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Concept: BLAST

174

BACKGROUND: Mild traumatic brain injury (mTBI) secondary to blast exposure is the most common battlefield injury in Southwest Asia. There has been little prospective work in the combat setting to test the efficacy of new countermeasures. The goal of this study was to compare the efficacy of N-acetyl cysteine (NAC) versus placebo on the symptoms associated with blast exposure mTBI in a combat setting. METHODS: This study was a randomized double blind, placebo-controlled study that was conducted on active duty service members at a forward deployed field hospital in Iraq. All symptomatic U.S. service members who were exposed to significant ordnance blast and who met the criteria for mTBI were offered participation in the study and 81 individuals agreed to participate. Individuals underwent a baseline evaluation and then were randomly assigned to receive either N-acetyl cysteine (NAC) or placebo for seven days. Each subject was re-evaluated at 3 and 7 days. Outcome measures were the presence of the following sequelae of mTBI: dizziness, hearing loss, headache, memory loss, sleep disturbances, and neurocognitive dysfunction. The resolution of these symptoms seven days after the blast exposure was the main outcome measure in this study. Logistic regression on the outcome of ‘no day 7 symptoms’ indicated that NAC treatment was significantly better than placebo (OR = 3.6, p = 0.006). Secondary analysis revealed subjects receiving NAC within 24 hours of blast had an 86% chance of symptom resolution with no reported side effects versus 42% for those seen early who received placebo. CONCLUSION: This study, conducted in an active theatre of war, demonstrates that NAC, a safe pharmaceutical countermeasure, has beneficial effects on the severity and resolution of sequelae of blast induced mTBI. This is the first demonstration of an effective short term countermeasure for mTBI. Further work on long term outcomes and the potential use of NAC in civilian mTBI is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00822263.

Concepts: Brain, Medical terms, Traumatic brain injury, Effectiveness, Term, Post-concussion syndrome, Concussion, BLAST

7

Choosing appropriate primers is probably the single most important factor affecting the polymerase chain reaction (PCR). Specific amplification of the intended target requires that primers do not have matches to other targets in certain orientations and within certain distances that allow undesired amplification. The process of designing specific primers typically involves two stages. First, the primers flanking regions of interest are generated either manually or using software tools; then they are searched against an appropriate nucleotide sequence database using tools such as BLAST to examine the potential targets. However, the latter is not an easy process as one needs to examine many details between primers and targets, such as the number and the positions of matched bases, the primer orientations and distance between forward and reverse primers. The complexity of such analysis usually makes this a time-consuming and very difficult task for users, especially when the primers have a large number of hits. Furthermore, although the BLAST program has been widely used for primer target detection, it is in fact not an ideal tool for this purpose as BLAST is a local alignment algorithm and does not necessarily return complete match information over the entire primer range.

Concepts: DNA, Polymerase chain reaction, DNA replication, DNA polymerase, Primer, BLAST

6

Sequence alignment is a long standing problem in bioinformatics. The Basic Local Alignment Search Tool (BLAST) is one of the most popular and fundamental alignment tools. The explosive growth of biological sequences calls for speedup of sequence alignment tools such as BLAST. To this end, we develop high speed BLASTN (HS-BLASTN), a parallel and fast nucleotide database search tool that accelerates MegaBLAST-the default module of NCBI-BLASTN. HS-BLASTN builds a new lookup table using the FMD-index of the database and employs an accurate and effective seeding method to find short stretches of identities (called seeds) between the query and the database. HS-BLASTN produces the same alignment results as MegaBLAST and its computational speed is much faster than MegaBLAST. Specifically, our experiments conducted on a 12-core server show that HS-BLASTN can be 22 times faster than MegaBLAST and exhibits better parallel performance than MegaBLAST. HS-BLASTN is written in C++ and the related source code is available at https://github.com/chenying2016/queries under the GPLv3 license.

Concepts: DNA, Bioinformatics, Computational phylogenetics, Computer program, Kinematics, Source code, Sequence alignment, BLAST

2

We propose SW#, a new CUDA GPU enabled and memory efficient implementation of dynamic programming algorithms for local alignment. It can be use as either a standalone application or a library. Although there are other GPU implementations of the Smith-Waterman algorithm, SW# is the only one publicly available that can produce sequence alignments on genome-wide scale. For long sequences, it is at least a few hundred times faster than a CPU version of the same algorithm.

Concepts: Algorithm, Computer, Computer program, Computer programming, Dynamic programming, BLAST, Smith–Waterman algorithm, Levenshtein distance

2

Since 2004 the European Bioinformatics Institute (EMBL-EBI) has provided access to a wide range of databases and analysis tools via Web Services interfaces. This comprises services to search across the databases available from the EMBL-EBI and to explore the network of cross-references present in the data (e.g. EB-eye), services to retrieve entry data in various data formats and to access the data in specific fields (e.g. dbfetch), and analysis tool services, for example, sequence similarity search (e.g. FASTA and NCBI BLAST), multiple sequence alignment (e.g. Clustal Omega and MUSCLE), pairwise sequence alignment and protein functional analysis (e.g. InterProScan and Phobius). The REST/SOAP Web Services (http://www.ebi.ac.uk/Tools/webservices/) interfaces to these databases and tools allow their integration into other tools, applications, web sites, pipeline processes and analytical workflows. To get users started using the Web Services, sample clients are provided covering a range of programming languages and popular Web Service tool kits, and a brief guide to Web Services technologies, including a set of tutorials, is available for those wishing to learn more and develop their own clients. Users of the Web Services are informed of improvements and updates via a range of methods.

