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.
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.
|Lee, Jung-Rok; Haddon, D James; Wand, Hannah E et al. (2016) Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus. Sci Rep 6:27623|
|Kidd, Marie J; Jackson, Katherine J L; Boyd, Scott D et al. (2016) DJ Pairing during VDJ Recombination Shows Positional Biases That Vary among Individuals with Differing IGHD Locus Immunogenotypes. J Immunol 196:1158-64|
|Fang, Fengqin; Yu, Mingcan; Cavanagh, Mary M et al. (2016) Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals. Cell Rep 14:1218-31|
|Looney, Timothy J; Lee, Ji-Yeun; Roskin, Krishna M et al. (2016) Human B-cell isotype switching origins of IgE. J Allergy Clin Immunol 137:579-586.e7|
|Su, Laura F; Del Alcazar, Daniel; Stelekati, Erietta et al. (2016) Antigen exposure shapes the ratio between antigen-specific Tregs and conventional T cells in human peripheral blood. Proc Natl Acad Sci U S A 113:E6192-E6198|
|Lund, Peder J; Elias, Joshua E; Davis, Mark M (2016) Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. J Immunol 197:3086-3098|
|Nair, N; Newell, E W; Vollmers, C et al. (2016) High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry. Mucosal Immunol 9:68-82|
|Finak, Greg; Langweiler, Marc; Jaimes, Maria et al. (2016) Standardizing Flow Cytometry Immunophenotyping Analysis from the Human ImmunoPhenotyping Consortium. Sci Rep 6:20686|
|Rubelt, Florian; Bolen, Christopher R; McGuire, Helen M et al. (2016) Individual heritable differences result in unique cell lymphocyte receptor repertoires of naÃ¯ve and antigen-experienced cells. Nat Commun 7:11112|
|Pan, Junliang; Dinh, Thanh Theresa; Rajaraman, Anusha et al. (2016) Patterns of expression of factor VIII and von Willebrand factor by endothelial cell subsets in vivo. Blood 128:104-9|
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