Reverse Engineering of Regulatory Networks逆向工程的调控网络.pptVIP

Reverse Engineering of Regulatory Networks Ka-Lok Ng Department of Bioinformatics Asia University Contents Introduction – Gene regulatory network (GRN) The steady-state approach - time-series model Introduction – Gene regulatory network (GRN) One gene can affect the expression of another gene by binding of the gene product of one gene to the promoter region of another gene 2 genes, we refer to the regulatory network as the regulatory interactions between the genes Given a larger number measurements of the expression levels of a number of genes, we should be able to model or reverse engineer the regulatory network that controls their expression level. 2 approaches ? the time-series and steady-state approaches The time-series approach Expression level of a gene at a certain time point xj(t) can be modeled as some function of the expression levels of all other genes at all previous time points xi(t-1), where i may or may not equal j, if i = j that means self regulate where ri,j is a weight factor representing how gene i affects gene j, that is, i ? j (activate) or i -| j (inhibit), positively or negatively Problem ! Many more genes number of time points Suppose there are g genes ? g2 possible connections among them (for instance, g = 4 ? 16 possibilities, including self-regulation) There are g(g+1)/2 possible interactions It is called one has a dimensionality problem A possible solution is cluster the genes that have similar behavior into gene clusters The time-series approach The time-series approach The time-series approach The time-series approach The time-series approach Reference Knudsen S. (2002). A biologist’s guide to analysis of data microarray data. J. Wiley * Example At t =0, gene c is induced, at t = 1,2,3,4 we follow the expression level of gene c and three other genes, a, b and d Deduce a GRN from the time-series data (5 time points). gene c ↑, but genes (a, b, d) ↓ gene c represses gene a ? -1 0 0 0 0 d 1 1 1 1 0 c -1 -1 0 0 0 b -1 -1 -1 0 0 a 4