Reverse engineering gene networks using singular value反向工程基因网络利用奇异值.pptVIP

Reverse engineering gene networks using singular value decomposition and robust regression M.K.Stephen Yeung Jesper Tegner James J. Collins General idea Reverse-engineer: Genome-wide scale Small amount of data No prior knowledge Using SVD for a family of possible solutions Using robust regression to choose from them If the system is near a steady state, dynamics can be approximated by linear system of N ODEs: xi = concentration of mRNA (reflects expression level of genes) λi = self-degradation rates bi = external stimuli ξi = noise Wij = type and strength of effect of jth gene on ith gene Suppositions made: No time-dependency in connections (so W is not time-dependent), and they are not changed by the tests System near steady state Noise will be discarded, so exact measurements are assumed can be calculated exactly enough In M experiments with N genes, each time apply stimuli (b1,…,bN) to the genes measure concentrations of N mRNAs (x1,…,xN) using a microarray You get: subscript i = mRNA number superscript j = experiment number Goal is to use as few measurements as possible. By this method (with exact measurements): M = O(log(N)) e.g. in 1st test, the results will be: System becomes: With A = W + diag(-λi) Compute by using several measurements of the data for X. (e.g. using interpolation) Goal = deduce W (or A) from the rest If M=N, compute (XT)-1, but mostly M N (this is our goal: M = log(N)) Therefore, use SVD (to find least squares sol.): Here, U and V are orthogonal (UT = U-1) and W is diag(w1,…,wN) with wi the singular values of X Suppose all wi = 0 are in the beginning, so wi = 0 for i = 1…L and wi ≠ 0 (i=L+1...L+N) Then the least squares (L2) solution to the problem is: With 1/wj replaced by 0 if wj = 0 So this formula tries to match every datapoint as closely as possible to the solution. But all possible solutions are: with C = (cij)NxN where cij = 0 if j L and otherwise just a scalar coefficient How to