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1. Perspective on recent developments and challenges in regulatory and systems genomics

Author

Zeiltinger, Julia, Roy, Sushmita, Ay, Ferhat, Mathelier, Anthony, Medina-Rivera, Alejandra, Mahony, Shaun, Sinha, Saurabh, and Ernst, Jason

Subjects
Quantitative Biology - Genomics
Abstract

Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regulatory code, the sequence rules by which non-coding regions regulate genes. In this perspective, we discuss recent computational progress and challenges towards solving this fundamental problem. We describe how cis-regulatory elements are mapped and how their sequence rules can be learned and interpreted with sequence-to-function neural networks, with the goal of identifying genetic variants in human disease. We also discuss how studies of the 3D chromatin organization could help identifying long-range regulatory effects and how current methods for mapping gene regulatory networks could better describe biological processes. We point out current gaps in knowledge along with technical limitations and benchmarking challenges of computational methods. Finally, we discuss newly emerging technologies, such as spatial transcriptomics, and outline strategies for creating a more general model of the cis-regulatory code that is more broadly applicable across cell types and individuals.

Published
2024

2. Contributors

Author

Aliev, Fazil, primary, Balderas-Martínez, Yalbi Itzel, additional, Bernstein, Alison I., additional, Burgess, Rebecca C., additional, Buschmann, Dominik, additional, Cripps, Richard M., additional, Das, Arundhati, additional, Das, Debojyoti, additional, Dluzen, Douglas F., additional, Driedonks, Tom, additional, Foss, Dana Vera, additional, Glaser, Rivka, additional, Green, Michael R., additional, Hildebrand, Erica M., additional, Hosur, Vishnu, additional, Hou, Huayun, additional, Hu, Kai, additional, Huang, Yiyao, additional, Hudson, Matthew, additional, Kochmanski, Joseph, additional, Kuo, Sally I-Chun, additional, Li, Rui, additional, Liang, Minggao, additional, Liu, Haibo, additional, Liu, Yu, additional, Lovato, TyAnna L., additional, Low, Benjamin E., additional, Luca, Francesca, additional, Makky, Khadijah, additional, Medina-Rivera, Alejandra, additional, Norris, Alexis Leigh, additional, Ou, Jianhong, additional, Pai, Athma A., additional, Pak, Magnolia, additional, Panda, Amaresh C., additional, Schmidt, Monika H.M., additional, Stark, Amy L., additional, Tosar, Juan Pablo, additional, Tourlakis, Marina E., additional, Tucker, Kimberly Pause, additional, Turchinovich, Andrey, additional, Villaseñor-Altamirano, Ana B., additional, Wang, Fan, additional, Wiles, Michael V., additional, Witwer, Kenneth W., additional, Wray, Charles, additional, and Zhu, Lihua Julie, additional

Published
2024
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6. Building national patient registries in Mexico: insights from the MexOMICS Consortium

Author

Reyes-Pérez, Paula, primary, Hernández-Ledesma, Ana Laura, additional, Román-López, Talía V., additional, García-Vilchis, Brisa, additional, Ramírez-González, Diego, additional, Lázaro-Figueroa, Alejandra, additional, Martinez, Domingo, additional, Flores-Ocampo, Victor, additional, Espinosa-Méndez, Ian M., additional, Tinajero-Nieto, Lizbet, additional, Peña-Ayala, Angélica, additional, Morelos-Figaredo, Eugenia, additional, Guerra-Galicia, Carlos M., additional, Torres-Valdez, Estefania, additional, Gordillo-Huerta, María Vanessa, additional, Gandarilla-Martínez, Nadia A, additional, Salinas-Barboza, Karla, additional, Félix-Rodríguez, Guillermo, additional, Frontana-Vázquez, Gabriel, additional, Matuk-Pérez, Yamil, additional, Estrada-Bellmann, Ingrid, additional, Alpizar-Rodríguez, Deshiré, additional, Rodríguez-Violante, Mayela, additional, Rentería, Miguel E., additional, Ruíz-Contreras, Alejandra E., additional, Alcauter, Sarael, additional, and Medina-Rivera, Alejandra, additional

Published
2024
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8. Closing the computational biology 'knowledge gap': Spanish Wikipedia as a case study.

Author

Sélem-Mojica, Nelly, Karakulak, Tülay, Anjum, Audra, Pashkov, Antón, Pérez-Estrada, Rafael, Enriquez-Guillén, Karina, DeBlasio, Dan, Ferreira-Gonzalez, Sofia, Medina-Rivera, Alejandra, Rodrigo-Torres, Daniel, Kilpatrick, Alastair M, Welch, Lonnie R, and Rahman, Farzana

Subjects
SCHOOL contests, ENGLISH language, EDUCATIONAL resources, COMMUNICATION barriers, DATA analysis
Abstract

Motivation Wikipedia is a vital open educational resource in computational biology. The quality of computational biology coverage in English-language Wikipedia has improved steadily in recent years. However, there is an increasingly large 'knowledge gap' between computational biology resources in English-language Wikipedia, and Wikipedias in non-English languages. Reducing this knowledge gap by providing educational resources in non-English languages would reduce language barriers which disadvantage non-native English speaking learners across multiple dimensions in computational biology. Results Here, we provide a comprehensive assessment of computational biology coverage in Spanish-language Wikipedia, the second most accessed Wikipedia worldwide. Using Spanish-language Wikipedia as a case study, we generate quantitative and qualitative data before and after a targeted educational event, specifically, a Spanish-focused student editing competition. Our data demonstrates how such events and activities can narrow the knowledge gap between English and non-English educational resources, by improving existing articles and creating new articles. Finally, based on our analysis, we suggest ways to prioritize future initiatives to improve open educational resources in other languages. Availability and Implementation Scripts for data analysis are available at: https://github.com/ISCBWikiTeam/spanish. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Neonatal CD4+ T cells have a characteristic transcriptome and epigenome and respond to TCR stimulation with proliferation and yet a limited immune response.

