01755nas a2200217   4500008004100000022001400041245008100055210006900136260001600205300000800221490000700229520109100236653001501327653000801342100002001350700002001370700002101390700002301411700002101434856008201455       2017                        eng d  a1471-210500aA new parallel pipeline for DNA methylation analysis of long reads datasets.0 anew parallel pipeline for DNA methylation analysis of long reads  c2017 Mar 09  a1610 v183 aBACKGROUND: DNA methylation is an important mechanism of epigenetic regulation in development and disease. New generation sequencers allow genome-wide measurements of the methylation status by reading short stretches of the DNA sequence (Methyl-seq). Several software tools for methylation analysis have been proposed over recent years. However, the current trend is that the new sequencers and the ones expected for an upcoming future yield sequences of increasing length, making these software tools inefficient and obsolete. RESULTS: In this paper, we propose a new software based on a strategy for methylation analysis of Methyl-seq sequencing data that requires much shorter execution times while yielding a better level of sensitivity, particularly for datasets composed of long reads. This strategy can be exported to other methylation, DNA and RNA analysis tools. CONCLUSIONS: The developed software tool achieves execution times one order of magnitude shorter than the existing tools, while yielding equal sensitivity for short reads and even better sensitivity for long reads.10aMethyl-Seq10aNGS1 aOlanda, Ricardo1 aPérez, Mariano1 aOrduña, Juan, M1 aTárraga, Joaquín1 aDopazo, Joaquín  uhttp://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-017-1574-303274nas a2200469   4500008004100000022001400041245010000055210006900155260001600224520184400240653001202084653000802096653001802104653002402122653001902146653000802165100002102173700001902194700001702213700002402230700002302254700002902277700002302306700002302329700002102352700001902373700002202392700003302414700002302447700001602470700002602486700002802512700002002540700002002560700002702580700002002607700002702627700001902654700002702673700002502700856007902725       2016                        eng d  a1537-171900a267 Spanish exomes reveal population-specific differences in disease-related genetic variation.0 a267 Spanish exomes reveal populationspecific differences in dise  c2016 Jan 133 aRecent 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.10adisease10aNGS10apolymorphisms10aPopulation genomics10aprioritization10aSNP1 aDopazo, Joaquín1 aAmadoz, Alicia1 aBleda, Marta1 aGarcía-Alonso, Luz1 aAlemán, Alejandro1 aGarcia-Garcia, Francisco1 aRodriguez, Juan, A1 aDaub, Josephine, T1 aMuntané, Gerard1 aRueda, Antonio1 aVela-Boza, Alicia1 aLópez-Domingo, Francisco, J1 aFlorido, Javier, P1 aArce, Pablo1 aRuiz-Ferrer, Macarena1 aMéndez-Vidal, Cristina1 aArnold, Todd, E1 aSpleiss, Olivia1 aAlvarez-Tejado, Miguel1 aNavarro, Arcadi1 aBhattacharya, Shomi, S1 aBorrego, Salud1 aSantoyo-López, Javier1 aAntiňolo, Guillermo  uhttps://mbe.oxfordjournals.org/content/early/2016/02/17/molbev.msw005.full02635nas a2200361   4500008004100000022001400041245014600055210006900201260001500270520148500285653002401770653000801794653001501802653000801817653001101825653001801836653002601854100001901880700002901899700001801928700002001946700002401966700002401990700002102014700001902035700002102054700003102075700003202106700002302138700002002161700002102181856007102202       2016                        eng d  a1943-781100aAssessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy.0 aAssessment of Targeted NextGeneration Sequencing as a Tool for t  c2016 Jan 23 aCharcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (<1%) were found in 12 cases. There were no candidate variants in 18 cases, and amplification failed for one sample. The DNAJB2 c.352+1G>A mutation was also detected in three additional families. On haplotype analysis, all of the patients from these five families shared the same haplotype; therefore, the DNAJB2 c.352+1G>A mutation may be a founder event. Our gene panel allowed us to perform a very rapid and cost-effective screening of genes involved in Charcot-Marie-Tooth disease/hereditary motor neuropathy. Our diagnostic strategy was robust in terms of both