A dynamic bead-based microarray for parallel DNA detection

NASA Astrophysics Data System (ADS)

Sochol, R. D.; Casavant, B. P.; Dueck, M. E.; Lee, L. P.; Lin, L.

2011-05-01

A microfluidic system has been designed and constructed by means of micromachining processes to integrate both microfluidic mixing of mobile microbeads and hydrodynamic microbead arraying capabilities on a single chip to simultaneously detect multiple bio-molecules. The prototype system has four parallel reaction chambers, which include microchannels of 18 × 50 µm2 cross-sectional area and a microfluidic mixing section of 22 cm length. Parallel detection of multiple DNA oligonucleotide sequences was achieved via molecular beacon probes immobilized on polystyrene microbeads of 16 µm diameter. Experimental results show quantitative detection of three distinct DNA oligonucleotide sequences from the Hepatitis C viral (HCV) genome with single base-pair mismatch specificity. Our dynamic bead-based microarray offers an effective microfluidic platform to increase parallelization of reactions and improve microbead handling for various biological applications, including bio-molecule detection, medical diagnostics and drug screening.

Parallel MR imaging: a user's guide.

PubMed

Glockner, James F; Hu, Houchun H; Stanley, David W; Angelos, Lisa; King, Kevin

2005-01-01

Parallel imaging is a recently developed family of techniques that take advantage of the spatial information inherent in phased-array radiofrequency coils to reduce acquisition times in magnetic resonance imaging. In parallel imaging, the number of sampled k-space lines is reduced, often by a factor of two or greater, thereby significantly shortening the acquisition time. Parallel imaging techniques have only recently become commercially available, and the wide range of clinical applications is just beginning to be explored. The potential clinical applications primarily involve reduction in acquisition time, improved spatial resolution, or a combination of the two. Improvements in image quality can be achieved by reducing the echo train lengths of fast spin-echo and single-shot fast spin-echo sequences. Parallel imaging is particularly attractive for cardiac and vascular applications and will likely prove valuable as 3-T body and cardiovascular imaging becomes part of standard clinical practice. Limitations of parallel imaging include reduced signal-to-noise ratio and reconstruction artifacts. It is important to consider these limitations when deciding when to use these techniques. (c) RSNA, 2005.

The instant sequencing task: Toward constraint-checking a complex spacecraft command sequence interactively

NASA Technical Reports Server (NTRS)

Horvath, Joan C.; Alkalaj, Leon J.; Schneider, Karl M.; Amador, Arthur V.; Spitale, Joseph N.

1993-01-01

Robotic spacecraft are controlled by sets of commands called 'sequences.' These sequences must be checked against mission constraints. Making our existing constraint checking program faster would enable new capabilities in our uplink process. Therefore, we are rewriting this program to run on a parallel computer. To do so, we had to determine how to run constraint-checking algorithms in parallel and create a new method of specifying spacecraft models and constraints. This new specification gives us a means of representing flight systems and their predicted response to commands which could be used in a variety of applications throughout the command process, particularly during anomaly or high-activity operations. This commonality could reduce operations cost and risk for future complex missions. Lessons learned in applying some parts of this system to the TOPEX/Poseidon mission will be described.

Arkas: Rapid reproducible RNAseq analysis

PubMed Central

Colombo, Anthony R.; J. Triche Jr, Timothy; Ramsingh, Giridharan

2017-01-01

The recently introduced Kallisto pseudoaligner has radically simplified the quantification of transcripts in RNA-sequencing experiments.  We offer cloud-scale RNAseq pipelines Arkas-Quantification, and Arkas-Analysis available within Illumina’s BaseSpace cloud application platform which expedites Kallisto preparatory routines, reliably calculates differential expression, and performs gene-set enrichment of REACTOME pathways .  Due to inherit inefficiencies of scale, Illumina's BaseSpace computing platform offers a massively parallel distributive environment improving data management services and data importing.   Arkas-Quantification deploys Kallisto for parallel cloud computations and is conveniently integrated downstream from the BaseSpace Sequence Read Archive (SRA) import/conversion application titled SRA Import.  Arkas-Analysis annotates the Kallisto results by extracting structured information directly from source FASTA files with per-contig metadata, calculates the differential expression and gene-set enrichment analysis on both coding genes and transcripts. The Arkas cloud pipeline supports ENSEMBL transcriptomes and can be used downstream from the SRA Import facilitating raw sequencing importing, SRA FASTQ conversion, RNA quantification and analysis steps. PMID:28868134

Flexible, fast and accurate sequence alignment profiling on GPGPU with PaSWAS.

PubMed

Warris, Sven; Yalcin, Feyruz; Jackson, Katherine J L; Nap, Jan Peter

2015-01-01

To obtain large-scale sequence alignments in a fast and flexible way is an important step in the analyses of next generation sequencing data. Applications based on the Smith-Waterman (SW) algorithm are often either not fast enough, limited to dedicated tasks or not sufficiently accurate due to statistical issues. Current SW implementations that run on graphics hardware do not report the alignment details necessary for further analysis. With the Parallel SW Alignment Software (PaSWAS) it is possible (a) to have easy access to the computational power of NVIDIA-based general purpose graphics processing units (GPGPUs) to perform high-speed sequence alignments, and (b) retrieve relevant information such as score, number of gaps and mismatches. The software reports multiple hits per alignment. The added value of the new SW implementation is demonstrated with two test cases: (1) tag recovery in next generation sequence data and (2) isotype assignment within an immunoglobulin 454 sequence data set. Both cases show the usability and versatility of the new parallel Smith-Waterman implementation.

Rapid protein alignment in the cloud: HAMOND combines fast DIAMOND alignments with Hadoop parallelism.

PubMed

Yu, Jia; Blom, Jochen; Sczyrba, Alexander; Goesmann, Alexander

2017-09-10

The introduction of next generation sequencing has caused a steady increase in the amounts of data that have to be processed in modern life science. Sequence alignment plays a key role in the analysis of sequencing data e.g. within whole genome sequencing or metagenome projects. BLAST is a commonly used alignment tool that was the standard approach for more than two decades, but in the last years faster alternatives have been proposed including RapSearch, GHOSTX, and DIAMOND. Here we introduce HAMOND, an application that uses Apache Hadoop to parallelize DIAMOND computation in order to scale-out the calculation of alignments. HAMOND is fault tolerant and scalable by utilizing large cloud computing infrastructures like Amazon Web Services. HAMOND has been tested in comparative genomics analyses and showed promising results both in efficiency and accuracy. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

A 64Cycles/MB, Luma-Chroma Parallelized H.264/AVC Deblocking Filter for 4K × 2K Applications

NASA Astrophysics Data System (ADS)

Shen, Weiwei; Fan, Yibo; Zeng, Xiaoyang

In this paper, a high-throughput debloking filter is presented for H.264/AVC standard, catering video applications with 4K × 2K (4096 × 2304) ultra-definition resolution. In order to strengthen the parallelism without simply increasing the area, we propose a luma-chroma parallel method. Meanwhile, this work reduces the number of processing cycles, the amount of external memory traffic and the working frequency, by using triple four-stage pipeline filters and a luma-chroma interlaced sequence. Furthermore, it eliminates most unnecessary off-chip memory bandwidth with a highly reusable memory scheme, and adopts a “slide window” buffer scheme. As a result, our design can support 4K × 2K at 30fps applications at the working frequency of only 70.8MHz.

Rapid evaluation and quality control of next generation sequencing data with FaQCs.

