03044nas a2200385   4500008004100000022001400041245012200055210006900177260001600246300000700262490000700269520175100276653001502027653001102042653001302053653004202066653001102108653002302119653001802142100002802160700002302188700002602211700002402237700002602261700003202287700003302319700002802352700003002380700001802410700002102428700002002449700001902469700002502488856014502513       2025                        eng d  a1479-587600aA genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice.0 agenomic strategy for precision medicine in rare diseases integra  c2025 Jan 20  a860 v233 a<p><b>BACKGROUND: </b>Despite the use of Next-Generation Sequencing (NGS) as the gold standard for the diagnosis of rare diseases, its clinical implementation has been challenging, limiting the cost-effectiveness of NGS and the understanding, control and safety essential for decision-making in clinical applications. Here, we describe a personalized NGS-based strategy integrating precision medicine into a public healthcare system and its implementation in the routine diagnosis process during a five-year pilot program.</p><p><b>METHODS: </b>Our approach involved customized probe designs, the generation of virtual panels and the development of a personalized medicine module (PMM) for variant prioritization. This strategy was applied to 6500 individuals including 6267 index patients and 233 NGS-based carrier screenings.</p><p><b>RESULTS: </b>Causative variants were identified in 2061 index patients (average 32.9%, ranging from 12 to 62% by condition). Also, 131 autosomal-recessive cases could be partially genetically diagnosed. These results led to over 5000 additional studies including carrier, prenatal and preimplantational tests or pharmacological and gene therapy treatments.</p><p><b>CONCLUSION: </b>This strategy has shown promising improvements in the diagnostic rate, facilitating timely diagnosis and gradually expanding our services portfolio for rare diseases. The steps taken towards the integration of clinical and genomic data are opening new possibilities for conducting both retrospective and prospective healthcare studies. Overall, this study represents a major milestone in the ongoing efforts to improve our understanding and clinical management of rare diseases, a crucial area of medical research and care.</p>10aAlgorithms10aFemale10aGenomics10aHigh-Throughput Nucleotide Sequencing10aHumans10aPrecision Medicine10arare diseases1 aMéndez-Vidal, Cristina1 aBravo-Gil, Nereida1 aPerez-Florido, Javier1 aMarcos-Luque, Irene1 aFernández, Raquel, M1 aFernandez-Rueda, Jose, Luis1 adel Pozo, María, González-1 aMartín-Sánchez, Marta1 aFernández-Suárez, Elena1 aMena, Marcela1 aCarmona, Rosario1 aDopazo, Joaquin1 aBorrego, Salud1 aAntiňolo, Guillermo  uhttps://www.clinbioinfosspa.es/content/genomic-strategy-precision-medicine-rare-diseases-integrating-customized-algorithms-clinical-practice02826nas a2200517   4500008004100000022001400041245009100055210006900146260001600215490000700231520126600238653001901504653001001523653001101533653001901544653002201563653002501585653001801610653001101628653000901639653003601648653001001684653002801694100002001722700002201742700002801764700002901792700002001821700002001841700002801861700002301889700002001912700002101932700002101953700002601974700002102000700002602021700002402047700001902071700002002090700001702110700002502127700001902152700002502171856011202196       2024                        eng d  a2073-442500aCharacterization of the Common Genetic Variation in the Spanish Population of Navarre.0 aCharacterization of the Common Genetic Variation in the Spanish   c2024 May 040 v153 a<p>Large-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from disease-causing ones. To this end, we conducted a comprehensive characterization of exonic variants in the population of Navarre (Spain), utilizing whole genome sequencing data from 358 unrelated individuals of Spanish origin. Our analysis revealed 61,410 biallelic single nucleotide variants (SNV) within the Navarrese cohort, with 35% classified as common (MAF > 1%). By comparing allele frequency data from 1000 Genome Project (excluding the Iberian cohort of Spain, IBS), Genome Aggregation Database, and a Spanish cohort (including IBS individuals and data from Medical Genome Project), we identified 1069 SNVs common in Navarre but rare (MAF ≤ 1%) in all other populations. We further corroborated this observation with a second regional cohort of 239 unrelated exomes, which confirmed 676 of the 1069 SNVs as common in Navarre. In conclusion, this study highlights the importance of population-specific characterization of genetic variation to improve allele frequency filtering in sequencing data analysis to identify disease-causing variants.