coverage and read depth for all of the genes and patient samples. These findings demonstrate the difficulty in achieving a definitive molecular diagnosis because of the complexity of interpreting new variants and the genetic heterogeneity that is associated with these neuropathies.10aCharcot-Marie-Tooth10aCMT10aDiagnostic10aNGS10aPanels10arare diseases10aTargeted resequencing1 aLupo, Vincenzo1 aGarcia-Garcia, Francisco1 aSancho, Paula1 aTello, Cristina1 aGarcía-Romero, Mar1 aVillarreal, Liliana1 aAlberti, Antonia1 aSivera, Rafael1 aDopazo, Joaquín1 aPascual-Pascual, Samuel, I1 aMárquez-Infante, Celedonio1 aCasasnovas, Carlos1 aSevilla, Teresa1 aEspinós, Carmen  uhttp://www.sciencedirect.com/science/article/pii/S152515781500261501901nas a2200241   4500008004100000022001400041245008000055210006900135260000900204300000800213490000700221520123600228653001101464653000801475653001301483653000801496100002301504700002301527700001901550700002001569700002001589856005001609       2016                        eng d  a1471-210500aHPG pore: an efficient and scalable framework for nanopore sequencing data.0 aHPG pore an efficient and scalable framework for nanopore sequen  c2016  a1070 v173 aBACKGROUND: The use of nanopore technologies is expected to spread in the future because they are portable and can sequence long fragments of DNA molecules without prior amplification. The first nanopore sequencer available, the MinION™ from Oxford Nanopore Technologies, is a USB-connected, portable device that allows real-time DNA analysis. In addition, other new instruments are expected to be released soon, which promise to outperform the current short-read technologies in terms of throughput. Despite the flood of data expected from this technology, the data analysis solutions currently available are only designed to manage small projects and are not scalable. RESULTS: Here we present HPG Pore, a toolkit for exploring and analysing nanopore sequencing data. HPG Pore can run on both individual computers and in the Hadoop distributed computing framework, which allows easy scale-up to manage the large amounts of data expected to result from extensive use of nanopore technologies in the future. CONCLUSIONS: HPG Pore allows for virtually unlimited sequencing data scalability, thus guaranteeing its continued management in near future scenarios. HPG Pore is available in GitHub at http://github.com/opencb/hpg-pore .10ahadoop10aHPC10ananopore10aNGS1 aTárraga, Joaquín1 aGallego, Asunción1 aArnau, Vicente1 aMedina, Ignacio1 aDopazo, Joaquin  uhttp://www.biomedcentral.com/1471-2105/17/10701932nas a2200253   4500008004100000022001400041245011000055210006900165260001600234300001400250490000700264520114400271653000801415653001301423653001501436653002001451100003601471700002401507700003001531700002301561700002001584700002101604856005301625       2015                        eng d  a1362-496200aAssessing the impact of mutations found in next generation sequencing data over human signaling pathways.0 aAssessing the impact of mutations found in next generation seque  c2015 Apr 16  aW270-W2750 v433 aModern sequencing technologies produce increasingly detailed data on genomic variation. However, conventional methods for relating either individual variants or mutated genes to phenotypes present known limitations given the complex, multigenic nature of many diseases or traits. Here we present PATHiVar, a web-based tool that integrates genomic variation data with gene expression tissue information. PATHiVar constitutes a new generation of genomic data analysis methods that allow studying variants found in next generation sequencing experiment in the context of signaling pathways. Simple Boolean models of pathways provide detailed descriptions of the impact of mutations in cell functionality so as, recurrences in functionality failures can easily be related to diseases, even if they are produced by mutations in different genes. Patterns of changes in signal transmission circuits, often unpredictable from individual genes mutated, correspond to patterns of affected functionalities that can be related to complex traits such as disease progression, drug response, etc. PATHiVar is available at: http://pathivar.babelomics.org.10aNGS10apathways10asignalling10aSystems biology1 