PubMed

Lo, Chien-Chi; Chain, Patrick S G

2014-11-19

Next generation sequencing (NGS) technologies that parallelize the sequencing process and produce thousands to millions, or even hundreds of millions of sequences in a single sequencing run, have revolutionized genomic and genetic research. Because of the vagaries of any platform's sequencing chemistry, the experimental processing, machine failure, and so on, the quality of sequencing reads is never perfect, and often declines as the read is extended. These errors invariably affect downstream analysis/application and should therefore be identified early on to mitigate any unforeseen effects. Here we present a novel FastQ Quality Control Software (FaQCs) that can rapidly process large volumes of data, and which improves upon previous solutions to monitor the quality and remove poor quality data from sequencing runs. Both the speed of processing and the memory footprint of storing all required information have been optimized via algorithmic and parallel processing solutions. The trimmed output compared side-by-side with the original data is part of the automated PDF output. We show how this tool can help data analysis by providing a few examples, including an increased percentage of reads recruited to references, improved single nucleotide polymorphism identification as well as de novo sequence assembly metrics. FaQCs combines several features of currently available applications into a single, user-friendly process, and includes additional unique capabilities such as filtering the PhiX control sequences, conversion of FASTQ formats, and multi-threading. The original data and trimmed summaries are reported within a variety of graphics and reports, providing a simple way to do data quality control and assurance.

Clinical validation of the 50 gene AmpliSeq Cancer Panel V2 for use on a next generation sequencing platform using formalin fixed, paraffin embedded and fine needle aspiration tumour specimens.

PubMed

Rathi, Vivek; Wright, Gavin; Constantin, Diana; Chang, Siok; Pham, Huong; Jones, Kerryn; Palios, Atha; Mclachlan, Sue-Anne; Conron, Matthew; McKelvie, Penny; Williams, Richard

2017-01-01

The advent of massively parallel sequencing has caused a paradigm shift in the ways cancer is treated, as personalised therapy becomes a reality. More and more laboratories are looking to introduce next generation sequencing (NGS) as a tool for mutational analysis, as this technology has many advantages compared to conventional platforms like Sanger sequencing. In Australia all massively parallel sequencing platforms are still considered in-house in vitro diagnostic tools by the National Association of Testing Authorities (NATA) and a comprehensive analytical validation of all assays, and not just mere verification, is a strict requirement before accreditation can be granted for clinical testing on these platforms. Analytical validation of assays on NGS platforms can prove to be extremely challenging for pathology laboratories. Although there are many affordable and easily accessible NGS instruments available, there are no standardised guidelines as yet for clinical validation of NGS assays. We present an accreditation development procedure that was both comprehensive and applicable in a setting of hospital laboratory for NGS services. This approach may also be applied to other NGS applications in service laboratories. Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Massively parallel sequencing and the emergence of forensic genomics: Defining the policy and legal issues for law enforcement.

PubMed

Scudder, Nathan; McNevin, Dennis; Kelty, Sally F; Walsh, Simon J; Robertson, James

2018-03-01

Use of DNA in forensic science will be significantly influenced by new technology in coming years. Massively parallel sequencing and forensic genomics will hasten the broadening of forensic DNA analysis beyond short tandem repeats for identity towards a wider array of genetic markers, in applications as diverse as predictive phenotyping, ancestry assignment, and full mitochondrial genome analysis. With these new applications come a range of legal and policy implications, as forensic science touches on areas as diverse as 'big data', privacy and protected health information. Although these applications have the potential to make a more immediate and decisive forensic intelligence contribution to criminal investigations, they raise policy issues that will require detailed consideration if this potential is to be realised. The purpose of this paper is to identify the scope of the issues that will confront forensic and user communities. Copyright © 2017 The Chartered Society of Forensic Sciences. All rights reserved.

"First generation" automated DNA sequencing technology.

PubMed

Slatko, Barton E; Kieleczawa, Jan; Ju, Jingyue; Gardner, Andrew F; Hendrickson, Cynthia L; Ausubel, Frederick M

2011-10-01

Beginning in the 1980s, automation of DNA sequencing has greatly increased throughput, reduced costs, and enabled large projects to be completed more easily. The development of automation technology paralleled the development of other aspects of DNA sequencing: better enzymes and chemistry, separation and imaging technology, sequencing protocols, robotics, and computational advancements (including base-calling algorithms with quality scores, database developments, and sequence analysis programs). Despite the emergence of high-throughput sequencing platforms, automated Sanger sequencing technology remains useful for many applications. This unit provides background and a description of the "First-Generation" automated DNA sequencing technology. It also includes protocols for using the current Applied Biosystems (ABI) automated DNA sequencing machines. © 2011 by John Wiley & Sons, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, Chien -Chi; Chain, Patrick S. G.

Background: Next generation sequencing (NGS) technologies that parallelize the sequencing process and produce thousands to millions, or even hundreds of millions of sequences in a single sequencing run, have revolutionized genomic and genetic research. Because of the vagaries of any platform's sequencing chemistry, the experimental processing, machine failure, and so on, the quality of sequencing reads is never perfect, and often declines as the read is extended. These errors invariably affect downstream analysis/application and should therefore be identified early on to mitigate any unforeseen effects. Results: Here we present a novel FastQ Quality Control Software (FaQCs) that can rapidly processmore » large volumes of data, and which improves upon previous solutions to monitor the quality and remove poor quality data from sequencing runs. Both the speed of processing and the memory footprint of storing all required information have been optimized via algorithmic and parallel processing solutions. The trimmed output compared side-by-side with the original data is part of the automated PDF output. We show how this tool can help data analysis by providing a few examples, including an increased percentage of reads recruited to references, improved single nucleotide polymorphism identification as well as de novo sequence assembly metrics. Conclusion: FaQCs combines several features of currently available applications into a single, user-friendly process, and includes additional unique capabilities such as filtering the PhiX control sequences, conversion of FASTQ formats, and multi-threading. The original data and trimmed summaries are reported within a variety of graphics and reports, providing a simple way to do data quality control and assurance.« less

Generic accelerated sequence alignment in SeqAn using vectorization and multi-threading.

PubMed

Rahn, René; Budach, Stefan; Costanza, Pascal; Ehrhardt, Marcel; Hancox, Jonny; Reinert, Knut

2018-05-03

Pairwise sequence alignment is undoubtedly a central tool in many bioinformatics analyses. In this paper, we present a generically accelerated module for pairwise sequence alignments applicable for a broad range of applications. In our module, we unified the standard dynamic programming kernel used for pairwise sequence alignments and extended it with a generalized inter-sequence vectorization layout, such that many alignments can be computed simultaneously by exploiting SIMD (Single Instruction Multiple Data) instructions of modern processors. We then extended the module by adding two layers of thread-level parallelization, where we a) distribute many independent alignments on multiple threads and b) inherently parallelize a single alignment computation using a work stealing approach producing a dynamic wavefront progressing along the minor diagonal. We evaluated our alignment vectorization and parallelization on different processors, including the newest Intel® Xeon® (Skylake) and Intel® Xeon Phi™ (KNL) processors, and use cases. The instruction set AVX512-BW (Byte and Word), available on Skylake processors, can genuinely improve the performance of vectorized alignments. We could run single alignments 1600 times faster on the Xeon Phi™ and 1400 times faster on the Xeon® than executing them with our previous sequential alignment module. The module is programmed in C++ using the SeqAn (Reinert et al., 2017) library and distributed with version 2.4. under the BSD license. We support SSE4, AVX2, AVX512 instructions and included UME::SIMD, a SIMD-instruction wrapper library, to extend our module for further instruction sets. We thoroughly test all alignment components with all major C++ compilers on various platforms. rene.rahn@fu-berlin.de.

Large-scale parallel genome assembler over cloud computing environment.

