1,444 results on '"Benoist, Christophe"'
Search Results
2. The interweaved signatures of common-gamma-chain cytokines across immunologic lineages
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Baysoy, Alev, Seddu, Kumba, Salloum, Tamara, Dawson, Caleb A, Lee, Juliana J, Yang, Liang, Gal-oz, Shani, Ner-Gaon, Hadas, Tellier, Julie, Millan, Alberto, Sasse, Alexander, Brown, Brian, Lanier, Lewis L, Shay, Tal, Nutt, Stephen, Dwyer, Daniel, Benoist, Christophe, and Consortium, The Immunological Genome Project
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Biomedical and Clinical Sciences ,Genetics ,Vaccine Related ,Underpinning research ,1.1 Normal biological development and functioning ,Cytokines ,CD8-Positive T-Lymphocytes ,Signal Transduction ,Cell Differentiation ,Immunological Genome Project Consortium ,Medical and Health Sciences ,Immunology ,Biomedical and clinical sciences ,Health sciences - Abstract
"γc" cytokines are a family whose receptors share a "common-gamma-chain" signaling moiety, and play central roles in differentiation, homeostasis, and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine. Responses include a major downregulation component and a broad Myc-controlled resetting of biosynthetic and metabolic pathways. Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises were uncovered: IL2 effects in mast cells, shifts between follicular and marginal zone B cells, paradoxical and cell-specific cross-talk between interferon and γc signatures, or an NKT-like program induced by IL21 in CD8+ T cells.
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- 2023
3. The XXL Survey L. Active galactic nucleus contamination in galaxy clusters: Detection and cosmological impact
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Bhargava, Sunayana, Garrel, Christian, Koulouridis, Elias, Pierre, Marguerite, Valtchanov, Ivan, Cerardi, Nicolas, Maughan, Ben J., Aguena, Michel, Benoist, Christophe, Baguley, Cale, Ramos-Ceja, Miriam E., Adami, Christophe, Chiappetti, Lucio, Vignali, Cristian, and Willis, Jon P.
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Astrophysics - Cosmology and Nongalactic Astrophysics ,Astrophysics - Astrophysics of Galaxies ,Astrophysics - High Energy Astrophysical Phenomena - Abstract
X-ray observations of galaxy clusters are impacted by the presence of active galactic nuclei (AGNs) in a manner that is challenging to quantify, leading to biases in the detection and measurement of cluster properties for both astrophysics and cosmological applications. We detect and characterise clusters contaminated by central AGNs within the XXL survey footprint and provide a systematic assessment of the cosmological impact of such systems in X-ray cluster samples. We introduce a new automated class for AGN-contaminated (AC) clusters in the XXL source detection pipeline. The majority of these systems are otherwise missed by current X-ray cluster-detection methods. The AC selection is also effective in distinguishing AGN and cool-core presence using supplementary optical and infrared information. We present 33 AC objects, including 25 clusters in the redshift range, $0.14 \leq z \leq 1.03$, and eight other sources with significantly peaked central profiles. Six of these are new confirmed clusters. We computed the missed fraction of the XXL survey, which is defined as the fraction of genuine clusters that are undetected due to their centrally peaked X-ray profiles. We report seven undetected AC clusters above $z > 0.6$, in the range where X-ray cluster detection efficiency drops significantly. The missed fraction is estimated to be at the level of $5\%$ for the 50 square-degree XXL area. The impact on cosmological estimates from missed clusters is negligible for XXL, but it produces a tension of $\sim 3\sigma$ with the fiducial cosmology when considering larger survey areas. Looking towards surveys such as eROSITA and \textit{Athena}, larger areas and increased sensitivity will significantly enhance cluster detection, and therefore robust methods for characterising AGN contamination will be crucial for precise cluster cosmology, particularly in the redshift $z > 1$ regime., Comment: 26 pages, 11 figures (33 images of AC objects presented in the appendix), 3 tables. Accepted for publication in A&A
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- 2023
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4. FOXP3 recognizes microsatellites and bridges DNA through multimerization
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Zhang, Wenxiang, Leng, Fangwei, Wang, Xi, Ramirez, Ricardo N., Park, Jinseok, Benoist, Christophe, and Hur, Sun
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- 2023
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5. A discrete ‘early-responder’ stromal-cell subtype orchestrates immunocyte recruitment to injured tissue
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Yaghi, Omar K., Hanna, Bola S., Langston, P. Kent, Michelson, Daniel A., Jayewickreme, Teshika, Marin-Rodero, Miguel, Benoist, Christophe, and Mathis, Diane
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- 2023
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6. Regulatory T cells in the face of the intestinal microbiota
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Ramanan, Deepshika, Pratama, Alvin, Zhu, Yangyang, Venezia, Olivia, Sassone-Corsi, Martina, Chowdhary, Kaitavjeet, Galván-Peña, Silvia, Sefik, Esen, Brown, Chrysothemis, Gélineau, Adélaïde, Mathis, Diane, and Benoist, Christophe
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- 2023
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7. Identification and Properties of Isolated Field Elliptical Galaxies from CFHTLS-W1
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Ulgen, E. Kaan, Alis, Sinan, Benoist, Christophe, Yelkenci, F. Korhan, Cakir, Oguzhan, Fisek, Suleyman, and Karatas, Yuksel
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Astrophysics - Astrophysics of Galaxies - Abstract
We present a catalogue of isolated field elliptical (IfE) galaxies drawn from the W1 field of the Canada-France-Hawaii Telescope Legacy Survey (CFHTLS). 228 IfEs were identified from a flux-limited (r<21.8) galaxy catalogue which corresponds to a density of 3 IfE/sq.deg. For comparison we consider a sample of elliptical galaxies living in dense environments, based on identification of the brightest cluster galaxies (BGCs) in the same survey. Using the same dataset for the comparison sample ensures a uniform selection, including in the redshift range as IfEs (i.e. 0.1 < z < 0.9). A comparison of elliptical galaxies in different environments reveals that IfEs and BCGs have similar behaviours in their colours, star formation activities, and scaling relations of mass-size and size-luminosity. IfEs and BCGs have similar slopes in the scaling relations with respect to cluster ellipticals within the $-24 \leq M_{r} \leq -22$ magnitude and $10.2< \textrm{log}( \textrm M_{*}/ \textrm M_\odot)\leq12.0$ mass ranges. Three IfEs identified in this study can be associated with fossil groups found in the same survey area which gives clues for future studies., Comment: 23 pages, 18 figures, 10 tables, accepted for publication in PASA
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- 2022
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8. Validating Synthetic Galaxy Catalogs for Dark Energy Science in the LSST Era
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Kovacs, Eve, Mao, Yao-Yuan, Aguena, Michel, Bahmanyar, Anita, Broussard, Adam, Butler, James, Campbell, Duncan, Chang, Chihway, Fu, Shenming, Heitmann, Katrin, Korytov, Danila, Lanusse, François, Larsen, Patricia, Mandelbaum, Rachel, Morrison, Christopher B., Payerne, Constantin, Ricci, Marina, Rykoff, Eli, Sánchez, F. Javier, Sevilla-Noarbe, Ignacio, Simet, Melanie, To, Chun-Hao, Vikraman, Vinu, Zhou, Rongpu, Avestruz, Camille, Benoist, Christophe, Benson, Andrew J., Bleem, Lindsey, Ćiprianović, Aleksandra, Combet, Céline, Gawiser, Eric, He, Shiyuan, Joseph, Remy, Newman, Jeffrey A., Prat, Judit, Schmidt, Samuel, Slosar, Anže, Zuntz, Joe, and Collaboration, The LSST Dark Energy Science
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Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
