The overall objective of the proposed center CCHI is to investigate the adaptive immune response in influenza vaccination and immunity. The genomics core will serve two research projects (Projects 2 and 3), and the purpose of the core is to provide leading edge genomic techniques, tools, and equipment to aid in the completion of the research objectives. We will 1) provide research projects with convenient and rapid access to highly multiplexed qRT-PCR as well as next-generation sequencing (NGS) including immune repertoire sequencing; 2) provide a novel platform and methodology to enable studies of immune cell responses to infection and vaccination at single-cell resolution; 3) optimize the single-cell approaches for each research project; 4) bridge the gap between research projects and the bioinformatics core by turning raw samples into pre-processed data ready for in-depth statistical and analytical analysis; and 5) serve as a source of information to research projects with respect to genomic technology and tools.
The specific aims of the genomics core are:
Specific Aim 1 - Provide access to genomics technologies. The Genomics Core will carry out NGS sequencing on the samples generated by the research projects, as well as provide access to the single-cell analysis platform. The core also has a variety of peripheral equipment for sequencing library preparation and quality control, which will also be available to the projects. The core can also process raw sequence data ready to be interfaced with the bioinformatics core's analytical tools, if needed.
Specific Aim 2 - Optimize single-cell approaches for whole transcriptome analysis of immune cells. The methodology and pipeline for single-cell whole transcriptome profiling allows elucidation of the transcriptional profile for all genes from each single cell in an automated fashion without complex hands-on workflows. This platform can be coupled with either NGS for whole transcriptome analysis, or with highly multiplexed qRT-PCR for targeted gene expression analysis. The core will optimize this methodology to work with immune cells, which are smaller in size and lower in RNA content than the epithelial cells that were used to initially validate the technology.

Public Health Relevance

The influenza virus negatively impacts public health and well being every year, and contributes a significant financial burden to the health system. The proposed CCHI center aims to understand the immune response to influenza at multiple levels, including at the genomic and transcriptomic level. The genomics core plays an essential role in this objective by providing research projects access to cutting edge genomic tools, thereby helping to address questions of immunological health in the context of influenza.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI057229-15
Application #
9648679
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Ramachandra, Lakshmi
Project Start
Project End
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
15
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Goltsev, Yury; Samusik, Nikolay; Kennedy-Darling, Julia et al. (2018) Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging. Cell 174:968-981.e15
Gee, Marvin H; Sibener, Leah V; Birnbaum, Michael E et al. (2018) Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro. Proc Natl Acad Sci U S A 115:E7369-E7378
Cheung, Peggie; Vallania, Francesco; Warsinske, Hayley C et al. (2018) Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell 173:1385-1397.e14
Mamedov, Murad R; Scholzen, Anja; Nair, Ramesh V et al. (2018) A Macrophage Colony-Stimulating-Factor-Producing ?? T Cell Subset Prevents Malarial Parasitemic Recurrence. Immunity 48:350-363.e7
Kooreman, Nigel G; Kim, Youngkyun; de Almeida, Patricia E et al. (2018) Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo. Cell Stem Cell 22:501-513.e7
Haynes, Winston A; Tomczak, Aurelie; Khatri, Purvesh (2018) Gene annotation bias impedes biomedical research. Sci Rep 8:1362
Sweeney, Timothy E; Thomas, Neal J; Howrylak, Judie A et al. (2018) Multicohort Analysis of Whole-Blood Gene Expression Data Does Not Form a Robust Diagnostic for Acute Respiratory Distress Syndrome. Crit Care Med 46:244-251
Kronstad, Lisa M; Seiler, Christof; Vergara, Rosemary et al. (2018) Differential Induction of IFN-? and Modulation of CD112 and CD54 Expression Govern the Magnitude of NK Cell IFN-? Response to Influenza A Viruses. J Immunol 201:2117-2131
Wilk, Aaron J; Blish, Catherine A (2018) Diversification of human NK cells: Lessons from deep profiling. J Leukoc Biol 103:629-641
Sweeney, Timothy E; Wynn, James L; Cernada, María et al. (2018) Validation of the Sepsis MetaScore for Diagnosis of Neonatal Sepsis. J Pediatric Infect Dis Soc 7:129-135

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