Concepts: DNA, Bioinformatics, Computational phylogenetics, Internet, Sequence alignment, BLAST, Clustal, Web service

2

The Basic Local Alignment Search Tool (BLAST) website at the National Center for Biotechnology (NCBI) is an important resource for searching and aligning sequences. A new BLAST report allows faster loading of alignments, adds navigation aids, allows easy downloading of subject sequences and reports and has improved usability. Here, we describe these improvements to the BLAST report, discuss design decisions, describe other improvements to the search page and database documentation and outline plans for future development. The NCBI BLAST URL is http://blast.ncbi.nlm.nih.gov.

Concepts: Bioinformatics, Computational phylogenetics, Searching, Sequence alignment, Dynamic programming, BLAST, FASTA, Smith–Waterman algorithm

1

Over the last decades, vast numbers of sequences were deposited in public databases. Bioinformatics tools allow homology and consequently functional inference for these sequences. New profile-based homology search tools have been introduced, allowing reliable detection of remote homologs, but have not been systematically benchmarked. To provide such a comparison, which can guide bioinformatics workflows, we extend and apply our previously developed benchmark approach to evaluate the “next generation” of profile-based approaches, including CS-BLAST, HHSEARCH and PHMMER, in comparison with the non-profile based search tools NCBI-BLAST, USEARCH, UBLAST and FASTA.

Concepts: Bioinformatics, Star Trek: The Next Generation, Next Generation, Benchmarking, BLAST

1

BlastKOALA and GhostKOALA are automatic annotation servers for genome and metagenome sequences, which perform KEGG Orthology (KO) assignments to characterize individual gene functions and reconstruct KEGG pathways, BRITE hierarchies and KEGG modules to infer high-level functions of the organism or the ecosystem. Both servers are made freely available at the KEGG website (http://www.kegg.jp/blastkoala/). In BlastKOALA the KO assignment is done by a modified version of the internally used KOALA algorithm after the BLAST search against a non-redundant dataset of pangenome sequences at the species, genus or family level, which is generated from the KEGG GENES database by retaining the KO content of each taxonomic category. In GhostKOALA, which utilizes more rapid GHOSTX for database search and is suitable for metagenome annotation, the pangenome dataset is supplemented with CD-HIT clusters including those for viral genes. The result files may be downloaded and manipulated for further KEGG Mapper analysis, such as comparative pathway analysis using multiple BlastKOALA results.

Concepts: DNA, Gene, Biology, Organism, Genome, Genomics, Species, BLAST

1

Since 1990, the Basic Local Alignment Search Tool (BLAST) has become one of the most popular and fundamental bioinformatics tools for sequence similarity searching, receiving extensive attention from the research community. The two pioneering papers on BLAST have received over 96,000 citations. Given the huge population of BLAST users and the increasing size of sequence databases, an urgent topic of study is how to improve the speed. Recently, graphics processing units (GPUs) have been widely used as low-cost, high-performance computing platforms. The existing GPU-BLAST is a promising software tool that uses a GPU to accelerate protein sequence alignment. Unfortunately, there is still no GPU-accelerated software tool for BLAST-based nucleotide sequence alignment.

Concepts: DNA, Protein, Bioinformatics, Parallel computing, 3D computer graphics, Sequence alignment, Graphics processing unit, BLAST

1

PURPOSE.: Blast-related (BR) traumatic brain injuries (TBIs) occur secondary to explosive blasts. Blast-related TBIs can be caused by the blast wave itself or by direct head trauma caused by events surrounding the blast. Non-blast-related (NBR) TBIs are caused by direct head trauma. Recent evidence shows that TBIs are associated with vision problems, particularly binocular system problems. The purpose of this study was to determine if similar types and amounts of vision problems are present in patients with BR TBIs and NBR TBIs. METHODS.: A retrospective analysis of eye examination records of 50 NBR TBI and 50 BR TBI patients was conducted. Frequencies of visual symptoms and abnormal vision function measurements were computed and compared for the two patient groups. RESULTS.: More than 65% of NRB TBI and BR TBI patients reported vision problems. Reading complaints were found in approximately 50% of the patients. Light sensitivity was reported significantly more often in BR TBI patients (67%) than in NBR TBI patients (33%) (p < 0.01). Saccadic dysfunction was measured more often in NBR TBI patients (85%) than in BR TBI patients (58%) (p < 0.01). High rates of accommodative dysfunction and convergence insufficiency were also found, but the group differences were not significant. Strabismus, pursuit abnormalities, fixation defects, and visual field defects were also common in both groups. CONCLUSIONS.: For most findings, the mechanism of injury (NBR vs. BR) did not result in different frequencies or types of visual dysfunction. The reasons for finding higher frequencies of light sensitivity in the BR TBI group and saccadic dysfunction in the NBR TBI group are unknown, and further research is needed. Overall, the rates of vision complaints and oculomotor defects were high in both groups, indicating a need for a thorough eye examination for any patient with a history of TBI.

Concepts: Brain, Traumatic brain injury, Eye, Vision, Visual system, Ophthalmology, Visual field, BLAST