The Experts below are selected from a list of 127194 Experts worldwide ranked by ideXlab platform
Stinus Lindgreen - One of the best experts on this subject based on the ideXlab platform.
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adapterremoval easy cleaning of Next Generation Sequencing reads
BMC Research Notes, 2012Co-Authors: Stinus LindgreenAbstract:With the advent of Next-Generation Sequencing there is an increased demand for tools to pre-process and handle the vast amounts of data generated. One recurring problem is adapter contamination in the reads, i.e. the partial or complete Sequencing of adapter sequences. These adapter sequences have to be removed as they can hinder correct mapping of the reads and influence SNP calling and other downstream analyses. We present a tool called AdapterRemoval which is able to pre-process both single and paired-end data. The program locates and removes adapter residues from the reads, it is able to combine paired reads if they overlap, and it can optionally trim low-quality nucleotides. Furthermore, it can look for adapter sequence in both the 5’ and 3’ ends of the reads. This is a flexible tool that can be tuned to accommodate different experimental settings and Sequencing platforms producing FASTQ files. AdapterRemoval is shown to be good at trimming adapters from both single-end and paired-end data. AdapterRemoval is a comprehensive tool for analyzing Next-Generation Sequencing data. It exhibits good performance both in terms of sensitivity and specificity. AdapterRemoval has already been used in various large projects and it is possible to extend it further to accommodate application-specific biases in the data.
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adapterremoval easy cleaning of Next Generation Sequencing reads
BMC Research Notes, 2012Co-Authors: Stinus LindgreenAbstract:Background With the advent of Next-Generation Sequencing there is an increased demand for tools to pre-process and handle the vast amounts of data generated. One recurring problem is adapter contamination in the reads, i.e. the partial or complete Sequencing of adapter sequences. These adapter sequences have to be removed as they can hinder correct mapping of the reads and influence SNP calling and other downstream analyses.
Steve Miller - One of the best experts on this subject based on the ideXlab platform.
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clinical metagenomic Next Generation Sequencing for pathogen detection
Annual Review of Pathology-mechanisms of Disease, 2019Co-Authors: Steve Miller, Charles Y ChiuAbstract:Nearly all infectious agents contain DNA or RNA genomes, making Sequencing an attractive approach for pathogen detection. The cost of high-throughput or Next-Generation Sequencing has been reduced ...
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validation of metagenomic Next Generation Sequencing tests for universal pathogen detection
Archives of Pathology & Laboratory Medicine, 2017Co-Authors: Robert Schlaberg, Steve Miller, Charles Y Chiu, Gary W Procop, George M WeinstockAbstract:Context.— Metagenomic Sequencing can be used for detection of any pathogens using unbiased, shotgun Next-Generation Sequencing (NGS), without the need for sequence-specific amplification. Proof-of-...
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Diagnosis of Neuroinvasive Astrovirus Infection in an Immunocompromised Adult With Encephalitis by Unbiased Next- Generation Sequencing
2016Co-Authors: Samia N. Naccache, Karl S. Peggs, Frank M. Mattes, Rahul Phadke, Jeremy A. Garson, Paul Grant, Erik Samayoa, Scot Federman, Steve Miller, Michael P. LunnAbstract:Metagenomic Next-Generation Sequencing (NGS) was used to diagnose an unusual and fatal case of progressive encephalitis in an immunocompromised adult presenting at disease onset as bilateral hearing loss. The Sequencing and confirmatory studies revealed neuroinvasive infection of the brain by an astrovirus belonging to a recently discovered VA/HMO clade. Keywords. VA/HMO astrovirus clade; encephalitis; deaf-ness; Next-Generation Sequencing; pathogen discovery. The etiology of acute encephalitis remains undiagnosed in ap-proximately 60 % of cases [1]. Timely diagnosis is hindered by the lack of available assays to rapidly survey the breadth of com-mon, rare, or unknown agents responsible for encephalitis. Un-biased metagenomic Next-Generation Sequencing (NGS) offers the possibility for pathogen identification without a priori knowledge of the target [2]. We recently developed a rapi