PubMed

Das, Arghya Kusum; Koppa, Praveen Kumar; Goswami, Sayan; Platania, Richard; Park, Seung-Jong

2017-06-01

The size of high throughput DNA sequencing data has already reached the terabyte scale. To manage this huge volume of data, many downstream sequencing applications started using locality-based computing over different cloud infrastructures to take advantage of elastic (pay as you go) resources at a lower cost. However, the locality-based programming model (e.g. MapReduce) is relatively new. Consequently, developing scalable data-intensive bioinformatics applications using this model and understanding the hardware environment that these applications require for good performance, both require further research. In this paper, we present a de Bruijn graph oriented Parallel Giraph-based Genome Assembler (GiGA), as well as the hardware platform required for its optimal performance. GiGA uses the power of Hadoop (MapReduce) and Giraph (large-scale graph analysis) to achieve high scalability over hundreds of compute nodes by collocating the computation and data. GiGA achieves significantly higher scalability with competitive assembly quality compared to contemporary parallel assemblers (e.g. ABySS and Contrail) over traditional HPC cluster. Moreover, we show that the performance of GiGA is significantly improved by using an SSD-based private cloud infrastructure over traditional HPC cluster. We observe that the performance of GiGA on 256 cores of this SSD-based cloud infrastructure closely matches that of 512 cores of traditional HPC cluster.

3D Data Denoising via Nonlocal Means Filter by Using Parallel GPU Strategies

PubMed Central

Cuomo, Salvatore; De Michele, Pasquale; Piccialli, Francesco

2014-01-01

Nonlocal Means (NLM) algorithm is widely considered as a state-of-the-art denoising filter in many research fields. Its high computational complexity leads researchers to the development of parallel programming approaches and the use of massively parallel architectures such as the GPUs. In the recent years, the GPU devices had led to achieving reasonable running times by filtering, slice-by-slice, and 3D datasets with a 2D NLM algorithm. In our approach we design and implement a fully 3D NonLocal Means parallel approach, adopting different algorithm mapping strategies on GPU architecture and multi-GPU framework, in order to demonstrate its high applicability and scalability. The experimental results we obtained encourage the usability of our approach in a large spectrum of applicative scenarios such as magnetic resonance imaging (MRI) or video sequence denoising. PMID:25045397

B-MIC: An Ultrafast Three-Level Parallel Sequence Aligner Using MIC.

PubMed

Cui, Yingbo; Liao, Xiangke; Zhu, Xiaoqian; Wang, Bingqiang; Peng, Shaoliang

2016-03-01

Sequence alignment is the central process for sequence analysis, where mapping raw sequencing data to reference genome. The large amount of data generated by NGS is far beyond the process capabilities of existing alignment tools. Consequently, sequence alignment becomes the bottleneck of sequence analysis. Intensive computing power is required to address this challenge. Intel recently announced the MIC coprocessor, which can provide massive computing power. The Tianhe-2 is the world's fastest supercomputer now equipped with three MIC coprocessors each compute node. A key feature of sequence alignment is that different reads are independent. Considering this property, we proposed a MIC-oriented three-level parallelization strategy to speed up BWA, a widely used sequence alignment tool, and developed our ultrafast parallel sequence aligner: B-MIC. B-MIC contains three levels of parallelization: firstly, parallelization of data IO and reads alignment by a three-stage parallel pipeline; secondly, parallelization enabled by MIC coprocessor technology; thirdly, inter-node parallelization implemented by MPI. In this paper, we demonstrate that B-MIC outperforms BWA by a combination of those techniques using Inspur NF5280M server and the Tianhe-2 supercomputer. To the best of our knowledge, B-MIC is the first sequence alignment tool to run on Intel MIC and it can achieve more than fivefold speedup over the original BWA while maintaining the alignment precision.

A Bioluminometric Method of DNA Sequencing

NASA Technical Reports Server (NTRS)

Ronaghi, Mostafa; Pourmand, Nader; Stolc, Viktor; Arnold, Jim (Technical Monitor)

2001-01-01

Pyrosequencing is a bioluminometric single-tube DNA sequencing method that takes advantage of co-operativity between four enzymes to monitor DNA synthesis. In this sequencing-by-synthesis method, a cascade of enzymatic reactions yields detectable light, which is proportional to incorporated nucleotides. Pyrosequencing has the advantages of accuracy, flexibility and parallel processing. It can be easily automated. Furthermore, the technique dispenses with the need for labeled primers, labeled nucleotides and gel-electrophoresis. In this chapter, the use of this technique for different applications is discussed.

Rapid evaluation and quality control of next generation sequencing data with FaQCs

DOE PAGES

Lo, Chien -Chi; Chain, Patrick S. G.

2014-12-01

Background: Next generation sequencing (NGS) technologies that parallelize the sequencing process and produce thousands to millions, or even hundreds of millions of sequences in a single sequencing run, have revolutionized genomic and genetic research. Because of the vagaries of any platform's sequencing chemistry, the experimental processing, machine failure, and so on, the quality of sequencing reads is never perfect, and often declines as the read is extended. These errors invariably affect downstream analysis/application and should therefore be identified early on to mitigate any unforeseen effects. Results: Here we present a novel FastQ Quality Control Software (FaQCs) that can rapidly processmore » large volumes of data, and which improves upon previous solutions to monitor the quality and remove poor quality data from sequencing runs. Both the speed of processing and the memory footprint of storing all required information have been optimized via algorithmic and parallel processing solutions. The trimmed output compared side-by-side with the original data is part of the automated PDF output. We show how this tool can help data analysis by providing a few examples, including an increased percentage of reads recruited to references, improved single nucleotide polymorphism identification as well as de novo sequence assembly metrics. Conclusion: FaQCs combines several features of currently available applications into a single, user-friendly process, and includes additional unique capabilities such as filtering the PhiX control sequences, conversion of FASTQ formats, and multi-threading. The original data and trimmed summaries are reported within a variety of graphics and reports, providing a simple way to do data quality control and assurance.« less

A technique for setting analytical thresholds in massively parallel sequencing-based forensic DNA analysis

PubMed Central

2017-01-01

Amplicon (targeted) sequencing by massively parallel sequencing (PCR-MPS) is a potential method for use in forensic DNA analyses. In this application, PCR-MPS may supplement or replace other instrumental analysis methods such as capillary electrophoresis and Sanger sequencing for STR and mitochondrial DNA typing, respectively. PCR-MPS also may enable the expansion of forensic DNA analysis methods to include new marker systems such as single nucleotide polymorphisms (SNPs) and insertion/deletions (indels) that currently are assayable using various instrumental analysis methods including microarray and quantitative PCR. Acceptance of PCR-MPS as a forensic method will depend in part upon developing protocols and criteria that define the limitations of a method, including a defensible analytical threshold or method detection limit. This paper describes an approach to establish objective analytical thresholds suitable for multiplexed PCR-MPS methods. A definition is proposed for PCR-MPS method background noise, and an analytical threshold based on background noise is described. PMID:28542338

A technique for setting analytical thresholds in massively parallel sequencing-based forensic DNA analysis.

PubMed

Young, Brian; King, Jonathan L; Budowle, Bruce; Armogida, Luigi

2017-01-01

Amplicon (targeted) sequencing by massively parallel sequencing (PCR-MPS) is a potential method for use in forensic DNA analyses. In this application, PCR-MPS may supplement or replace other instrumental analysis methods such as capillary electrophoresis and Sanger sequencing for STR and mitochondrial DNA typing, respectively. PCR-MPS also may enable the expansion of forensic DNA analysis methods to include new marker systems such as single nucleotide polymorphisms (SNPs) and insertion/deletions (indels) that currently are assayable using various instrumental analysis methods including microarray and quantitative PCR. Acceptance of PCR-MPS as a forensic method will depend in part upon developing protocols and criteria that define the limitations of a method, including a defensible analytical threshold or method detection limit. This paper describes an approach to establish objective analytical thresholds suitable for multiplexed PCR-MPS methods. A definition is proposed for PCR-MPS method background noise, and an analytical threshold based on background noise is described.

SS-Wrapper: a package of wrapper applications for similarity searches on Linux clusters.

