Dr. Zhiwei Cao

College of life science and biotechnology, Tongji University;

Shanghai Center for Bioinformation Technology

Computational Platform for Mechanistic Study of Chinese

Herb

Overview

1. Introduction of Mechanistic Study of Chinese Herb

2. Computational Platform: Resources and Technologies

3. Case Study

4. Ongoing and future development

1. Introduction: Mechanism of Herbs Multiple 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 su

pport 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 ingre

dient 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 2006Getting improved both in BIDD and SCBIT Getting Co-developed with Bridgeway hig

h-computing company ( www.bridgeway.com.cn) in Oct, 2007

2.3 Target network construction based on （ ISHIP）

1. Experimental and predicted PPI > 610,000 pairs；

2. > 29,000 with experimental evidence；3. Covering whole human genome, with confid

ence scoring system；4. Linking to genetic disease database (OMI

M）；

5. 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

PIN

bioverse

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

Zhao J, …, Cao ZW, Li YX. Hierarchical modularity of nested bow-ties in metabolic networks. BMC Bioinformatics. 2006 Aug 18;7:386.

E.Coli 代谢网络的 12 个子网络之间的关系 . 每个子网络具有相对独立的功能 , 是生物学功能模块

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 network Molecular 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

…

Acknowledgements 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 Moder

nizations Center

“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