Author

Kempis-Calanis, Linda Aimara, Rodríguez-Jorge, Otoniel, Gutiérrez-Reyna, Darely Yarazeth, Ventura-Martínez, Carlos Jesús, Spicuglia, Salvatore, Medina-Rivera, Alejandra, Thieffry, Denis, González, Aitor, and Santana, María Angélica

Subjects
T cells, B cells, IMMUNE response, TRANSCRIPTOMES, GENE expression profiling, ANTIBODY formation
Abstract

The adaptive immune response is coordinated by CD4+ T cells, which determine the type and strength of the immune response and the effector cells involved. It has been reported that CD4+ T cells are less responsive in neonates, leading to low activation of the cellular response and poor antibody production by B cells. This low response is essential for the tolerant window that favors birth transition from the sterile environment in the womb to the outside world but leaves neonates vulnerable to infection, which is still an important health issue. Neonates have a high morbidity and mortality rate due to infections, and the molecular reasons are still understudied. We asked whether the neonatal naive CD4+ T cells have a genomic program that predisposes them to a low response. Therefore, we evaluated the transcriptome and epigenome of human neonatal and adult naive CD4+ T cells. Our results point to a gene expression profile forming a distinct regulatory network in neonatal cells, which favors proliferation and a low T-cell response. Such expression profile is supported by a characteristic epigenetic landscape of neonatal CD4+ T cells, which correlates with the characteristic transcriptome of the neonatal cells. These results were confirmed by experiments showing a low response to activation signals, higher proliferation, and lower expression of cytokines of neonatal CD4+ T cells as compared to adult cells. Understanding this network could lead to novel vaccine formulations and better deal with life-threatening diseases during this highly vulnerable period of our lives. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Neonatal CD4+T cells have a characteristic transcriptome and epigenome and respond to TCR stimulation with proliferation and yet a limited immune response

Author

Kempis-Calanis, Linda Aimara, primary, Rodríguez-Jorge, Otoniel, additional, Gutiérrez-Reyna, Darely Yarazeth, additional, Ventura-Martínez, Carlos Jesús, additional, Spicuglia, Salvatore, additional, Medina-Rivera, Alejandra, additional, Thieffry, Denis, additional, González, Aimara, additional, and Santana, María Angélica, additional

Published
2023
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14. Neonatal CD4+T cells have a characteristic transcriptome and epigenome and respond to TCR stimulation with proliferation and yet a limited immune response

Author

Kempis-Calanis, Linda Aimara, Rodríguez-Jorge, Otoniel, Gutiérrez-Reyna, Darely Yarazeth, Ventura-Martínez, Carlos Jesús, Spicuglia, Salvatore, Medina-Rivera, Alejandra, Thieffry, Denis, González, Aitor, and Santana, María Angélica

Abstract

The adaptive immune response is coordinated by CD4+T cells, which determine the type and strength of the immune response and the effector cells involved. It has been reported that CD4+T cells are less responsive in neonates, leading to low activation of the cellular response and poor antibody production by B cells. This low response is essential for the tolerant window that favors birth transition from the sterile environment in the womb to the outside world but leaves neonates vulnerable to infection, which is still an important health issue. Neonates have a high morbidity and mortality rate due to infections, and the molecular reasons are still understudied. We asked whether the neonatal naive CD4+T cells have a genomic program that predisposes them to a low response. Therefore, we evaluated the transcriptome and epigenome of human neonatal and adult naive CD4+T cells. Our results point to a gene expression profile forming a distinct regulatory network in neonatal cells, which favors proliferation and a low T-cell response. Such expression profile is supported by a characteristic epigenetic landscape of neonatal CD4+T cells, which correlates with the characteristic transcriptome of the neonatal cells. These results were confirmed by experiments showing a low response to activation signals, higher proliferation, and lower expression of cytokines of neonatal CD4+T cells as compared to adult cells. Understanding this network could lead to novel vaccine formulations and better deal with life-threatening diseases during this highly vulnerable period of our lives.The regulatory network controlling the expression profile in neonatal CD4+T cells favors proliferation and a yet a low T-cell response.

Published
2024
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15. TwinsMX: Exploring the Genetic and Environmental Influences on Health Traits in the Mexican Population.

Author

García-Vilchis, Brisa, Román-López, Talia V., Ramírez-González, Diego, López-Camaño, Xanat J., Murillo-Lechuga, Vanessa, Díaz-Téllez, Xóchitl, Sánchez-Moncada, C. Itzamná, Espinosa-Méndez, Ian M., Zenteno-Morales, Diego, Espinosa-Valdes, Zaida X., Pradel-Jiménez, Sofia, Tapia-Atilano, Andrea, Zanabria-Pérez, Ana V., Livas-Gangas, Federica, Aldana-Assad, Oscar, Caballero-Sánchez, Ulises, Dominguez-Frausto, César A., Rentería, Miguel E., Medina-Rivera, Alejandra, and Alcauter, Sarael

Subjects
MEXICANS, ENVIRONMENTAL health, NATURE & nurture, ECOLOGICAL genetics, MAGNETIC resonance imaging
Abstract

TwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and mental health traits among the country's population. With a multidisciplinary approach, TwinsMX aims to advance our knowledge of the genetic and environmental mechanisms underlying ethnic variations in complex traits and diseases, including behavioral, psychometric, anthropometric, metabolic, cardiovascular and mental disorders. With information gathered from over 2800 twins, this article updates the prevalence of several complex traits; and describes the advances and novel ideas we have implemented such as magnetic resonance imaging. The future expansion of the TwinsMX registry will enhance our comprehension of the intricate interplay between genetics and environment in shaping health and disease in the Mexican population. Overall, this report describes the progress in the building of a solid database that will allow the study of complex traits in the Mexican population, valuable not only for our consortium, but also for the worldwide scientific community, by providing new insights of understudied genetically admixed populations. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Building National Patient Registries in Mexico: Insights from the MexOMICS Consortium.

Author

Reyes-Pérez, Paula, primary, Hernández-Ledesma, Ana Laura, additional, Román-López, Talía V., additional, García-Vilchis, Brisa, additional, Ramírez-González, Diego, additional, Lázaro-Figueroa, Alejandra, additional, Martínez, Domingo, additional, Flores-Ocampo, Victor, additional, Espinosa-Méndez, Ian M., additional, Tinajero-Nieto, Lizbet, additional, Peña-Ayala, Angélica, additional, Morelos-Figaredo, Eugenia, additional, Guerra-Galicia, Carlos M., additional, Torres-Valdez, Estefania, additional, Gordillo-Huerta, María Vanessa, additional, Gandarilla-Martínez, Nadia A., additional, Salinas-Barboza, Karla, additional, Félix-Rodríguez, Guillermo, additional, Frontana-Vázquez, Gabriel, additional, Matuk-Pérez, Yamil, additional, Estrada-Bellmann, Ingrid, additional, Alpízar-Rodríguez, Deshiré, additional, Rodríguez-Violante, Mayela, additional, Rentería, Miguel E., additional, Ruíz-Contreras, Alejandra E., additional, Alcauter, Sarael, additional, and Medina-Rivera, Alejandra, additional

Published
2023
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17. Estimating the Genetic Contribution to Astigmatism and Myopia in the Mexican Population

Author

Román-López, Talía V., primary, García-Vilchis, Brisa, additional, Murillo-Lechuga, Vanessa, additional, Chiu-Han, Enrique, additional, López-Camaño, Xanat, additional, Aldana-Assad, Oscar, additional, Diaz-Torres, Santiago, additional, Caballero-Sánchez, Ulises, additional, Ortega-Mora, Ivett, additional, Ramírez-González, Diego, additional, Zenteno, Diego, additional, Espinosa-Valdés, Zaida, additional, Tapia-Atilano, Andrea, additional, Pradel-Jiménez, Sofía, additional, Rentería, Miguel E., additional, Medina-Rivera, Alejandra, additional, Ruiz-Contreras, Alejandra E., additional, and Alcauter, Sarael, additional