PubMed

Wang, Chunlin; Lefkowitz, Elliot J

2004-10-28

Large-scale sequence comparison is a powerful tool for biological inference in modern molecular biology. Comparing new sequences to those in annotated databases is a useful source of functional and structural information about these sequences. Using software such as the basic local alignment search tool (BLAST) or HMMPFAM to identify statistically significant matches between newly sequenced segments of genetic material and those in databases is an important task for most molecular biologists. Searching algorithms are intrinsically slow and data-intensive, especially in light of the rapid growth of biological sequence databases due to the emergence of high throughput DNA sequencing techniques. Thus, traditional bioinformatics tools are impractical on PCs and even on dedicated UNIX servers. To take advantage of larger databases and more reliable methods, high performance computation becomes necessary. We describe the implementation of SS-Wrapper (Similarity Search Wrapper), a package of wrapper applications that can parallelize similarity search applications on a Linux cluster. Our wrapper utilizes a query segmentation-search (QS-search) approach to parallelize sequence database search applications. It takes into consideration load balancing between each node on the cluster to maximize resource usage. QS-search is designed to wrap many different search tools, such as BLAST and HMMPFAM using the same interface. This implementation does not alter the original program, so newly obtained programs and program updates should be accommodated easily. Benchmark experiments using QS-search to optimize BLAST and HMMPFAM showed that QS-search accelerated the performance of these programs almost linearly in proportion to the number of CPUs used. We have also implemented a wrapper that utilizes a database segmentation approach (DS-BLAST) that provides a complementary solution for BLAST searches when the database is too large to fit into the memory of a single node. Used together, QS-search and DS-BLAST provide a flexible solution to adapt sequential similarity searching applications in high performance computing environments. Their ease of use and their ability to wrap a variety of database search programs provide an analytical architecture to assist both the seasoned bioinformaticist and the wet-bench biologist.

SS-Wrapper: a package of wrapper applications for similarity searches on Linux clusters

PubMed Central

Wang, Chunlin; Lefkowitz, Elliot J

2004-01-01

Background Large-scale sequence comparison is a powerful tool for biological inference in modern molecular biology. Comparing new sequences to those in annotated databases is a useful source of functional and structural information about these sequences. Using software such as the basic local alignment search tool (BLAST) or HMMPFAM to identify statistically significant matches between newly sequenced segments of genetic material and those in databases is an important task for most molecular biologists. Searching algorithms are intrinsically slow and data-intensive, especially in light of the rapid growth of biological sequence databases due to the emergence of high throughput DNA sequencing techniques. Thus, traditional bioinformatics tools are impractical on PCs and even on dedicated UNIX servers. To take advantage of larger databases and more reliable methods, high performance computation becomes necessary. Results We describe the implementation of SS-Wrapper (Similarity Search Wrapper), a package of wrapper applications that can parallelize similarity search applications on a Linux cluster. Our wrapper utilizes a query segmentation-search (QS-search) approach to parallelize sequence database search applications. It takes into consideration load balancing between each node on the cluster to maximize resource usage. QS-search is designed to wrap many different search tools, such as BLAST and HMMPFAM using the same interface. This implementation does not alter the original program, so newly obtained programs and program updates should be accommodated easily. Benchmark experiments using QS-search to optimize BLAST and HMMPFAM showed that QS-search accelerated the performance of these programs almost linearly in proportion to the number of CPUs used. We have also implemented a wrapper that utilizes a database segmentation approach (DS-BLAST) that provides a complementary solution for BLAST searches when the database is too large to fit into the memory of a single node. Conclusions Used together, QS-search and DS-BLAST provide a flexible solution to adapt sequential similarity searching applications in high performance computing environments. Their ease of use and their ability to wrap a variety of database search programs provide an analytical architecture to assist both the seasoned bioinformaticist and the wet-bench biologist. PMID:15511296

Partial structure of the phylloxin gene from the giant monkey frog, Phyllomedusa bicolor: parallel cloning of precursor cDNA and genomic DNA from lyophilized skin secretion.

PubMed

Chen, Tianbao; Gagliardo, Ron; Walker, Brian; Zhou, Mei; Shaw, Chris

2005-12-01

Phylloxin is a novel prototype antimicrobial peptide from the skin of Phyllomedusa bicolor. Here, we describe parallel identification and sequencing of phylloxin precursor transcript (mRNA) and partial gene structure (genomic DNA) from the same sample of lyophilized skin secretion using our recently-described cloning technique. The open-reading frame of the phylloxin precursor was identical in nucleotide sequence to that previously reported and alignment with the nucleotide sequence derived from genomic DNA indicated the presence of a 175 bp intron located in a near identical position to that found in the dermaseptins. The highly-conserved structural organization of skin secretion peptide genes in P. bicolor can thus be extended to include that encoding phylloxin (plx). These data further reinforce our assertion that application of the described methodology can provide robust genomic/transcriptomic/peptidomic data without the need for specimen sacrifice.

Massively parallel polymerase cloning and genome sequencing of single cells using nanoliter microwells

PubMed Central

Gole, Jeff; Gore, Athurva; Richards, Andrew; Chiu, Yu-Jui; Fung, Ho-Lim; Bushman, Diane; Chiang, Hsin-I; Chun, Jerold; Lo, Yu-Hwa; Zhang, Kun

2013-01-01

Genome sequencing of single cells has a variety of applications, including characterizing difficult-to-culture microorganisms and identifying somatic mutations in single cells from mammalian tissues. A major hurdle in this process is the bias in amplifying the genetic material from a single cell, a procedure known as polymerase cloning. Here we describe the microwell displacement amplification system (MIDAS), a massively parallel polymerase cloning method in which single cells are randomly distributed into hundreds to thousands of nanoliter wells and simultaneously amplified for shotgun sequencing. MIDAS reduces amplification bias because polymerase cloning occurs in physically separated nanoliter-scale reactors, facilitating the de novo assembly of near-complete microbial genomes from single E. coli cells. In addition, MIDAS allowed us to detect single-copy number changes in primary human adult neurons at 1–2 Mb resolution. MIDAS will further the characterization of genomic diversity in many heterogeneous cell populations. PMID:24213699

Protein Science by DNA Sequencing: How Advances in Molecular Biology Are Accelerating Biochemistry.

PubMed

Higgins, Sean A; Savage, David F

2018-01-09

A fundamental goal of protein biochemistry is to determine the sequence-function relationship, but the vastness of sequence space makes comprehensive evaluation of this landscape difficult. However, advances in DNA synthesis and sequencing now allow researchers to assess the functional impact of every single mutation in many proteins, but challenges remain in library construction and the development of general assays applicable to a diverse range of protein functions. This Perspective briefly outlines the technical innovations in DNA manipulation that allow massively parallel protein biochemistry and then summarizes the methods currently available for library construction and the functional assays of protein variants. Areas in need of future innovation are highlighted with a particular focus on assay development and the use of computational analysis with machine learning to effectively traverse the sequence-function landscape. Finally, applications in the fundamentals of protein biochemistry, disease prediction, and protein engineering are presented.

Pair-barcode high-throughput sequencing for large-scale multiplexed sample analysis

PubMed Central

2012-01-01

Background The multiplexing becomes the major limitation of the next-generation sequencing (NGS) in application to low complexity samples. Physical space segregation allows limited multiplexing, while the existing barcode approach only permits simultaneously analysis of up to several dozen samples. Results Here we introduce pair-barcode sequencing (PBS), an economic and flexible barcoding technique that permits parallel analysis of large-scale multiplexed samples. In two pilot runs using SOLiD sequencer (Applied Biosystems Inc.), 32 independent pair-barcoded miRNA libraries were simultaneously discovered by the combination of 4 unique forward barcodes and 8 unique reverse barcodes. Over 174,000,000 reads were generated and about 64% of them are assigned to both of the barcodes. After mapping all reads to pre-miRNAs in miRBase, different miRNA expression patterns are captured from the two clinical groups. The strong correlation using different barcode pairs and the high consistency of miRNA expression in two independent runs demonstrates that PBS approach is valid. Conclusions By employing PBS approach in NGS, large-scale multiplexed pooled samples could be practically analyzed in parallel so that high-throughput sequencing economically meets the requirements of samples which are low sequencing throughput demand. PMID:22276739

Pair-barcode high-throughput sequencing for large-scale multiplexed sample analysis.