Large simulation efforts are required to provide synthetic galaxy catalogs for ongoing and upcoming cosmology surveys. These extragalactic catalogs are being used for many diverse purposes covering a wide range of scientific topics. In order to be useful, they must offer realistically complex information about the galaxies they contain. Hence, it is critical to implement a rigorous validation procedure that ensures that the simulated galaxy properties faithfully capture observations and delivers an assessment of the level of realism attained by the catalog. We present here a suite of validation tests that have been developed by the Rubin Observatory Legacy Survey of Space and Time (LSST) Dark Energy Science Collaboration (DESC). We discuss how the inclusion of each test is driven by the scientific targets for static ground-based dark energy science and by the availability of suitable validation data. The validation criteria that are used to assess the performance of a catalog are flexible and depend on the science goals. We illustrate the utility of this suite by showing examples for the validation of cosmoDC2, the extragalactic catalog recently released for the LSST DESC second Data Challenge., Comment: 46 pages, 33 figures
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- 2021
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9. Adipose-tissue Treg cells restrain differentiation of stromal adipocyte precursors to promote insulin sensitivity and metabolic homeostasis
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Wang, Gang, Muñoz-Rojas, Andrés R., Spallanzani, Raul German, Franklin, Ruth A., Benoist, Christophe, and Mathis, Diane
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- 2024
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10. Gut complement induced by the microbiota combats pathogens and spares commensals
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Wu, Meng, Zheng, Wen, Song, Xinyang, Bao, Bin, Wang, Yuanyou, Ramanan, Deepshika, Yang, Daping, Liu, Rui, Macbeth, John C., Do, Elyza A., Andrade, Warrison A., Yang, Tiandi, Cho, Hyoung-Soo, Gazzaniga, Francesca S., Ilves, Marit, Coronado, Daniela, Thompson, Charlotte, Hang, Saiyu, Chiu, Isaac M., Moffitt, Jeffrey R., Hsiao, Ansel, Mekalanos, John J., Benoist, Christophe, and Kasper, Dennis L.
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- 2024
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11. Mutations from patients with IPEX ported to mice reveal different patterns of FoxP3 and Treg dysfunction
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Leon, Juliette, Chowdhary, Kaitavjeet, Zhang, Wenxiang, Ramirez, Ricardo N., André, Isabelle, Hur, Sun, Mathis, Diane, and Benoist, Christophe
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- 2023
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12. A variegated model of transcription factor function in the immune system
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Chowdhary, Kaitavjeet and Benoist, Christophe
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- 2023
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13. The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries
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Hanna, Bola S., Wang, Gang, Galván-Peña, Silvia, Mann, Alexander O., Ramirez, Ricardo N., Muñoz-Rojas, Andrés R., Smith, Kathleen, Wan, Min, Benoist, Christophe, and Mathis, Diane
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- 2023
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14. ImmGen at 15
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Aguilar, Stephanie Vargas, Aguilar, Oscar, Allan, Rhys, Amir, El Ad David, Angeli, Veronique, Artyomov, Maxim N, Asinovski, Natasha, Astarita, Jilian, Austen, K Frank, Bajpai, Geetika, Barrett, Nora, Baysoy, Alev, Benoist, Christophe, Bellemare-Pelletier, Angelique, Berg, Brad, Best, Adam, Bezman, Natalie, Blair, David, Blander, Julie M, Bogunovic, Milena, Brennan, Patrick, Brenner, Michael, Brown, Brian, Buechler, Matthew, Buenrostro, Jason, Casanova, Maria Acebes, Choi, Kyunghee, Chow, Andrew, Chudnovskiy, Aleksey, Cipoletta, Daniela, Cohen, Nadia, Collins, James J, Colonna, Marco, Cook, Alison, Costello, James, Cremasco, Viviana, Crowl, Ty, Crozat, Karine, Cruse, Richard, D'Angelo, June, Dalod, Marc, Davis, Scott, Demiralp, Cagatay, Deng, Tianda, Desai, Jigar V, Desland, Fiona, Dhainaut, Maxime, Ding, Jiarui, Doedens, Andrew, Dominguez, Claudia, Doran, Graeme, Dress, Regine, Dustin, Michael, Dwyer, Daniel, Dzhagalov, Ivan, Elpek, Kutlu, Ergun, Ayla, Ericson, Jeff, Esomonu, Eunice, Fairfax, Keke, Fletcher, Anne, Frascoli, Michela, Fuchs, Anja, Gainullina, Anastasiia, Gal-Oz, Shani, Gallagher, Michael, Gautier, Emmanuel, Gazit, Roi, Gibbings, Sophie, Giraud, Matthieu, Ginhoux, Florent, Goldrath, Ananda, Gotthardt, Dagmar, Gray, Daniel, Greter, Melanie, Grieshaber-Bouyer, Ricardo, Guilliams, Martin, Haidermota, Sara, Hardy, Randy, Hashimoto, Daigo, Helft, Julie, Hendricks, Deborah, Heng, Tracy, Hill, Jonathan, Hyatt, Gordon, Idoyaga, Juliana, Jakubzick, Claudia, Jarjoura, Jessica, Jepson, Daniel, Jia, Baosen, Jianu, Radu, Johanson, Tim, Jordan, Stefan, Jojic, Vladimir, Kamimura, Yosuke, Kana, Veronica, Kang, Joonsoo, Kapoor, Varun, and Kenigsberg, Ephriam
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Animals ,Gene Expression Regulation ,Gene Regulatory Networks ,Genomics ,History ,21st Century ,Immune System ,Immunologic Techniques ,Mice ,Immunological Genome Project ,Immunology - Published
- 2020
15. The Human Cell Atlas White Paper
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Regev, Aviv, Teichmann, Sarah, Rozenblatt-Rosen, Orit, Stubbington, Michael, Ardlie, Kristin, Amit, Ido, Arlotta, Paola, Bader, Gary, Benoist, Christophe, Biton, Moshe, Bodenmiller, Bernd, Bruneau, Benoit, Campbell, Peter, Carmichael, Mary, Carninci, Piero, Castelo-Soccio, Leslie, Clatworthy, Menna, Clevers, Hans, Conrad, Christian, Eils, Roland, Freeman, Jeremy, Fugger, Lars, Goettgens, Berthold, Graham, Daniel, Greka, Anna, Hacohen, Nir, Haniffa, Muzlifah, Helbig, Ingo, Heuckeroth, Robert, Kathiresan, Sekar, Kim, Seung, Klein, Allon, Knoppers, Bartha, Kriegstein, Arnold, Lander, Eric, Lee, Jane, Lein, Ed, Linnarsson, Sten, Macosko, Evan, MacParland, Sonya, Majovski, Robert, Majumder, Partha, Marioni, John, McGilvray, Ian, Merad, Miriam, Mhlanga, Musa, Naik, Shalin, Nawijn, Martijn, Nolan, Garry, Paten, Benedict, Pe'er, Dana, Philippakis, Anthony, Ponting, Chris, Quake, Steve, Rajagopal, Jayaraj, Rajewsky, Nikolaus, Reik, Wolf, Rood, Jennifer, Saeb-Parsy, Kourosh, Schiller, Herbert, Scott, Steve, Shalek, Alex, Shapiro, Ehud, Shin, Jay, Skeldon, Kenneth, Stratton, Michael, Streicher, Jenna, Stunnenberg, Henk, Tan, Kai, Taylor, Deanne, Thorogood, Adrian, Vallier, Ludovic, van Oudenaarden, Alexander, Watt, Fiona, Weicher, Wilko, Weissman, Jonathan, Wells, Andrew, Wold, Barbara, Xavier, Ramnik, Zhuang, Xiaowei, and Committee, Human Cell Atlas Organizing
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Quantitative Biology - Tissues and Organs - Abstract
The Human Cell Atlas (HCA) will be made up of comprehensive reference maps of all human cells - the fundamental units of life - as a basis for understanding fundamental human biological processes and diagnosing, monitoring, and treating disease. It will help scientists understand how genetic variants impact disease risk, define drug toxicities, discover better therapies, and advance regenerative medicine. A resource of such ambition and scale should be built in stages, increasing in size, breadth, and resolution as technologies develop and understanding deepens. We will therefore pursue Phase 1 as a suite of flagship projects in key tissues, systems, and organs. We will bring together experts in biology, medicine, genomics, technology development and computation (including data analysis, software engineering, and visualization). We will also need standardized experimental and computational methods that will allow us to compare diverse cell and tissue types - and samples across human communities - in consistent ways, ensuring that the resulting resource is truly global. This document, the first version of the HCA White Paper, was written by experts in the field with feedback and suggestions from the HCA community, gathered during recent international meetings. The White Paper, released at the close of this yearlong planning process, will be a living document that evolves as the HCA community provides additional feedback, as technological and computational advances are made, and as lessons are learned during the construction of the atlas.