aHernansaiz-Ballesteros, Rosa, D1 aSalavert, Francisco1 aSebastián-Leon, Patricia1 aAlemán, Alejandro1 aMedina, Ignacio1 aDopazo, Joaquín  uhttp://nar.oxfordjournals.org/content/43/W1/W27002445nas a2200469   4500008004100000022001400041245008300055210006900138260001600207300001400223490000700237520108700244653001501331653002101346653002201367653001601389653002101405653000801426653001201434653002001446653002001466100002001486700002401506700002901530700003101559700001701590700002401607700002301631700002201654700002401676700002101700700001801721700002201739700001901761700003601780700002301816700002301839700002001862700002001882700002001902856005301922       2015                        eng d  a1362-496200aBabelomics 5.0: functional interpretation for new generations of genomic data.0 aBabelomics 50 functional interpretation for new generations of g  c2015 Apr 20  aW117-W1210 v433 aBabelomics has been running for more than one decade offering a user-friendly interface for the functional analysis of gene expression and genomic data. Here we present its fifth release, which includes support for Next Generation Sequencing data including gene expression (RNA-seq), exome or genome resequencing. Babelomics has simplified its interface, being now more intuitive. Improved visualization options, such as a genome viewer as well as an interactive network viewer, have been implemented. New technical enhancements at both, client and server sides, makes the user experience faster and more dynamic. Babelomics offers user-friendly access to a full range of methods that cover: (i) primary data analysis, (ii) a variety of tests for different experimental designs and (iii) different enrichment and network analysis algorithms for the interpretation of the results of such tests in the proper functional context. In addition to the public server, local copies of Babelomics can be downloaded and installed. Babelomics is freely available at: http://www.babelomics.org.10ababelomics10adata integration10agene set analysis10ainteractome10anetwork analysis10aNGS10aRNA-seq10aSystems biology10atranscriptomics1 aAlonso, Roberto1 aSalavert, Francisco1 aGarcia-Garcia, Francisco1 aCarbonell-Caballero, José1 aBleda, Marta1 aGarcía-Alonso, Luz1 aSanchis-Juan, Alba1 aPerez-Gil, Daniel1 aMarin-Garcia, Pablo1 aSánchez, Rubén1 aCubuk, Cankut1 aHidalgo, Marta, R1 aAmadoz, Alicia1 aHernansaiz-Ballesteros, Rosa, D1 aAlemán, Alejandro1 aTárraga, Joaquín1 aMontaner, David1 aMedina, Ignacio1 aDopazo, Joaquin  uhttp://nar.oxfordjournals.org/content/43/W1/W11703376nas a2200793   4500008004100000022001400041245011500055210006900170260001600239520112300255653001101378653000801389653002001397100001901417700002601436700001201462700001801474700002201492700002701514700002201541700002201563700001901585700002901604700002301633700002001656700002001676700002301696700002501719700002201744700002201766700002101788700004001809700001201849700001701861700001201878700001601890700001901906700001801925700002101943700001601964700002001980700002402000700002002024700001802044700001302062700001702075700001802092700002102110700002402131700002002155700002102175700001702196700002102213700002502234700002102259700001902280700001902299700002102318700001602339700001402355700001702369700001502386700001302401700003102414700002102445700002102466700002002487856007502507       2015                        eng d  a1548-710500aCombining tumor genome simulation with crowdsourcing to benchmark somatic single-nucleotide-variant detection.0 aCombining tumor genome simulation with crowdsourcing to benchmar  c2015 May 183 aThe detection of somatic mutations from cancer genome sequences is key to understanding the genetic basis of disease progression, patient survival and response to therapy. Benchmarking is needed for tool assessment and improvement but is complicated by a lack of gold standards, by extensive resource requirements and by difficulties in sharing personal genomic information. To resolve these issues, we launched the ICGC-TCGA DREAM Somatic Mutation Calling Challenge, a crowdsourced benchmark of somatic mutation detection algorithms. Here we report the BAMSurgeon tool for simulating cancer genomes and the results of 248 analyses of three in silico tumors created with it. Different algorithms exhibit characteristic