The Bioinformatics and Single Cell Analysis Core

SUMMARY The Bioinformatics and Single Cell Core (BSCAC) in the Digestive and Liver Disease Research Center (CU- DLDRC) seeks to enhance our understanding of the mechanisms that drive the development of digestive diseases. Single cell-based and spatial transcriptomics in conjunction with innovative bioinformatic analyses are transforming our ability to understand dynamic and multidimensional biological processes in digestive diseases and provide deep insights into the complex cell-cell, ligand-receptor and gene regulatory networks that regulate health and disease. BSCAC will provide state-of-the-art analyses of human and murine sequencing data that go far beyond the capability of most individual CU-DLDRC labs. For this, the BSCAC will provide its members with digestive organ-focused analyses of bulk, single-cell (sc), single-nucleus (sn) and single-organoid RNA- sequencing (RNA-seq), scATAC-seq, and spatial transcriptomics, as well as innovative analyses of cell-cell interactions and transcriptional master regulators. Understanding these processes may provide novel opportunities for diagnosis and/or therapeutic interventions. Through multi-core workflows that link the BSCAC to the Clinical Biobanking & Research Core (CBRC), the Organoid& Cell Culture Core (OCCC) and Bioimaging Core (BIC) for analyses of patient, cell and organoid samples, the BSCAC will enable translational and multi- disciplinary research. BSCAC will significantly benefit the CU-DLDRC and its members by (i) providing cost- effective and prioritized access to state-of-the-art analyses; (ii) empowering CU-DLDRC researchers to perform cutting-edge research on digestive tract epithelial biology, homeostasis and interactions, there closely linking to the central theme of the CU-DLDRC; (iii) contributing a platform for translational research and collaboration between clinical and basic researchers; and (iv) educating and training CU-DLDRC members, Pilot and Feasibility awardees, and their labs in innovative technologies and novel developments in this rapidly evolving field. The BSCAC will be led by scientists with strong track records in bioinformatics and single cell analysis. Dr. Peter Sims, Associate Professor of Systems Biology, will serve as director and Dr. Robert Schwabe, Professor of Medicine, as associate director. BSCAC will be a highly utilized resource with 92% of CU-DLDRC members indicating use in surveys. BASCAC will contribute to the CU-DLDRC’s mission through these interrelated Specific Aims: To provide CU-DLDRC members with digestive organ-focused bioinformatic analyses of bulk RNA-seq, sc/snRNA-seq and spatial transcriptomics data from human and mouse samples (Aim 1). To provide CU-DLDRC members with advanced digestive organ-focused bioinformatic analyses of cell-cell interactions, transcriptional master regulator and cell trajectories (Aim 2). To provide training and education to CU-DLDRC members via workshops and seminars (Aim 3). Through these Aims as well as seamless integration with the other CU-DLDRC cores, BSCAC will contribute to the mission of the CU-DLDRC and provide significant benefit to its members.