Reconstruction and analysis of human liver-specific metabolic network based on CNHLPP data

1. Reconstruction and analysis of human liver-specific metabolic network based on CNHLPP data Jing Zhao Logistical Engineering University The 6th Chinese Conference of Complex Networks，October 15-18, 2010. Suzhou, China

2. OutLine • Background • Reconstruction of metabolic networks • Basic topological features of metabolic networks for human liver and Homo sapiens genome • Functional organization of liver revealed by topological modules in liver-specific metabolic network • Enzyme abundance in topological modules of liver-specific metabolic network • Comparison of metabolic network of human liver with that of the Homo sapiens genome

3. Function of liver • producing substances that break down fats • converting glucose to glycogen • producing urea • making certain amino acids • filtering harmful substances from the blood • storing vitamins and minerals • maintaining a proper level of glucose in the blood

4. Network representation of Metabolism: Substrate graph

5. HLPP: The Human Liver Proteome Project The first initiative on human tissues/organs launched by the Human Proteome Organization (HUPO)

6. Liver metabolic network Human metabolic network Data used in this study • Data from CNHLPP • 6788 distinct proteins (IPI codes) and protein quantitation data , confidence level 95% • 6220 distinct genes • 1421 genes encode 721 distinct enzymes • BiGG database • 3311 reactions • 1555 enzyme-catalyzed reactions • 1756 auto-catalytic reactions

7. Reconstruction of liver metabolic network CNHLPP data BiGG 380 enzymes, 1047 enzyme-catalyzed reactions • original core reaction set : 1047 liver enzyme-catalyzed reactions initial candidate reaction set: all of the auto-catalytic reactions • Extract all metabolites appearing in core reaction set to get core metabolite set. • Scan the list of candidate reactions for core metabolites. If all substrates for one reaction can be found in core metabolite set, add this reaction into core reaction set and remove it from the candidate set. • If step 3 cannot add any more reactions into core reaction set, stop; else, go to step 2. Added: 427 auto-catalytic reactions

8. Basic graph metrics of metabolic networks

9. Comparison of the liver metabolic network with its random counterparts

10. Functional organization of liver revealed by topological modules in liver metabolic network Core-periphery organization

12. Main derivative metabolism functions of the topological modules for human liver-specific metabolic network

13. Enzyme abundance in topological modules of liver-specific metabolic network P (Q >2.35)=10%; P (Q <0.5)=70%.

14. Comparison of metabolic network of human liver with that of the Homo sapiens genome

15. P-value 10 of the 16 modules ( Module 1,2,3,4,6,8,9,11,12,13) : P-value < 0.05

17. Quantitative difference between categories: overlap score Prototypical overlap score Normalized overlap score X ,Y : two categorizations X(x) ,Y(y) : the fraction of metabolites in category xX, yY, respectively XY(x,y): the joint frequency of x and y, i.e. the fraction of vertices that are categorized both as xX and yY.

18. Quantative difference between a feature of the real metabolic network and its randomized counterparts: Z- score f: the metric of the feature in the real network : the mean of the corresponding metric in the randomized ensemble : the standard deviation of the corresponding metric in the randomized ensemble v = 0.72; Z =68.5

20. Acknowledgement Shanghai Center for Bioinformation and Technology: Lin Tao, Duanfeng Zhang, Kailin Tang ,Ruixin Zhu , Hong Yu ,Yixue Li, Zhiwei Cao Beijing Proteome Research Center: Chao Geng, Ying Jiang,Fuchu He Second Military Medical University: Weidong Zhang National Natural Science Foundation of China (10971227, 30900832) Ministry of Science and Technology China(2006AA02312, 2009zx10004-601, 2010CB833601 Shanghai Municipal Education Commission (2000236018). Petter Holme Eytan Ruppin Livnat Jerby Ori Folger

21. Thanks!