?What ar

3、e their targeted pathways?How can we analyze the network?. 第5頁，共24頁。2. Platform: Resources and Technologies1. 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. Softwar

4、e license obtained:Human intergrated PPI database (SCBIT)4. China patent filed: Computational platform and methodologies to support herbal mechanistic study (SCBIT)第6頁，共24頁。2.1 Herbal Ingredient and Content database（HICD)Above 30 related journals ;3200 literatures being curated;Herbs from 39 countri

5、es;15,000 ingredient with Content information; Including all potential factors affecting ingredient contentCollecting time, site herbal part Processing methodsMethod to measure the contentTherapeutic effects Diseases第7頁，共24頁。第8頁，共24頁。2.2. Computational Method to Identify Potential Targets (INVDOCK)

6、US patent authorized: 6,519,611 B1 (Feb.11.2003 )German Merck testing in 2006Getting improved both in BIDD and SCBIT Getting Co-developed with Bridgeway high-computing company ( ) in Oct, 2007第9頁，共24頁。2.3 Target network construction based on （ISHIP）Experimental and predicted PPI 610,000 pairs； 29,00

7、0 with experimental evidence；Covering whole human genome, with confidence scoring system；Linking to genetic disease database (OMIM）；Software licensed: 2006SR05464。第10頁，共24頁。1.3 Integrated Source of Human interacting proteins（ISHIP）第11頁，共24頁。Supporting various queries支持多種檢索方式Protein accessionGene sym

8、bolGeneIDIPI accessionKeywordBLASTGene symbol search第12頁，共24頁。2.4 Network analysis: System biologyPajekPINbioverse第13頁，共24頁。Network Decomposition TechnologyComplex networks theory for analyzing metabolic networks Chinese Science Bulletin 2006 vol. 51 No. 13， 1529-1537 第14頁，共24頁。E.Coli代謝網(wǎng)絡12個功能模塊的GSC

9、部分的連接圖.此圖的每個強連通子圖對應一個蝴蝶結結構 Zhao J, , Cao ZW, Li YX. Hierarchical modularity of nested bow-ties in metabolic networks. BMC Bioinformatics. 2006 Aug 18;7:386. 第15頁，共24頁。E.Coli代謝網(wǎng)絡的12個子網(wǎng)絡之間的關系.每個子網(wǎng)絡具有相對獨立的功能,是生物學功能模塊第16頁，共24頁。Identifying topological modules and their functionsModular co-evolution of me

10、tabolic networks. BMC Bioinformatics 2007，8:311.第17頁，共24頁。3. Case study: ganoderic acid D Main ingredient of tri-terpenoids in Ganoderma lucidum (靈芝）. Inhibit hela cell proliferation apoptosis Target: 2-DE: 21 proteinsQuestion: whats the target & pathway?第18頁，共24頁。第19頁，共24頁。Minimization :21 proteins

11、 (steiner)Proteomic characterization of the cytotoxic mechanism of ganoderic acid D and computer automated estimation of the possible drug-target network Molecular Cell Proteomics：2007.12.31第20頁，共24頁。4. Future development Improvement of target-searching technology ( with BIDD, NUS) Clustering and si

12、milarity search of active ingredients (with BIDD and Tongji) Herbal toxicity study ( with Shanghai TCM university) Formula validation. ( with .? )第21頁，共24頁。Collaborative Opportunities Experts on Chinese HerbExperts on computational chemistry and physicsExperts on biologists第22頁，共24頁。AcknowledgementsFunding from Shanghai Commission of Science and Technology863 funding from China Ministry of Science and Technology Prof. Chen yuzong BIDD group, NUS Prof. Li Yixue, SCBITShanghai TCM Modernizations Center“Whether from the East or the West, we share the same