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Diagnosis of Neuroinvasive Astrovirus Infection in an Immunocompromised Adult With Encephalitis by Unbiased Next- Generation Sequencing
2016Co-Authors: Samia N. Naccache, Karl S. Peggs, Frank M. Mattes, Rahul Phadke, Jeremy A. Garson, Paul Grant, Erik Samayoa, Scot Federman, Steve Miller, Michael P. LunnAbstract:(See the Major Article by Brown et al on pages 881–8, and the Editorial Commentary by Calistri and Palù on pages 889–91.) Metagenomic Next-Generation Sequencing (NGS) was used to diagnose an unusual and fatal case of progressive encephalitis in an immunocompromised adult presenting at disease onset as bilateral hearing loss. The Sequencing and confirmatory studies revealed neuroinvasive infection of the brain by an astrovirus belonging to a recently discovered VA/HMO clade. Keywords. VA/HMO astrovirus clade; encephalitis; deaf-ness; Next-Generation Sequencing; pathogen discovery. The etiology of acute encephalitis remains undiagnosed in ap-proximately 60 % of cases [1]. Timely diagnosis is hindered by the lack of available assays to rapidly survey the breadth of com-mon, rare, or unknown agents responsible for encephalitis. Un-biased metagenomic Next-Generation Sequencing (NGS) offer
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actionable diagnosis of neuroleptospirosis by Next Generation Sequencing
The New England Journal of Medicine, 2014Co-Authors: Michael R Wilson, Samia N. Naccache, Erik Samayoa, Scot Federman, Steve Miller, Mark Biagtan, Hiba Bashir, Shahriar M Salamat, Sneha Somasekar, Robert SokolicAbstract:A 14-year-old boy with severe combined immunodeficiency presented three times to a medical facility over a period of 4 months with fever and headache that progressed to hydrocephalus and status epilepticus necessitating a medically induced coma. Diagnostic workup including brain biopsy was unrevealing. Unbiased Next-Generation Sequencing of the cerebrospinal fluid identified 475 of 3,063,784 sequence reads (0.016%) corresponding to leptospira infection. Clinical assays for leptospirosis were negative. Targeted antimicrobial agents were administered, and the patient was discharged home 32 days later with a status close to his premorbid condition. Polymerase-chain-reaction (PCR) and serologic testing at the Centers for Disease Control and Prevention (CDC) subsequently confirmed evidence of Leptospira santarosai infection.
Rasmus Nielsen - One of the best experts on this subject based on the ideXlab platform.
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angsd analysis of Next Generation Sequencing data
BMC Bioinformatics, 2014Co-Authors: Thorfinn Sand Korneliussen, Anders Albrechtsen, Rasmus NielsenAbstract:High-throughput DNA Sequencing technologies are generating vast amounts of data. Fast, flexible and memory efficient implementations are needed in order to facilitate analyses of thousands of samples simultaneously. We present a multithreaded program suite called ANGSD. This program can calculate various summary statistics, and perform association mapping and population genetic analyses utilizing the full information in Next Generation Sequencing data by working directly on the raw Sequencing data or by using genotype likelihoods. The open source c/c++ program ANGSD is available at http://www.popgen.dk/angsd . The program is tested and validated on GNU/Linux systems. The program facilitates multiple input formats including BAM and imputed beagle genotype probability files. The program allow the user to choose between combinations of existing methods and can perform analysis that is not implemented elsewhere.
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Genotype and SNP calling from Next-Generation Sequencing data
Nature Reviews Genetics, 2011Co-Authors: Rasmus Nielsen, Joshua S Paul, Anders Albrechtsen, Yun S SongAbstract:Meaningful analysis of Next-Generation Sequencing (NGS) data, which are produced extensively by genetics and genomics studies, relies crucially on the accurate calling of SNPs and genotypes. Recently developed statistical methods both improve and quantify the considerable uncertainty associated with genotype calling, and will especially benefit the growing number of studies using low- to medium-coverage data. We review these methods and provide a guide for their use in NGS studies.
Josep Brugada - One of the best experts on this subject based on the ideXlab platform.