</p>10aCohort Studies10aExome10aFemale10aGene Frequency10aGenetic Variation10aGenetics, Population10aGenome, Human10aHumans10aMale10aPolymorphism, Single Nucleotide10aSpain10aWhole Genome Sequencing1 aMaillo, Alberto1 aHuergo, Estefania1 aApellániz-Ruiz, María1 aUrrutia-Lafuente, Edurne1 aMiranda, María1 aSalgado, Josefa1 aPasalodos-Sanchez, Sara1 aDelgado-Mora, Luna1 aTeijido, Óscar1 aGoicoechea, Ibai1 aCarmona, Rosario1 aPerez-Florido, Javier1 aAquino, Virginia1 aLópez-López, Daniel1 aPeña-Chilet, Maria1 aBeltran, Sergi1 aDopazo, Joaquin1 aLasa, Iñigo1 aBeloqui, Juan, José1 aAlonso, Ángel1 aGomez-Cabrero, David  uhttps://www.clinbioinfosspa.es/content/characterization-common-genetic-variation-spanish-population-navarre01089nas a2200349   4500008004100000022001400041245005600055210004900111260001600160100002300176700002600199700002500225700002300250700003200273700001800305700002100323700002000344700002200364700001900386700002600405700003300431700002400464700002100488700002000509700001600529700001500545700002100560700002000581700002000601700003000621856008800651       2024                        eng d  a1673-852700aThe Iberian Roma Population Variant Server (IRPVS).0 aIberian Roma Population Variant Server IRPVS  c2024 Mar 261 aMavillard, Fabiola1 aPerez-Florido, Javier1 aOrtuno, Francisco, M1 aValladares, Amador1 aÁlvarez-Villegas, Miren, L1 aRoldán, Gema1 aCarmona, Rosario1 aSoriano, Manuel1 aSusarte, Santiago1 aFuentes, Pilar1 aLópez-López, Daniel1 aNuñez-Negrillo, Ana, María1 aCarvajal, Alejandra1 aMorgado, Yolanda1 aArteaga, Daniel1 aUfano, Rosa1 aMir, Pablo1 aGamella, Juan, F1 aDopazo, Joaquin1 aParadas, Carmen1 aCabrera-Serrano, Macarena  uhttps://www.clinbioinfosspa.es/content/iberian-roma-population-variant-server-irpvs02759nas a2200265   4500008004100000022001400041245011700055210006900172260001600241520176800257100003002025700002102055700002002076700002302096700002302119700001902142700002602161700002602187700003302213700002302246700002002269700003602289700002202325856014602347       2024                        eng d  a1476-557800aMutational landscape of risk variants in comorbid depression and obesity: a next-generation sequencing approach.0 aMutational landscape of risk variants in comorbid depression and  c2024 May 283 a<p>Major depression (MD) and obesity are complex genetic disorders that are frequently comorbid. However, the study of both diseases concurrently remains poorly addressed and therefore the underlying genetic mechanisms involved in this comorbidity remain largely unknown. Here we examine the contribution of common and rare variants to this comorbidity through a next-generation sequencing (NGS) approach. Specific genomic regions of interest in MD and obesity were sequenced in a group of 654 individuals from the PISMA-ep epidemiological study. We obtained variants across the entire frequency spectrum and assessed their association with comorbid MD and obesity, both at variant and gene levels. We identified 55 independent common variants and a burden of rare variants in 4 genes (PARK2, FGF21, HIST1H3D and RSRC1) associated with the comorbid phenotype. Follow-up analyses revealed significantly enriched gene-sets associated with biological processes and pathways involved in metabolic dysregulation, hormone signaling and cell cycle regulation. Our results suggest that, while risk variants specific to the comorbid phenotype have been identified, the genes functionally impacted by the risk variants share cell biological processes and signaling pathways with MD and obesity phenotypes separately. To the best of our knowledge, this is the first study involving a targeted sequencing approach toward the study of the comorbid MD and obesity. The framework presented here allowed a deep characterization of the genetics of the co-occurring MD and obesity, revealing insights into the mutational and functional profile that underlies this comorbidity and contributing to a better understanding of the relationship between these two disabling disorders.