Core C (Computational Core) - Abstract/Summary Over the past years, the Computational Core has successfully completed multiple large-scale bioinformatics software development and data generation/analysis projects and built an extensible computational infrastructure to accommodate various computational needs. The experience acquired, the software base built, and the infrastructure developed can be leveraged to provide effective and high-quality computational support to all P01 Project teams. Aim 1 will build an integration/analysis hub to gather public data for the prosecution of in silico studies that are complementary or in addition to those that Project investigators conduct in their respective groups. Computational Core supports P01 researchers in the common goal of defining and validating signatures/biomarkers predicting the reliance of PDAC on alternative pathways or regulatory networks responsible for tumor growth – particularly in the context of facile comparison to external data. In silico external data validation has the advantage of being able to scan the available large data sets to seek for quick answers that would otherwise require commitment of both time and money to accomplish. Aim 2 focuses on high-quality cancer genomic data analysis. We will provide support to P01 investigators in statistical analysis on genomic and transcriptomic data to identify differentially expressed genes between cell populations, genomic groups, disease subtypes, or treatment conditions for biomarker discovery. To better support the increasing need of tumor microenvironment (TME) research, we implemented advanced analytic approaches on bulk and single-cell RNA data for biomarker discovery, immuno-clustering, and cancer driving feature identification. Combining insights from single-cell analysis and bulk sequencing data will greatly help the advance of cancer immunotherapy research. Aim 3 will enable P01 investigators to perform genomic characterization using next generation sequencing technology by leveraging our existing pipeline. We have built a production level NGS data processing and analysis pipeline that has been used intensively for internal projects and collaborative research. The automated pipeline can also be used to support the NGS related efforts of P01 Projects 1, 2 and 3 to maintain high quality and standards. In summary, the Computational Core is an experienced team with proven records of analytical innovation in response to scientific needs. We expect that technologies and analytical approaches relevant to P01 Projects will continue to evolve rapidly and new opportunities will arise. The Computational Core will keep providing P01 investigators with the needed expertise and infrastructure critical to conducting the proposed research.