若手研究者インターナショナル・トレーニング・プログラム(ITP)
バイオインフォマティクスとシステムズバイオロジーの国際連携教育研究プログラム 応募書類

Name: Yang Zhao
Title: Modelling the Robustness of Metabolic Pathways
Institute: Bioinformatics Center, Institute for Chemical Research, Kyoto University
Partner institute of your choice: Centre for Computational Biology, Mines ParisTech
Duration of your choice: September 9, 2011 – November 27, 2011

PlanBackgroundMy current research focuses on analysis of tree-like compounds, which deals with synthesis
analysis, tree-structured data compression and enumeration of tree-like compounds.
For synthesis analysis, a dynamic programming algorithm was proposed to predict synthesis
processes of tree-structured compounds with graph grammar. This research was presented in
the Tenth Annual International Workshop on Bioinformatics and Systems Biology (IBSB2010)
held in Kyoto, Japan.
The second study firstly proposed integer programming-based methods for finding the minimum
grammars to generate given strings, ordered trees and unordered trees. We applied thesemethods to glycan tree structure data to confirm the accuracy, and extract interesting patterns.
This research was presented in SIG-FPAI 78 held in Kobe, Japan and in The 21st International
Conference on Genome Informatics (GIW2010) held in Hangzhou, China. And this research wasalso published in BMC Bioinformatics, BioMed Central, 11(Suppl 11): S4, 2010.
The ongoing research is enumeration of chemical molecules. In this work, an efficient algorithm
to enumerate tree-like molecules without duplications has been proposed by similarly treating
tree-like molecules as rooted trees. As computational experiments indicated, this method
reduces the search space and has high speed. For chemical molecules which have cycles, anextension of this proposed method is being done.
Research objectiveThe partner laboratory is Centre for Computational Biology belonging to Mines ParisTech. The
group leader is Prof. Jean-Philippe Vert. One of the researches of this lab is bioinformatics
analysis of cancer genomic data. As we know that metabolic pathways are complex systems ofchemical reactions taking place in every living cell to degrade substrates and synthesize
molecules needed for life. Reactions can be perturbed by, e.g., drugs or mutations in DNA. Whenone or a few reactions are perturbed, the impact of this perturbation on the cell can vary widely,depending on how many other reactions are impacted in cascade. The group is recentlyinterested in the project of modeling the robustness of metabolic pathways in cancer research.
And the motivation is to propose and implement new computational models to quantify theimpact of inhibiting one or a few reactions on the global metabolic network, and to evaluate therobustness of metabolic networks based on this model.

若手研究者インターナショナル・トレーニング・プログラム(ITP)
バイオインフォマティクスとシステムズバイオロジーの国際連携教育研究プログラム 応募書類

Plan
The specific work is as follows:Learn related knowledge about kernel methods, Bayesian network, branching process andnetwork biology from Prof. Jean-Philippe Vert, who is an expert in these fields.

Study a similar model which better takes into account the structural properties of themetabolic network than the recent one (<Analysis of the impact degree distribution inmetabolic networks using branching process approximation>, Physica A, to appear) did.

Learn how to implement this model to quantify the impact of inhibiting one or a few
reactions on the global metabolic network, and also learn how to evaluate the robustness of
metabolic networks based on this model.

Develop advanced computational and mathematical methods for modelling the robustnessof metabolic pathways in cancer research, such as computational tools to predict the effectsof combinatorial inhibitions, which could help in the design of new cocktails of drugs
targeting several proteins.

Improve English skill by communicating with native speakers, giving presentations andwriting academic papers.

Learn the way of international collaboration through collaboration on this project.