Systems Biology and Biostatistics Core

CORE 2 SUMMARY The overall goal of the Systems Biology and Biostatistics Core is to provide service to advance the knowledge of systemic and gut human immunity in children and adults, by furnishing systems biology, bioinformatics, and biostatistics expertise to strengthen, support, and augment the research conducted in the Research Projects.

The Systems Biology and Biostatistics Core aims to deliver expertise and service to perform integrative network modeling of multiscale, multi-OMICs data to identify key drivers of disease severity and host response to vaccination and infection. To reach this overall goal, the System Biology and Biostatistics Core will i) support the

Research Projects within the proposed Enteric CCHI by integrating the rich multi-OMICs, immunological, imaging and clinical data generated within each project; ii) aid in validating the hypotheses generated in the Research Projects to further our understanding of the protective immunological mechanisms of mucosal and systemic

immunity to vaccination and infection with enteric pathogens in children and adults; and iii) provide advanced Biostatistics expertise. Such an endeavor requires state-of-the art integrative network approaches to construct, analyze and validate multiscale networks of enteric bacterial infection and vaccination through integration of

large-scale molecular, cellular, and pathophysiological data in an unbiased manner. Our approaches will incorporate these multi-dimensional data into mechanistic network models to predict outcomes of exposure to wild-type and vaccine-strain bacteria and/or epigenetic immune modulators or adjuvants. Specifically, we will

develop and apply several novel differential analysis and multiscale network inference approaches to identify molecular signatures, coexpression modules and causal relationships that will be further employed to discover key regulators and pathways underlying vaccination and infection pertaining enteric pathogens. Such systems

approaches are completely data-driven and present global and unbiased maps of regulatory relationships involving hundreds of thousands of interactions, with significantly improved power to uncover novel host- pathogen pathways and driver genes. For this purpose, the Systems Biology and Biostatistics Core will deliver

the following: Aim 1, assembled large scale multi-omics datasets, identified molecular, clinical and immunological signatures and integrated bulk and single-cell data, in particular cell-type information and B-cell antibody repertoire; Aim 2, mechanistic molecular networks in response to vaccination and infection with enteric

pathogens; Aim 3, validated multiscale multi-Omics networks; and Aim 4, biostatistics expertise to help in the development of optimal experimental designs. The Core’s leadership have demonstrated a strong track record of employing systems biology and biostatistics approaches, ensuring the success of the proposed aims.

Therefore, we expect the service and expertise provided by the Systems Biology and Biostatistics Core will have a profound impact on the proposed Enteric CCHI to advance our knowledge of systemic and gut human immunity to accelerate the development of novel and better vaccines for enteric bacterial pathogens.