An alternative is to weight each gene by the number of its neighbors buy peptide online in the network genes, 3 are generated as above with s1 _ 0. 25 and the other 3 with s2 _ 3. The rest of genes are modelled as N and are therefore not discriminatory. We call this synthetic data set SimSet2, while the previous one we refer to as SimSet1. The algorithms described previously are then applied to the simulated data to infer pathway activity levels. To objectively compare the different algorithms we apply a variational Bayesian Gaussian Mixture Model to the pathway activity level. The variational Bayesian approach provides an objective estimate of the number of clusters in the pathway activity level profile. The clusters map to different activity levels and the cluster with the lowest where ki is the number of neighbors of gene i in the network.

Normally, this would include neighbors that are both in PU and in PD. The normalisation factor ensures that sW AV, if interpreted as a random variable, is of unit variance. Celecoxib COX inhibitor Simulated data To test the principles on which our algorithm is based we generated synthetic gene expression data as follows. We generated a toy data matrix of dimension 24 genes times 100 samples. We assume 40 samples to have no pathway activity, while the other 60 have variable levels of pathway activity. The 24 genes activity level defines the ground state of no activation. Hence we can compare the different algorithms in terms of the accuracy of correctly assigning samples with no activity to the ground state and samples with activity to any of the higher levels, which will depend on the predicted pathway activity levels.

Evaluation based on pathway correlations One way to evaluate and compare the different estima tion procedures is to consider pairs of pathways for which the corresponding estimated activites are signifi cantly correlated in a training set and then see if the same pattern is observed in a series Lymphatic system of validation sets. Thus, significant pathway correlations derived from a given discovery/training set can be viewed as hypotheses, which if true, must validate in the indepen dent data sets. We thus compare the algorithms in their ability to identify pathway correlations which are also valid in independent data. Specifically, for a given pathway activity estimation algo rithm and for a given pair of pathways, we first corre late the pathway activation levels using a linear regression model.

Under the null, the z scores are distributed accord ing to t statistics, therefore we let tij denote the t statistic and pij the corresponding P value. We declare a significant association as one ALK inhibitor with pij 0. 05, and if so it generates a hypothesis. To test the consistency of the predicted inter pathway Pearson correlation in the validation data sets D, we use the following performance measure Vij: knowledge from pathway databases can be obtained by first evaluating if the prior information is consistent with the data being investigated.