Dr. Zhiwei Cao

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Computational Platform for Mechanistic Study of
Chinese Herb

• Dr. Zhiwei Cao
• College of life science and biotechnology,
• Tongji University
• Shanghai Center for Bioinformation Technology

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Overview

1. Introduction of Mechanistic Study of Chinese Herb
2. Computational Platform Resources and
   Technologies
3. Case Study
4. Ongoing and future development

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1. Introduction Mechanism of Herbs Multiple
Ingredients, Multiple Targets, Network
Pharmacology Therapeutics 2000, 86191-198
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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?
• ..

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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)

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2.1 Herbal Ingredient and Content database(HICD)

• Above 30 related journals
• gt3200 literatures being curated
• Herbs from 39 countries
• gt15,000 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

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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

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2.3 Target network construction based on (ISHIP)

1. Experimental and predicted PPI gt 610,000 pairs
2. gt 29,000 with experimental evidence
3. Covering whole human genome, with confidence
   scoring system
4. Linking to genetic disease database (OMIM)
5. Software licensed 2006SR05464?

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1.3 Integrated Source of Human interacting
proteins(ISHIP)
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Supporting various queries

• ????????
• Protein accession
• Gene symbol
• GeneID
• IPI accession
• Keyword
• BLAST

Gene symbol search
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2.4 Network analysis System biology
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Network Decomposition Technology
Complex networks theory for analyzing metabolic
networks Chinese Science Bulletin 2006 vol. 51
No. 13, 1529-1537
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E.Coli????12??????GSC??????.???????????????????
Zhao J, , Cao ZW, Li YX. Hierarchical
modularity of nested bow-ties in metabolic
networks. BMC Bioinformatics. 2006 Aug 187386.
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E.Coli?????12?????????.??????????????,????????
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Identifying topological modules and their
functions
Modular co-evolution of metabolic networks. BMC
Bioinformatics 2007,8311.
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3. Case study ganoderic acid D

• Main ingredient of tri-terpenoids in Ganoderma
  lucidum (??).
• Inhibit hela cell proliferation? apoptosis
• Target 2-DE 21 proteins
• Question whats the target pathway?

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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
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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 .? )

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Collaborative Opportunities

• Experts on Chinese Herb
• Experts on computational chemistry and physics
• Experts on biologists

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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 Modernizations Center

Whether from the East or the West, we share the
same goal of improving human health.
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If there is any technology that could lead to a
breakthrough in traditional Chinese medicine, it
will be systems biology, NATUREVol 44812
July 2007