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-irpvs03339nas a2200445   4500008004100000022001400041245013500055210006900190260001600259300001000275490000700285520187800292653001202170653003102182653002202213653001302235653001102248653001502259653002202274653002802296100003302324700002602357700002302383700001702406700001902423700003302442700001802475700002202493700002702515700002202542700002602564700002002590700001902610700002002629700002802649700002302677700002002700700002002720856015302740       2024                        eng d  a2045-232200aThe integrated genomic surveillance system of Andalusia (SIEGA) provides a One Health regional resource connected with the clinic.0 aintegrated genomic surveillance system of Andalusia SIEGA provid  c2024 Aug 19  a192000 v143 a<p>The One Health approach, recognizing the interconnectedness of human, animal, and environmental health, has gained significance amid emerging zoonotic diseases and antibiotic resistance concerns. This paper aims to demonstrate the utility of a collaborative tool, the SIEGA, for monitoring infectious diseases across domains, fostering a comprehensive understanding of disease dynamics and risk factors, highlighting the pivotal role of One Health surveillance systems. Raw whole-genome sequencing is processed through different species-specific open software that additionally reports the presence of genes associated to anti-microbial resistances and virulence. The SIEGA application is a Laboratory Information Management System, that allows customizing reports, detect transmission chains, and promptly alert on alarming genetic similarities. The SIEGA initiative has successfully accumulated a comprehensive collection of more than 1900 bacterial genomes, including Salmonella enterica, Listeria monocytogenes, Campylobacter jejuni, Escherichia coli, Yersinia enterocolitica and Legionella pneumophila, showcasing its potential in monitoring pathogen transmission, resistance patterns, and virulence factors. SIEGA enables customizable reports and prompt detection of transmission chains, highlighting its contribution to enhancing vigilance and response capabilities. Here we show the potential of genomics in One Health surveillance when supported by an appropriate bioinformatic tool. By facilitating precise disease control strategies and antimicrobial resistance management, SIEGA enhances global health security and reduces the burden of infectious diseases. The integration of health data from humans, animals, and the environment, coupled with advanced genomics, underscores the importance of a holistic One Health approach in mitigating health threats.</p>10aAnimals10aDrug Resistance, Bacterial10aGenome, Bacterial10aGenomics10aHumans10aOne Health10aVirulence Factors10aWhole Genome Sequencing1 aCasimiro-Soriguer, Carlos, S1 aPerez-Florido, Javier1 aRobles, Enrique, A1 aLara, María1 aAguado, Andrea1 aIglesias, Manuel, A Rodrígu1 aLepe, Jose, A1 aGarcía, Federico1 aPérez-Alegre, Mónica1 aAndújar, Eloísa1 aJiménez, Victoria, E1 aCamino, Lola, P1 aLoruso, Nicola1 aAmeyugo, Ulises1 aVazquez, Isabel, María1 aLozano, Carlota, M1 aChaves, Alberto1 aDopazo, Joaquin  uhttps://www.clinbioinfosspa.es/content/integrated-genomic-surveillance-system-andalusia-siega-provides-one-health-regional-resource-connected-clinic02743nas a2200313   4500008004100000022001400041245009700055210006900152260001300221300001000234490000600244520172000250100003301970700002602003700001702029700002802046700002302074700002602097700002302123700001702146700002002163700002002183700002802203700002002231700001802251700002002269700002202289856011802311       2024                        eng d  a2398-883500aMolecular and phylogenetic characterization of the monkeypox outbreak in the South of Spain.0 aMolecular and phylogenetic characterization of the monkeypox out  c2024 Mar  ae19650 v73 a<p><b>BACKGROUND AND AIM: </b>Until the May 2022 Monkeypox (MPXV) outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the MPXV outbreak in the South of Spain.</p><p><b>METHODS: </b>Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak.</p><p><b>RESULTS: </b>Whole genome sequencing of a total of 160 MPXV viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of MPXV viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating MPXV viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing before treatment.