Published
2023
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18. MEX-PD: A National Network for the Epidemiological & Genetic Research of Parkinson's Disease

Author

Lázaro-Figueroa, Alejandra, primary, Reyes-Pérez, Paula, additional, Morelos-Figaredo, Eugenia, additional, Guerra-Galicia, Carlos M., additional, Estrada-Bellmann, Ingrid, additional, Salinas-Barboza, Karla, additional, Matuk, Yamil, additional, Gandarilla-Martínez, Nadia A., additional, Caballero-Sánchez, Ulises, additional, Flores-Ocampo, Victor, additional, Montés-Alcántara, Pablo, additional, Espinosa-Méndez, Ian, additional, Zayas-Del Moral, Alejandra, additional, Gaspar-Martínez, Edith, additional, Vazquez-Guevara, Damaris, additional, Rodríguez-Violante, Mayela, additional, Inca-Martinez, Miguel, additional, Mata, Ignacio F., additional, Alcauter, Sarael, additional, Rentería, Miguel E., additional, Medina-Rivera, Alejandra, additional, and Ruiz-Contreras, Alejandra E., additional

Published
2023
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20. PulmonDB: a curated lung disease gene expression database

Author

Villaseñor-Altamirano, Ana B., Moretto, Marco, Maldonado, Mariel, Zayas-Del Moral, Alejandra, Munguía-Reyes, Adrián, Romero, Yair, García-Sotelo, Jair. S., Aguilar, Luis A., Aldana-Assad, Oscar, Engelen, Kristof, Selman, Moisés, Collado-Vides, Julio, Balderas-Martínez, Yalbi I., and Medina-Rivera, Alejandra

Published
2020
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22. Antarctic Bedmap data: Findable, Accessible, Interoperable, and Reusable (FAIR) sharing of 60 years of ice bed, surface, and thickness data

Author

Frémand, Alice, Fretwell, Peter, Bodart, Julien A., Pritchard, Hamish D., Aitken, Alan, Bamber, Jonathan L., Bell, Robin, Bianchi, Cesidio, Bingham, Robert G., Blankenship, Donald, Casassa, Gino, Catania, Ginny, Christianson, Knut, Conway, Howard, Corr, Hugh F. J., Cui, Xiangbin, Damaske, Detlef, Damm, Volkmar, Drews, Reinhard, Eagles, Graeme, Eisen, Olaf, Eisermann, Hannes, Ferraccioli, Fausto, Field, Elena, Forsberg, René, Franke, Steven, Fujita, Shuji, Gim, Yonggyu, Goel, Vikram, Gogineni, Siva Prasad, Greenbaum, Jamin Stevens, Hills, Benjamin, Hindmarsh, Richard C. A., Hoffman, Andrew O., Holmlund, Per, Holschuh, Nicholas, Holt, John W., Horlings, Annika, Humbert, Angelika, Jacobel, Robert, Jansen, Daniela, Jenkins, Adrian, Jokat, Wilfried, Jordan, Tom, King, Edward, Kohler, Jack, Krabill, William, Kusk Gillespie, Mette, Langley, Kirsty, Lee, Joohan, Leitchenkov, German, Leuschen, Carlton, Luyendyk, Bruce, MacGregor, Joseph A., MacKie, Emma, Matsuoka, Kenichi, Morlighem, Mathieu, Mouginot, Jeremie, Nitsche, Frank, Nogi, Yoshifumi, Nost, Ole, Paden, John, Pattyn, Frank, Popov, Sergey V., Rignot, Eric, Rippin, David, Medina-Rivera, Alejandra, Roberts, Jason, Ross, Neil, Ruppel, Anotonia, Schroeder, Dustin M., Siegert, Martin J., Smith, Andrew M., Steinhage, Daniel, Studinger, Michael, Sun, Bo, Tabacco, Ignazio, Tinto, Kirsty, Urbini, Stefano, Vaughan, David, Welch, Brian, Wilson, Douglas S., Young, Duncan A., Zirizzotti, Achille, Frémand, Alice, Fretwell, Peter, Bodart, Julien A., Pritchard, Hamish D., Aitken, Alan, Bamber, Jonathan L., Bell, Robin, Bianchi, Cesidio, Bingham, Robert G., Blankenship, Donald, Casassa, Gino, Catania, Ginny, Christianson, Knut, Conway, Howard, Corr, Hugh F. J., Cui, Xiangbin, Damaske, Detlef, Damm, Volkmar, Drews, Reinhard, Eagles, Graeme, Eisen, Olaf, Eisermann, Hannes, Ferraccioli, Fausto, Field, Elena, Forsberg, René, Franke, Steven, Fujita, Shuji, Gim, Yonggyu, Goel, Vikram, Gogineni, Siva Prasad, Greenbaum, Jamin Stevens, Hills, Benjamin, Hindmarsh, Richard C. A., Hoffman, Andrew O., Holmlund, Per, Holschuh, Nicholas, Holt, John W., Horlings, Annika, Humbert, Angelika, Jacobel, Robert, Jansen, Daniela, Jenkins, Adrian, Jokat, Wilfried, Jordan, Tom, King, Edward, Kohler, Jack, Krabill, William, Kusk Gillespie, Mette, Langley, Kirsty, Lee, Joohan, Leitchenkov, German, Leuschen, Carlton, Luyendyk, Bruce, MacGregor, Joseph A., MacKie, Emma, Matsuoka, Kenichi, Morlighem, Mathieu, Mouginot, Jeremie, Nitsche, Frank, Nogi, Yoshifumi, Nost, Ole, Paden, John, Pattyn, Frank, Popov, Sergey V., Rignot, Eric, Rippin, David, Medina-Rivera, Alejandra, Roberts, Jason, Ross, Neil, Ruppel, Anotonia, Schroeder, Dustin M., Siegert, Martin J., Smith, Andrew M., Steinhage, Daniel, Studinger, Michael, Sun, Bo, Tabacco, Ignazio, Tinto, Kirsty, Urbini, Stefano, Vaughan, David, Welch, Brian, Wilson, Douglas S., Young, Duncan A., and Zirizzotti, Achille