error profiles, and, intriguingly, false positives show a trinucleotide profile very similar to one found in human tumors. Although the three simulated tumors differ in sequence contamination (deviation from normal cell sequence) and in subclonality, an ensemble of pipelines outperforms the best individual pipeline in all cases. BAMSurgeon is available at https://github.com/adamewing/bamsurgeon/.10acancer10aNGS10avariant calling1 aEwing, Adam, D1 aHoulahan, Kathleen, E1 aHu, Yin1 aEllrott, Kyle1 aCaloian, Cristian1 aYamaguchi, Takafumi, N1 aBare, Christopher1 aP’ng, Christine1 aWaggott, Daryl1 aSabelnykova, Veronica, Y1 aKellen, Michael, R1 aNorman, Thea, C1 aHaussler, David1 aFriend, Stephen, H1 aStolovitzky, Gustavo1 aMargolin, Adam, A1 aStuart, Joshua, M1 aBoutros, Paul, C1 aparticipants, ICGC-TCGA, DREAM Soma1 aXi, Liu1 aDewal, Ninad1 aFan, Yu1 aWang, Wenyi1 aWheeler, David1 aWilm, Andreas1 aTing, Grace, Hui1 aLi, Chenhao1 aBertrand, Denis1 aNagarajan, Niranjan1 aChen, Qing-Rong1 aHsu, Chih-Hao1 aHu, Ying1 aYan, Chunhua1 aKibbe, Warren1 aMeerzaman, Daoud1 aCibulskis, Kristian1 aRosenberg, Mara1 aBergelson, Louis1 aKiezun, Adam1 aRadenbaugh, Amie1 aSertier, Anne-Sophie1 aFerrari, Anthony1 aTonton, Laurie1 aBhutani, Kunal1 aHansen, Nancy, F1 aWang, Difei1 aSong, Lei1 aLai, Zhongwu1 aLiao, Yang1 aShi, Wei1 aCarbonell-Caballero, José1 aDopazo, Joaquín1 aLau, Cheryl, C K1 aGuinney, Justin  uhttp://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.3407.html01828nas a2200253   4500008004100000022001400041245007200055210006900127260001700196300001300213490000700226520106800233653000801301653000801309653002301317100002101340700002301361700002001384700002301404700002201427700002001449700003001469856007501499       2015                        eng d  a1557-996400aConcurrent and Accurate Short Read Mapping on Multicore Processors.0 aConcurrent and Accurate Short Read Mapping on Multicore Processo  c2015 Sep-Oct  a995-10070 v123 aWe introduce a parallel aligner with a work-flow organization for fast and accurate mapping of RNA sequences on servers equipped with multicore processors. Our software, [Formula: see text] ([Formula: see text] is an open-source application. The software is available at http://www.opencb.org, exploits a suffix array to rapidly map a large fraction of the RNA fragments (reads), as well as leverages the accuracy of the Smith-Waterman algorithm to deal with conflictive reads. The aligner is enhanced with a careful strategy to detect splice junctions based on an adaptive division of RNA reads into small segments (or seeds), which are then mapped onto a number of candidate alignment locations, providing crucial information for the successful alignment of the complete reads. The experimental results on a platform with Intel multicore technology report the parallel performance of [Formula: see text], on RNA reads of 100-400 nucleotides, which excels in execution time/sensitivity to state-of-the-art aligners such as TopHat 2+Bowtie 2, MapSplice, and STAR.10aHPC10aNGS10ashort real mapping1 aMartinez, Hector1 aTárraga, Joaquín1 aMedina, Ignacio1 aBarrachina, Sergio1 aCastillo, Maribel1 aDopazo, Joaquin1 aQuintana-Orti, Enrique, S  uhttp://ieeexplore.ieee.org/xpl/articleDetails.jsp?tp=&arnumber=701000502548nas a2200373   4500008004100000022001400041245009200055210006900147260000900216300001000225490000600235520144500241653001501686653001601701653000801717653001901725100002301744700001901767700002601786700002501812700002601837700002001863700002001883700002601903700002601929700002201955700001701977700003601994700002102030700002502051700003402076700001902110856004502129       2015                        eng d  a2045-232200aExome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease.0 aExome sequencing reveals a high genetic heterogeneity on familia  c2015  a164730 v53 aHirschsprung disease (HSCR; OMIM 142623) is a developmental disorder characterized by aganglionosis along variable lengths of the distal gastrointestinal tract, which results in intestinal obstruction. Interactions among known HSCR genes and/or unknown disease susceptibility loci lead to variable severity of phenotype. Neither linkage nor genome-wide association studies have efficiently contributed to completely dissect the genetic pathways underlying