New approaches are being developed to maximally integrate information from the data generated using "omics" technologies to uncover pathways involved in disease pathogenesis. In this program project, we will take advantage of state-of-the-art molecular and analytic tools through well-integrated Projects and Cores to better understand how biological processes are defined at the molecular level, how they can be disrupted to cause nonsyndromic coronal craniosynostosis, and how we can assess the risk of and intervene to prevent this birth defect. Molecular/Analytic Core B objective is to generate high quality genomic and imaging data and provide analytic support for all three Projects to allow comprehensive integrative analyses for the Craniosynostosis Network. The Molecular/Analytic Core will fulfill five major tasks: 1) to generate and quality- control high- and medium throughput genetic and genomic data to be used by Projects II and III;2) to generate analyzable morphometric craniofacial data from pre-operational computer tomography (CT) scans;3) to integrate clinical information obtained from the participating sites with imaging and genetic/genomic data and organize them so that they meet the needs of different Projects, 4) to provide general and specialized statistical support to Project I and Project II, and 5) to facilitate the selection of the top genetic signals observed across all Projects within the Craniosynostosis Network for the replication study. DNA samples will be processed and analyzed using the Illumina HumanOmniExpressExome high throughput genotyping chip, whole exome sequencing, and medium throughput genotyping for the replication studies in the DNA core at Icahn School of Medicine at Mount Sinai. CT images will be processed to generate craniofacial measurements and craniosynostosis severity scores to be used for association studies and to select most informative individuals for sequencing. Genomic and imaging data will be quality-controlled and linked with the phenotype data obtained from the participating sites. The Molecular/Analytic Core will also facilitate bioinformatics and statistical analyses pertinent to each project, including gene expression analysis, rare variant analysis, genome-wide association studies, pathway-based analysis, and replication studies by generating appropriate dataset formats and disseminating results obtained by each project. In addition, the Molecular/Analytic Core will be responsible for data storage and integration across the Projects and Cores, as well as dataset preparation for future data deposition and sharing.