PubMed

Tu, Jing; Ge, Qinyu; Wang, Shengqin; Wang, Lei; Sun, Beili; Yang, Qi; Bai, Yunfei; Lu, Zuhong

2012-01-25

The multiplexing becomes the major limitation of the next-generation sequencing (NGS) in application to low complexity samples. Physical space segregation allows limited multiplexing, while the existing barcode approach only permits simultaneously analysis of up to several dozen samples. Here we introduce pair-barcode sequencing (PBS), an economic and flexible barcoding technique that permits parallel analysis of large-scale multiplexed samples. In two pilot runs using SOLiD sequencer (Applied Biosystems Inc.), 32 independent pair-barcoded miRNA libraries were simultaneously discovered by the combination of 4 unique forward barcodes and 8 unique reverse barcodes. Over 174,000,000 reads were generated and about 64% of them are assigned to both of the barcodes. After mapping all reads to pre-miRNAs in miRBase, different miRNA expression patterns are captured from the two clinical groups. The strong correlation using different barcode pairs and the high consistency of miRNA expression in two independent runs demonstrates that PBS approach is valid. By employing PBS approach in NGS, large-scale multiplexed pooled samples could be practically analyzed in parallel so that high-throughput sequencing economically meets the requirements of samples which are low sequencing throughput demand.

The minimal amount of starting DNA for Agilent’s hybrid capture-based targeted massively parallel sequencing

PubMed Central

Chung, Jongsuk; Son, Dae-Soon; Jeon, Hyo-Jeong; Kim, Kyoung-Mee; Park, Gahee; Ryu, Gyu Ha; Park, Woong-Yang; Park, Donghyun

2016-01-01

Targeted capture massively parallel sequencing is increasingly being used in clinical settings, and as costs continue to decline, use of this technology may become routine in health care. However, a limited amount of tissue has often been a challenge in meeting quality requirements. To offer a practical guideline for the minimum amount of input DNA for targeted sequencing, we optimized and evaluated the performance of targeted sequencing depending on the input DNA amount. First, using various amounts of input DNA, we compared commercially available library construction kits and selected Agilent’s SureSelect-XT and KAPA Biosystems’ Hyper Prep kits as the kits most compatible with targeted deep sequencing using Agilent’s SureSelect custom capture. Then, we optimized the adapter ligation conditions of the Hyper Prep kit to improve library construction efficiency and adapted multiplexed hybrid selection to reduce the cost of sequencing. In this study, we systematically evaluated the performance of the optimized protocol depending on the amount of input DNA, ranging from 6.25 to 200 ng, suggesting the minimal input DNA amounts based on coverage depths required for specific applications. PMID:27220682

A review of bioinformatic methods for forensic DNA analyses.

PubMed

Liu, Yao-Yuan; Harbison, SallyAnn

2018-03-01

Short tandem repeats, single nucleotide polymorphisms, and whole mitochondrial analyses are three classes of markers which will play an important role in the future of forensic DNA typing. The arrival of massively parallel sequencing platforms in forensic science reveals new information such as insights into the complexity and variability of the markers that were previously unseen, along with amounts of data too immense for analyses by manual means. Along with the sequencing chemistries employed, bioinformatic methods are required to process and interpret this new and extensive data. As more is learnt about the use of these new technologies for forensic applications, development and standardization of efficient, favourable tools for each stage of data processing is being carried out, and faster, more accurate methods that improve on the original approaches have been developed. As forensic laboratories search for the optimal pipeline of tools, sequencer manufacturers have incorporated pipelines into sequencer software to make analyses convenient. This review explores the current state of bioinformatic methods and tools used for the analyses of forensic markers sequenced on the massively parallel sequencing (MPS) platforms currently most widely used. Copyright © 2017 Elsevier B.V. All rights reserved.

HTSFinder: Powerful Pipeline of DNA Signature Discovery by Parallel and Distributed Computing

PubMed Central

Karimi, Ramin; Hajdu, Andras

2016-01-01

Comprehensive effort for low-cost sequencing in the past few years has led to the growth of complete genome databases. In parallel with this effort, a strong need, fast and cost-effective methods and applications have been developed to accelerate sequence analysis. Identification is the very first step of this task. Due to the difficulties, high costs, and computational challenges of alignment-based approaches, an alternative universal identification method is highly required. Like an alignment-free approach, DNA signatures have provided new opportunities for the rapid identification of species. In this paper, we present an effective pipeline HTSFinder (high-throughput signature finder) with a corresponding k-mer generator GkmerG (genome k-mers generator). Using this pipeline, we determine the frequency of k-mers from the available complete genome databases for the detection of extensive DNA signatures in a reasonably short time. Our application can detect both unique and common signatures in the arbitrarily selected target and nontarget databases. Hadoop and MapReduce as parallel and distributed computing tools with commodity hardware are used in this pipeline. This approach brings the power of high-performance computing into the ordinary desktop personal computers for discovering DNA signatures in large databases such as bacterial genome. A considerable number of detected unique and common DNA signatures of the target database bring the opportunities to improve the identification process not only for polymerase chain reaction and microarray assays but also for more complex scenarios such as metagenomics and next-generation sequencing analysis. PMID:26884678

HTSFinder: Powerful Pipeline of DNA Signature Discovery by Parallel and Distributed Computing.

PubMed

Karimi, Ramin; Hajdu, Andras

2016-01-01

Comprehensive effort for low-cost sequencing in the past few years has led to the growth of complete genome databases. In parallel with this effort, a strong need, fast and cost-effective methods and applications have been developed to accelerate sequence analysis. Identification is the very first step of this task. Due to the difficulties, high costs, and computational challenges of alignment-based approaches, an alternative universal identification method is highly required. Like an alignment-free approach, DNA signatures have provided new opportunities for the rapid identification of species. In this paper, we present an effective pipeline HTSFinder (high-throughput signature finder) with a corresponding k-mer generator GkmerG (genome k-mers generator). Using this pipeline, we determine the frequency of k-mers from the available complete genome databases for the detection of extensive DNA signatures in a reasonably short time. Our application can detect both unique and common signatures in the arbitrarily selected target and nontarget databases. Hadoop and MapReduce as parallel and distributed computing tools with commodity hardware are used in this pipeline. This approach brings the power of high-performance computing into the ordinary desktop personal computers for discovering DNA signatures in large databases such as bacterial genome. A considerable number of detected unique and common DNA signatures of the target database bring the opportunities to improve the identification process not only for polymerase chain reaction and microarray assays but also for more complex scenarios such as metagenomics and next-generation sequencing analysis.

Single molecule real-time (SMRT) sequencing comes of age: applications and utilities for medical diagnostics

PubMed Central

Ardui, Simon; Ameur, Adam; Vermeesch, Joris R; Hestand, Matthew S

2018-01-01

Abstract Short read massive parallel sequencing has emerged as a standard diagnostic tool in the medical setting. However, short read technologies have inherent limitations such as GC bias, difficulties mapping to repetitive elements, trouble discriminating paralogous sequences, and difficulties in phasing alleles. Long read single molecule sequencers resolve these obstacles. Moreover, they offer higher consensus accuracies and can detect epigenetic modifications from native DNA. The first commercially available long read single molecule platform was the RS system based on PacBio's single molecule real-time (SMRT) sequencing technology, which has since evolved into their RSII and Sequel systems. Here we capsulize how SMRT sequencing is revolutionizing constitutional, reproductive, cancer, microbial and viral genetic testing. PMID:29401301

On the Impact of Widening Vector Registers on Sequence Alignment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daily, Jeffrey A.; Kalyanaraman, Anantharaman; Krishnamoorthy, Sriram

