Quality control Quality control is done in two rounds of processing. In the first round, which is part of the gene selection, some drugs came by with no signature gene sets. this is a result that no genes were consistently differentially expressed in samples from this drug. The samples from those drugs were removed. Although selleck chem Nutlin-3a some drugs were determined with a signature gene set, one or more of the outlier sam ples may not agree with the rest. To address this pro blem, a second round of further quality control process was also performed on the cMap samples. In order to remove these inconsistent samples, a new scheme was proposed in Figure 6. MoA and MoNet generation According to the definition of MoA, two compounds are in the same MoA if they share the same genomic signa ture.

This is equivalent to say that the samples from these two compounds are highly correlated. In contrast, the samples from different MoAs should have a correlation distributed according to the distribution of the population correlation. To determine if two drugs i and j belong to a MoA, a hypothesis testing formulation is developed with the null hypothesis defined by where Dij is the Distance assessment between sample i and j, and pb is the the distribution of the population distance. pb is estimated empirically based on the pair wise distances between all sample pairs of the same cell line. Then, a p value of 0. 01 is chosen as the significance level and the corresponding distance is determined as the threshold. Hierarchical clustering is performed on all the samples distances.

then clusters are determined by cutting the linkage at the threshold and the resulted clusters were defined as the MoAs. Notice that since each MoA was generated totally based on the threshold obtained from the background distribution, some MoAs may contain large number of samples while other MoAs only contain few samples from one or two drugs. this is natural and reasonable because some compounds just do not share the treatment effectiveness with others. Once the MoAs were identified, it was then desirable to reveal the relationship of the MoAs in terms of their therapeutic effects. Instead of investigating individual compound in an isolated fashion, MoNet will enable research to explore a set of compounds that share the same MoA Signature genes, as well as their correlated MoAs. Drug Effectiveness Prediction Using the MoNet and the MoA, one Cilengitide can 1 predict this research drug effectiveness of a new compound and/or 2 screen compounds to predict the therapeutic effectiveness of different compounds if applied to an indi vidual tumor. For drug effectiveness prediction, the expression profile of cells/tissue treated by a new compound needs to be obtained and the goal is to identify the MoA of the compound.