03508nas 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
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/.
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-variability02194nas a2200241 4500008004100000022001400041245006800055210006700123260001500190300001200205490000700217520142700224653001901651653002601670653001101696653002301707100002701730700002001757700002201777700002201799700002501821856010601846 2019 eng d a1477-405400aPrecision medicine needs pioneering clinical bioinformaticians.0 aPrecision medicine needs pioneering clinical bioinformaticians c2019 05 21 a752-7660 v203 aSuccess in precision medicine depends on accessing high-quality genetic and molecular data from large, well-annotated patient cohorts that couple biological samples to comprehensive clinical data, which in conjunction can lead to effective therapies. From such a scenario emerges the need for a new professional profile, an expert bioinformatician with training in clinical areas who can make sense of multi-omics data to improve therapeutic interventions in patients, and the design of optimized basket trials. In this review, we first describe the main policies and international initiatives that focus on precision medicine. Secondly, we review the currently ongoing clinical trials in precision medicine, introducing the concept of 'precision bioinformatics', and we describe current pioneering bioinformatics efforts aimed at implementing tools and computational infrastructures for precision medicine in health institutions around the world. Thirdly, we discuss the challenges related to the clinical training of bioinformaticians, and the urgent need for computational specialists capable of assimilating medical terminologies and protocols to address real clinical questions. We also propose some skills required to carry out common tasks in clinical bioinformatics and some tips for emergent groups. Finally, we explore the future perspectives and the challenges faced by precision medicine bioinformatics.
10aCohort Studies10aComputational Biology10aHumans10aPrecision Medicine1 aGómez-López, Gonzalo1 aDopazo, Joaquin1 aCigudosa, Juan, C1 aValencia, Alfonso1 aAl-Shahrour, Fátima uhttps://www.clinbioinfosspa.es/content/precision-medicine-needs-pioneering-clinical-bioinformaticians02048nas a2200313 4500008004100000022001400041245012900055210006900184260001600253300001400269490000600283520099600289653002601285653002001311653002901331653001101360653001301371653001401384653002301398653002701421653002401448100002201472700001801494700001901512700002401531700003101555700002001586856012801606 2017 eng d a1949-255300aHigh throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes.0 aHigh throughput estimation of functional cell activities reveals c2017 Jan 17 a5160-51780 v83 aUnderstanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measurements of changes in the activity of signaling circuits, which ultimately constitute high-throughput estimations of cell functionalities caused by gene activity within the pathway. Moreover, such estimations can be obtained either at cohort-level, in case/control comparisons, or personalized for individual patients. The accuracy of the method is demonstrated in an extensive analysis involving 5640 patients from 12 different cancer types. Circuit activity measurements not only have a high diagnostic value but also can be related to relevant disease outcomes such as survival, and can be used to assess therapeutic interventions.
10aComputational Biology10agene expression10aGene Regulatory Networks10aHumans10amutation10aNeoplasms10aPrecision Medicine10aSequence Analysis, RNA10aSignal Transduction1 aHidalgo, Marta, R1 aCubuk, Cankut1 aAmadoz, Alicia1 aSalavert, Francisco1 aCarbonell-Caballero, José1 aDopazo, Joaquin uhttps://www.clinbioinfosspa.es/content/high-throughput-estimation-functional-cell-activities-reveals-disease-mechanisms-and02426nas a2200325 4500008004100000022001400041245006600055210006400121260001300185300001000198490000700208520140200215653002501617653003401642653003701676653001101713653002201724653002101746653003601767653002301803100002101826700001701847700002001864700002201884700003201906700001901938700002201957700002101979856010002000 2016 eng d a2363-891500aProgress in pharmacogenetics: consortiums and new strategies.0 aProgress in pharmacogenetics consortiums and new strategies c2016 Mar a17-230 v313 aPharmacogenetics (PGx), as a field dedicated to achieving the goal of personalized medicine (PM), is devoted to the study of genes involved in inter-individual response to drugs. Due to its nature, PGx requires access to large samples; therefore, in order to progress, the formation of collaborative consortia seems to be crucial. Some examples of this collective effort are the European Society of Pharmacogenomics and personalized Therapy and the Ibero-American network of Pharmacogenetics. As an emerging field, one of the major challenges that PGx faces is translating their discoveries from research bench to bedside. The development of genomic high-throughput technologies is generating a revolution and offers the possibility of producing vast amounts of genome-wide single nucleotide polymorphisms for each patient. Moreover, there is a need of identifying and replicating associations of new biomarkers, and, in addition, a greater effort must be invested in developing regulatory organizations to accomplish a correct standardization. In this review, we outline the current progress in PGx using examples to highlight both the importance of polymorphisms and the research strategies for their detection. These concepts need to be applied together with a proper dissemination of knowledge to improve clinician and patient understanding, in a multidisciplinary team-based approach.
10aCooperative Behavior10aGenome-Wide Association Study10aHigh-Throughput Screening Assays10aHumans10aPatient Care Team10apharmacogenetics10aPolymorphism, Single Nucleotide10aPrecision Medicine1 aMaroñas, Olalla1 aLatorre, Ana1 aDopazo, Joaquin1 aPirmohamed, Munir1 aRodríguez-Antona, Cristina1 aSiest, Gérard1 aCarracedo, Ángel1 aLLerena, Adrián uhttps://www.clinbioinfosspa.es/content/progress-pharmacogenetics-consortiums-and-new-strategies