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- 2018
16. Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on superenhancers
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Bansal, Kushagra, Michelson, Daniel A., Ramirez, Ricardo N., Viny, Aaron D., Levine, Ross L., Benoist, Christophe, and Mathis, Diane
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- 2021
17. Profound Treg perturbations correlate with COVID-19 severity
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MGH COVID-19 Collection & Processing Team, Galván-Peña, Silvia, Leon, Juliette, Chowdhary, Kaitavjeet, Michelson, Daniel A., Vijaykumar, Brinda, Yang, Liang, Magnuson, Angela M., Chen, Felicia, Manickas-Hill, Zachary, Piechocka-Trocha, Alicja, Worrall, Daniel P., Hall, Kathryn E., Ghebremichael, Musie, Walker, Bruce D., Li, Jonathan Z., Yu, Xu G., Mathis, Diane, and Benoist, Christophe
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- 2021
18. PPARγ marks splenic precursors of multiple nonlymphoid-tissue Treg compartments
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Li, Chaoran, Muñoz-Rojas, Andrés R., Wang, Gang, Mann, Alexander O., Benoist, Christophe, and Mathis, Diane
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- 2021
19. DES Science Portal: Computing Photometric Redshifts
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Gschwend, Julia, Rosell, Aurelio Carnero, Ogando, Ricardo, Neto, Angelo Fausti, Maia, Marcio, da Costa, Luiz, Lima, Marcos, Pellegrini, Paulo, Campisano, Riccardo, Singulani, Cristiano, Adean, Carlos, Benoist, Christophe, Aguena, Michel, Kind, Matias Carrasco, Davis, Tamara, de Vicente, Juan, Hartley, Will, Hoyle, Ben, Palmese, Antonella, Sadeh, Iftach, Abbot, Tim, Abdalla, Filipe, Allam, Sahar, Annis, James, Asorey, Jacobo, Brooks, David, Calcino, Josh, Carollo, Daniela, Castander, Francisco, D'Andrea, Chris, Desai, Shantanu, Evrard, August, Fosalba, Pablo, Frieman, Josh, Garcia-Bellido, Juan, Glazebrook, Karl, Gerdes, David, Gruendl, Robert, Gutierrez, Gaston, Hinton, Samuel, Hollowood, Devon, Honscheid, Klaus, Hoormann, Janie, James, David, Kuehn, Kyler, Kuropatkin, Nikolay, Lahav, Ofer, Lewis, Geraint, Lidman, Chris, Lin, Huan, Macaulay, Edward, Marshall, Jeniffer, Melchior, Peter, Miquel, Ramon, Moller, Anais, Plazas, Andrés, Sanchez, Eusebio, Santiago, Basilio, Scarpine, Vic, Schindler, Rafe, Sevilla, Ignacio, Smith, Mathew, Sobreira, Flavia, Sommer, Natalia Eiré, Suchyta, Eric, Swanson, Molly, Tarle, Gregory, Tucker, Brad, Tucker, Douglas, Uddin, Syed, and Walker, Alistair
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
A significant challenge facing photometric surveys for cosmological purposes is the need to produce reliable redshift estimates. The estimation of photometric redshifts (photo-zs) has been consolidated as the standard strategy to bypass the high production costs and incompleteness of spectroscopic redshift samples. Training-based photo-z methods require the preparation of a high-quality list of spectroscopic redshifts, which needs to be constantly updated. The photo-z training, validation, and estimation must be performed in a consistent and reproducible way in order to accomplish the scientific requirements. To meet this purpose, we developed an integrated web-based data interface that not only provides the framework to carry out the above steps in a systematic way, enabling the ease testing and comparison of different algorithms, but also addresses the processing requirements by parallelizing the calculation in a transparent way for the user. This framework called the Science Portal (hereafter Portal) was developed in the context the Dark Energy Survey (DES) to facilitate scientific analysis. In this paper, we show how the Portal can provide a reliable environment to access vast data sets, provide validation algorithms and metrics, even in the case of multiple photo-zs methods. It is possible to maintain the provenance between the steps of a chain of workflows while ensuring reproducibility of the results. We illustrate how the Portal can be used to provide photo-z estimates using the DES first year (Y1A1) data. While the DES collaboration is still developing techniques to obtain more precise photo-zs, having a structured framework like the one presented here is critical for the systematic vetting of DES algorithmic improvements and the consistent production of photo-zs in the future DES releases., Comment: The first paper of the series about the DES Science Portal, submitted to the Astronomy & Computing journal. It shows the infrastructure of pipelines related to the production of photometric redshifts to feed science-ready catalogs
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- 2017
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20. Evolution of the real-space correlation function from next generation cluster surveys
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Sridhar, Srivatsan, Maurogordato, Sophie, Benoist, Christophe, Cappi, Alberto, and Marulli, Federico
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Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We investigate to which accuracy it is possible to recover the real-space two-point correlation function of galaxy clusters from cluster catalogues based on photometric redshifts, and test our ability to measure the redshift and mass evolution of the correlation length and the bias parameter as a function of the redshift uncertainty. We calculate the correlation function for cluster sub-samples covering various mass and redshift bins selected from a light-cone catalogue. To simulate the distribution of clusters in photometric redshift space, we assign to each cluster a redshift randomly extracted from a Gaussian distribution. The dispersion is varied in the range $\sigma_{(z=0)} = 0.001$ to $0.050$. The correlation function in real-space is computed through estimation and deprojection of $w_{p}(r_{p})$. Four mass ranges (from $M_{halo}> 2 \times 10^{13}$ to $M_{halo}> 2 \times 10^{14}$) and six redshift slices covering the redshift range [0,2] are investigated, using cosmological redshifts and photo-z configurations. We find a clear increase of the correlation amplitude as a function of redshift and mass for the $z_{c}$ samples. The evolution of the derived bias parameter is in agreement with theoretical expectations. From our pilot sample limited to $M_{halo}> 5 \times 10^{13} (0.4 < z < 0.7)$, we find that the real-space correlation function can be recovered by deprojection of $w_{p}(r_{p})$ within an accuracy of 5% for $\sigma_{z} = 0.001 \times (1 + z_{c})$ and within 10% for $\sigma_{z} = 0.03 \times (1 + z_{c})$. The evolution of the correlation in redshift and mass is clearly detected for all $\sigma_{z}$ tested. The best-fit parameters $(r_{0}$ and ${\gamma})$ as well as the bias obtained from the deprojection method for all $\sigma_{z}$ are within the $1 \sigma$ uncertainty of the $z_{c}$ sample., Comment: Final version after language correction. Accepted for publication in Astronomy&Astrophysics (A&A)
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- 2016
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21. Deep learning of immune cell differentiation
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Immunological Genome Project, Maslova, Alexandra, Ramirez, Ricardo N., Ma, Ke, Schmutz, Hugo, Wang, Chendi, Fox, Curtis, Ng, Bernard, Benoist, Christophe, and Mostafavi, Sara
- Published
- 2020
22. Genetic determinants of co-accessible chromatin regions in activated T cells across humans