</p>1 aPérez-Gutiérrez, Ana, M1 aCarmona, Rosario1 aLoucera, Carlos1 aCervilla, Jorge, A1 aGutiérrez, Blanca1 aMolina, Esther1 aLópez-López, Daniel1 aPerez-Florido, Javier1 aZarza-Rebollo, Juan, Antonio1 aLópez-Isac, Elena1 aDopazo, Joaquin1 aMartinez-Gonzalez, Luis, Javier1 aRivera, Margarita  uhttps://www.clinbioinfosspa.es/content/mutational-landscape-risk-variants-comorbid-depression-and-obesity-next-generation-sequencing-approach02536nas a2200373   4500008004100000022001400041245010000055210006900155260001600224490000700240520133200247653003101579653001701610653002001627653001101647653000901658653001301667653002501680100002301705700002801728700003101756700002501787700002101812700001601833700002101849700002501870700002101895700001901916700001601935700002701951700002901978700001902007856013602026       2024                        eng d  a2073-440900aPrimary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel  Variant and Possible Modifier Gene.0 aPrimary Ciliary Dyskinesia and Retinitis Pigmentosa Novel Varian  c2024 Mar 160 v133 a<p>We report a novel  missense variant co-segregated with a familial X-linked retinitis pigmentosa (XLRP) case. The brothers were hemizygous for this variant, but only the proband presented with primary ciliary dyskinesia (PCD). Thus, we aimed to elucidate the role of the  variant and other modifier genes in the phenotypic variability observed in the family and its impact on motile cilia. The pathogenicity of the variant on the RPGR protein was evaluated by in vitro studies transiently transfecting the mutated  gene, and immunofluorescence analysis on nasal brushing samples. Whole-exome sequencing was conducted to identify potential modifier variants. In vitro studies showed that the mutated RPGR protein could not localise to the cilium and impaired cilium formation. Accordingly, RPGR was abnormally distributed in the siblings' nasal brushing samples. In addition, a missense variant in  was identified. The concurrent  variant influenced ciliary mislocalisation of the protein. We provide a comprehensive characterisation of motile cilia in this XLRP family, with only the proband presenting PCD symptoms. The variant's pathogenicity was confirmed, although it alone does not explain the respiratory symptoms. Finally, the  gene may be a potential modifier for respiratory symptoms in patients with  mutations.</p>10aCiliary Motility Disorders10aEye Proteins10aGenes, Modifier10aHumans10aMale10amutation10aRetinitis pigmentosa1 aBaz-Redón, Noelia1 aSánchez-Bellver, Laura1 aFernández-Cancio, Mónica1 aRovira-Amigo, Sandra1 aBurgoyne, Thomas1 aRanjit, Rai1 aAquino, Virginia1 aToro-Barrios, Noemí1 aCarmona, Rosario1 aPolverino, Eva1 aCols, Maria1 aMoreno-Galdó, Antonio1 aCamats-Tarruella, Núria1 aMarfany, Gemma  uhttps://www.clinbioinfosspa.es/content/primary-ciliary-dyskinesia-and-retinitis-pigmentosa-novel-variant-and-possible-modifier-gene02668nas a2200301   4500008004100000022001400041245008600055210006900141260001600210300000700226490000700233520168700240100002601927700001801953700002901971700002302000700002102023700002102044700002602065700002202091700002002113700002702133700002602160700002402186700002002210710002902230856010702259       2023                        eng d  a1479-736400aA crowdsourcing database for the copy-number variation of the Spanish population.0 acrowdsourcing database for the copynumber variation of the Spani  c2023 Mar 09  a200 v173 a<p><b>BACKGROUND: </b>Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants.</p><p><b>RESULTS: </b>Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/ .</p><p><b>CONCLUSION: </b>SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database.