BIOINFORMATICS CORE

CORE B The overarching theme of this PPG is to understand the genetics and biology of von Willebrand factor (VWF) and von Willebrand disease (VWD). As a large percentage of the proposal includes Genomics and Multi-Omics approaches of large cohorts that will require extensive bioinformatic analyses, we propose to centralize the process by establishing a Bioinformatics Core led by Nathan Stitziel, MD, PhD. The data generated from these experiments will require extensive analysis, including sophisticated computational, bioinformatics and statistical analyses. Core B will serve the genomic sequencing, proteomics, lipidomics and metabolomics needs of the different Projects, centralize the bioinformatics data analyses and facilitate the flow of data with a secure interface. For the completion of these goals we propose three specific aims: Specific Aim 1. To oversee data transfer, sample processing, and quality control. Core B will receive the clinical/phenotypic data associated with the patient samples, and the specimens from Core C. The clinical/phenotypic data will be standardized and harmonized to comply with the Protected Health Information (PHI) and HIPAA guidelines and will be available for all four projects through a dedicated resource: the Zimmerman Analytic Platform (ZAP). All data will be de identified. Specimens will be processed at GTAC and/or MTAC centers to generate sequencing and multi-omics data. All multi-omics data samples will be processed in RIS, including the upstream pre-processing steps of the raw data, using the same computational pipelines, workflows and quality controls in order to ensure integrity, compatibility and reproducible data for all four projects and all cores supported by this PPG. Specific Aim 2: To perform bioinformatic data analysis. Core B leaders and the dedicated team will work closely with all investigators involved in this PPG to provide comprehensive and innovative support for study design, analysis, interpretation, and integration of a broad range of the genomics and multi-omics data. Data analysis for all projects will be performed using appropriate statistical and computing methodologies. We will also utilize several publicly available resources to provide custom annotations. Specific Aim 3: To secure data management and data sharing. Core B will establish a centralized interactive database system and data management structure that facilitates the entry, storage and retrieval of all data generated by the program projects, and permits the controlled exchange of information across all Projects and Cores. By providing data access to investigators, sharing technical capabilities, and ensuring the quality of the data, the data management component of this core will facilitate achievement of the Project’s aims and encourage exploratory analyses beyond those stated in the application. Core B will also ensure that raw and/or processed data are submitted to stable repositories in accordance with NIH Data sharing policy. In addition, Core B will make available a new open access resource called Zimmerman Analytic Platform (ZAP), which is a user-friendly website that will include summary statistics for the genomic and phenotypic association and the multi-omics integration data from all Projects. Project Number: 1P01HL173579-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Nathan Stitziel | Institution: WASHINGTON UNIVERSITY, SAINT LOUIS, MO | Award Amount: $337,604 | Activity Code: P01 | Study Section: Special Emphasis Panel[ZHL1 PPG-F (O1)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1P01HL17357901A1