Abstract

One of the key components of this research has been the mapping of Antarctic bed topography and ice thickness parameters that are crucial for modelling ice flow and hence for predicting future ice loss andthe ensuing sea level rise. Supported by the Scientific Committee on Antarctic Research (SCAR), the Bedmap3 Action Group aims not only to produce newgridded maps of ice thickness and bed topography for the internationalscientific community, but also to standardize and make available all thegeophysical survey data points used in producing the Bedmap griddedproducts. Here, we document the survey data used in the latest iteration,Bedmap3, incorporating and adding to all of the datasets previously used forBedmap1 and Bedmap2, including ice bed, surface and thickness point data from all Antarctic geophysical campaigns since the 1950s. More specifically,we describe the processes used to standardize and make these and futuresurveys and gridded datasets accessible under the Findable, Accessible, Interoperable, and Reusable (FAIR) data principles. With the goals of making the gridding process reproducible and allowing scientists to re-use the data freely for their own analysis, we introduce the new SCAR Bedmap Data Portal(https://bedmap.scar.org, last access: 1 March 2023) created to provideunprecedented open access to these important datasets through a web-map interface. We believe that this data release will be a valuable asset to Antarctic research and will greatly extend the life cycle of the data heldwithin it. Data are available from the UK Polar Data Centre: https://data.bas.ac.uk (last access: 5 May 2023​​​​​​​). See the Data availability section for the complete list of datasets., info:eu-repo/semantics/published

Published
2023

23. Lupus RGMX: Social and Clinical Characteristics and their Contribution to Quality of Life in a Mexican Cohort with SLE

Author

Hernández-Ledesma Ana Laura, Martínez Domingo, Fajardo-Brigido Elizabeth, Talía V. Román-López, Nuñez-Reza Karen, Vera del Valle Sandra Valentina, Domínguez-Zúñiga Donaji, Tinajero-Nieto Lizbet, Peña-Ayala Angélica, Torres-Valdez Estefania, Frontana-Vázquez Gabriel, Gutierrez-Arcelus Maria, Rosetti Florencia, Alcauter Sarael, Miguel E. Rentería, Alejandra E. Ruiz-Contreras, Alpízar-Rodríguez Deshiré, and Medina-Rivera Alejandra

Abstract

BACKGROUNDAlthough higher prevalence, disease activity, damage accumulation and mortality of systemic lupus erythematosus (SLE) are observed among Latin American, North American admixed population, African descendants and Native Americans, the information about SLE in Latin American countries, such as Mexico, is scarce.OBJECTIVESTo present Lupus RGMX, a multidisciplinary effort to generate a national digital patient registry to enrich the understanding of Mexican people with SLE.METHODSMexican patients with SLE registered between May 2021 and January 2023 in Lupus RGMX were included. Sociodemographic, socioeconomic, and clinical characteristics, along with quality-of-life perception (QoL) were assessed using self-reported data. We compared the QoL obtained from patients with SLE with two groups of non-SLE Mexican subjects. Descriptive statistics, comparisons analyses and a multivariate nonparametric regression model were performed.RESULTSA total of 1172 of lupus patients were included; of which 93.9% were women. The mean age±SD was 36.6±10.7 years, with 37.1% of the individuals between 41 and 50 years. The 24.9% reported a calculated monthly income of 430 USD (8,612 MXN). Lower QoL scores were observed in the SLE group, especially in subjects with lower socioeconomic level. Health perception, QoL perception and socioeconomic status were the variables with greater importance to predict total WHOQoL scores.CONCLUSIONThe design and implementation of Lupus RGMX imply a pioneering approach to unraveling SLE in Mexicans. Further studies from Lupus RGMX will be focused on enriching the representation of the Mexican population and include other aspects that may allow us to improve our understanding of the disease in our population.

Published
2023

26. RSAT 2022: regulatory sequence analysis tools

Author

Institut Universitaire de France, Consejo Nacional de Ciencia y Tecnología (México), Universidad Nacional Autónoma de México, Agencia Estatal de Investigación (España), European Commission, Gobierno de Aragón, Institut Français de Bioinformatique, Contreras-Moreira, Bruno [0000-0002-5462-907X], Santana-Garcia, Walter, Castro-Mondragon, Jaime A., Padilla-Gálvez, Mónica, Nguyen, Nga Thi Thuy, Elizondo-Salas, Ana, Ksouri, Najla, Gerbes, François, Thieffry, Denis, Vincens, Pierre, Contreras-Moreira, Bruno, van Helden, Jacques, Thomas-Chollier, Morgane, Medina-Rivera, Alejandra, Institut Universitaire de France, Consejo Nacional de Ciencia y Tecnología (México), Universidad Nacional Autónoma de México, Agencia Estatal de Investigación (España), European Commission, Gobierno de Aragón, Institut Français de Bioinformatique, Contreras-Moreira, Bruno [0000-0002-5462-907X], Santana-Garcia, Walter, Castro-Mondragon, Jaime A., Padilla-Gálvez, Mónica, Nguyen, Nga Thi Thuy, Elizondo-Salas, Ana, Ksouri, Najla, Gerbes, François, Thieffry, Denis, Vincens, Pierre, Contreras-Moreira, Bruno, van Helden, Jacques, Thomas-Chollier, Morgane, and Medina-Rivera, Alejandra

Abstract

RSAT (Regulatory Sequence Analysis Tools) enables the detection and the analysis of cis-regulatory elements in genomic sequences. This software suite performs (i) de novo motif discovery (including from genome-wide datasets like ChIP-seq/ATAC-seq) (ii) genomic sequences scanning with known motifs, (iii) motif analysis (quality assessment, comparisons and clustering), (iv) analysis of regulatory variations and (v) comparative genomics. RSAT comprises 50 tools. Six public Web servers (including a teaching server) are offered to meet the needs of different biological communities. RSAT philosophy and originality are: (i) a multi-modal access depending on the user needs, through web forms, command-line for local installation and programmatic web services, (ii) a support for virtually any genome (animals, bacteria, plants, totalizing over 10 000 genomes directly accessible). Since the 2018 NAR Web Software Issue, we have developed a large REST API, extended the support for additional genomes and external motif collections, enhanced some tools and Web forms, and developed a novel tool that builds or refine gene regulatory networks using motif scanning (network-interactions). The RSAT website provides extensive documentation, tutorials and published protocols. RSAT code is under open-source license and now hosted in GitHub. RSAT is available at http://www.rsat.eu/.

Published
2022

27. RSAT 2022: regulatory sequence analysis tools

Author

Santana-Garcia, Walter, primary, Castro-Mondragon, Jaime A, additional, Padilla-Gálvez, Mónica, additional, Nguyen, Nga Thi Thuy, additional, Elizondo-Salas, Ana, additional, Ksouri, Najla, additional, Gerbes, François, additional, Thieffry, Denis, additional, Vincens, Pierre, additional, Contreras-Moreira, Bruno, additional, van Helden, Jacques, additional, Thomas-Chollier, Morgane, additional, and Medina-Rivera, Alejandra, additional

Published
2022
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30. Epromoters function as a hub to recruit key transcription factors required for the inflammatory response

