Lee metbolic eng synthetic bio BME 162 GuestLecture Apr2_2012

I o definition sauro hm mol syst biol 2008 4166

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Unformatted text preview: olism Zhao et al. (2006) BMC Bioinformatics. 7:386. 4/2/12 BME 162 Guest Lecture 44 Modules Across and Within Pathways Spirin et al. (2006) Proc Natl Acad Sci. 103(23):8774-9. 4/2/12 BME 162 Guest Lecture 45 Graph Theore0cal Representa0on 4/2/12 BME 162 Guest Lecture 46 Structural Modularity Ravasz et al., Science, 2002, 297(5586):1551-5. 4/2/12 BME 162 Guest Lecture 47 Cluster Coefficient •  Cluster coefficient, Ci number edges connec0ng the ni neighbors of i maximum possible number of connec0ons, ni(ni –1)/2 –  describes extent to which the nodes adjacent to i communicate = •  Average cluster coefficient for nodes with degree k, C(k) –  C(k) characterizes the extent of network modularity C• = 1 4/2/12 C• = ½ BME 162 Guest Lecture C• = 0 48 Modular Networks •  Characteris0cs –  modules (clusters of nodes) possessing •  large inter ­cluster connec0vity •  small intra ­cluster connec0vity –  C(k) independent of k for scale ­free and modular networks Modular Network C(k) C(k) ≈ k0 k 4/2/12 BME 162 Guest Lecture 49 Hierarchical Networks •  Characteris0cs –  many small interconnected modules –  combine in a hierarchical manner to form larger modules of lesser connec0vity –  C(k) ~ k–1 –  metabolic networks are hierarchical 4/2/12 BME 162 Guest Lecture 50 Func0onal Modularity Engineering (I-O) definition Sauro HM, Mol Syst Biol, 2008, 4:166. Biological definition (a)  the sub-system should perform a biologically relevant function in some mode of the total system, e.g. regulate the ATP concentration, entry of mitosis or apoptosis (b)  the sub-system should only weakly interact with its environment, that is, respond to few external inputs, produce few outputs and otherwise be essentially unaffected by changes in the environment. Nordling et al., Mol Biosyst, 2007, 3(8):523-9 4/2/12 BME 162 Guest Lecture 51 Cyclical Interac0on as Key Feature of Modules •  Retroac0vity –  A downstream component influences an upstream component –  Retroac0ve connec0ons within a module >> retroac0ve connec0ons between modules Saez-Rodriguez, et al. Bioinfor...
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