Genetic network analysis – gene and protein expression measurements.ppt

If NM, then or For a K gene separator: N M E K nK simulated nK calculated 500 100 4 3 1172455±123637 1174430 500 100 8 3 69630 ± 17487 66605 300 50 15 3 760 ± 579 785 200 40 20 4 2032 ± 1639 1713 how many cell lines do we need in order to avoid accidental separators ? for N=10000 M=1000 for p0.001 K=1 E=7 Higher order separator K=2 E=15 K=3 E=25 K=4 E=38 K=5 E=54 K=6 E=73 Genes are not independently regulated Generative models (gene expression operator) will simulate realistic looking gene expression matrices ? - the number of genes that can be mis-regulated - the independence of gene mis-regulation. N1 N2 N3 . . .. Ni T1 T2 T3 . . . . . . . . . . . . . . . . . Ti gene1 gene2 gene3 gene4 0 0 0 0 0 0 0 1 1 0 0 1 0 0 0 0 1 0 1 0 1 1 ………………………..0 1 0 ……………………… ..1 0 1 ………………………...0 0 1 …………………………1 Algorithm to extract Boolean separators from a gene expression matrix. U. Alon data set (colon tumors) : N=2000, Maverage=180 K=2 E Alon data calc. Num. sim. 10 708 131 130 11 120 ~ 1 1 12 45 8.6 x 10-3 8.6 x 10-3 13 3 7.0 x 10-5 - 14 3 5.6 x 10-7 - 15 1 4.6 x 10-9 - 16 1 3.7 x 10-11 - Generative model: 4+/-2 separators yij = gene expression level in the ith row and jth column Pearson-disproportion of an array: * Theoretical limitations of massively parallel biology Genetic network analysis – gene and protein expression measurements Zoltan Szallasi Children’s Hospital Informatics Program Harvard Medic