Author

Santiago-Algarra, David, Souaid, Charbel, Singh, Himanshu, Dao, Lan, Hussain, Saadat, Medina-Rivera, Alejandra, Ramirez-Navarro, Lucia, Castro-Mondragon, Jaime, Sadouni, Nori, Charbonnier, Guillaume, Spicuglia, Salvatore, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad Nacional Autónoma de México (UNAM), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), ANR-18-CE12-0019,Epromoters,Contrôle de la réponse au stress par une nouvelle classe de promoteurs à activité enhancer(2018), ANR-17-CE12-0035,Silencer,Identification et analyse des éléments répresseurs génomiques(2017), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Spinelli, Lionel, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE - - Amidex2011 - ANR-11-IDEX-0001 - IDEX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Contrôle de la réponse au stress par une nouvelle classe de promoteurs à activité enhancer - - Epromoters2018 - ANR-18-CE12-0019 - AAPG2018 - VALID, and Identification et analyse des éléments répresseurs génomiques - - Silencer2017 - ANR-17-CE12-0035 - AAPG2017 - VALID

Subjects
Inflammation, Lipopolysaccharides, Science, [SDV]Life Sciences [q-bio], Macrophages, Interferon-alpha, STAT2 Transcription Factor, Article, Gene regulation, [SDV] Life Sciences [q-bio], Mice, Enhancer Elements, Genetic, STAT1 Transcription Factor, Gene Expression Regulation, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Multigene Family, Interferon Regulatory Factors, Interferon Type I, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, K562 Cells, Promoter Regions, Genetic, HeLa Cells
Abstract

Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response., Some promoters, termed Epromoters, can display enhancer activity and regulate distal genes in their endogenous context. Here the authors report the broad involvement of Epromoters in the coordinated activation of interferon (IFN) response. They show activation of a number of IFN-inducible genes is a result of Epromoters regulating expression of an entire IFN response gene cluster.

Published
2020

31. MACE: model based analysis of ChIP-exo

Author

Wang, Liguo, Chen, Junsheng, Wang, Chen, Uusküla-Reimand, Liis, Chen, Kaifu, Medina-Rivera, Alejandra, Young, Edwin J., Zimmermann, Michael T., Yan, Huihuang, Sun, Zhifu, Zhang, Yuji, Wu, Stephen T., Huang, Haojie, Wilson, Michael D., Kocher, Jean-Pierre A., and Li, Wei

Published
2014
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32. IL-12 Signaling Contributes to the Reprogramming of Neonatal CD8+ T Cells

Author

Gutiérrez-Reyna, Darely, Cedillo-Baños, Alejandra, Kempis-Calanis, Linda, Ramírez-Pliego, Oscar, Bargier, Lisa, Puthier, Denis, Abad-Flores, Jose, Thomas-Chollier, Morgane, Thieffry, Denis, Medina-Rivera, Alejandra, Spicuglia, Salvatore, Santana, Maria, Centro de Investigation en Ciencias-(IICBA), Universidad Autonoma del Estado de Morelos (UAEM), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad Nacional Autónoma de México (UNAM), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), and Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS)

Subjects
T cell activation, CD8 + T cells, Immunology, Infant, Newborn, RNA-sequencing, neonatal immunity, CD8-Positive T-Lymphocytes, CD8+ T cells, Cellular Reprogramming, Interleukin-12, IL-12, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Immunology and Allergy, Original Research, Signal Transduction, neonatal T cells
Abstract

International audience; Neonates are highly susceptible to intracellular pathogens, leading to high morbidity and mortality rates. CD8 + T lymphocytes are responsible for the elimination of infected cells. Understanding the response of these cells to normal and high stimulatory conditions is important to propose better treatments and vaccine formulations for neonates. We have previously shown that human neonatal CD8 + T cells overexpress innate inflammatory genes and have a low expression of cytotoxic and cell signaling genes. To investigate the activation potential of these cells, we evaluated the transcriptome of human neonatal and adult naïve CD8 + T cells after TCR/CD28 signals ± IL-12. We found that in neonatal cells, IL-12 signals contribute to the adult-like expression of genes associated with cell-signaling, T-cell cytokines, metabolism, and cell division. Additionally, IL-12 signals contributed to the downregulation of the neutrophil signature transcription factor CEBPE and other immaturity related genes. To validate the transcriptome results, we evaluated the expression of a series of genes by RT-qPCR and the promoter methylation status on independent samples. We found that in agreement with the transcriptome, IL-12 signals contributed to the chromatin closure of neutrophil-like genes and the opening of cytotoxicity genes, suggesting that IL-12 signals contribute to the epigenetic reprogramming of neonatal lymphocytes. Furthermore, high expression of some inflammatory genes was observed in naïve and stimulated neonatal cells, in agreement with the high inflammatory profile of neonates to infections. Altogether our results point to an important contribution of IL-12 signals to the reprogramming of the neonatal CD8 + T cells.

Published
2020

34. RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more

Author

Salgado, Heladia, Peralta-Gil, Martin, Gama-Castro, Socorro, Santos-Zavaleta, Alberto, Muñiz-Rascado, Luis, García-Sotelo, Jair S., Weiss, Verena, Solano-Lira, Hilda, Martínez-Flores, Irma, Medina-Rivera, Alejandra, Salgado-Osorio, Gerardo, Alquicira-Hernández, Shirley, Alquicira-Hernández, Kevin, López-Fuentes, Alejandra, Porrón-Sotelo, Liliana, Huerta, Araceli M., Bonavides-Martínez, César, Balderas-Martínez, Yalbi I., Pannier, Lucia, Olvera, Maricela, Labastida, Aurora, Jiménez-Jacinto, Verónica, Vega-Alvarado, Leticia, del Moral-Chávez, Victor, Hernández-Alvarez, Alfredo, Morett, Enrique, and Collado-Vides, Julio

Published
2013
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37. RegulonDB version 7.0: transcriptional regulation of Escherichia coli K-12 integrated within genetic sensory response units (Gensor Units)

Author

Gama-Castro, Socorro, Salgado, Heladia, Peralta-Gil, Martin, Santos-Zavaleta, Alberto, Muñiz-Rascado, Luis, Solano-Lira, Hilda, Jimenez-Jacinto, Verónica, Weiss, Verena, García-Sotelo, Jair S., López-Fuentes, Alejandra, Porrón-Sotelo, Liliana, Alquicira-Hernández, Shirley, Medina-Rivera, Alejandra, Martínez-Flores, Irma, Alquicira-Hernández, Kevin, Martínez-Adame, Ruth, Bonavides-Martínez, César, Miranda-Ríos, Juan, Huerta, Araceli M., Mendoza-Vargas, Alfredo, Collado-Torres, Leonardo, Taboada, Blanca, Vega-Alvarado, Leticia, Olvera, Maricela, Olvera, Leticia, Grande, Ricardo, Morett, Enrique, and Collado-Vides, Julio

Published
2011
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39. TwinsMX: Uncovering the Basis of Health and Disease in the Mexican Population