</p>1 aLópez-López, Daniel1 aRoldán, Gema1 aFernandez-Rueda, Jose, L1 aBostelmann, Gerrit1 aCarmona, Rosario1 aAquino, Virginia1 aPerez-Florido, Javier1 aOrtuno, Francisco1 aPita, Guillermo1 aNúñez-Torres, Rocío1 aGonzález-Neira, Anna1 aPeña-Chilet, Maria1 aDopazo, Joaquin1 aCSVS Crowdsourcing Group  uhttps://www.clinbioinfosspa.es/content/crowdsourcing-database-copy-number-variation-spanish-population02629nas a2200205   4500008004100000022001400041245020600055210006900261260001600330520167600346100002002022700002102042700002302063700003102086700002102117700003202138700002002170700002002190856021302210       2023                        eng d  a1578-898900aEvidence of the association between increased use of direct oral anticoagulants and a reduction in the rate of atrial fibrillation-related stroke and major bleeding at the population level (2012-2019).0 aEvidence of the association between increased use of direct oral  c2023 Nov 203 a<p><b>BACKGROUND: </b>The introduction of direct-acting oral anticoagulants (DOACs) has shown to decrease atrial fibrillation (AF)-related stroke and bleeding rates in clinical studies, but there is no certain evidence about their effects at the population level. Our aim was to assess changes in AF-related stroke and major bleeding rates between 2012 and 2019 in Andalusia (Spain), and the association between DOACs use and events rates at the population level.</p><p><b>METHODS: </b>All patients with an AF diagnosis from 2012 to 2019 were identified using the Andalusian Health Population Base, that provides clinical information on all Andalusian people. Annual ischemic and hemorrhagic stroke, major bleeding rates, and used antithrombotic treatments were determined. Marginal hazard ratios (HR) were calculated for each treatment.</p><p><b>RESULTS: </b>A total of 95,085 patients with an AF diagnosis were identified. Mean age was 76.1±10.2 years (49.7% women). An increase in the use of DOACs was observed throughout the study period in both males and females (p<0.001). The annual rate of ischemic stroke decreased by one third, while that of hemorrhagic stroke and major bleeding decreased 2-3-fold from 2012 to 2019. Marginal HR was lower than 0.50 for DOACs compared to VKA for all ischemic or hemorrhagic events.</p><p><b>CONCLUSIONS: </b>In this contemporary population-based study using clinical and administrative databases in Andalusia, a significant reduction in the incidence of AF-related ischemic and hemorrhagic stroke and major bleeding was observed between 2012 and 2019. The increased use of DOACs seems to be associated with this reduction.</p>1 aLoucera, Carlos1 aCarmona, Rosario1 aBostelmann, Gerrit1 aMuñoyerro-Muñiz, Dolores1 aVillegas, Román1 aGonzalez-Manzanares, Rafael1 aDopazo, Joaquin1 aAnguita, Manuel  uhttps://www.clinbioinfosspa.es/content/evidence-association-between-increased-use-direct-oral-anticoagulants-and-reduction-rate-atrial-fibrillation-related-stroke-and-major-bleeding-population-level-2012-201902339nas a2200229   4500008004100000022001400041245013100055210006900186260001600255300000800271490000700279520147800286100002001764700002101784700002701805700002301832700003101855700002101886700002401907700002001931856015801951       2023                        eng d  a1743-422X00aReal-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments.0 aRealworld evidence with a retrospective cohort of 15968 COVID19   c2023 Oct 06  a2260 v203 a<p><b>PURPOSE: </b>Despite the extensive vaccination campaigns in many countries, COVID-19 is still a major worldwide health problem because of its associated morbidity and mortality. Therefore, finding efficient treatments as fast as possible is a pressing need. Drug repurposing constitutes a convenient alternative when the need for new drugs in an unexpected medical scenario is urgent, as is the case with COVID-19.</p><p><b>METHODS: </b>Using data from a central registry of electronic health records (the Andalusian Population Health Database), the effect of prior consumption of drugs for other indications previous to the hospitalization with respect to patient outcomes, including survival and lymphocyte progression, was studied on a retrospective cohort of 15,968 individuals, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020.</p><p><b>RESULTS: </b>Covariate-adjusted hazard ratios and analysis of lymphocyte progression curves support a significant association between consumption of 21 different drugs and better patient survival. Contrarily, one drug, furosemide, displayed a significant increase in patient mortality.