2016-09-22

Vector extensions, such as SSE, have been part of the x86 since the 1990s, with applications in graphics, signal processing, and scientific applications. Although many algorithms and applications can naturally benefit from automatic vectorization techniques, there are still many that are difficult to vectorize due to their dependence on irregular data structures, dense branch operations, or data dependencies. Sequence alignment, one of the most widely used operations in bioinformatics workflows, has a computational footprint that features complex data dependencies. In this paper, we demonstrate that the trend of widening vector registers adversely affects the state-of-the-art sequence alignment algorithm based onmore » striped data layouts. We present a practically efficient SIMD implementation of a parallel scan based sequence alignment algorithm that can better exploit wider SIMD units. We conduct comprehensive workload and use case analyses to characterize the relative behavior of the striped and scan approaches and identify the best choice of algorithm based on input length and SIMD width.« less

Malleable architecture generator for FPGA computing

NASA Astrophysics Data System (ADS)

Gokhale, Maya; Kaba, James; Marks, Aaron; Kim, Jang

1996-10-01

The malleable architecture generator (MARGE) is a tool set that translates high-level parallel C to configuration bit streams for field-programmable logic based computing systems. MARGE creates an application-specific instruction set and generates the custom hardware components required to perform exactly those computations specified by the C program. In contrast to traditional fixed-instruction processors, MARGE's dynamic instruction set creation provides for efficient use of hardware resources. MARGE processes intermediate code in which each operation is annotated by the bit lengths of the operands. Each basic block (sequence of straight line code) is mapped into a single custom instruction which contains all the operations and logic inherent in the block. A synthesis phase maps the operations comprising the instructions into register transfer level structural components and control logic which have been optimized to exploit functional parallelism and function unit reuse. As a final stage, commercial technology-specific tools are used to generate configuration bit streams for the desired target hardware. Technology- specific pre-placed, pre-routed macro blocks are utilized to implement as much of the hardware as possible. MARGE currently supports the Xilinx-based Splash-2 reconfigurable accelerator and National Semiconductor's CLAy-based parallel accelerator, MAPA. The MARGE approach has been demonstrated on systolic applications such as DNA sequence comparison.

Parallel algorithms for large-scale biological sequence alignment on Xeon-Phi based clusters.

PubMed

Lan, Haidong; Chan, Yuandong; Xu, Kai; Schmidt, Bertil; Peng, Shaoliang; Liu, Weiguo

2016-07-19

Computing alignments between two or more sequences are common operations frequently performed in computational molecular biology. The continuing growth of biological sequence databases establishes the need for their efficient parallel implementation on modern accelerators. This paper presents new approaches to high performance biological sequence database scanning with the Smith-Waterman algorithm and the first stage of progressive multiple sequence alignment based on the ClustalW heuristic on a Xeon Phi-based compute cluster. Our approach uses a three-level parallelization scheme to take full advantage of the compute power available on this type of architecture; i.e. cluster-level data parallelism, thread-level coarse-grained parallelism, and vector-level fine-grained parallelism. Furthermore, we re-organize the sequence datasets and use Xeon Phi shuffle operations to improve I/O efficiency. Evaluations show that our method achieves a peak overall performance up to 220 GCUPS for scanning real protein sequence databanks on a single node consisting of two Intel E5-2620 CPUs and two Intel Xeon Phi 7110P cards. It also exhibits good scalability in terms of sequence length and size, and number of compute nodes for both database scanning and multiple sequence alignment. Furthermore, the achieved performance is highly competitive in comparison to optimized Xeon Phi and GPU implementations. Our implementation is available at https://github.com/turbo0628/LSDBS-mpi .

Reproducibility of Illumina platform deep sequencing errors allows accurate determination of DNA barcodes in cells.

PubMed

Beltman, Joost B; Urbanus, Jos; Velds, Arno; van Rooij, Nienke; Rohr, Jan C; Naik, Shalin H; Schumacher, Ton N

2016-04-02

Next generation sequencing (NGS) of amplified DNA is a powerful tool to describe genetic heterogeneity within cell populations that can both be used to investigate the clonal structure of cell populations and to perform genetic lineage tracing. For applications in which both abundant and rare sequences are biologically relevant, the relatively high error rate of NGS techniques complicates data analysis, as it is difficult to distinguish rare true sequences from spurious sequences that are generated by PCR or sequencing errors. This issue, for instance, applies to cellular barcoding strategies that aim to follow the amount and type of offspring of single cells, by supplying these with unique heritable DNA tags. Here, we use genetic barcoding data from the Illumina HiSeq platform to show that straightforward read threshold-based filtering of data is typically insufficient to filter out spurious barcodes. Importantly, we demonstrate that specific sequencing errors occur at an approximately constant rate across different samples that are sequenced in parallel. We exploit this observation by developing a novel approach to filter out spurious sequences. Application of our new method demonstrates its value in the identification of true sequences amongst spurious sequences in biological data sets.

History, applications, and challenges of immune repertoire research.

PubMed

Liu, Xiao; Wu, Jinghua

2018-02-27

The diversity of T and B cells in terms of their receptor sequences is huge in the vertebrate's immune system and provides broad protection against the vast diversity of pathogens. Immune repertoire is defined as the sum of T cell receptors and B cell receptors (also named immunoglobulin) that makes the organism's adaptive immune system. Before the emergence of high-throughput sequencing, the studies on immune repertoire were limited by the underdeveloped methodologies, since it was impossible to capture the whole picture by the low-throughput tools. The massive paralleled sequencing technology suits perfectly the researches on immune repertoire. In this article, we review the history of immune repertoire studies, in terms of technologies and research applications. Particularly, we discuss several aspects of challenges in this field and highlight the efforts to develop potential solutions, in the era of high-throughput sequencing of the immune repertoire.

Next-generation sequencing: advances and applications in cancer diagnosis

PubMed Central

Serratì, Simona; De Summa, Simona; Pilato, Brunella; Petriella, Daniela; Lacalamita, Rosanna; Tommasi, Stefania; Pinto, Rosamaria

2016-01-01

Technological advances have led to the introduction of next-generation sequencing (NGS) platforms in cancer investigation. NGS allows massive parallel sequencing that affords maximal tumor genomic assessment. NGS approaches are different, and concern DNA and RNA analysis. DNA sequencing includes whole-genome, whole-exome, and targeted sequencing, which focuses on a selection of genes of interest for a specific disease. RNA sequencing facilitates the detection of alternative gene-spliced transcripts, posttranscriptional modifications, gene fusion, mutations/single-nucleotide polymorphisms, small and long noncoding RNAs, and changes in gene expression. Most applications are in the cancer research field, but lately NGS technology has been revolutionizing cancer molecular diagnostics, due to the many advantages it offers compared to traditional methods. There is greater knowledge on solid cancer diagnostics, and recent interest has been shown also in the field of hematologic cancer. In this review, we report the latest data on NGS diagnostic/predictive clinical applications in solid and hematologic cancers. Moreover, since the amount of NGS data produced is very large and their interpretation is very complex, we briefly discuss two bioinformatic aspects, variant-calling accuracy and copy-number variation detection, which are gaining a lot of importance in cancer-diagnostic assessment. PMID:27980425

Rapid DNA Sequencing by Direct Nanoscale Reading of Nucleotide Bases on Individual DNA Chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, James Weifu; Meller, Amit

2007-01-01

Since the independent invention of DNA sequencing by Sanger and by Gilbert 30 years ago, it has grown from a small scale technique capable of reading several kilobase-pair of sequence per day into today's multibillion dollar industry. This growth has spurred the development of new sequencing technologies that do not involve either electrophoresis or Sanger sequencing chemistries. Sequencing by Synthesis (SBS) involves multiple parallel micro-sequencing addition events occurring on a surface, where data from each round is detected by imaging. New High Throughput Technologies for DNA Sequencing and Genomics is the second volume in the Perspectives in Bioanalysis series, whichmore » looks at the electroanalytical chemistry of nucleic acids and proteins, development of electrochemical sensors and their application in biomedicine and in the new fields of genomics and proteomics. The authors have expertly formatted the information for a wide variety of readers, including new developments that will inspire students and young scientists to create new tools for science and medicine in the 21st century. Reviews of complementary developments in Sanger and SBS sequencing chemistries, capillary electrophoresis and microdevice integration, MS sequencing and applications set the framework for the book.« less

Scalable Parallel Methods for Analyzing Metagenomics Data at Extreme Scale

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daily, Jeffrey A.