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Gate, Rachel E, Cheng, Christine S, Aiden, Aviva P, Siba, Atsede, Tabaka, Marcin, Lituiev, Dmytro, Machol, Ido, Gordon, M Grace, Subramaniam, Meena, Shamim, Muhammad, Hougen, Kendrick L, Wortman, Ivo, Huang, Su-Chen, Durand, Neva C, Feng, Ting, De Jager, Philip L, Chang, Howard Y, Aiden, Erez Lieberman, Benoist, Christophe, Beer, Michael A, Ye, Chun J, and Regev, Aviv
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Human Genome ,Stem Cell Research ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Autoimmune Diseases ,CD4-Positive T-Lymphocytes ,Chromatin ,Female ,Gene Expression Regulation ,Genotype ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Regulatory Sequences ,Nucleic Acid ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression.
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- 2018
23. The Human Cell Atlas.
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Regev, Aviv, Teichmann, Sarah A, Lander, Eric S, Amit, Ido, Benoist, Christophe, Birney, Ewan, Bodenmiller, Bernd, Campbell, Peter, Carninci, Piero, Clatworthy, Menna, Clevers, Hans, Deplancke, Bart, Dunham, Ian, Eberwine, James, Eils, Roland, Enard, Wolfgang, Farmer, Andrew, Fugger, Lars, Göttgens, Berthold, Hacohen, Nir, Haniffa, Muzlifah, Hemberg, Martin, Kim, Seung, Klenerman, Paul, Kriegstein, Arnold, Lein, Ed, Linnarsson, Sten, Lundberg, Emma, Lundeberg, Joakim, Majumder, Partha, Marioni, John C, Merad, Miriam, Mhlanga, Musa, Nawijn, Martijn, Netea, Mihai, Nolan, Garry, Pe'er, Dana, Phillipakis, Anthony, Ponting, Chris P, Quake, Stephen, Reik, Wolf, Rozenblatt-Rosen, Orit, Sanes, Joshua, Satija, Rahul, Schumacher, Ton N, Shalek, Alex, Shapiro, Ehud, Sharma, Padmanee, Shin, Jay W, Stegle, Oliver, Stratton, Michael, Stubbington, Michael JT, Theis, Fabian J, Uhlen, Matthias, van Oudenaarden, Alexander, Wagner, Allon, Watt, Fiona, Weissman, Jonathan, Wold, Barbara, Xavier, Ramnik, Yosef, Nir, and Human Cell Atlas Meeting Participants
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Human Cell Atlas Meeting Participants ,Eukaryotic Cells ,Humans ,Human Body ,International Cooperation ,Atlases as Topic ,cell atlas ,cell biology ,computational biology ,human ,lineage ,mouse ,science forum ,single-cell genomics ,systems biology ,Biochemistry and Cell Biology - Abstract
The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.
- Published
- 2017
24. Adipose-tissue regulatory T cells are a consortium of subtypes that evolves with age and diet
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Muñoz-Rojas, Andrés R., primary, Wang, Gang, additional, Benoist, Christophe, additional, and Mathis, Diane, additional
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- 2024
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25. A dynamic atlas of immunocyte migration from the gut
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Galván-Peña, Silvia, primary, Zhu, Yangyang, additional, Hanna, Bola S., additional, Mathis, Diane, additional, and Benoist, Christophe, additional
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- 2024
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26. Neuronal, stromal, and T-regulatory cell crosstalk in murine skeletal muscle
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Wang, Kathy, Yaghi, Omar K., Spallanzani, Raul German, Chen, Xin, Zemmour, David, Lai, Nicole, Chiu, Isaac M., Benoist, Christophe, and Mathis, Diane
- Published
- 2020
27. Interferon-α-producing plasmacytoid dendritic cells drive the loss of adipose tissue regulatory T cells during obesity
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Li, Chaoran, Wang, Gang, Sivasami, Pulavendran, Ramirez, Ricardo N., Zhang, Yanbo, Benoist, Christophe, and Mathis, Diane
- Published
- 2021
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28. A new method to assign galaxy cluster membership using photometric redshifts
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Castignani, Gianluca and Benoist, Christophe
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Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We introduce a new effective strategy to assign group and cluster membership probabilities $P_{mem}$ to galaxies using photometric redshift information. Large dynamical ranges both in halo mass and cosmic time are considered. The method takes the magnitude distribution of both cluster and field galaxies as well as the radial distribution of galaxies in clusters into account using a non-parametric formalism and relies on Bayesian inference to take photometric redshift uncertainties into account. We successfully test the method against 1,208 galaxy clusters within redshifts $z=0.05-2.58$ and masses $10^{13.29-14.80}~M_\odot$ drawn from wide field simulated galaxy mock catalogs developed for the Euclid mission. Median purity $(55^{+17}_{-15})\%$ and completeness $(95^{+5}_{-10})\%$ are reached for galaxies brighter than 0.25$L_\ast$ within $r_{200}$ of each simulated halo and for a statistical photometric redshift accuracy $\sigma((z_s-z_p)/(1+z_s))=0.03$. The mean values $p=56\%$ and $c=93\%$ have sub-percent uncertainties. Accurate photometric redshifts ($\sigma((z_s-z_p)/(1+z_s))\lesssim0.05$) and robust estimates for the cluster redshift and the center coordinates are required. The method is applied to derive accurate richness estimates. A statistical comparison between the true ($N_{\rm true}$) vs estimated richness ($\lambda=\sum P_{mem}$) yields on average to unbiased results, $Log(\lambda/N_{\rm true})=-0.0051\pm0.15$. The scatter around the mean of the logarithmic difference between $\lambda$ and the halo mass is 0.10~dex, for massive halos $\gtrsim10^{14.5}~M_\odot$. Our estimates could be useful to calibrate independent cluster mass estimates from weak lensing, SZ, and X-ray studies. Our method can be applied to any list of galaxy clusters or groups in both present and forthcoming surveys such as SDSS, CFHTLS, DES, LSST, and Euclid., Comment: 24 pages, 10 figures, version corrected for typos, A&A in press
- Published
- 2016
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29. T cell receptor specificity drives accumulation of a reparative population of regulatory T cells within acutely injured skeletal muscle
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Cho, Jun, Kuswanto, Wilson, Benoist, Christophe, and Mathis, Diane
- Published
- 2019
30. Single-cell analysis of FOXP3 deficiencies in humans and mice unmasks intrinsic and extrinsic CD4+ T cell perturbations
- Author
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Zemmour, David, Charbonnier, Louis-Marie, Leon, Juliette, Six, Emmanuelle, Keles, Sevgi, Delville, Marianne, Benamar, Mehdi, Baris, Safa, Zuber, Julien, Chen, Karin, Neven, Benedicte, Garcia-Lloret, Maria I., Ruemmele, Frank M., Brugnara, Carlo, Cerf-Bensussan, Nadine, Rieux-Laucat, Frederic, Cavazzana, Marina, André, Isabelle, Chatila, Talal A., Mathis, Diane, and Benoist, Christophe
- Published
- 2021
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31. Galaxy formation history through hod model from euclid mock catalogs
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Sakr, Ziad and Benoist, Christophe
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
