Led by Dr. Daphne Koller, together with Drs. Robert Tibshirani and AtuI Butte, this series of bioinformatics projects will focus on the development of computational methods for analyzing the cellular network underlying the immune system and for understanding how this network is perturbed by the response to vaccine. This project will build on our successful development of new deconvolution software (csSAM) to extend it to the development of applications to other datasets in addition to whole blood gene expression such as serum cytokines and phosphoflow. Building on existing successful tools this team has previously developed, cell-specific deconvolved data will then be used to construct the regulatory network of each of the different cell-types present in peripheral blood as well as the inter-cellular network between them. Integrating the data collected from all ofthe other projects in this proposal, this project will develop computational tools for predicting vaccine responses, and for identifying common vaccine mechanisms and genetic correlates with response. The learned models will provide novel scientific insights regarding the immune system, including: the relationships between genotype, gene expression, phosphoprotein levels, and phenotype;the interactions between genes within an immune cell;and the cytokine-mediated interaction between different immune cells. All these will be used for the specification of human immune metrics.
The specific aims for Project 7 are to develop:
Aim 1 : Methods for analysis of data derived from mixed samples;
Aim 2 : Methods for using diverse data to construct network models for immune system cells;
Aim 3 : Methods for understanding the factors affecting immune response;and to:
Aim 4 : Use systems-level analysis to identify causal polymorphisms that affect immune response.

Public Health Relevance

This proposal will integrate diverse high-throughput data into a unified framework that provides a deeper scientific understanding about the role of different immune system components and the mechanisms by which they communicate with each other. These tools will also significantly impact human health in supporting the development of better diagnostic tools and personalized treatment of disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI090019-05
Application #
8705367
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
City
Stanford
State
CA
Country
United States
Zip Code
94304
Bongen, Erika; Vallania, Francesco; Utz, Paul J et al. (2018) KLRD1-expressing natural killer cells predict influenza susceptibility. Genome Med 10:45
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
Nair, Nitya; Feng, Ningguo; Blum, Lisa K et al. (2017) VP4- and VP7-specific antibodies mediate heterotypic immunity to rotavirus in humans. Sci Transl Med 9:
Brodin, Petter; Davis, Mark M (2017) Human immune system variation. Nat Rev Immunol 17:21-29
Haddon, D James; Wand, Hannah E; Jarrell, Justin A et al. (2017) Proteomic Analysis of Sera from Individuals with Diffuse Cutaneous Systemic Sclerosis Reveals a Multianalyte Signature Associated with Clinical Improvement during Imatinib Mesylate Treatment. J Rheumatol 44:631-638
Furman, David; Chang, Junlei; Lartigue, Lydia et al. (2017) Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat Med 23:174-184
HIPC-CHI Signatures Project Team; HIPC-I Consortium (2017) Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses. Sci Immunol 2:
O'Gorman, W E; Kong, D S; Balboni, I M et al. (2017) Mass cytometry identifies a distinct monocyte cytokine signature shared by clinically heterogeneous pediatric SLE patients. J Autoimmun :
Blazkova, Jana; Gupta, Sarthak; Liu, Yudong et al. (2017) Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy. J Immunol 198:2479-2488
Rubelt, Florian; Bolen, Christopher R; McGuire, Helen M et al. (2016) Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells. Nat Commun 7:11112

Showing the most recent 10 out of 121 publications