The Immunological Genome Project (ImmGen) is a collaborative group of immunology and computational biology laboratories who have performed in current grant period using a rigorous data generation and QC pipeline, a thorough dissection of gene expression and its regulation in >250 defined cell populations of the mouse immune system. These data were used to computationally define co-regulated gene modules and predict putative regulators. ImmGen data have become an important resource for the immunology community, with frequently consulted web and smartphone supports. The proposed continuation will harness the collective strengths of the ImmGen group. It will complete the existing compendium (missing or recently described populations, transcriptome changes upon cell migration). Consortium labs will analyze the response to a panel of molecular triggers (vaccination, adjuvants, gut microbes, super-antigens, TLR ligands, allergic challenge): are there responses in un-recognized target cells, how does transcriptional activation resonate secondarily system-wide? The profiling will also extend to non-coding mlRNAs and lincRNAs, and apply high-throughput RNA-sequencing to augment and refine the microarray data. In addition, we will build on our computational analyses of regulatory networks, validating and strengthening these predictions, and assessing their molecular underpinning. Chromatin immunoprecipitation detected by sequencing (ChlP-seq) will be used to relate the expression profiles to the underlying chromatin structure, loading with Pol-ll, and DNA methylation, in a set of 30 cell types already profiled in ImmGen. This will provide a unique perspective on chromatin/transcription relationships in primary cells in vivo. We will also collaborate with the international Knockout Mouse Project (KOMP) to analyze transcriptional changes and their immunological consequences in a panel of 200 KG animals. 50 of these will be chosen to target transcription factors (TFs) predicted to be essential nodes by our existing studies;in complement, the genomic locations of these TFs will be mapped by ChlP-seq by collaborators at Genentech. ImmGen data and meta-data serve a need in Immunology research and are widely used. This important resource will be maintained and curated, expanding the several browsing modes already in place to support more complex user queries and data requests, enriching the data presented and its connectivity. The smartphone/tablet information space will continue to be supported, enriching the content served locally or addressable through on-line queries.
Through the high quality gene expression data it has generated, ImmGen has become an important resource in Immunology research. This next cycle of funding will explore broadly the response to microbial and antigenic challenge, laying the groundwork for a fuller understanding of how the immune system responds to triggers.
|Stubbington, Michael J T; Rozenblatt-Rosen, Orit; Regev, Aviv et al. (2017) Single-cell transcriptomics to explore the immune system in health and disease. Science 358:58-63|
|Mostafavi, Sara; Yoshida, Hideyuki; Moodley, Devapregasan et al. (2016) Parsing the Interferon Transcriptional Network and Its Disease Associations. Cell 164:564-78|
|Dwyer, Daniel F; Barrett, Nora A; Austen, K Frank et al. (2016) Expression profiling of constitutive mast cells reveals a unique identity within the immune system. Nat Immunol 17:878-87|
|ImmGen Consortium (2016) Open-source ImmGen: mononuclear phagocytes. Nat Immunol 17:741|
|Cortez, Victor S; Cervantes-Barragan, Luisa; Robinette, Michelle L et al. (2016) Transforming Growth Factor-? Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands. Immunity 44:1127-39|
|Robinette, Michelle L; Fuchs, Anja; Cortez, Victor S et al. (2015) Transcriptional programs define molecular characteristics of innate lymphoid cell classes and subsets. Nat Immunol 16:306-17|
|Mostafavi, Sara; Ortiz-Lopez, Adriana; Bogue, Molly A et al. (2014) Variation and genetic control of gene expression in primary immunocytes across inbred mouse strains. J Immunol 193:4485-96|
|Desch, A Nicole; Gibbings, Sophie L; Clambey, Eric T et al. (2014) Dendritic cell subsets require cis-activation for cytotoxic CD8 T-cell induction. Nat Commun 5:4674|
|Ericson, Jeffrey A; Duffau, Pierre; Yasuda, Kei et al. (2014) Gene expression during the generation and activation of mouse neutrophils: implication of novel functional and regulatory pathways. PLoS One 9:e108553|
|Jakubzick, Claudia; Gautier, Emmanuel L; Gibbings, Sophie L et al. (2013) Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39:599-610|
Showing the most recent 10 out of 39 publications