Author

Leon-Apodaca, Ana V., primary, Chiu-Han, Enrique, additional, Ortega-Mora, Ivett, additional, Román-López, Talía V., additional, Caballero-Sánchez, Ulises, additional, Aldana-Assad, Oscar, additional, Campos, Adrián I., additional, Cuellar-Partida, Gabriel, additional, Ruiz-Contreras, Alejandra E., additional, Alcauter, Sarael, additional, Rentería, Miguel E., additional, and Medina-Rivera, Alejandra, additional

Published
2019
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40. RSAT variation-tools: An accessible and flexible framework to predict the impact of regulatory variants on transcription factor binding

Author

Consejo Nacional de Ciencia y Tecnología (México), Universidad Nacional Autónoma de México, Gobierno de Aragón, Santana-García, Walter, Rocha-Acevedo, María, Ramírez-Navarro, Lucía, Mbouamboua, Yvon, Thieffry, Denis, Thomas-Chollier, Morgane, Contreras-Moreira, Bruno, van Helden, Jacques, Medina-Rivera, Alejandra, Consejo Nacional de Ciencia y Tecnología (México), Universidad Nacional Autónoma de México, Gobierno de Aragón, Santana-García, Walter, Rocha-Acevedo, María, Ramírez-Navarro, Lucía, Mbouamboua, Yvon, Thieffry, Denis, Thomas-Chollier, Morgane, Contreras-Moreira, Bruno, van Helden, Jacques, and Medina-Rivera, Alejandra

Abstract

Gene regulatory regions contain short and degenerated DNA binding sites recognized by transcription factors (TFBS). When TFBS harbor SNPs, the DNA binding site may be affected, thereby altering the transcriptional regulation of the target genes. Such regulatory SNPs have been implicated as causal variants in Genome-Wide Association Study (GWAS) studies. In this study, we describe improved versions of the programs Variation-tools designed to predict regulatory variants, and present four case studies to illustrate their usage and applications. In brief, Variation-tools facilitate i) obtaining variation information, ii) interconversion of variation file formats, iii) retrieval of sequences surrounding variants, and iv) calculating the change on predicted transcription factor affinity scores between alleles, using motif scanning approaches. Notably, the tools support the analysis of haplotypes. The tools are included within the well-maintained suite Regulatory Sequence Analysis Tools (RSAT, http://rsat.eu), and accessible through a web interface that currently enables analysis of five metazoa and ten plant genomes. Variation-tools can also be used in command-line with any locally-installed Ensembl genome. Users can input personal collections of variants and motifs, providing flexibility in the analysis.

Published
2019

41. RSAT 2018: regulatory sequence analysis tools 20th anniversary

Author

Nguyen, Nga Thi Thuy, Contreras-Moreira, Bruno, Castro-Mondragón, Jaime A., Santana-García, Walter, Ossio, Raúl, Robles-Espinoza, Carla Daniela, Bahin, Mathieu, Collombet, Samuel, Vincens, Pierre, Thieffry, Denis, van Helden, Jacques, Medina-Rivera, Alejandra, Thomas-Chollier, Morgane, Universidad Nacional Autónoma de México, Aix-Marseille Université, Research Council of Norway, Ministerio de Economía y Competitividad (España), Agence Nationale de la Recherche (France), Estn Expt Aula Dei, Spanish National Research Council (CSIC), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modélisation mathématique et statistique en biologie et médecine, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad Nacional Autónoma de México (UNAM), Université Paris sciences et lettres (PSL), ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011), ANR-14-CE11-0006,Echinodal,Dissection et modélisation du réseau génétique gouvernant la régionalisation de l'ectoderme au cours du développement de l'embryon d'oursin: caractérisation de nouveaux régulateurs de la formation de l'axe dorso-ventral en amont et en aval de Nodal.(2014), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris

Subjects
Internet, [STAT.AP]Statistics [stat]/Applications [stat.AP], RSAT, Genetic Variation, High-Throughput Nucleotide Sequencing, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Genomics, History, 20th Century, Regulatory Sequences, Nucleic Acid, History, 21st Century, SOAP/WSDL (Simple Object Access Protocol/Web Services Description Language), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Web Server Issue, Nucleotide Motifs, Genome Sequence Assembly, Software, ComputingMilieux_MISCELLANEOUS
Abstract

6 Pags.- 1 Tabl.- 1 Fig. © The Authors 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com, RSAT (Regulatory Sequence Analysis Tools) is a suite of modular tools for the detection and the analysis of cis-regulatory elements in genome sequences. Its main applications are (i) motif discovery, including from genome-wide datasets like ChIP-seq/ATAC-seq, (ii) motif scanning, (iii) motif analysis (quality assessment, comparisons and clustering), (iv) analysis of regulatory variations, (v) comparative genomics. Six public servers jointly support 10 000 genomes from all kingdoms. Six novel or refactored programs have been added since the 2015 NAR Web Software Issue, including updated programs to analyse regulatory variants (retrieve-variation-seq, variation-scan, convert-variations), along with tools to extract sequences from a list of coordinates (retrieve-seq-bed), to select motifs from motif collections (retrieve-matrix), and to extract orthologs based on Ensembl Compara (get-orthologs-compara). Three use cases illustrate the integration of new and refactored tools to the suite. This Anniversary update gives a 20-year perspective on the software suite. RSAT is well-documented and available through Web sites, SOAP/WSDL (Simple Object Access Protocol/Web Services Description Language) web services, virtual machines and stand-alone programs at http://www.rsat.eu/., French Government implemented by RENABI-IFB program [ANR-11-INSB-0013] to N.T.T.N.; ANR [ANR-14-CE11-0006-02] to M.T.C. and D.T.; A.M.-R.’s laboratory is supported by a CONACYT grant [269449]; Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica – Universidad Nacional Autónoma de México (PAPIIT-UNAM) grant [IA206517]; M.T.-C., A.M.R and D.T. further acknowledge SEP-CONACYT – ECOS-ANUIES support. J.A.C.M. benefited from a PhD grant from the Ecole Doctorale des Sciences de la Vie et de la Sant´e, Aix-Marseille Université, and is supported by Norwegian Research Council [187615]; Helse Sør-Øst, and University of Oslo through the Centre for Molecular Medicine Norway (NCMM); B.C.M. was funded by Spanish MINECO [AGL2016-80967-R] and by Aix-Marseille Universit´e as Chercheur Invit´e in 2015; C.D.R.-E.’s laboratory is supported by a Wellcome Trust Seed Award [204562/Z/16/Z]; PAPIIT-UNAM grant [IA200318]; R.O. is supported by a PhD studentship from CONACYT. Funding for open access charge: Agence Nationale de la Recherche.