Halo Occupation Distribution (HOD) is a model giving the average number of galaxies in a dark matter halo, function of its mass and other intrinsic properties, like distance from halo center, luminosity and redshift of its constituting galaxies. It is believed that these parameters could also be related to the galaxy history of formation. We want to investigate more this relation in order to test and better refine this model. To do that, we extract HOD indicators from EUCLID mock catalogs for different luminosity cuts and for redshifts ranges going from 0.1 < z < 3.0. We study and interpret the trends of indicators function of these variations and tried to retrace galaxy formation history following the idea that galaxy evolution is the combination rather than the conflict of the two main proposed ideas nowadays: the older hierarchical mass merger driven paradigm and the recent downsizing star formation driven approach., Comment: Published in the 2014 Proceedings of the Annual meeting of the French Society of Astronomy and Astrophysics. Eds.: J. Ballet, F. Martins, F. Bournaud, R. Monier, C. Reyl\'e
- Published
- 2015
32. Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes
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Kiner, Evgeny, Willie, Elijah, Vijaykumar, Brinda, Chowdhary, Kaitavjeet, Schmutz, Hugo, Chandler, Jodie, Schnell, Alexandra, Thakore, Pratiksha I., LeGros, Graham, Mostafavi, Sara, Mathis, Diane, and Benoist, Christophe
- Published
- 2021
- Full Text
- View/download PDF
33. Lymph node stromal cell responses to perinatal T cell waves, a temporal atlas
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Jayewickreme, Teshika, primary, Benoist, Christophe, additional, and Mathis, Diane, additional
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- 2023
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34. Homeostatic, repertoire and transcriptional relationships between colon T regulatory cell subsets
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Ramanan, Deepshika, primary, Chowdhary, Kaitavjeet, additional, Candéias, Serge M., additional, Sassone-Corsi, Martina, additional, Gelineau, Adelaide, additional, Mathis, Diane, additional, and Benoist, Christophe, additional
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- 2023
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35. Abell 2384: the galaxy population of a cluster post-merger
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Pranger, Florian, Böhm, Asmus, Ferrari, Chiara, Maurogordato, Sophie, Benoist, Christophe, Höller, Harald, and Schindler, Sabine
- Subjects
Astrophysics - Astrophysics of Galaxies ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We combine multi-object spectroscopy from the 2dF and EFOSC2 spectrographs with optical imaging of the inner 30'x30' of A2384 taken with the ESO Wide Field Imager. We carry out a kinematical analysis using the EMMIX algorithm and biweight statistics. We address the possible presence of cluster substructures with the Dressler-Shectman test. Cluster galaxies are investigated with respect to [OII] and H{\alpha} equivalent width. Galaxies covered by our optical imaging observations are additionally analysed in terms of colour, star formation rate and morphological descriptors such as Gini coefficient and M20 index. We study cluster galaxy properties as a function of clustercentric distance and investigate the distribution of various galaxy types in colour-magnitude and physical space. The Dressler-Shectman test reveals a substructure in the east of the 2dF field-of-view. We determine the mass ratio between the northern and southern subcluster to be 1.6:1. In accordance with other cluster studies, we find that a large fraction of the disk galaxies close to the cluster core show no detectable star formation. Probably these are systems which are quenched due to ram-pressure stripping. The sample of quenched disks populates the transition area between the blue cloud and the red sequence in colour-magnitude space. We also find a population of morphologically distorted galaxies in the central cluster region. The substructure in the east of A2384 might be a group of galaxies falling onto the main cluster. We speculate that our sample of quenched spirals represents an intermediate phase in the ram-pressure driven transformation of infalling field spirals into cluster S0s. This is motivated by their position in colour-magnitude space. The occurrence of morphologically distorted galaxies in the cluster core complies with the hypothesis of A2384 representing a post merger system., Comment: 14 pages, 18 figures, A&A accepted
- Published
- 2014
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36. Orientation Bias of Optically Selected Galaxy Clusters and Its Impact on Stacked Weak Lensing Analyses
- Author
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Dietrich, Jörg P., Zhang, Yuanyuan, Song, Jeeseon, Davis, Christopher P., McKay, Timothy A., Baruah, Leon, Becker, Matthew, Benoist, Christophe, Busha, Michael, da Costa, Luiz A. N., Hao, Jiangang, Maia, Marcio A. G., Miller, Christopher J., Ogando, Ricardo, Romer, A. Kathy, Rozo, Eduardo, Rykoff, Eli, and Wechsler, Risa
- Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
Weak-lensing measurements of the averaged shear profiles of galaxy clusters binned by some proxy for cluster mass are commonly converted to cluster mass estimates under the assumption that these cluster stacks have spherical symmetry. In this paper we test whether this assumption holds for optically selected clusters binned by estimated optical richness. Using mock catalogues created from N-body simulations populated realistically with galaxies, we ran a suite of optical cluster finders and estimated their optical richness. We binned galaxy clusters by true cluster mass and estimated optical richness and measure the ellipticity of these stacks. We find that the processes of optical cluster selection and richness estimation are biased, leading to stacked structures that are elongated along the line-of-sight. We show that weak-lensing alone cannot measure the size of this orientation bias. Weak lensing masses of stacked optically selected clusters are overestimated by up to 3-6 per cent when clusters can be uniquely associated with haloes. This effect is large enough to lead to significant biases in the cosmological parameters derived from large surveys like the Dark Energy Survey, if not calibrated via simulations or fitted simultaneously. This bias probably also contributes to the observed discrepancy between the observed and predicted Sunyaev-Zel'dovich signal of optically-selected clusters., Comment: Accepted for publication in MNRAS, minor changes to figures following referee comments
- Published
- 2014
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- View/download PDF
37. The ImmGen consortium OpenSource T cell project
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Zemmour, David, Goldrath, Ananda, Kronenberg, Mitchell, Kang, Joonsoo, and Benoist, Christophe
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- 2022
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38. Identification and validation of a tumor-infiltrating Treg transcriptional signature conserved across species and tumor types
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Magnuson, Angela M., Kiner, Evgeny, Ergun, Ayla, Park, Jun Seok, Asinovski, Natasha, Ortiz-Lopez, Adriana, Kilcoyne, Aoife, Paoluzzi-Tomada, Elisa, Weissleder, Ralph, Mathis, Diane, and Benoist, Christophe
- Published
- 2018
39. Hugh O. McDevitt 1930–2022
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Mathis, Diane and Benoist, Christophe
- Published
- 2022
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40. Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis
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Song, Xinyang, Sun, Ximei, Oh, Sungwhan F., Wu, Meng, Zhang, Yanbo, Zheng, Wen, Geva-Zatorsky, Naama, Jupp, Ray, Mathis, Diane, Benoist, Christophe, and Kasper, Dennis L.