</p>1 aCasimiro-Soriguer, Carlos, S1 aPerez-Florido, Javier1 aLara, María1 aCamacho-Martinez, Pedro1 aMerino-Diaz, Laura1 aPupo-Ledo, Inmaculada1 ade Salazar, Adolfo1 aFuentes, Ana1 aViñuela, Laura1 aChueca, Natalia1 aMartinez-Martinez, Luis1 aLorusso, Nicola1 aLepe, Jose, A1 aDopazo, Joaquin1 aGarcía, Federico  uhttps://www.clinbioinfosspa.es/content/molecular-and-phylogenetic-characterization-monkeypox-outbreak-south-spain02759nas 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-approach01708nas a2200181   4500008004100000245013000041210006900171260000900240300001200249490000700261520105400268100001801322700003401340700003401374700002601408700003301434856005901467       2023                        eng d00aCase report: Analysis of phage therapy failure in a patient with a Pseudomonas aeruginosa prosthetic vascular graft infection0 aCase report Analysis of phage therapy failure in a patient with   c2023  a11996570 v103 a<p>Clinical case of a patient with a  multidrug-resistant prosthetic vascular graft infection which was treated with a cocktail of phages (PT07, 14/01, and PNM) in combination with ceftazidime-avibactam (CZA). After the application of the phage treatment and in absence of antimicrobial therapy, a new  bloodstream infection (BSI) with a septic residual limb metastasis occurred, now involving a wild-type strain being susceptible to ß-lactams and quinolones. Clinical strains were analyzed by microbiology and whole genome sequencing techniques. In relation with phage administration, the clinical isolates of  before phage therapy (HE2011471) and post phage therapy (HE2105886) showed a clonal relationship but with important genomic changes which could be involved in the resistance to this therapy. Finally, phenotypic studies showed a decrease in Minimum Inhibitory Concentration (MIC) to ß-lactams and quinolones as well as an increase of the biofilm production and phage resistant mutants in the clinical isolate of  post phage therapy.</p>1 aBlasco, Lucia1 aLópez-Hernández, Inmaculada1 aRodríguez-Fernández, Miguel1 aPerez-Florido, Javier1 aCasimiro-Soriguer, Carlos, S  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235614/02668nas 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-population02373nas a2200337   4500008004100000022001400041245017900055210006900234260001600303490000700319520115700326100002601483700003301509700002201542700002901564700001901593700001701612700002101629700003401650700002801684700002301712700002601735700002301761700002001784700001701804700002001821700002201841700002001863700001801883856013401901       2023                        eng d  a1422-006700aDetection of High Level of Co-Infection and the Emergence of Novel SARS CoV-2 Delta-Omicron and Omicron-Omicron Recombinants in the Epidemiological Surveillance of Andalusia.0 aDetection of High Level of CoInfection and the Emergence of Nove  c2023 Jan 260 v243 a<p>Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity.</p>1 aPerez-Florido, Javier1 aCasimiro-Soriguer, Carlos, S1 aOrtuno, Francisco1 aFernandez-Rueda, Jose, L1 aAguado, Andrea1 aLara, María1 aRiazzo, Cristina1 aRodriguez-Iglesias, Manuel, A1 aCamacho-Martinez, Pedro1 aMerino-Diaz, Laura1 aPupo-Ledo, Inmaculada1 ade Salazar, Adolfo1 aViñuela, Laura1 aFuentes, Ana1 aChueca, Natalia1 aGarcía, Federico1 aDopazo, Joaquin1 aLepe, Jose, A  uhttps://www.clinbioinfosspa.es/content/detection-high-level-co-infection-and-emergence-novel-sars-cov-2-delta-omicron-and-omicron02293nas a2200301   4500008004100000022001400041245015200055210006900207260001600276300000900292490000800301520121000309653001201519653001301531653002101544653001101565653004001576653001501616653003201631100002601663700002301689700001701712700002001729700002601749700002001775700002201795856017401817       2023                        eng d  a1469-440900aEvaluation of a combined detection of SARS-CoV-2 and its variants using real-time allele-specific PCR strategy: an advantage for clinical practice.0 aEvaluation of a combined detection of SARSCoV2 and its variants   c2023 Nov 24  ae2010 v1513 a<p>This study aimed to assess the ability of a real-time reverse transcription polymerase chain reaction (RT-PCR) with multiple targets to detect SARS-CoV-2 and its variants in a single test. Nasopharyngeal specimens were collected from patients in Granada, Spain, between January 2021 and December 2022. Five allele-specific RT-PCR kits were used sequentially, with each kit designed to detect a predominant variant at the time. When the Alpha variant was dominant, the kit included the HV69/70 deletion, E and N genes. When Delta replaced Alpha, the kit incorporated the L452R mutation in addition to E and N genes. When Omicron became dominant, L452R was replaced with the N679K mutation. Before incorporating each variant kit, a comparative analysis was carried out with SARS-CoV-2 whole genome sequencing (WGS). The results demonstrated that RT-PCR with multiple targets can provide rapid and effective detection of SARS-CoV-2 and its variants in a single test. A very high degree of agreement (96.2%) was obtained between the comparison of RT-PCR and WGS. Allele-specific RT-PCR assays make it easier to implement epidemiological surveillance systems for effective public health decision making.