</p><p><b>CONCLUSIONS: </b>In this study we have taken advantage of the availability of a regional clinical database to study the effect of drugs, which patients were taking for other indications, on their survival. The large size of the database allowed us to control covariates effectively.</p>1 aLoucera, Carlos1 aCarmona, Rosario1 aEsteban-Medina, Marina1 aBostelmann, Gerrit1 aMuñoyerro-Muñiz, Dolores1 aVillegas, Román1 aPeña-Chilet, Maria1 aDopazo, Joaquin  uhttps://www.clinbioinfosspa.es/content/real-world-evidence-retrospective-cohort-15968-covid-19-hospitalized-patients-suggests-21-new-effective-treatments02575nas a2200457   4500008004100000022001400041245008300055210006900138260001600207490000700223520116500230653001301395653001801408653001101426653001301437653001401450653001401464653001501478100002001493700002601513700003301539700002501572700002101597700002301618700003201641700003101673700002101704700002901725700002601754700002001780700002501800700002701825700002801852700002301880700002301903700002001926700001801946700002201964700002001986856011102006       2022                        eng d  a1999-491500aAssessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival.0 aAssessing the Impact of SARSCoV2 Lineages and Mutations on Patie  c2022 Aug 270 v143 a<p><b>OBJECTIVES: </b>More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain.</p><p><b>METHODS: </b>A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis.</p><p><b>RESULTS: </b>A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins.</p><p><b>CONCLUSIONS: </b>This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.</p>10aCOVID-1910aGenome, Viral10aHumans10amutation10aPandemics10aPhylogeny10aSARS-CoV-21 aLoucera, Carlos1 aPerez-Florido, Javier1 aCasimiro-Soriguer, Carlos, S1 aOrtuno, Francisco, M1 aCarmona, Rosario1 aBostelmann, Gerrit1 aMartínez-González, Javier1 aMuñoyerro-Muñiz, Dolores1 aVillegas, Román1 aRodríguez-Baño, Jesús1 aRomero-Gómez, Manuel1 aLorusso, Nicola1 aGarcia-León, Javier1 aNavarro-Marí, Jose, M1 aCamacho-Martinez, Pedro1 aMerino-Diaz, Laura1 ade Salazar, Adolfo1 aViñuela, Laura1 aLepe, Jose, A1 aGarcía, Federico1 aDopazo, Joaquin  uhttps://www.clinbioinfosspa.es/content/assessing-impact-sars-cov-2-lineages-and-mutations-patient-survival03523nas a2200553   4500008004100000022001400041245007400055210006900129260001300198300001000211490000700221520170300228100002701931700002001958700003101978700002802009700003002037700002502067700001702092700002702109700003202136700002602168700002602194700003502220700003102255700001702286700003102303700003002334700003302364700003302397700003502430700003302465700002502498700003102523700002602554700002502580700002002605700002302625700002302648700002102671700002902692700003102721700002002752700002002772700002102792700002702813710002202840856010702862       2022                        eng d  a1579-212900aIncidence and Prevalence of Children's Diffuse Lung Disease in Spain.0 aIncidence and Prevalence of Childrens Diffuse Lung Disease in Sp  c2022 Jan  a22-290 v583 a<p><b>BACKGROUND: </b>Children's diffuse lung disease, also known as children's Interstitial Lung Diseases (chILD), are a heterogeneous group of rare diseases with relevant morbidity and mortality, which diagnosis and classification are very complex. Epidemiological data are scarce. The aim of this study was to analyse incidence and prevalence of chILD in Spain.</p><p><b>METHODS: </b>Multicentre observational prospective study in patients from 0 to 18 years of age with chILD to analyse its incidence and prevalence in Spain, based on data reported in 2018 and 2019.</p><p><b>RESULTS: </b>A total of 381 cases with chILD were notified from 51 paediatric pulmonology units all over Spain, covering the 91.7% of the paediatric population. The average incidence of chILD was 8.18 (CI 95% 6.28-10.48) new cases/million of children per year. The average prevalence of chILD was 46.53 (CI 95% 41.81-51.62) cases/million of children. The age group with the highest prevalence were children under 1 year of age. Different types of disorders were seen in children 2-18 years of age compared with children 0-2 years of age. Most frequent cases were: primary pulmonary interstitial glycogenosis in neonates (17/65), neuroendocrine cell hyperplasia of infancy in infants from 1 to 12 months (44/144), idiopathic pulmonary haemosiderosis in children from 1 to 5 years old (13/74), hypersensitivity pneumonitis in children from 5 to 10 years old (9/51), and scleroderma in older than 10 years old (8/47).