this complex genetic disorder. We have performed whole exome sequencing of 16 HSCR patients from 8 unrelated families with SOLID platform. Variants shared by affected relatives were validated by Sanger sequencing. We searched for genes recurrently mutated across families. Only variations in the FAT3 gene were significantly enriched in five families. Within-family analysis identified compound heterozygotes for AHNAK and several genes (N = 23) with heterozygous variants that co-segregated with the phenotype. Network and pathway analyses facilitated the discovery of polygenic inheritance involving FAT3, HSCR known genes and their gene partners. Altogether, our approach has facilitated the detection of more than one damaging variant in biologically plausible genes that could jointly contribute to the phenotype. Our data may contribute to the understanding of the complex interactions that occur during enteric nervous system development and the etiopathology of familial HSCR.10ababelomics10aHirschprung10aNGS10aprioritization1 aLuzón-Toro, Berta1 aGui, Hongsheng1 aRuiz-Ferrer, Macarena1 aTang, Clara, Sze-Man1 aFernández, Raquel, M1 aSham, Pak-Chung1 aTorroglosa, Ana1 aTam, Paul, Kwong-Hang1 aEspino-Paisán, Laura1 aCherny, Stacey, S1 aBleda, Marta1 aEnguix-Riego, María, Del Valle1 aDopazo, Joaquín1 aAntiňolo, Guillermo1 aGarcia-Barceló, Maria-Mercè1 aBorrego, Salud  uhttp://www.nature.com/articles/srep1647302283nas a2200253   4500008004100000022001400041245009200055210006900147260001600216300001400232490000700246520154200253653001101795653000801806653001601814653000801830100002301838700002001861700002101881700001701902700002001919700002101939856006901960       2015                        eng d  a1367-481100aA Parallel and Sensitive Software Tool for Methylation Analysis on Multicore Platforms.0 aParallel and Sensitive Software Tool for Methylation Analysis on  c2015 Jun 10  a3130-31380 v313 aMOTIVATION: DNA methylation analysis suffers from very long processing time, since the advent of Next-Generation Sequencers (NGS) has shifted the bottleneck of genomic studies from the sequencers that obtain the DNA samples to the software that performs the analysis of these samples. The existing software for methylation analysis does not seem to scale efficiently neither with the size of the dataset nor with the length of the reads to be analyzed. Since it is expected that the sequencers will provide longer and longer reads in the near future, efficient and scalable methylation software should be developed. RESULTS: We present a new software tool, called HPG-Methyl, which efficiently maps bisulfite sequencing reads on DNA, analyzing DNA methylation. The strategy used by this software consists of leveraging the speed of the Burrows-Wheeler Transform to map a large number of DNA fragments (reads) rapidly, as well as the accuracy of the Smith-Waterman algorithm, which is exclusively employed to deal with the most ambiguous and shortest reads. Experimental results on platforms with Intel multicore processors show that HPGMethyl significantly outperforms in both execution time and sensitivity state-of-the-art software such as Bismark, BS-Seeker or BSMAP, particularly for long bisulfite reads. AVAILABILITY: Software in the form of C libraries and functions, together with instructions to compile and execute this software. Available by sftp to anonymous@clariano.uv.es (password "anonymous"). CONTACT: Juan.Orduna@uv.es.10aBS-seq10aHPC10amethylation10aNGS1 aTárraga, Joaquín1 aPérez, Mariano1 aOrduña, Juan, M1 aDuato, José1 aMedina, Ignacio1 aDopazo, Joaquín  uhttp://bioinformatics.oxfordjournals.org/content/31/19/3130.long01441nas a2200265   4500008004100000022001400041245009700055210006900152260001600221300001400237490000700251520057300258653000800831653004300839100002300882700001900905700002100924700001700945700001900962700002700981700002901008700002101037700002001058856009701078       2014                        eng d  a1367-481100aAcceleration of short and long DNA read mapping without loss of accuracy using suffix array.0 aAcceleration of short and long DNA read mapping without loss of   c2014 Aug 20  a3396-33980 v303 aHPG Aligner applies suffix arrays for DNA read mapping. This implementation produces a highly sensitive and extremely fast mapping of DNA