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identification of genetic alterations as causative genetic defects in long qt syndrome using Next Generation Sequencing technology
PLOS ONE, 2014Co-Authors: Oscar Campuzano, Georgia Sarquellabrugada, Irene Mademontsoler, Catarina Allegue, Sergi Cesar, Carles Ferrercosta, Monica Coll, Jesus Mates, Anna Iglesias, Josep BrugadaAbstract:Background Long QT Syndrome is an inherited channelopathy leading to sudden cardiac death due to ventricular arrhythmias. Despite that several genes have been associated with the disease, nearly 20% of cases remain without an identified genetic cause. Other genetic alterations such as copy number variations have been recently related to Long QT Syndrome. Our aim was to take advantage of current genetic technologies in a family affected by Long QT Syndrome in order to identify the cause of the disease. Methods Complete clinical evaluation was performed in all family members. In the index case, a Next Generation Sequencing custom-built panel, including 55 sudden cardiac death-related genes, was used both for detection of sequence and copy number variants. Next Generation Sequencing variants were confirmed by Sanger method. Copy number variations variants were confirmed by Multiplex Ligation dependent Probe Amplification method and at the mRNA level. Confirmed variants and copy number variations identified in the index case were also analyzed in relatives. Results In the index case, Next Generation Sequencing revealed a novel variant in TTN and a large deletion in KCNQ1, involving exons 7 and 8. Both variants were confirmed by alternative techniques. The mother and the brother of the index case were also affected by Long QT Syndrome, and family cosegregation was observed for the KCNQ1 deletion, but not for the TTN variant. Conclusions Next Generation Sequencing technology allows a comprehensive genetic analysis of arrhythmogenic diseases. We report a copy number variation identified using Next Generation Sequencing analysis in Long QT Syndrome. Clinical and familiar correlation is crucial to elucidate the role of genetic variants identified to distinguish the pathogenic ones from genetic noise.
Andrea H Nemeth - One of the best experts on this subject based on the ideXlab platform.
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Next Generation Sequencing for molecular diagnosis of neurological disorders using ataxias as a model
Brain, 2013Co-Authors: Andrea H Nemeth, A Kwasniewska, Stefano Lise, Ricardo Parolin Schnekenberg, Esther B E Becker, Katarzyna D BeraAbstract:Many neurological conditions are caused by immensely heterogeneous gene mutations. The diagnostic process is often long and complex with most patients undergoing multiple invasive and costly investigations without ever reaching a conclusive molecular diagnosis. The advent of massively parallel, Next-Generation Sequencing promises to revolutionize genetic testing and shorten the 'diagnostic odyssey' for many of these patients. We performed a pilot study using heterogeneous ataxias as a model neurogenetic disorder to assess the introduction of Next-Generation Sequencing into clinical practice. We captured 58 known human ataxia genes followed by Illumina Next-Generation Sequencing in 50 highly heterogeneous patients with ataxia who had been extensively investigated and were refractory to diagnosis. All cases had been tested for spinocerebellar ataxia 1-3, 6, 7 and Friedrich's ataxia and had multiple other biochemical, genetic and invasive tests. In those cases where we identified the genetic mutation, we determined the time to diagnosis. Pathogenicity was assessed using a bioinformatics pipeline and novel variants were validated using functional experiments. The overall detection rate in our heterogeneous cohort was 18% and varied from 8.3% in those with an adult onset progressive disorder to 40% in those with a childhood or adolescent onset progressive disorder. The highest detection rate was in those with an adolescent onset and a family history (75%). The majority of cases with detectable mutations had a childhood onset but most are now adults, reflecting the long delay in diagnosis. The delays were primarily related to lack of easily available clinical testing, but other factors included the presence of atypical phenotypes and the use of indirect testing. In the cases where we made an eventual diagnosis, the delay was 3-35 years (mean 18.1 years). Alignment and coverage metrics indicated that the capture and Sequencing was highly efficient and the consumable cost was ∼£400 (€460 or US$620). Our pathogenicity interpretation pathway predicted 13 different mutations in eight different genes: PRKCG, TTBK2, SETX, SPTBN2, SACS, MRE11, KCNC3 and DARS2 of which nine were novel including one causing a newly described recessive ataxia syndrome. Genetic testing using targeted capture followed by Next-Generation Sequencing was efficient, cost-effective, and enabled a molecular diagnosis in many refractory cases. A specific challenge of Next-Generation Sequencing data is pathogenicity interpretation, but functional analysis confirmed the pathogenicity of novel variants showing that the pipeline was robust. Our results have broad implications for clinical neurology practice and the approach to diagnostic testing.
