麻豆传媒

Computational biology approaches to study (epi)genomic regulation

I am Lecturer in Computational Biology at the Biosciences Institute in the University of 麻豆传媒, UK. I lead the Computational Epigenomics Laboratory, focused in studying the gene regulatory programs and epigenomes of immune cells. More specifically, we want to understand the molecular mechanisms underlying the differences of the immune system in men and women, health and disease (cancer and infections).

Before joining 麻豆传媒, I have been deeply involved in the bioinformatics coordination two large-scale projects: the Spanish , studying the genome, epigenome and transcriptome of chronic lymphocytic leukemia (, , ), and the  that has generated human reference epigenomes for most hematopoietic cell types and several leukemias (see ). Moreover, I have led important methodological developments to dissect complex gene expression patterns from heterogeneous samples (, ), combining over hundred ChIP-seq experiments to reconstruct the first network of chromatin communication between proteins, histone marks and DNA modifications () and their relationship with the three-dimensional genome structure (). Finally, I have a long-standing interest in understanding how DNA replication and chromatin structure influence copy number variation and gene evolution (see our model in ).

An updated and complete list of publications is available in and . You can follow me on  or read our  to stay tuned for information about our research.

Group members

, Research Associate

, PhD student

Juliana Arcila-Galvis, PhD student

Alumni

Sex-dependent gene regulation in immune cells

Despite the relevance of sexual dimorphism in both health and disease, there is still an important gap in our understanding of the role of sex in immune responses. The immune systems of men and women show remarkable differences, especially after puberty. For example, there is evidence showing significant differences in T-cell activation and proliferation, phagocytosis efficiency, cytokine production and response to vaccination. In general, reported differences include males being more exposed to infection risk than females, while in turn women show a higher risk of suffering autoimmune diseases but the biological mechanisms for these clinical-epidemiological observations remain unknown.

Any given cell’s developmental state and its future possible fates are believed to be determined by the epigenomic states of its chromatin. The epigenomic makeup of a cell not only conditions the genes that are switched on or off but also those (poised) genes that can be switched on under certain stimuli. In the context of autoimmunity, several studies have provided examples of epigenetic alterations that appear to be disease-associated and could offer a possible mechanism for the disproportionate sex ratios observed. However, most studies so far just focus on individual epigenetic features or particular genes and we need a more complete genome-wide picture of the molecular differences in immune cells in men and women.

A more complete genome-wide picture of the molecular differences in immune cells in men and women needs to be constructed to fully understand how the sex-encoded information of the genome influence their regulatory programmes. This genome-wide picture is challenging to construct because the high dimensionality of the epigenomic information, which it is dispersed in different un-connected databases and the need for new computational methods for analysis. Different data types must be processed, combined and interpreted.

We are developing integrative bioinformatics approaches to mine both publicly available data and new data generated by collaborators at 麻豆传媒. Focusing on the delineation of sex-dependent transcriptomic and epigenomic differences within the immune system, we are performing a systematic collection of the dispersed data and integrating the different layers in a common analytical framework. The ultimate goal of this effort is to connect the sex-specific gene expression programmes with the corresponding sex-specific chromatin configuration.

Funding

 Seed Award in Science - ‘Sex-dependent gene regulation in immune cells’  

I regularly offer computational biology research projects for Bsc, Msc and MRes students at the  