</p><p><b>CONCLUSIONS: </b>We found a higher incidence and prevalence of chILD than previously described probably due to greater understanding and increased clinician awareness of these rare diseases.</p>1 aTorrent-Vernetta, Alba1 aGaboli, Mirella1 aCastillo-Corullón, Silvia1 aMondéjar-López, Pedro1 aSantiago, Verónica, Sanz1 aCosta-Colomer, Jordi1 aOsona, Borja1 aTorres-Borrego, Javier1 ade la Serna-Blázquez, Olga1 aAlonso, Sara, Bellón1 aAguilera, Pilar, Caro1 ade Atauri, Álvaro, Gimeno-Dí1 aSoria, Alfredo, Valenzuela1 aAyats, Roser1 ade Vicente, Carlos, Martin1 aGonzález, Valle, Velasco1 aGonzález, José, Domingo Mo1 aCalderín, Elisa, María Can1 aPastor-Vivero, María, Dolores1 aÁlvarez, María, Ángeles V1 aRovira-Amigo, Sandra1 aSerrano, Ignacio, Iglesias1 aIzquierdo, Ana, Díez1 aMessa, Inés, de Mir1 aGartner, Silvia1 aNavarro, Alexandra1 aBaz-Redón, Noelia1 aCarmona, Rosario1 aCamats-Tarruella, Núria1 aFernández-Cancio, Mónica1 aRapp, Christina1 aDopazo, Joaquin1 aGriese, Matthias1 aMoreno-Galdó, Antonio1 aChILD-Spain Group  uhttps://www.clinbioinfosspa.es/content/incidence-and-prevalence-childrens-diffuse-lung-disease-spain-003091nas a2200241   4500008004100000022001400041245013700055210006900192260001600261300001000277490000700287520215900294100002402453700003202477700003202509700002102541700002102562700002602583700004102609700002002650700004302670856013602713       2022                        eng d  a2045-232200aProtein and functional isoform levels and genetic variants of the BAFF and APRIL pathway components in systemic lupus erythematosus.0 aProtein and functional isoform levels and genetic variants of th  c2022 Jul 02  a112190 v123 a<p>Systemic lupus erythematosus (SLE) is the prototype of an autoimmune disease. Belimumab, a monoclonal antibody targets BAFF, is the only biologic approved for SLE and active lupus nephritis. BAFF is a cytokine with a key-regulatory role in the B cell homeostasis, which acts by binding to three receptors: BAFF-R, TACI and BCMA. TACI and BCMA also bind APRIL. Many studies reported elevated soluble BAFF and APRIL levels in the sera of SLE patients, but other questions about the role of this system in the disease remain open. The study aimed to investigate the utility of the cytokine levels in serum and urine as biomarkers, the role of non-functional isoforms, and the association of gene variants with the disease. This case-control study includes a cohort (women, 18-60 years old) of 100 patients (48% with nephritis) and 100 healthy controls. We used ELISA assays to measure the cytokine concentrations in serum (sBAFF and sAPRIL) and urine (uBAFF and uAPRIL); TaqMan Gene Expression Assays to quantify the relative mRNA expression of ΔBAFF, βAPRIL, and εAPRIL, and next-generation sequencing to genotype the cytokine (TNFSF13 and TNFSF13B) and receptor (TNFRSF13B, TNFRSF17 and TNFRSF13C) genes. The statistical tests used were: Kruskal-Wallis (qualitative variables), the Spearman Rho coefficient (correlations), the Chi-square and SKAT (association of common and rare genetic variants, respectively). As expected, sBAFF and sAPRIL levels were higher in patients than in controls (p ≤ 0.001) but found differences between patient subgroups. sBAFF and sAPRIL significantly correlated only in patients with nephritis (r = 0.67, p ≤ 0.001) and βAPRIL levels were lower in patients with nephritis (p = 0.04), and ΔBAFF levels were lower in patients with dsDNA antibodies (p = 0.04). Rare variants of TNFSF13 and TNFRSF13B and TNFSF13 p.Gly67Arg and TNFRSF13B p.Val220Ala were associated with SLE. Our study supports differences among SLE patient subgroups with diverse clinical features in the BAFF/APRIL pathway. In addition, it suggests the involvement of genetic variants in the susceptibility to the disease.