The Computational and Bioinformatics Analysis Core (Core D) functions in an advisory capacity to determine the direction and set-up of experiments, and, most importantly, in a service capacity to perform detailed analyses of the microarray data generated by the three Program Projects and Cores B and C. The analysis core will closely work with these cores and investigators from Program Projects 1-3 to refine the questions to be asked. Generally, the analysis of microarray data will be directed at elucidating whether differences in chromatin structure, i.e. histone modifications and DMA methylation, exist between different human embryonic stem cell lines, which in turn influence their hematopoietic, neural, and germ line differentiation potential. As high-throughput datasets from all three Program Projects become available, we will integrate data from the different ES cell lines and the three differentiation pathways and utilize the expression, histone modification and DMA methylation data in combination with published transcription factor binding data sets to begin to understand i) how change cell fate are reflected in changes in chromatin structure; and ii) if there we can detect details in chromatin structure in the different ES cell lines that predict into which cell type the different ES cells preferentially differentiate. The Core is strongly supported by Dr. Matteo Pellegrini, who's laboratory utilizes the data generated by high throughput sequencers and high-density microarrays to model regulatory networks. In addition to analyzing microarray data, the core will perform standard statistical analysis of data obtained from in vivo studies on the functionality of differentiated cells. One example for this type of analysis is to test if there are different reconstitution frequencies and ex vivo cellular functional responses of T cells differentiated in vitro from different parental ES cell lines.