2015-05-01

The field of bioinformatics and computational biology is currently experiencing a data revolution. The exciting prospect of making fundamental biological discoveries is fueling the rapid development and deployment of numerous cost-effective, high-throughput next-generation sequencing technologies. The result is that the DNA and protein sequence repositories are being bombarded with new sequence information. Databases are continuing to report a Moore’s law-like growth trajectory in their database sizes, roughly doubling every 18 months. In what seems to be a paradigm-shift, individual projects are now capable of generating billions of raw sequence data that need to be analyzed in the presence of alreadymore » annotated sequence information. While it is clear that data-driven methods, such as sequencing homology detection, are becoming the mainstay in the field of computational life sciences, the algorithmic advancements essential for implementing complex data analytics at scale have mostly lagged behind. Sequence homology detection is central to a number of bioinformatics applications including genome sequencing and protein family characterization. Given millions of sequences, the goal is to identify all pairs of sequences that are highly similar (or “homologous”) on the basis of alignment criteria. While there are optimal alignment algorithms to compute pairwise homology, their deployment for large-scale is currently not feasible; instead, heuristic methods are used at the expense of quality. In this dissertation, we present the design and evaluation of a parallel implementation for conducting optimal homology detection on distributed memory supercomputers. Our approach uses a combination of techniques from asynchronous load balancing (viz. work stealing, dynamic task counters), data replication, and exact-matching filters to achieve homology detection at scale. Results for a collection of 2.56M sequences show parallel efficiencies of ~75-100% on up to 8K cores, representing a time-to-solution of 33 seconds. We extend this work with a detailed analysis of single-node sequence alignment performance using the latest CPU vector instruction set extensions. Preliminary results reveal that current sequence alignment algorithms are unable to fully utilize widening vector registers.« less

Quantitative phenotyping via deep barcode sequencing.

PubMed

Smith, Andrew M; Heisler, Lawrence E; Mellor, Joseph; Kaper, Fiona; Thompson, Michael J; Chee, Mark; Roth, Frederick P; Giaever, Guri; Nislow, Corey

2009-10-01

Next-generation DNA sequencing technologies have revolutionized diverse genomics applications, including de novo genome sequencing, SNP detection, chromatin immunoprecipitation, and transcriptome analysis. Here we apply deep sequencing to genome-scale fitness profiling to evaluate yeast strain collections in parallel. This method, Barcode analysis by Sequencing, or "Bar-seq," outperforms the current benchmark barcode microarray assay in terms of both dynamic range and throughput. When applied to a complex chemogenomic assay, Bar-seq quantitatively identifies drug targets, with performance superior to the benchmark microarray assay. We also show that Bar-seq is well-suited for a multiplex format. We completely re-sequenced and re-annotated the yeast deletion collection using deep sequencing, found that approximately 20% of the barcodes and common priming sequences varied from expectation, and used this revised list of barcode sequences to improve data quality. Together, this new assay and analysis routine provide a deep-sequencing-based toolkit for identifying gene-environment interactions on a genome-wide scale.

Solving the multiple-set split equality common fixed-point problem of firmly quasi-nonexpansive operators.

PubMed

Zhao, Jing; Zong, Haili

2018-01-01

In this paper, we propose parallel and cyclic iterative algorithms for solving the multiple-set split equality common fixed-point problem of firmly quasi-nonexpansive operators. We also combine the process of cyclic and parallel iterative methods and propose two mixed iterative algorithms. Our several algorithms do not need any prior information about the operator norms. Under mild assumptions, we prove weak convergence of the proposed iterative sequences in Hilbert spaces. As applications, we obtain several iterative algorithms to solve the multiple-set split equality problem.

Capturing the 'ome': the expanding molecular toolbox for RNA and DNA library construction.

PubMed

Boone, Morgane; De Koker, Andries; Callewaert, Nico

2018-04-06

All sequencing experiments and most functional genomics screens rely on the generation of libraries to comprehensively capture pools of targeted sequences. In the past decade especially, driven by the progress in the field of massively parallel sequencing, numerous studies have comprehensively assessed the impact of particular manipulations on library complexity and quality, and characterized the activities and specificities of several key enzymes used in library construction. Fortunately, careful protocol design and reagent choice can substantially mitigate many of these biases, and enable reliable representation of sequences in libraries. This review aims to guide the reader through the vast expanse of literature on the subject to promote informed library generation, independent of the application.

WImpiBLAST: web interface for mpiBLAST to help biologists perform large-scale annotation using high performance computing.

PubMed

Sharma, Parichit; Mantri, Shrikant S

2014-01-01

The function of a newly sequenced gene can be discovered by determining its sequence homology with known proteins. BLAST is the most extensively used sequence analysis program for sequence similarity search in large databases of sequences. With the advent of next generation sequencing technologies it has now become possible to study genes and their expression at a genome-wide scale through RNA-seq and metagenome sequencing experiments. Functional annotation of all the genes is done by sequence similarity search against multiple protein databases. This annotation task is computationally very intensive and can take days to obtain complete results. The program mpiBLAST, an open-source parallelization of BLAST that achieves superlinear speedup, can be used to accelerate large-scale annotation by using supercomputers and high performance computing (HPC) clusters. Although many parallel bioinformatics applications using the Message Passing Interface (MPI) are available in the public domain, researchers are reluctant to use them due to lack of expertise in the Linux command line and relevant programming experience. With these limitations, it becomes difficult for biologists to use mpiBLAST for accelerating annotation. No web interface is available in the open-source domain for mpiBLAST. We have developed WImpiBLAST, a user-friendly open-source web interface for parallel BLAST searches. It is implemented in Struts 1.3 using a Java backbone and runs atop the open-source Apache Tomcat Server. WImpiBLAST supports script creation and job submission features and also provides a robust job management interface for system administrators. It combines script creation and modification features with job monitoring and management through the Torque resource manager on a Linux-based HPC cluster. Use case information highlights the acceleration of annotation analysis achieved by using WImpiBLAST. Here, we describe the WImpiBLAST web interface features and architecture, explain design decisions, describe workflows and provide a detailed analysis.

WImpiBLAST: Web Interface for mpiBLAST to Help Biologists Perform Large-Scale Annotation Using High Performance Computing

PubMed Central

Sharma, Parichit; Mantri, Shrikant S.

2014-01-01

The function of a newly sequenced gene can be discovered by determining its sequence homology with known proteins. BLAST is the most extensively used sequence analysis program for sequence similarity search in large databases of sequences. With the advent of next generation sequencing technologies it has now become possible to study genes and their expression at a genome-wide scale through RNA-seq and metagenome sequencing experiments. Functional annotation of all the genes is done by sequence similarity search against multiple protein databases. This annotation task is computationally very intensive and can take days to obtain complete results. The program mpiBLAST, an open-source parallelization of BLAST that achieves superlinear speedup, can be used to accelerate large-scale annotation by using supercomputers and high performance computing (HPC) clusters. Although many parallel bioinformatics applications using the Message Passing Interface (MPI) are available in the public domain, researchers are reluctant to use them due to lack of expertise in the Linux command line and relevant programming experience. With these limitations, it becomes difficult for biologists to use mpiBLAST for accelerating annotation. No web interface is available in the open-source domain for mpiBLAST. We have developed WImpiBLAST, a user-friendly open-source web interface for parallel BLAST searches. It is implemented in Struts 1.3 using a Java backbone and runs atop the open-source Apache Tomcat Server. WImpiBLAST supports script creation and job submission features and also provides a robust job management interface for system administrators. It combines script creation and modification features with job monitoring and management through the Torque resource manager on a Linux-based HPC cluster. Use case information highlights the acceleration of annotation analysis achieved by using WImpiBLAST. Here, we describe the WImpiBLAST web interface features and architecture, explain design decisions, describe workflows and provide a detailed analysis. PMID:24979410

Forensic Loci Allele Database (FLAD): Automatically generated, permanent identifiers for sequenced forensic alleles.