reads that scales up almost linearly with read length. The approach presented here is faster (over 20x for long reads) and more sensitive (over 98% in a wide range of read lengths) than the current, state-of-the-art mappers. HPG Aligner is not only an optimal alternative for current sequencers but also the only solution available to cope with longer reads and growing throughputs produced by forthcoming sequencing technologies.10aNGS10ashort read mapping. HPC. suffix arrays1 aTárraga, Joaquín1 aArnau, Vicente1 aMartinez, Hector1 aMoreno, Raul1 aCazorla, Diego1 aSalavert-Torres, José1 aBlanquer-Espert, Ignacio1 aDopazo, Joaquín1 aMedina, Ignacio  uhttp://bioinformatics.oxfordjournals.org/content/early/2014/08/19/bioinformatics.btu553.long01916nas a2200253   4500008004100000022001400041245013800055210006900193260001600262300001400278490000700292520118400299653000801483653001201491653000901503100001101512700001601523700000501539700001501544700000501559700001601564700001101580856007101591       2014                        eng d  a1546-169600aA comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium.0 acomprehensive assessment of RNAseq accuracy reproducibility and   c2014 Aug 24  a903–9140 v323 aWe present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the US Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for junction discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed for all examined platforms, including qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcript-level profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings.10aNGS10aRNA-seq10aSEQC1 aSu, Z.1 aLabaj, P.P.1 a1 aDopazo, J.1 a1 aMason, C.E.1 aShi, L  uhttp://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.2957.html02492nas a2200577   4500008004100000022001400041245006100055210005800116260001500174300001600189490000700205520082400212653000801036653001901044653001701063100001801080700002101098700002101119700002801140700002301168700001701191700002201208700002201230700003001252700001601282700002001298700002601318700002901344700002201373700002201395700002001417700002901437700002701466700002101493700001701514700002201531700002101553700002401574700002201598700002901620700002701649700002001676700002001696700002501716700002101741700002001762700001601782700002801798700002101826856006701847       2014                        eng d  a1098-100400aA New Overgrowth Syndrome is Due to Mutations in RNF125.0 aNew Overgrowth Syndrome is Due to Mutations in RNF125  c2014 Sep 5  a1436–14410 v353 aOvergrowth syndromes (OGS) are a group of disorders in which all parameters of growth and physical development are above the mean for age and sex. We evaluated a series of 270 families from the Spanish Overgrowth Syndrome Registry with no known overgrowth syndrome. We identified one de novo deletion and three missense mutations in RNF125 in six patients from 4 families with overgrowth, macrocephaly, intellectual disability, mild hydrocephaly, hypoglycaemia and inflammatory diseases resembling Sjögren syndrome. RNF125 encodes an E3 ubiquitin ligase and is a novel gene of OGS. Our studies of the RNF125 pathway point to upregulation of RIG-I-IPS1-MDA5 and/or disruption of the PI3K-AKT and interferon signaling pathways as the putative final effectors. This article is protected by copyright. All rights reserved.10aNGS10aprioritization10aRare Disease1 aTenorio, Jair1 aMansilla, Alicia1 aValencia, María1 aMartínez-Glez, Víctor1 aRomanelli, Valeria1 aArias, Pedro1 aCastrejón, Nerea1 aPoletta, Fernando1 aGuillén-Navarro, Encarna1 aGordo, Gema1 aMansilla, Elena1 aGarcía-Santiago, Fé1 aGonzález-Casado, Isabel1 aVallespín, Elena1 aPalomares, María1 aMori, María, A1 aSantos-Simarro, Fernando1 aGarcía-Miñaur, Sixto1 aFernández, Luis1 aMena, Rocío1 aBenito-Sanz, Sara1 aDel Pozo, Angela1 aSilla, Juan, Carlos1 aIbañez, Kristina1 aLópez-Granados, Eduardo1 aMartín-Trujillo, Alex1 aMontaner, David1 aHeath, Karen, E1 aCampos-Barros, Angel1 aDopazo, Joaquín1 aNevado, Julián1 aMonk, David1 aRuiz-Pérez, Víctor, L1 aLapunzina, Pablo  uhttp://onlinelibrary.wiley.com/doi/10.1002/humu.22689/abstract02468nas a2200325   4500008004100000022001400041245005000055210004800105260001500153300001200168490000700180520163100187653000801818653001801826653001001844653001501854653003101869653000801900653000801908653000801916100002001924700002401944700002101968700002401989700002002013700001902033700001702052700002102069856005202090       