Data management and analysis core

Yale University, New Haven CT

Investigators

Abstract

CORE 4 – Data Management and Analysis Core – SUMMARY Right after birth, the neonatal immune system, adapted for the unique challenges of in utero development including maternal tolerance, must develop rapidly to tackle rapid microbial colonization post-delivery and provide protection against infections and other stresses that the newborn will encounter during the first year of life and beyond. Trajectories of immune components during the first year of life, shaped by exposure to infections and perturbed in cases of preterm birth, could dramatically shape the baseline immune state and “set point” of an individual to impact subsequent immune response in early childhood and beyond. These baseline immune states continue to evolve with age as a function of intrinsic development and continual environmental exposures and can determine the protective responses to infections and vaccination. In addition to environmental exposures, genetics can play an important role as abnormal immune development and defects in the establishment of protective baseline immune states can arise in individuals with inborn errors in immunity (IEIs), resulting in immune pathologies including susceptibility to infections and uncontrolled inflammation. There remain major knowledge gaps in 1) the understanding of the establishment, dynamics, and future immune response impacts of baseline homeostatic immune states during childhood, 2) the molecular underpinnings of numerous IEIs, and 3) how genetics and inflammatory exposures together shape immune status to impact future immune response outcomes. The Program will carry out high-throughput, multimodal characterization of immune cells and molecules from multiple pediatric cohorts and use a systems immunology approach to integrate datasets, identifying the key principles underlying pediatric immune development and response. The Data Management and Analysis (DMAC) Core will facilitate this systems immunology program by providing a centralized infrastructure for data management and storage, and an innovative strategy for sharing data and resources that prioritizes timely dissemination of data both in and outside the Program and easy replication of computational analyses by the scientific community. The Core will provide biostatistical support and consultation across projects to ensure reproducibility, responsible statistical interpretation, and optimal resource usage via iterative study design. The data generated across projects will be analyzed by the Core using standardized, state-of-the-art bioinformatics procedures. Crucially, the Core will work with the Project teams to compare and integrate the predictors and immune signatures identified across modalities and projects, with the goal of developing a framework capable of connecting immune status and response behavior across pediatric development to generate testable predictions and hypotheses. The Core will utilize and integrate statistical, machine learning, and dynamical modeling approaches. Overall, the DMAC Core will support and advance the overarching goal of the Program to elucidate the key principles of pediatric immune development and response in humans.