The problem can be seen as a model selection problem, blog of sinaling pathways where different comparisons are thought of as different model structures Inhibitors,Modulators,Libraries and, given experimental lineage commitment profile data D, the marginal likelihood P, j 1.. ,5, is used to score different models. Using the Bayes theorem, the marginal likelihoods can be converted into posterior probabilities of different hypothesis. These Bayesian mo del scores can be used further to quantify genes, which are specific for a certain lineage. For example, the pro bability of a gene being differentially regulated in Th2 lineage, i. e. score for Th2 is P P P P P. Genes which are dif ferentially regulated in each of the conditions can be found by quantifying the probabilities P P or the three probabilities of differential regulation.
Inhibitors,Modulators,Libraries Each score quantifies the amount of differential regulation, which refers to distinct temporal behavior from other lineages. Inhibitors,Modulators,Libraries The methodology generalizes to any number of lineages conditions. Our method copes with non uniform sampling, is able to model non stationary biological pro cesses, can make comparisons for paired samples, and can carry out the analysis with dif ferent number of replicates and missing data. Importantly, the method affords comparison of more than two condi tions of interest and is widely applicable to different ex perimental platforms. LIGAP identifies signatures of Th0, Th1 and Th2 cell lineages We analyzed the genome wide gene expression time course data from Th0, Th1 and Th2 lineages using LIGAP.
For all genes, the method outputs the posterior Inhibitors,Modulators,Libraries probability values for each of the five hypotheses and also computes the scores for genes being differentially regulated in the Th Inhibitors,Modulators,Libraries subsets. An overview of the differen selleckchem tially regulated genes is shown in Figure 2, where the four dimensional data points representing the condition specificities are projected into a plane using the principle component analysis. This demonstrates the con venience of the presented method as we are able to reduce highly complex data into a meaningful four dimensional representation using a unified probabilistic framework. In Figure 2 individual points represent different genes and every gene is associated with four probabilities, P, P, P, and P. Note that IFN�� has the three probabilities P, P, and P close to unity because the probability P is close to unity. We set a criterion for the probabilities to call the differentially regulated probe sets, this threshold is in accordance with the Jeffreys interpretation of strong evidence for the Bayes factor. In addition, we required a minimum of two fold change between a lineage and all other lineages at some time point during the differentiation for a gene to be called as differentially regulated.