2013                        eng d  a1362-496200aGenome Maps, a new generation genome browser.0 aGenome Maps a new generation genome browser  c2013 Jun 8  aW41-W460 v413 aGenome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https://github.com/compbio-bigdata-viz/genome-maps). Genome Maps is available at: http://www.genomemaps.org.10aBAM10agenome viewer10aHTML510ajavascript10aNext Generation Sequencing10aNGS10aSVG10aVCF1 aMedina, Ignacio1 aSalavert, Francisco1 aSánchez, Rubén1 aDe Maria, Alejandro1 aAlonso, Roberto1 aEscobar, Pablo1 aBleda, Marta1 aDopazo, Joaquín  uhttp://nar.oxfordjournals.org/content/41/W1/W4102674nas a2200313   4500008004100000022001400041245008800055210006900143260001600212300000700228490000600235520174000241653000801981100002101989700001602010700001602026700001902042700002002061700002602081700002002107700002902127700002802156700003302184700001702217700002702234700002502261700002002286856005402306       2012                        eng d  a1756-994X00aA map of human microRNA variation uncovers unexpectedly high levels of variability.0 amap of human microRNA variation uncovers unexpectedly high level  c2012 Aug 20  a620 v43 aABSTRACT: BACKGROUND: MicroRNAs (miRNAs) are key components of the gene regulatory network in many species. During the past few years, these regulatory elements have been shown to be involved in an increasing number and range of diseases. Consequently, the compilation of a comprehensive map of natural variability in healthy population seems an obvious requirement for future research on miRNA-related pathologies. METHODS: Data on 14 populations from the 1000 Genomes Project were analysed, along with new data extracted from 60 exomes of healthy individuals from a southern Spain population, sequenced in the context of the Medical Genome Project, to derive an accurate map of miRNA variability. RESULTS: Despite the common belief that miRNAs are highly conserved elements, analysis of the sequences of the 1,152 individuals indicated that the observed level of variability is double what was expected. A total of 527 variants were found. Among these, 45 variants affected the recognition region of the corresponding miRNA and were found in 43 different miRNAs, 26 of which are known to be involved in 57 diseases. Different parts of the mature structure of the miRNA were affected to different degrees by variants, which suggests the existence of a selective pressure related to the relative functional impact of the change. Moreover, 41 variants showed a significant deviation from the Hardy-Weinberg equilibrium, which supports the existence of a selective process against some alleles. The average number of variants per individual in miRNAs was 28. CONCLUSIONS: Despite an expectation that miRNAs would be highly conserved genomic elements, our study reports a level of variability comparable to that observed for coding genes.10aNGS1 aCarbonell, José1 aAlloza, Eva1 aArce, Pablo1 aBorrego, Salud1 aSantoyo, Javier1 aRuiz-Ferrer, Macarena1 aMedina, Ignacio1 aJiménez-Almazán, Jorge1 aMéndez-Vidal, Cristina1 adel Pozo, María, González-1 aVela, Alicia1 aBhattacharya, Shomi, S1 aAntiňolo, Guillermo1 aDopazo, Joaquin  uhttp://genomemedicine.com/content/4/8/62/abstract01929nas a2200253   4500008004100000022001400041245006800055210006500123260001600188300001100204490000700215520118200222653000801404100003001412700002901442700002101471700001801492700001801510700002001528700002101548700002101569700001601590856006901606       2012                        eng d  a1367-481100aQualimap: evaluating next-generation sequencing alignment data.0 aQualimap evaluating nextgeneration sequencing alignment data  c2012 Oct 15  a2678-90 v283 aMOTIVATION: The sequence alignment/map (SAM) and the binary alignment/map (BAM) formats have become the standard method of representation of nucleotide sequence alignments for next-generation sequencing data. SAM/BAM files usually contain information from tens to hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted biases in these data. The systematic detection of such biases is a non-trivial task that is crucial to drive appropriate downstream