Published
2018

42. PulmonDB: a curated lung disease gene expression database

Author

Villaseñor-Altamirano, Ana B., primary, Moretto, Marco, additional, Zayas-Del Moral, Alejandra, additional, Maldonado, Mariel, additional, Munguía-Reyes, Adrián, additional, Romero, Yair, additional, García-Sotelo, Jair. S., additional, Aguilar, Luis Alberto, additional, Oscar, Aldana-Assad, additional, Engelen, Kristof, additional, Selman, Moisés, additional, Collado-Vides, Julio, additional, Balderas-Martínez, Yalbi I., additional, and Medina-Rivera, Alejandra, additional

Published
2019
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44. RSAT 2018: regulatory sequence analysis tools 20th anniversary

Author

Universidad Nacional Autónoma de México, Aix-Marseille Université, Research Council of Norway, Ministerio de Economía y Competitividad (España), Agence Nationale de la Recherche (France), Nguyen, Nga Thi Thuy, Contreras-Moreira, Bruno, Castro-Mondragón, Jaime A., Santana-García, Walter, Ossio, Raúl, Robles-Espinoza, Carla Daniela, Bahin, Mathieu, Collombet, Samuel, Vincens, Pierre, Thieffry, Denis, van Helden, Jacques, Medina-Rivera, Alejandra, Thomas-Chollier, Morgane, Universidad Nacional Autónoma de México, Aix-Marseille Université, Research Council of Norway, Ministerio de Economía y Competitividad (España), Agence Nationale de la Recherche (France), Nguyen, Nga Thi Thuy, Contreras-Moreira, Bruno, Castro-Mondragón, Jaime A., Santana-García, Walter, Ossio, Raúl, Robles-Espinoza, Carla Daniela, Bahin, Mathieu, Collombet, Samuel, Vincens, Pierre, Thieffry, Denis, van Helden, Jacques, Medina-Rivera, Alejandra, and Thomas-Chollier, Morgane

Abstract

RSAT (Regulatory Sequence Analysis Tools) is a suite of modular tools for the detection and the analysis of cis-regulatory elements in genome sequences. Its main applications are (i) motif discovery, including from genome-wide datasets like ChIP-seq/ATAC-seq, (ii) motif scanning, (iii) motif analysis (quality assessment, comparisons and clustering), (iv) analysis of regulatory variations, (v) comparative genomics. Six public servers jointly support 10 000 genomes from all kingdoms. Six novel or refactored programs have been added since the 2015 NAR Web Software Issue, including updated programs to analyse regulatory variants (retrieve-variation-seq, variation-scan, convert-variations), along with tools to extract sequences from a list of coordinates (retrieve-seq-bed), to select motifs from motif collections (retrieve-matrix), and to extract orthologs based on Ensembl Compara (get-orthologs-compara). Three use cases illustrate the integration of new and refactored tools to the suite. This Anniversary update gives a 20-year perspective on the software suite. RSAT is well-documented and available through Web sites, SOAP/WSDL (Simple Object Access Protocol/Web Services Description Language) web services, virtual machines and stand-alone programs at http://www.rsat.eu/.

Published
2018

45. Management of Severe Bleeding in Patients Treated with Direct Oral Anticoagulants

Author

Dennis, Jessica, Medina-Rivera, Alejandra, Truong, Vinh, Antounians, Lina, Zwingerman, Nora, Carrasco, Giovana, Strug, Lisa, Wells, Phil, Trégouët, France, Morange, France, Wilson, Michael, Gagnon, France, Albaladejo, Pierre, Samama, Marc, Sié, Pierre, Kauffmann, Sophie, Mémier, Vincent, Suchon, Pierre, Viallon, Alain, David, Stéphane, Gruel, Yves, Bellamy, Lorenn, de Maistre, Emmanuel, Romegoux, Pauline, Thoret, Sophie, Pernod, Gilles, Bosson, Jean-Luc, Bazin, Etienne, Combaret, Nicolas, Cherprenet, Anne, Fares, Moustafa, Dufraisse, Sophie, Minville, Vincent, Morange, Pierre-Emmanuel, Leone, Marc, Cohen, William, Néant, Nadège, Marlu, Raphaël, Carpentier, Françoise, Defaye, Pascal, Mismetti, Patrick, Molliex, Serge, Lanoiselée, Julien, Piriou, Vincent, Delaleu-Rague, Carine, Lefèvre, Mathilde, Lagrange, Sophie, Ardillon, Lauren, Ozier, Yves, Bovet, Julien, Steib, Annick, Mebaouj, Sonia, Profumo, Louis, Roullet, Stéphanie, Smadja, David, Meyer, Guy, Journois, Didier, Trinh-Duc, Albert, Viard, Thibault, Belle, Loic, Levrat, Albrice, Gautheron, Etienne, Heluwaert, Frédéric, Schlumberger, Sylvie, Blanié, Antonia, Benhamou, Dan, Flaujac, Claire, Rosencher, Nadia, Beloeil, Hélène, Blery, Catherine, Daviet, Lauren, Guéret, Pierre, Faraoni, David, Schved, Jean François, Deras, Pauline, Jaber, Samir, Gueugniaud, Pierre Yves, Floccard, Bernard, Asehnoune, Karim, Paulus, Jerome, Amrani, Omar, Gonthier, Marie Caroline, Huisse, Marie Geneviève, Josserand, Julien, de Raucourt, Emmanuelle, Defournel, Cécile, Dubois, Yohann, Bouvier, Stéphane, Roy, Pierre-Marie, Lasocki, Sigismond, Carmagnac, Christian, Chastagner, Catherine, Thouret, Jean Marc, Sevestre, Marie Antoinette, Meaudre, Eric, Cungi, Pierre-Julien, Susen, Sophie, Lefrant, Jean Yves, Macey, Stéphane, Rieu, Jean Baptiste, Godier, Anne, University of Toronto, Program in genetics and genome biology, The Hospital for sick children [Toronto] (SickKids), Department of Molecular Genetics, Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Division of Biostatistics, Dalla Lana School of Public Health, Ottawa Hospital Research Institute, ThEMAS, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Pôle Anesthésie Réanimation, CHU Grenoble-Hôpital Michallon-CHU Grenoble-Hôpital Michallon, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Biotechnologies, Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Service des urgences, CHU Grenoble, Cardiac Stimulation and Rhythmology, Groupe de recherche sur la thrombose, pharmacologie des antithrombotiques et situations à risque (GRT), Université Jean Monnet - Saint-Étienne (UJM), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Cardiovasculaire, Hôpital Cardiologique de Lyon, Service de réanimation médicale polyvalente [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anesthésie-Réanimation (TP - SAR), CHU Strasbourg, Espace Ethiques et Politiques - Institut Hannah Arendt (EEP), Université Paris-Est Marne-la-Vallée (UPEM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Accueil des Urgences (AGEN - SAU), Centre Hospitalier d'Agen, Université de Bordeaux (UB), Service de Cardiologie (hôpital d'Annecy), Centre hospitalier de la région d'Annecy, Service d'hépato-gastroentérologie, Hôpital Cochin [AP-HP], Service d'anesthésie réanimation chirurgicale [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de réanimation chirurgicale, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Clinique de réanimation médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Laboratoire SUBATECH Nantes (SUBATECH), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Service des Urgences (PMR), CHRU - ANGERS, CHU d'Angers [Département Urgences], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Pôle de Pathologie cardiologie-vasculaire, Institut d'Hématologie-Transfusion-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de soins intensifs, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université Sorbonne Paris Cité (USPC), Universidad Nacional Autónoma de México (UNAM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Pôle Anesthésie Réanimation, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Service d'Anesthésie-Réanimation, CHU Toulouse [Toulouse]-Institut Louis Bugnard-Hôpital de Rangueil, CHU Toulouse [Toulouse], INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Cochin [AP-HP], Service Anesthésie et Réanimation, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Pôle Anesthésie Réanimation, Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Nantes (UN)-Mines Nantes (Mines Nantes), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Institut Louis Bugnard, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Ingénierie et Santé (CIS-ENSMSE), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)