</p>10aAlleles10aCOVID-1910aCOVID-19 Testing10aHumans10aReal-Time Polymerase Chain Reaction10aSARS-CoV-210aSensitivity and Specificity1 aChaves-Blanco, Lucía1 ade Salazar, Adolfo1 aFuentes, Ana1 aViñuela, Laura1 aPerez-Florido, Javier1 aDopazo, Joaquin1 aGarcía, Federico  uhttps://www.clinbioinfosspa.es/content/evaluation-combined-detection-sars-cov-2-and-its-variants-using-real-time-allele-specific-pcr-strategy-advantage-clinical-practice02575nas 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-survival03091nas 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-variability02553nas a2200301   4500008004100000022001400041245009700055210006900152260001500221490000700236520154600243653001801789653001401807653001501821653002801836100002501864700002001889700003301909700001801942700002901960700002401989700002302013700002002036700002202056700002602078700002002104856012702124       2021                        eng d  a2047-217X00aHighly accurate whole-genome imputation of SARS-CoV-2 from partial or low-quality sequences.0 aHighly accurate wholegenome imputation of SARSCoV2 from partial   c2021 12 020 v103 a<p><b>BACKGROUND: </b>The current SARS-CoV-2 pandemic has emphasized the utility of viral whole-genome sequencing in the surveillance and control of the pathogen. An unprecedented ongoing global initiative is producing hundreds of thousands of sequences worldwide. However, the complex circumstances in which viruses are sequenced, along with the demand of urgent results, causes a high rate of incomplete and, therefore, useless sequences. Viral sequences evolve in the context of a complex phylogeny and different positions along the genome are in linkage disequilibrium. Therefore, an imputation method would be able to predict missing positions from the available sequencing data.</p><p><b>RESULTS: </b>We have developed the impuSARS application, which takes advantage of the enormous number of SARS-CoV-2 genomes available, using a reference panel containing 239,301 sequences, to produce missing data imputation in viral genomes. ImpuSARS was tested in a wide range of conditions (continuous fragments, amplicons or sparse individual positions missing), showing great fidelity when reconstructing the original sequences, recovering the lineage with a 100% precision for almost all the lineages, even in very poorly covered genomes (<20%).</p><p><b>CONCLUSIONS: </b>Imputation can improve the pace of SARS-CoV-2 sequencing production by recovering many incomplete or low-quality sequences that would be otherwise discarded. ImpuSARS can be incorporated in any primary data processing pipeline for SARS-CoV-2 whole-genome sequencing.</p>10aGenome, Viral10aPhylogeny10aSARS-CoV-210aWhole Genome Sequencing1 aOrtuno, Francisco, M1 aLoucera, Carlos1 aCasimiro-Soriguer, Carlos, S1 aLepe, Jose, A1 aMartinez, Pedro, Camacho1 aDiaz, Laura, Merino1 ade Salazar, Adolfo1 aChueca, Natalia1 aGarcía, Federico1 aPerez-Florido, Javier1 aDopazo, Joaquin  uhttps://www.clinbioinfosspa.es/content/highly-accurate-whole-genome-imputation-sars-cov-2-partial-or-low-quality-sequences00782nas a2200229   4500008004100000245009000041210006900131260001600200300000800216490000700224100003400231700002600265700003000291700002600321700002700347700002000374700003600394700002800430700002000458700002900478856004500507       2021                        eng d00aPhylogenetic Analysis of the 2020 West Nile Virus (WNV) Outbreak in Andalusia (Spain)0 aPhylogenetic Analysis of the 2020 West Nile Virus WNV Outbreak i  cJan-05-2021  a8360 v131 aCasimiro-Soriguer, Carlos, S.1 aPerez-Florido, Javier1 aFernandez-Rueda, Jose, L.1 aPedrosa-Corral, Irene1 aGuillot-Sulay, Vicente1 aLorusso, Nicola1 aMartinez-Gonzalez, Luis, Javier1 aNavarro-Marí, Jose, M.1 aDopazo, Joaquin1 aSanbonmatsu-Gámez, Sara  uhttps://www.mdpi.com/1999-4915/13/5/836 