</p>1 aOrtiz-Aljaro, Pilar1 aMontes-Cano, Marco, Antonio1 aGarcía-Lozano, José-Raúl1 aAquino, Virginia1 aCarmona, Rosario1 aPerez-Florido, Javier1 aGarcía-Hernández, Francisco, José1 aDopazo, Joaquin1 aGonzález-Escribano, María, Francisca  uhttps://www.clinbioinfosspa.es/content/protein-and-functional-isoform-levels-and-genetic-variants-baff-and-april-pathway-components03508nas a2200709   4500008004100000022001400041245008200055210006900137260001500206300001600221490000700237520139500244653001201639653002301651653001801674653002301692653001001715653001901725653002201744653002501766653001801791653001301809653001101822653001301833653002301846653001301869653001001882100002401892700001801916700002601934700002501960700002101985700002102006700002602027700002002053700002902073700002302102700002902125700002602154700002002180700002702200700002702227700001802254700001902272700003002291700001802321700003402339700001902373700002902392700002702421700001902448700002502467700001702492700002802509700002802537700001902565700002202584700001902606700002002625710004302645856011002688       2021                        eng d  a1362-496200aCSVS, a crowdsourcing database of the Spanish population genetic variability.0 aCSVS a crowdsourcing database of the Spanish population genetic   c2021 01 08  aD1130-D11370 v493 a<p>The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variability worldwide. CSVS is also part of the GA4GH Beacon network. CSVS can be accessed at: http://csvs.babelomics.org/.</p>10aAlleles10aChromosome Mapping10aCrowdsourcing10aDatabases, Genetic10aExome10aGene Frequency10aGenetic Variation10aGenetics, Population10aGenome, Human10aGenomics10aHumans10aInternet10aPrecision Medicine10aSoftware10aSpain1 aPeña-Chilet, Maria1 aRoldán, Gema1 aPerez-Florido, Javier1 aOrtuno, Francisco, M1 aCarmona, Rosario1 aAquino, Virginia1 aLópez-López, Daniel1 aLoucera, Carlos1 aFernandez-Rueda, Jose, L1 aGallego, Asunción1 aGarcia-Garcia, Francisco1 aGonzález-Neira, Anna1 aPita, Guillermo1 aNúñez-Torres, Rocío1 aSantoyo-López, Javier1 aAyuso, Carmen1 aMinguez, Pablo1 aAvila-Fernandez, Almudena1 aCorton, Marta1 aMoreno-Pelayo, Miguel, Ángel1 aMorin, Matías1 aGallego-Martinez, Alvaro1 aLopez-Escamez, Jose, A1 aBorrego, Salud1 aAntiňolo, Guillermo1 aAmigo, Jorge1 aSalgado-Garrido, Josefa1 aPasalodos-Sanchez, Sara1 aMorte, Beatriz1 aCarracedo, Ángel1 aAlonso, Ángel1 aDopazo, Joaquin1 aSpanish Exome Crowdsourcing Consortium  uhttps://www.clinbioinfosspa.es/content/csvs-crowdsourcing-database-spanish-population-genetic-variability02128nas a2200325   4500008004100000022001400041245008900055210006900144260001200213300001400225490000700239520106200246653001801308653003101326653004201357653001101399653003101410653001301441653003901454100002601493700002001519700002101539700002101560700002001581700002001601700002001621700001901641700002001660856012201680       2020                        eng d  a1098-100400aSMN1 copy-number and sequence variant analysis from next-generation sequencing data.0 aSMN1 copynumber and sequence variant analysis from nextgeneratio  c2020 12  a2073-20770 v413 a<p>Spinal muscular atrophy (SMA) is a severe neuromuscular autosomal recessive disorder affecting 1/10,000 live births. Most SMA patients present homozygous deletion of SMN1, while the vast majority of SMA carriers present only a single SMN1 copy. The sequence similarity between SMN1 and SMN2, and the complexity of the SMN locus makes the estimation of the SMN1 copy-number by next-generation sequencing (NGS) very difficult. Here, we present SMAca, the first python tool to detect SMA carriers and estimate the absolute SMN1 copy-number using NGS data. Moreover, SMAca takes advantage of the knowledge of certain variants specific to SMN1 duplication to also identify silent carriers. This tool has been validated with a cohort of 326 samples from the Navarra 1000 Genomes Project (NAGEN1000). SMAca was developed with a focus on execution speed and easy installation. This combination makes it especially suitable to be integrated into production NGS pipelines. Source code and documentation are available at https://www.github.com/babelomics/SMAca.</p>10aBase Sequence10aDNA Copy Number Variations10aHigh-Throughput Nucleotide Sequencing10aHumans10aReproducibility of Results10aSoftware10aSurvival of Motor Neuron 1 Protein1 aLópez-López, Daniel1 aLoucera, Carlos1 aCarmona, Rosario1 aAquino, Virginia1 aSalgado, Josefa1 aPasalodos, Sara1 aMiranda, María1 aAlonso, Ángel1 aDopazo, Joaquin  uhttps://www.clinbioinfosspa.es/content/smn1-copy-number-and-sequence-variant-analysis-next-generation-sequencing-data