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- 2020
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41. Brd4 bridges the transcriptional regulators, Aire and P-TEFb, to promote elongation of peripheral-tissue antigen transcripts in thymic stromal cells
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Yoshida, Hideyuki, Bansal, Kushagra, Schaefer, Uwe, Chapman, Trevor, Rioja, Inmaculada, Proekt, Irina, Anderson, Mark S, Prinjha, Rab K, Tarakhovsky, Alexander, Benoist, Christophe, and Mathis, Diane
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Genetics ,Biotechnology ,2.1 Biological and endogenous factors ,Aetiology ,Acetylation ,Amino Acid Sequence ,Animals ,Epithelial Cells ,Gene Expression Regulation ,HEK293 Cells ,Heterocyclic Compounds ,4 or More Rings ,Humans ,Immune Tolerance ,Lysine ,Mice ,Models ,Biological ,Molecular Sequence Data ,Mutation ,Nuclear Proteins ,Phosphorylation ,Positive Transcriptional Elongation Factor B ,Protein Binding ,Protein Interaction Mapping ,Protein Structure ,Tertiary ,RNA Splicing ,Stromal Cells ,Thymus Gland ,Transcription Elongation ,Genetic ,Transcription Factors ,Transcriptome ,immunological tolerance ,thymus ,Aire ,bromodomain protein ,transcriptional elongation - Abstract
Aire controls immunologic tolerance by inducing a battery of thymic transcripts encoding proteins characteristic of peripheral tissues. Its unusually broad effect is achieved by releasing RNA polymerase II paused just downstream of transcriptional start sites. We explored Aire's collaboration with the bromodomain-containing protein, Brd4, uncovering an astonishing correspondence between those genes induced by Aire and those inhibited by a small-molecule bromodomain blocker. Aire:Brd4 binding depended on an orchestrated series of posttranslational modifications within Aire's caspase activation and recruitment domain. This interaction attracted P-TEFb, thereby mobilizing downstream transcriptional elongation and splicing machineries. Aire:Brd4 association was critical for tolerance induction, and its disruption could account for certain point mutations that provoke human autoimmune disease. Our findings evoke the possibility of unanticipated immunologic mechanisms subtending the potent antitumor effects of bromodomain blockers.
- Published
- 2015
42. The galaxy population of the complex cluster system Abell 3921
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Pranger, Florian, Böhm, Asmus, Ferrari, Chiara, Diaferio, Antonaldo, Hunstead, Richard, Maurogordato, Sophie, Benoist, Christophe, Brinchmann, Jarle, and Schindler, Sabine
- Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We present a spectrophotometric analysis of the galaxy pop. in the area of the merging cluster Abell 3921 at redshift 0.093. We investigate the impact of the complex cluster environment on galaxy properties such as morphology or star formation rate. We combine multi-object spectroscopy from the 2dF spectrograph with optical imaging taken with the ESO WFI. We carry out a redshift analysis and determine cluster velocity dispersions using biweight statistics. Applying a Dressler-Shectman (DS-)test we seek evidence for cluster substructure. Cluster and field galaxies are investigated with respect to [OII] and H{\alpha} equivalent width, SFR and morphological descriptors such as concentration index and Gini coefficient. We study these cluster galaxy properties as a function of clustercentric distance and investigate the spatial distribution of various galaxy types. Applying the DS-test we find a 3rd component (A3921-C) in addition to the two main subclusters (A3921-A and A3921-B) already known. The re-determined mass ratio between the main components A and B is approx. 2:1. Similar to prev. studies of galaxy clusters, we find that a large fraction of the disk galaxies close to the cluster core show no detectable star formation. These are likely systems that are quenched due to ram pressure stripping. We also find quenched spirals at rather large distances of 3 to 4 Mpc from the cluster core. A3921-C might be a group of galaxies falling onto the main cluster components. We speculate that the unexpected population of quenched spirals at large clustercentric radii in A3921-A and A3921-B might be an effect of the ongoing cluster merger: shocks in the ICM might give raise to enhanced ram pressure stripping and at least in part be the cause for the quenching of star formation. These quenched spirals might be an interm. stage in the morphological transformation of field spirals into cluster S0s., Comment: 14 pages, 22 figures, accepted version (Astronomy & Astrophysics) 1 page corrigendum (1 figure)
- Published
- 2013
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43. Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells.
- Author
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Fu, Wenxian, Farache, Julia, Clardy, Susan M, Hattori, Kimie, Mander, Palwinder, Lee, Kevin, Rioja, Inmaculada, Weissleder, Ralph, Prinjha, Rab K, Benoist, Christophe, and Mathis, Diane
- Subjects
CD4-Positive T-Lymphocytes ,Monocytes ,Macrophages ,Animals ,Mice ,Inbred NOD ,Diabetes Mellitus ,Type 1 ,Inflammation ,NF-kappa B ,Regeneration ,Signal Transduction ,Transcription ,Genetic ,Epigenesis ,Genetic ,Phenotype ,Female ,Insulin-Secreting Cells ,Heterocyclic Compounds ,4 or More Rings ,NF-KB ,autoimmune diabetes ,bromodomain inhibitor ,immunology ,mouse ,Mice ,Inbred NOD ,Diabetes Mellitus ,Type 1 ,Transcription ,Genetic ,Epigenesis ,Heterocyclic Compounds ,or More Rings ,Biochemistry and Cell Biology - Abstract
Epigenetic modifiers are an emerging class of anti-tumor drugs, potent in multiple cancer contexts. Their effect on spontaneously developing autoimmune diseases has been little explored. We report that a short treatment with I-BET151, a small-molecule inhibitor of a family of bromodomain-containing transcriptional regulators, irreversibly suppressed development of type-1 diabetes in NOD mice. The inhibitor could prevent or clear insulitis, but had minimal influence on the transcriptomes of infiltrating and circulating T cells. Rather, it induced pancreatic macrophages to adopt an anti-inflammatory phenotype, impacting the NF-κB pathway in particular. I-BET151 also elicited regeneration of islet β-cells, inducing proliferation and expression of genes encoding transcription factors key to β-cell differentiation/function. The effect on β cells did not require T cell infiltration of the islets. Thus, treatment with I-BET151 achieves a 'combination therapy' currently advocated by many diabetes investigators, operating by a novel mechanism that coincidentally dampens islet inflammation and enhances β-cell regeneration.