• Adrover JM, Aroca-Crevillen A, Crainiciuc G, Ostos F, Rojas-Vega Y, Rubio-Ponce A, Cilloniz C, Bonzon-Kulichenko E, Calvo E, Rico D, Moro MA, Weber C, Lizasoain I, Torres A, Ruiz-Cabello J, Vazquez J, Hidalgo A. . Nature Immunology 2020, 21(2), 135-144.
• Rigau M, Juan D, Valencia A, Rico D. . PLoS Genetics 2017, 15(1), e1007902.
• Urdinguio RG, Lopez V, Bayon GF, Diaz de la Guardia R, Sierra MI, Garcia-Torano E, Perez RF, Garcia MG, Carella A, Pruneda PC, Prieto C, Dmitrijeva M, Santamarina P, Belmonte T, Mangas C, Diaconu E, Ferrero C, Tejedor JR, Fernandez-Morera JL, Bravo C, Bueno C, Sanjuan-Pla A, Rodriguez RM, Suarez-Alvarez B, Lopez-Larrea C, Bernal T, Colado E, Balbin M, Garcia-Suarez O, Chiara MD, Saenz-de-Santa-Maria I, Rodriguez F, Pando-Sandoval A, Rodrigo L, Santos L, Salas A, Vallejo-Diaz J, Carrera AC, Rico D, Hernandez-Lopez I, Vaya A, Ricart JM, Seto E, Sima-Teruel N, Vaquero A, Valledor L, Canal MJ, Pisano D, Grana-Castro O, Thomas T, Voss AK, Menendez P, Villar-Garea A, Deutzmann R, Fernandez AF, Fraga MF. . Nucleic Acids Research 2019, 47(10), 5016-5037.
• Carrillo-de-Santa-Pau E, Juan D, Pancaldi V, Were F, Martin-Subero I, Rico D, Valencia A, The BLUEPRINT Consortium. . Nucleic Acids Research 2017, 45(16), 9244-9259.
• Ecker S, Chen L, Pancaldi V, Bagger FO, Fernandez JM, Carrillo-de-Santa-Pau E, Juan D, Mann AL, Watt S, Casale FP, Sidiropoulos N, Rapin N, Merkel A, BLUEPRINT Consortium, Stunnenberg HG, Stegle O, Frontini M, Downes K, Pastinen T, Kuijpers TW, Rico D, Valencia A, Beck B, Soranzo N, Paul DS. . Genome Biology 2017, 18, 18.
• Pancaldi V, Carrillo-de-Santa-Pau E, Javierre BM, Juan D, Fraser P, Valencia A, Rico D. . Genome Biology 2016, 17, 152.
• Juan D, Perner D, Carrillo de Santa Pau E, Marsili S, Ochoa D, Chung HR, Vingron M, Rico D, Valencia A. . Cell Reports 2016, 14(5), 1246-1257.
• Chen L, Ge B, Casale FP, Vasquez L, Kwan T, Garrido-Martin D, Watt S, Yan Y, Kundu K, Ecker S, Datta A, Richardson D, Burden F, Mead D, Mann AL, Fernandez JM, Rowlston S, Wilder SP, Farrow S, Shao XJ, Lambourne JJ, Redensek A, Albers CA, Amstislavskiy V, Ashford S, Berentsen K, Bomba L, Bourque G, Bujold D, Busche S, Caron M, Chen SH, Cheung W, Delaneau O, Dermitzakis ET, Elding H, Colgiu I, Bagger FO, Flicek P, Habibi E, Iotchkova V, Janssen-Megens E, Kim B, Lehrach H, Lowy E, Mandoli A, Matarese F, Maurano MT, Morris JA, Pancaldi V, Pourfarzad F, Rehnstrom K, Rendon A, Risch T, Sharifi N, Simon MM, Sultan M, Valencia A, Walter K, Wang SY, Frontini M, Antonarakis SE, Clarke L, Yaspo ML, Beck S, Guigo R, Rico D, Martens JHA, Ouwehand WH, Kuijpers TW, Paul DS, Stunnenberg HG, Stegle O, Downes K, Pastinen T, Soranzo N. . Cell 2016, 167(5), 1398-1414.
• Stunnenberg HG, International-Human-Epigenome Consortium, Hirst M. . Cell 2016, 167(5), 1145-1149.
• Fernández JM, de-la-Torre V, Richardson D, Royo R, Puiggròs M, Moncunill V, Fragkogianni S, Clarke L, BLUEPRINT Consortium, Flicek P, Rico D, Torrents D, Carrillo-de-Santa-Pau E, Valencia A. . Cell Systems 2016, 3(5), 491-495.e5.
• Astle WJ, Elding H, Jiang T, Allen D, Ruklisa D, Mann AL, Mead D, Bouman H, Riveros-Mckay F, Kostadima MA, Lambourne JJ, Sivapalaratnam S, Downes K, Kundu K, Bomba L, Berentsen K, Bradley JR, Daugherty LC, Delaneau O, Freson K, Garner SF, Grassi L, Guerrero J, Haimel M, Janssen-Megens EM, Kaan A, Kamat M, Kim B, Mandoli A, Marchini J, Martens JH, Meacham S, Megy K, O'Connell J, Petersen R, Sharifi N, Sheard SM, Staley JR, Tuna S, van der Ent M, Walter K, Wang SY, Wheeler E, Wilder SP, Iotchkova V, Moore C, Sambrook J, Stunnenberg HG, Di Angelantonio E, Kaptoge S, Kuijpers TW, Carrillo-de-Santa-Pau E, Juan D, Rico D, Valencia A, Chen L, Ge B, Vasquez L, Kwan T, Garrido-Martín D, Watt S, Yang Y, Guigo R, Beck S, Paul DS, Pastinen T, Bujold D, Bourque G, Frontini M, Danesh J, Roberts DJ, Ouwehand WH, Butterworth AS, Soranzo N. . Cell 2016, 167(5), 1415-1429.e19.
• Feichtinger J, Hernandez I, Fischer C, Hanscho M, Auer N, Hackl M, Jadhav V, Baumann M, Krempl P, Schmidl C, Farlik M, Schuster M, Merkel A, Sommer A, Heath S, Rico D, Bock C, Thallinger G, Borth N. . Biotechnology and Bioengineering 2016, 113(10), 2241-2253.
• Esker S, Pancaldi V, Rico D, Valencia A. . Genome Medicine 2015, 7(8).
• Kulis M, Merkel A, Heath S, Queirós AC, Schuyler RP, Castellano G, Beekman R, Raineri E, Esteve A, Clot G, Verdaguer-Dot N, Duran-Ferrer M, Russiñol N, Vilarrasa-Blasi R, Ecker S, Pancaldi V, Rico D, Agueda L, Blanc J, Richardson D, Clarke L, Datta A, Pascual M, Agirre X, Prosper F, Alignani D, Paiva B, Caron G, Fest T, Muench MO, Fomin ME, Lee ST, Wiemels JL, Valencia A, Gut M, Flicek P, Stunnenberg HG, Siebert R, Küppers R, Gut IG, Campo E, Martín-Subero JI. . Nature Genetics 2015, 47, 746-756.
• Martinez-Garcia M, Juan D, Rausell A, Muñoz M, Baños N, Menéndez C, López-Casas PP, Rico D, Valencia A, Hidalgo M. . Genome Medicine 2014, 6, 27.
• Rico D, Juan D, Marques-Bonet T, Fernández-Capetillo O, Valencia A. . Biology Open 2014, 3, 231-231.
• Rigau M, Juan D, Valencia A, Rico D. . PLoS Genetics 2019, 15(1), e1007902.