analyses. RESULTS: We have developed Qualimap, a Java application that supports user-friendly quality control of mapping data, by considering sequence features and their genomic properties. Qualimap takes sequence alignment data and provides graphical and statistical analyses for the evaluation of data. Such quality-control data are vital for highlighting problems in the sequencing and/or mapping processes, which must be addressed prior to further analyses. AVAILABILITY: Qualimap is freely available from http://www.qualimap.org. CONTACT: aconesa@cipf.es SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.10aNGS1 aGarcía-Alcalde, Fernando1 aOkonechnikov, Konstantin1 aCarbonell, José1 aCruz, Luis, M1 aGötz, Stefan1 aTarazona, Sonia1 aDopazo, Joaquín1 aMeyer, Thomas, F1 aConesa, Ana  uhttp://bioinformatics.oxfordjournals.org/content/28/20/2678.long01857nas a2200265   4500008004100000022001400041245011600055210006900171260001600240300001400256490000600270520098400276653003001260653001801290653001001308653000801318100002701326700003001353700002901383700002301412700002001435700002101455700002001476856009501496       2012                        eng d  a1557-996400aUsing GPUs for the Exact Alignment of Short-read Genetic Sequences by Means of the Burrows–Wheeler Transform.0 aUsing GPUs for the Exact Alignment of Shortread Genetic Sequence  c2012 Mar 20  a1245-12560 v93 aGeneral Purpose Graphic Processing Units (GPGPUs) constitute an inexpensive resource for computing-intensive applications that could exploit an intrinsic fine-grain parallelism. This paper presents the design and implementation in GPGPUs of an exact alignment tool for nucleotide sequences based on the Burrows-Wheeler Transform. We compare this algorithm with state-of-the-art implementations of the same algorithm over standard CPUs, and considering the same conditions in terms of I/O. Excluding disk transfers, the implementation of the algorithm in GPUs shows a speedup larger than 12x, when compared to CPU execution. This implementation exploits the parallelism by concurrently searching different sequences on the same reference search tree, maximising memory locality and ensuring a symmetric access to the data. The article describes the behaviour of the algorithm in GPU, showing a good scalability in the performance, only limited by the size of the GPU inner memory.10aBurrows-Wheeler transform10aCPU execution10aGPGPU10aNGS1 aTorres, Jose, Salavert1 aEspert, Ignacio, Blanquer1 aDominguez, Andres, Tomas1 aHernendez, Vicente1 aMedina, Ignacio1 aTerraga, Joaquin1 aDopazo, Joaquin  uhttp://ieeexplore.ieee.org.sire.ub.edu/xpl/articleDetails.jsp?reload=true&arnumber=617588801700nas a2200265   4500008004100000245004500041210004400086260000900130300001300139490000600152520096600158653000801124653001401132100002001146700001601166700002701182700002001209700002001229700002301249700001901272700001901291700002001310700002001330856008401350       2010                        eng d00aInitial genomics of the human nucleolus.0 aInitial genomics of the human nucleolus  c2010  ae10008890 v63 a<p>We report for the first time the genomics of a nuclear compartment of the eukaryotic cell. 454 sequencing and microarray analysis revealed the pattern of nucleolus-associated chromatin domains (NADs) in the linear human genome and identified different gene families and certain satellite repeats as the major building blocks of NADs, which constitute about 4% of the genome. Bioinformatic evaluation showed that NAD-localized genes take part in specific biological processes, like the response to other organisms, odor perception, and tissue development. 3D FISH and immunofluorescence experiments illustrated the spatial distribution of NAD-specific chromatin within interphase nuclei and its alteration upon transcriptional changes. Altogether, our findings describe the nature of DNA sequences associated with the human nucleolus and provide insights into the function of the nucleolus in genome organization and establishment of nuclear architecture.</p>10aNGS10anucleolus1 aNémeth, Attila1 aConesa, Ana1 aSantoyo-López, Javier1 aMedina, Ignacio1 aMontaner, David1 aPéterfia, Bálint1 aSolovei, Irina1 aCremer, Thomas1 aDopazo, Joaquin1 aLängst, Gernot  uhttp://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000889