- Published
- 2014
44. Single-cell mass cytometry of TCR signaling: Amplification of small initial differences results in low ERK activation in NOD mice
- Author
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Mingueneau, Michael, Krishnaswamy, Smita, Spitzer, Matthew H, Bendall, Sean C, Stone, Erica L, Hedrick, Stephen M, Pe'er, Dana, Mathis, Diane, Nolan, Garry P, and Benoist, Christophe
- Subjects
Autoimmune Disease ,1.1 Normal biological development and functioning ,Underpinning research ,Inflammatory and immune system ,Animals ,Diabetes Mellitus ,Type 1 ,Disease Models ,Animal ,Enzyme Activation ,Extracellular Signal-Regulated MAP Kinases ,Genetic Variation ,I-kappa B Proteins ,Immune Tolerance ,Immunity ,Cellular ,Immunologic Deficiency Syndromes ,Immunologic Memory ,Lymph Nodes ,Lymphopoiesis ,MAP Kinase Signaling System ,Male ,Mass Spectrometry ,Mice ,Mice ,Inbred C57BL ,Mice ,Inbred NOD ,Mice ,Knockout ,Mitogen-Activated Protein Kinase 1 ,NF-KappaB Inhibitor alpha ,Phosphorylation ,Protein Processing ,Post-Translational ,Receptors ,Antigen ,T-Cell ,Self Tolerance ,Single-Cell Analysis ,Thymus Gland ,CyTOF ,signaling ,single-cell ,NOD ,diabetes - Abstract
Signaling from the T-cell receptor (TCR) conditions T-cell differentiation and activation, requiring exquisite sensitivity and discrimination. Using mass cytometry, a high-dimensional technique that can probe multiple signaling nodes at the single-cell level, we interrogate TCR signaling dynamics in control C57BL/6 and autoimmunity-prone nonobese diabetic (NOD) mice, which show ineffective ERK activation after TCR triggering. By quantitating signals at multiple steps along the signaling cascade and parsing the phosphorylation level of each node as a function of its predecessors, we show that a small impairment in initial pCD3ζ activation resonates farther down the signaling cascade and results in larger defects in activation of the ERK1/2-S6 and IκBα modules. This nonlinear property of TCR signaling networks, which magnifies small initial differences during signal propagation, also applies in cells from B6 mice activated at different levels of intensity. Impairment in pCD3ζ and pSLP76 is not a feedback consequence of a primary deficiency in ERK activation because no proximal signaling defect was observed in Erk2 KO T cells. These defects, which were manifest at all stages of T-cell differentiation from early thymic pre-T cells to memory T cells, may condition the imbalanced immunoregulation and tolerance in NOD T cells. More generally, this amplification of small initial differences in signal intensity may explain how T cells discriminate between closely related ligands and adopt strongly delineated cell fates.
- Published
- 2014
45. Variation and Genetic Control of Gene Expression in Primary Immunocytes across Inbred Mouse Strains
- Author
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Mostafavi, Sara, Ortiz-Lopez, Adriana, Bogue, Molly A, Hattori, Kimie, Pop, Cristina, Koller, Daphne, Mathis, Diane, Benoist, Christophe, Blair, David A, Dustin, Michael L, Shinton, Susan A, Hardy, Richard R, Shay, Tal, Regev, Aviv, Cohen, Nadia, Brennan, Patrick, Brenner, Michael, Kim, Francis, Rao, Tata Nageswara, Wagers, Amy, Heng, Tracy, Ericson, Jeffrey, Rothamel, Katherine, Kreslavsky, Taras, Fletcher, Anne, Elpek, Kutlu, Bellemare-Pelletier, Angelique, Malhotra, Deepali, Turley, Shannon, Miller, Jennifer, Brown, Brian, Merad, Miriam, Gautier, Emmanuel L, Jakubzick, Claudia, Randolph, Gwendalyn J, Monach, Paul, Best, Adam J, Knell, Jamie, Goldrath, Ananda, Jojic, Vladimir, Laidlaw, David, Collins, Jim, Gazit, Roi, Rossi, Derrick J, Malhotra, Nidhi, Sylvia, Katelyn, Kang, Joonsoo, Bezman, Natalie A, Sun, Joseph C, Min-Oo, Gundula, Kim, Charlie C, and Lanier, Lewis L
- Subjects
Human Genome ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Animals ,CD4-Positive T-Lymphocytes ,Chromosome Mapping ,Cluster Analysis ,Computational Biology ,Gene Expression Profiling ,Gene Expression Regulation ,Gene Regulatory Networks ,Genetic Variation ,Genotype ,Humans ,Immunity ,Mice ,Mice ,Inbred Strains ,Neutrophils ,Quantitative Trait Loci ,Reproducibility of Results ,Transcriptome ,Immunological Genome Consortium ,Immunology - Abstract
To determine the breadth and underpinning of changes in immunocyte gene expression due to genetic variation in mice, we performed, as part of the Immunological Genome Project, gene expression profiling for CD4(+) T cells and neutrophils purified from 39 inbred strains of the Mouse Phenome Database. Considering both cell types, a large number of transcripts showed significant variation across the inbred strains, with 22% of the transcriptome varying by 2-fold or more. These included 119 loci with apparent complete loss of function, where the corresponding transcript was not expressed in some of the strains, representing a useful resource of "natural knockouts." We identified 1222 cis-expression quantitative trait loci (cis-eQTL) that control some of this variation. Most (60%) cis-eQTLs were shared between T cells and neutrophils, but a significant portion uniquely impacted one of the cell types, suggesting cell type-specific regulatory mechanisms. Using a conditional regression algorithm, we predicted regulatory interactions between transcription factors and potential targets, and we demonstrated that these predictions overlap with regulatory interactions inferred from transcriptional changes during immunocyte differentiation. Finally, comparison of these and parallel data from CD4(+) T cells of healthy humans demonstrated intriguing similarities in variability of a gene's expression: the most variable genes tended to be the same in both species, and there was an overlap in genes subject to strong cis-acting genetic variants. We speculate that this "conservation of variation" reflects a differential constraint on intraspecies variation in expression levels of different genes, either through lower pressure for some genes, or by favoring variability for others.
