@article {410, title = {LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus.}, journal = {Nat Commun}, volume = {9}, year = {2018}, month = {2018 04 16}, pages = {1488}, abstract = {

Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis. Here, we show that BL001, a small LRH-1 agonist, impedes hyperglycemia progression and the immune-dependent inflammation of pancreas in murine models of T1DM, and beta cell apoptosis in islets of type 2 diabetic patients, while increasing beta cell mass and insulin secretion. Thus, we suggest that LRH-1 agonism favors a dialogue between immune and islet cells, which could be druggable to protect against diabetes mellitus.

}, keywords = {Animals, Apoptosis, Cell Communication, Cell Survival, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Humans, Hypoglycemic Agents, Immunity, Innate, insulin, Insulin-Secreting Cells, Islets of Langerhans, Islets of Langerhans Transplantation, Macrophages, Male, Mice, Mice, Inbred C57BL, Phenalenes, Receptors, Cytoplasmic and Nuclear, Streptozocin, T-Lymphocytes, Regulatory, Transplantation, Heterologous}, issn = {2041-1723}, doi = {10.1038/s41467-018-03943-0}, author = {Cobo-Vuilleumier, Nadia and Lorenzo, Petra I and Rodr{\'\i}guez, Noelia Garc{\'\i}a and Herrera G{\'o}mez, Irene de Gracia and Fuente-Martin, Esther and L{\'o}pez-Noriega, Livia and Mellado-Gil, Jos{\'e} Manuel and Romero-Zerbo, Silvana-Yanina and Baqui{\'e}, Mathurin and Lachaud, Christian Claude and Stifter, Katja and Perdomo, German and Bugliani, Marco and De Tata, Vincenzo and Bosco, Domenico and Parnaud, Geraldine and Pozo, David and Hmadcha, Abdelkrim and Florido, Javier P and Toscano, Miguel G and de Haan, Peter and Schoonjans, Kristina and S{\'a}nchez Palaz{\'o}n, Luis and Marchetti, Piero and Schirmbeck, Reinhold and Mart{\'\i}n-Montalvo, Alejandro and Meda, Paolo and Soria, Bernat and Berm{\'u}dez-Silva, Francisco-Javier and St-Onge, Luc and Gauthier, Benoit R} } @article {1184, title = {267 Spanish exomes reveal population-specific differences in disease-related genetic variation.}, journal = {Molecular biology and evolution}, year = {2016}, month = {2016 Jan 13}, abstract = {Recent results from large-scale genomic projects suggest that allele frequencies, which are highly relevant for medical purposes, differ considerably across different populations. The need for a detailed catalogue of local variability motivated the whole exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population. Like in other studies, a considerable number of rare variants were found (almost one third of the described variants). There were also relevant differences in allelic frequencies in polymorphic variants, including about 10,000 polymorphisms private to the Spanish population. The allelic frequencies of variants conferring susceptibility to complex diseases (including cancer, schizophrenia, Alzheimer disease, type 2 diabetes and other pathologies) were overall similar to those of other populations. However, the trend is the opposite for variants linked to Mendelian and rare diseases (including several retinal degenerative dystrophies and cardiomyopathies) that show marked frequency differences between populations. Interestingly, a correspondence between differences in allelic frequencies and disease prevalence was found, highlighting the relevance of frequency differences in disease risk. These differences are also observed in variants that disrupt known drug binding sites, suggesting an important role for local variability in population-specific drug resistances or adverse effects. We have made the Spanish population variant server web page that contains population frequency information for the complete list of 170,888 variant positions we found publicly available (http://spv.babelomics.org/), We show that it if fundamental to determine population-specific variant frequencies in order to distinguish real disease associations from population-specific polymorphisms.}, keywords = {disease, NGS, polymorphisms, Population genomics, prioritization, SNP}, issn = {1537-1719}, doi = {10.1093/molbev/msw005}, url = {https://mbe.oxfordjournals.org/content/early/2016/02/17/molbev.msw005.full}, author = {Joaqu{\'\i}n Dopazo and Amadoz, Alicia and Bleda, Marta and Garc{\'\i}a-Alonso, Luz and Alem{\'a}n, Alejandro and Garcia-Garcia, Francisco and Rodriguez, Juan A and Daub, Josephine T and Muntan{\'e}, Gerard and Antonio Rueda and Vela-Boza, Alicia and L{\'o}pez-Domingo, Francisco J and Florido, Javier P and Arce, Pablo and Ruiz-Ferrer, Macarena and M{\'e}ndez-Vidal, Cristina and Arnold, Todd E and Spleiss, Olivia and Alvarez-Tejado, Miguel and Navarro, Arcadi and Bhattacharya, Shomi S and Borrego, Salud and Santoyo-L{\'o}pez, Javier and Anti{\v n}olo, Guillermo} } @article {482, title = {ngsCAT: a tool to assess the efficiency of targeted enrichment sequencing.}, journal = {Bioinformatics}, volume = {30}, year = {2014}, month = {2014 Jun 15}, pages = {1767-8}, abstract = {

MOTIVATION: Targeted enrichment sequencing by next-generation sequencing is a common approach to interrogate specific loci or the whole exome in the human genome. The efficiency and the lack of bias in the enrichment process need to be assessed as a quality control step before performing downstream analysis of the sequence data. Tools that can report on the sensitivity, specificity, uniformity and other enrichment-specific features are needed.

RESULTS: We have implemented the next-generation sequencing data Capture Assessment Tool (ngsCAT), a tool that takes the information of the mapped reads and the coordinates of the targeted regions as input files, and generates a report with metrics and figures that allows the evaluation of the efficiency of the enrichment process. The tool can also take as input the information of two samples allowing the comparison of two different experiments.

AVAILABILITY AND IMPLEMENTATION: Documentation and downloads for ngsCAT can be found at http://www.bioinfomgp.org/ngscat.

}, keywords = {Exome, Genome, Human, High-Throughput Nucleotide Sequencing, Humans, Sequence Analysis, DNA, Software}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btu108}, author = {L{\'o}pez-Domingo, Francisco J and Florido, Javier P and Rueda, Antonio and Dopazo, Joaquin and Santoyo-L{\'o}pez, Javier} }