Subjects
Rivaroxaban, business.industry, [SDV]Life Sciences [q-bio], Renal function, 030204 cardiovascular system & hematology, 3. Good health, Dabigatran, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Anesthesia, Medicine, Apixaban, Observational study, In patient, 030212 general & internal medicine, business, Prospective cohort study, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Cohort study
Abstract

Background The use of prothrombin complex concentrates and the role of plasma concentration of anticoagulants in the management of bleeding in patients treated with direct oral anticoagulants are still debated. Our aim was to describe management strategies and outcomes of severe bleeding events in patients treated with direct oral anticoagulants. Methods We performed a prospective cohort study of 732 patients treated with dabigatran, rivaroxaban, or apixaban hospitalized for severe bleeding, included prospectively in the registry from June 2013 to November 2015. Results Bleeding was gastrointestinal or intracranial in 37% (212 of 732) and 24% (141 of 732) of the cases, respectively. Creatinine clearance was lower than 60 ml/min in 61% (449 of 732) of the cases. The plasma concentration of direct oral anticoagulants was determined in 62% (452 of 732) of the cases and was lower than 50 ng/ml or higher than 400 ng/ml in 9.2% (41 of 452) and in 6.6% (30 of 452) of the cases, respectively. Activated or nonactivated prothrombin complex concentrates were administered in 38% of the cases (281 of 732). Mortality by day 30 was 14% (95% CI, 11 to 16). Conclusions Management of severe bleeding in patients treated with direct oral anticoagulants appears to be complex. The use of prothrombin complex concentrates differs depending on bleeding sites and direct oral anticoagulant plasma concentrations. Mortality differs according to bleeding sites and was similar to previous estimates.

Published
2017

46. IL-12 Signaling Contributes to the Reprogramming of Neonatal CD8+ T Cells.

Author

Gutiérrez-Reyna, Darely Y., Cedillo-Baños, Alejandra, Kempis-Calanis, Linda A., Ramírez-Pliego, Oscar, Bargier, Lisa, Puthier, Denis, Abad-Flores, Jose D., Thomas-Chollier, Morgane, Thieffry, Denis, Medina-Rivera, Alejandra, Spicuglia, Salvatore, and Santana, Maria A.

Subjects
T cells, INTRACELLULAR pathogens, CELL division, TRANSCRIPTION factors, LYMPHOCYTES
Abstract

Neonates are highly susceptible to intracellular pathogens, leading to high morbidity and mortality rates. CD8+ T lymphocytes are responsible for the elimination of infected cells. Understanding the response of these cells to normal and high stimulatory conditions is important to propose better treatments and vaccine formulations for neonates. We have previously shown that human neonatal CD8+ T cells overexpress innate inflammatory genes and have a low expression of cytotoxic and cell signaling genes. To investigate the activation potential of these cells, we evaluated the transcriptome of human neonatal and adult naïve CD8+ T cells after TCR/CD28 signals ± IL-12. We found that in neonatal cells, IL-12 signals contribute to the adult-like expression of genes associated with cell-signaling, T-cell cytokines, metabolism, and cell division. Additionally, IL-12 signals contributed to the downregulation of the neutrophil signature transcription factor CEBPE and other immaturity related genes. To validate the transcriptome results, we evaluated the expression of a series of genes by RT-qPCR and the promoter methylation status on independent samples. We found that in agreement with the transcriptome, IL-12 signals contributed to the chromatin closure of neutrophil-like genes and the opening of cytotoxicity genes, suggesting that IL-12 signals contribute to the epigenetic reprogramming of neonatal lymphocytes. Furthermore, high expression of some inflammatory genes was observed in naïve and stimulated neonatal cells, in agreement with the high inflammatory profile of neonates to infections. Altogether our results point to an important contribution of IL-12 signals to the reprogramming of the neonatal CD8+ T cells. [ABSTRACT FROM AUTHOR]

Published
2020
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50. Genetic variation 25.1 Mb upstream of tissue factor pathway inhibitor is associated with TFPI plasma levels and venous thromboembolism

Author

Dennis, Jessica, Truong, Vinh, Aïssi, Dylan, Medina-Rivera, Alejandra, Blankenberg, Stefan, Germain, Marine, Lemire, Mathieu, Antounians, Lina, Civelek, Mete, Schnabel, Renate, Wells, Phil, Wilson, Michael D., Morange, Pierre-Emmanuel, Trégouët, David-Alexandre, Gagnon, France, Dalla Lana School of Public Health, University of Toronto, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Universidad Nacional Autónoma de México (UNAM), Program in genetics and genome biology, The Hospital for sick children [Toronto] (SickKids), Department of General and Interventional Cardiology, University Heart Center Hamburg, Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Department of Molecular Genetics [Toronto], University of Virginia [Charlottesville], Ottawa Hospital Research Institute [Ottawa] (OHRI), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL-UPMC, Gestionnaire, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), University of Virginia, Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Canadian Institutes of Health Research [MOP 86466], Heart and Stroke Foundation of Canada [T6484], Heart and Stroke Foundation of Ontario [7486], Region Ile de France, Pierre and Marie Curie University, ICAN Institute for Cardiometabolism and Nutrition [ANR-10-IAHU-05], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Genetic Linkage, Thrombosis, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Blood Coagulation, Tissue Factor Pathway Inhibitor, Genetic Association Studies, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract

International audience; BackgroundTissue factor pathway inhibitor (TFPI) regulates fibrin clot formation, and low TFPI plasma levels increase the risk of arterial and venous thromboembolism (VTE). TFPI plasma levels are also heritable, and a previous linkage scan implicated the chromosome 2q region, but no specific genes.ObjectivesWe sought to replicate the linkage region in an independent sample and to identify the causal locus. MethodsWe first ran a linkage analysis of microsatellite markers and TFPI plasma levels in 251 individuals from the F5L Family Study and replicated the linkage peak on chromosome 2q (LOD=3.06). We next defined a follow-up region that included 112603 SNPs under the linkage peak, and meta-analyzed associations between these SNPs and TFPI plasma levels across the F5L Family Study and MARTHA, a study of 1033 unrelated VTE patients. SNPs with FDR q

Published
2016

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