- Published
- 2014
46. The XMM Cluster Survey: Optical analysis methodology and the first data release
- Author
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Mehrtens, Nicola, Romer, A. Kathy, Lloyd-Davies, E. J., Hilton, Matt, Miller, Christopher J., Stanford, S. A., Hosmer, Mark, Hoyle, Ben, Collins, Chris A., Liddle, Andrew R., Viana, Pedro T. P., Nichol, Robert C., Stott, John P., Dubois, E. Naomi, Kay, Scott T., Sahlen, Martin, Young, Owain, Short, C. J., Christodoulou, L., Watson, William A., Davidson, Michael, Harrison, Craig D., Baruah, Leon, Smith, Mathew, Burke, Claire, Deadman, Paul-James, Rooney, Philip J., Edmondson, Edward M., West, Michael, Campbell, Heather C., Edge, Alastair C., Mann, Robert G., Wake, David, Benoist, Christophe, da Costa, Luiz, Maia, Marcio A. G., and Ogando, Ricardo
- Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMM-Newton Science Archive. Its main aims are to measure cosmological parameters and trace the evolution of X-ray scaling relations. In this paper we present the first data release from the XMM Cluster Survey (XCS-DR1). This consists of 503 optically confirmed, serendipitously detected, X-ray clusters. Of these clusters, 255 are new to the literature and 356 are new X-ray discoveries. We present 464 clusters with a redshift estimate (0.06 < z < 1.46), including 261 clusters with spectroscopic redshifts. In addition, we have measured X-ray temperatures (Tx) for 402 clusters (0.4 < Tx < 14.7 keV). We highlight seven interesting subsamples of XCS-DR1 clusters: (i) 10 clusters at high redshift (z > 1.0, including a new spectroscopically-confirmed cluster at z = 1.01); (ii) 67 clusters with high Tx (> 5 keV); (iii) 131 clusters/groups with low Tx (< 2 keV); (iv) 27 clusters with measured Tx values in the SDSS `Stripe 82' co-add region; (v) 78 clusters with measured Tx values in the Dark Energy Survey region; (vi) 40 clusters detected with sufficient counts to permit mass measurements (under the assumption of hydrostatic equilibrium); (vii) 105 clusters that can be used for applications such as the derivation of cosmological parameters and the measurement of cluster scaling relations. The X-ray analysis methodology used to construct and analyse the XCS-DR1 cluster sample has been presented in a companion paper, Lloyd-Davies et al. (2010)., Comment: MNRAS submitted, 30 pages, 20 figures, 3 electronic tables. The X-ray analysis methodology used to construct and analyse the XCS-DR1 cluster sample is presented in the companion paper, Lloyd-Davies et al. (2010). The XCS-DR1 catalogue, together with optical and X-ray (colour-composite and greyscale) images for each cluster, is publicly available from http://xcs-home.org/datareleases
- Published
- 2011
- Full Text
- View/download PDF
47. Intersection of population variation and autoimmunity genetics in human T cell activation
- Author
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Ye, Chun Jimmie, Feng, Ting, Kwon, Ho-Keun, Raj, Towfique, Wilson, Michael T, Asinovski, Natasha, McCabe, Cristin, Lee, Michelle H, Frohlich, Irene, Paik, Hyun-il, Zaitlen, Noah, Hacohen, Nir, Stranger, Barbara, De Jager, Philip, Mathis, Diane, Regev, Aviv, and Benoist, Christophe
- Subjects
Human Genome ,Genetics ,Clinical Research ,Biotechnology ,Autoimmune Disease ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Asians ,Autoimmunity ,Blacks ,CD4-Positive T-Lymphocytes ,Cytokines ,Gene Expression Regulation ,Genetic Variation ,Genome-Wide Association Study ,Humans ,Lymphocyte Activation ,Multigene Family ,Quantitative Trait Loci ,Th17 Cells ,Whites ,Asian People ,White People ,Black People ,General Science & Technology - Abstract
T lymphocyte activation by antigen conditions adaptive immune responses and immunopathologies, but we know little about its variation in humans and its genetic or environmental roots. We analyzed gene expression in CD4(+) T cells during unbiased activation or in T helper 17 (T(H)17) conditions from 348 healthy participants representing European, Asian, and African ancestries. We observed interindividual variability, most marked for cytokine transcripts, with clear biases on the basis of ancestry, and following patterns more complex than simple T(H)1/2/17 partitions. We identified 39 genetic loci specifically associated in cis with activated gene expression. We further fine-mapped and validated a single-base variant that modulates YY1 binding and the activity of an enhancer element controlling the autoimmune-associated IL2RA gene, affecting its activity in activated but not regulatory T cells. Thus, interindividual variability affects the fundamental immunologic process of T helper activation, with important connections to autoimmune disease.
- Published
- 2014
48. Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes
- Author
-
Raj, Towfique, Rothamel, Katie, Mostafavi, Sara, Ye, Chun, Lee, Mark N, Replogle, Joseph M, Feng, Ting, Lee, Michelle, Asinovski, Natasha, Frohlich, Irene, Imboywa, Selina, Von Korff, Alina, Okada, Yukinori, Patsopoulos, Nikolaos A, Davis, Scott, McCabe, Cristin, Paik, Hyun-il, Srivastava, Gyan P, Raychaudhuri, Soumya, Hafler, David A, Koller, Daphne, Regev, Aviv, Hacohen, Nir, Mathis, Diane, Benoist, Christophe, Stranger, Barbara E, and De Jager, Philip L
- Subjects
Aging ,Neurodegenerative ,Genetics ,Dementia ,Acquired Cognitive Impairment ,Clinical Research ,Brain Disorders ,Human Genome ,Prevention ,Neurosciences ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Adaptive Immunity ,Alleles ,Alzheimer Disease ,Autoimmune Diseases ,Autoimmunity ,CD4-Positive T-Lymphocytes ,Ethnicity ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Immunity ,Innate ,Monocytes ,Multiple Sclerosis ,Neurodegenerative Diseases ,Parkinson Disease ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Rheumatic Fever ,Transcriptome ,General Science & Technology - Abstract
To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4(+) T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell-specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.
- Published
- 2014
49. Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells
- Author
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Lee, Mark N, Ye, Chun, Villani, Alexandra-Chloé, Raj, Towfique, Li, Weibo, Eisenhaure, Thomas M, Imboywa, Selina H, Chipendo, Portia I, Ran, F Ann, Slowikowski, Kamil, Ward, Lucas D, Raddassi, Khadir, McCabe, Cristin, Lee, Michelle H, Frohlich, Irene Y, Hafler, David A, Kellis, Manolis, Raychaudhuri, Soumya, Zhang, Feng, Stranger, Barbara E, Benoist, Christophe O, De Jager, Philip L, Regev, Aviv, and Hacohen, Nir
- Subjects
Infectious Diseases ,Influenza ,Genetics ,Biodefense ,Emerging Infectious Diseases ,Vaccine Related ,Prevention ,Pneumonia & Influenza ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Inflammatory and immune system ,Adult ,Autoimmune Diseases ,Communicable Diseases ,Dendritic Cells ,Escherichia coli ,Female ,Gene-Environment Interaction ,Genetic Loci ,Genome-Wide Association Study ,HEK293 Cells ,Host-Pathogen Interactions ,Humans ,Influenza A virus ,Interferon Regulatory Factor-7 ,Interferon-beta ,Lipopolysaccharides ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,STAT Transcription Factors ,Transcriptome ,Young Adult ,General Science & Technology - Abstract
Little is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses to Escherichia coli lipopolysaccharide, influenza, or interferon-β (IFN-β). We localized and validated causal variants to binding sites of pathogen-activated STAT (signal transducer and activator of transcription) and IRF (IFN-regulatory factor) transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I IFN induction in response to influenza infection. Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases.
- Published
- 2014
50. T reg cells limit IFN-γ production to control macrophage accrual and phenotype during skeletal muscle regeneration
- Author
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Panduro, Marisella, Benoist, Christophe, and Mathis, Diane
- Published
- 2018
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