2018;0:e018324. doi:10.1136/ bmjopen-2017-018324
Cohort Profile: GCAT|Genomes for Life. A Prospective Cohort study of the Genomes of Catalonia. Obón-Santacana M, Vilardell M, Carreras A, Durán X, Velasco J,Galván-Femenía I, Alonso T, Puig L, Sumoy L, Duell, E.J, Perucho M, Moreno V, de Cid R.
The prevalence of chronic non-communicable diseases (NCDs) is increasing worldwide. NCDs are the leading cause of both morbidity and mortality, and it is estimated that by 2030, they will be responsible for 80% of deaths across the world. Therefore, it is important to design and develop new primary and secondary prevention strategies to reduce these exposures to a hazard risk factor. The Genomes for Life (GCAT) project is a long-term prospective cohort study that was designed to integrate and assess the role of epidemiologic, genomic, and epigenomic factors in the development of cancer and other major chronic diseases in Catalonia, a northeast region of Spain.
Descarregar (PDF 813,51 Kb)
ADAR1 affects HCV infection by modulating innate immune response. Maria Pujantell, Sandra Franco, Iván Galván-Femenía, Roger Badia, Marc Castellví, Edurne Garcia-Vidal, Bonaventura Clotet, Rafael de Cid, Cristina Tural, Miguel A. Martínez, Eva Riveira-Muñoz, José A. Esté, Ester Ballana
The hepatitis C virus (HCV) is a globally prevalent infectious pathogen. As many as 80% of people infected with HCV do not control the virus and develop a chronic infection. Response to interferon (IFN) therapy is widely variable in chronic HCV infected patients, suggesting that HCV has evolved mechanisms to suppress and evade innate immunity responsible for its control and elimination. Adenosine deaminase acting on RNA 1 (ADAR1) is a relevant factor in the regulation of the innate immune response. The loss of ADAR1 RNA-editing activity and the resulting loss of inosine bases in RNA are critical in producing aberrant RLR-mediated innate immune response, mediated by RNA sensors MDA5 and RIG-I. Here, we describe ADAR1 role as a regulator of innate and antiviral immune function in HCV infection, both in vitro and in patients. Polymorphisms within ADAR1 gene were found significantly associated to poor clinical outcome to HCV therapy and advanced liver fibrosis in a cohort of HCV and HIV-1 coinfected patients. Moreover, ADAR1 knockdown in primary macrophages and Huh7 hepatoma cells enhanced IFN and IFN stimulated gene expression and increased HCV replication in vitro. Overall, our results demonstrate that ADAR1 regulates innate immune signaling and is an important contributor to the outcome of the HCV virus-host interaction. ADAR1 is a potential target to boost antiviral immune response in HCV infection.
Descarregar (PDF 34,01 Kb)
Pipeline design to identify key features and classify the chemotherapy response on lung cancer patients using large-scale genetic data
BMC Systems Biology
Pipeline design to identify key features and classify the chemotherapy response on lung cancer patients using large-scale genetic data. MG Valdés*, I Galván-Femenía*, Ribas R, Durán X, Yokota J, Rafael-Palou X, and de Cid R. *co-author
During the last decade, the interest to apply machine learning algorithms to genomic data has increased in many bioinformatics applications. Analyzing this type of data entails difficulties for managing high-dimensional data, class imbalance for knowledge extraction, identifying important features and classifying individuals. In this study, we propose a general framework to tackle these challenges with different machine learning algorithms and techniques. We apply the configuration of this framework on lung cancer patients, identifying genetic signatures for classifying response to drug treatment response. We intersect these relevant SNPs with the GWAS Catalog of the National Human Genome Research Institute and explore the Regulomedb, GTEx databases for functional analysis purposes.
Descarregar (PDF 59,89 Kb)
Genomic profiling in advanced stage non-small-cell lung cancer patients with platinum-based chemotherapy identifies germline variants with prognostic value in SMYD2
Cancer Treatment and Research Communications
2018. doi: 10.1016/j.ctarc.2018.02.003
Genomic profiling in advanced stage non-small-cell lung cancer patients with platinum-based chemotherapy identifies germline variants with prognostic value in SMYD2. I Galván-Femenía, M Guindo, X Duran, S Calabuig-Fariñas, J M Mercader, J L Ramirez, R Rosell, D Torrents, A Carreras, T Kohno, E Jantus-Lewintre, C Campsc, M Perucho , L Sumoy, J Yokota and R de Cid.
A two-Stage Genome wide association study in Caucasian population reveals germline genetic variation in SMYD2 associated to progression disease in first-line platinum-based treatment in advanced NSCLC patients. SMYD2 profiling might have prognostic / predictive value directing choice of therapy and enlighten current knowledge on pathways involved in human carcinogenesis as well in resistance to chemotherapy.
Descarregar (PDF 927,47 Kb)