PubMed

Van Neste, Christophe; Van Criekinge, Wim; Deforce, Dieter; Van Nieuwerburgh, Filip

2016-01-01

It is difficult to predict if and when massively parallel sequencing of forensic STR loci will replace capillary electrophoresis as the new standard technology in forensic genetics. The main benefits of sequencing are increased multiplexing scales and SNP detection. There is not yet a consensus on how sequenced profiles should be reported. We present the Forensic Loci Allele Database (FLAD) service, made freely available on http://forensic.ugent.be/FLAD/. It offers permanent identifiers for sequenced forensic alleles (STR or SNP) and their microvariants for use in forensic allele nomenclature. Analogous to Genbank, its aim is to provide permanent identifiers for forensically relevant allele sequences. Researchers that are developing forensic sequencing kits or are performing population studies, can register on http://forensic.ugent.be/FLAD/ and add loci and allele sequences with a short and simple application interface (API). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Theory and procedures for finding a correct kinetic model for the bacteriorhodopsin photocycle.

PubMed

Hendler, R W; Shrager, R; Bose, S

2001-04-26

In this paper, we present the implementation and results of new methodology based on linear algebra. The theory behind these methods is covered in detail in the Supporting Information, available electronically (Shragerand Hendler). In brief, the methods presented search through all possible forward sequential submodels in order to find candidates that can be used to construct a complete model for the BR-photocycle. The methodology is limited only to forward sequential models. If no such models are compatible with the experimental data,none will be found. The procedures apply objective tests and filters to eliminate possibilities that cannot be correct, thus cutting the total number of candidate sequences to be considered. In the current application,which uses six exponentials, the total sequences were cut from 1950 to 49. The remaining sequences were further screened using known experimental criteria. The approach led to a solution which consists of a pair of sequences, one with 5 exponentials showing BR* f L(f) M(f) N O BR and the other with three exponentials showing BR* L(s) M(s) BR. The deduced complete kinetic model for the BR photocycle is thus either a single photocycle branched at the L intermediate or a pair of two parallel photocycles. Reasons for preferring the parallel photocycles are presented. Synthetic data constructed on the basis of the parallel photocycles were indistinguishable from the experimental data in a number of analytical tests that were applied.

Electrical tweezer for highly parallelized electrorotation measurements over a wide frequency bandwidth.

PubMed

Rohani, Ali; Varhue, Walter; Su, Yi-Hsuan; Swami, Nathan S

2014-07-01

Electrorotation (ROT) is a powerful tool for characterizing the dielectric properties of cells and bioparticles. However, its application has been somewhat limited by the need to mitigate disruptions to particle rotation by translation under positive DEP and by frictional interactions with the substrate. While these disruptions may be overcome by implementing particle positioning schemes or field cages, these methods restrict the frequency bandwidth to the negative DEP range and permit only single particle measurements within a limited spatial extent of the device geometry away from field nonuniformities. Herein, we present an electrical tweezer methodology based on a sequence of electrical signals, composed of negative DEP using 180-degree phase-shifted fields for trapping and levitation of the particles, followed by 90-degree phase-shifted fields over a wide frequency bandwidth for highly parallelized electrorotation measurements. Through field simulations of the rotating electrical field under this wave-sequence, we illustrate the enhanced spatial extent for electrorotation measurements, with no limitations to frequency bandwidth. We apply this methodology to characterize subtle modifications in morphology and electrophysiology of Cryptosporidium parvum with varying degrees of heat treatment, in terms of shifts in the electrorotation spectra over the 0.05-40 MHz region. Given the single particle sensitivity and the ability for highly parallelized electrorotation measurements, we envision its application toward characterizing heterogeneous subpopulations of microbial and stem cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Robustness of Massively Parallel Sequencing Platforms

PubMed Central

Kavak, Pınar; Yüksel, Bayram; Aksu, Soner; Kulekci, M. Oguzhan; Güngör, Tunga; Hach, Faraz; Şahinalp, S. Cenk; Alkan, Can; Sağıroğlu, Mahmut Şamil

2015-01-01

The improvements in high throughput sequencing technologies (HTS) made clinical sequencing projects such as ClinSeq and Genomics England feasible. Although there are significant improvements in accuracy and reproducibility of HTS based analyses, the usability of these types of data for diagnostic and prognostic applications necessitates a near perfect data generation. To assess the usability of a widely used HTS platform for accurate and reproducible clinical applications in terms of robustness, we generated whole genome shotgun (WGS) sequence data from the genomes of two human individuals in two different genome sequencing centers. After analyzing the data to characterize SNPs and indels using the same tools (BWA, SAMtools, and GATK), we observed significant number of discrepancies in the call sets. As expected, the most of the disagreements between the call sets were found within genomic regions containing common repeats and segmental duplications, albeit only a small fraction of the discordant variants were within the exons and other functionally relevant regions such as promoters. We conclude that although HTS platforms are sufficiently powerful for providing data for first-pass clinical tests, the variant predictions still need to be confirmed using orthogonal methods before using in clinical applications. PMID:26382624

The Sequencing Bead Array (SBA), a Next-Generation Digital Suspension Array

PubMed Central

Akhras, Michael S.; Pettersson, Erik; Diamond, Lisa; Unemo, Magnus; Okamoto, Jennifer; Davis, Ronald W.; Pourmand, Nader

2013-01-01

Here we describe the novel Sequencing Bead Array (SBA), a complete assay for molecular diagnostics and typing applications. SBA is a digital suspension array using Next-Generation Sequencing (NGS), to replace conventional optical readout platforms. The technology allows for reducing the number of instruments required in a laboratory setting, where the same NGS instrument could be employed from whole-genome and targeted sequencing to SBA broad-range biomarker detection and genotyping. As proof-of-concept, a model assay was designed that could distinguish ten Human Papillomavirus (HPV) genotypes associated with cervical cancer progression. SBA was used to genotype 20 cervical tumor samples and, when compared with amplicon pyrosequencing, was able to detect two additional co-infections due to increased sensitivity. We also introduce in-house software Sphix, enabling easy accessibility and interpretation of results. The technology offers a multi-parallel, rapid, robust, and scalable system that is readily adaptable for a multitude of microarray diagnostic and typing applications, e.g. genetic signatures, single nucleotide polymorphisms (SNPs), structural variations, and immunoassays. SBA has the potential to dramatically change the way we perform probe-based applications, and allow for a smooth transition towards the technology offered by genomic sequencing. PMID:24116138

A parallel strategy for predicting the secondary structure of polycistronic microRNAs.

PubMed

Han, Dianwei; Tang, Guiliang; Zhang, Jun

2013-01-01

The biogenesis of a functional microRNA is largely dependent on the secondary structure of the microRNA precursor (pre-miRNA). Recently, it has been shown that microRNAs are present in the genome as the form of polycistronic transcriptional units in plants and animals. It will be important to design efficient computational methods to predict such structures for microRNA discovery and its applications in gene silencing. In this paper, we propose a parallel algorithm based on the master-slave architecture to predict the secondary structure from an input sequence. We conducted some experiments to verify the effectiveness of our parallel algorithm. The experimental results show that our algorithm is able to produce the optimal secondary structure of polycistronic microRNAs.

MC64-ClustalWP2: A Highly-Parallel Hybrid Strategy to Align Multiple Sequences in Many-Core Architectures

PubMed Central

Díaz, David; Esteban, Francisco J.; Hernández, Pilar; Caballero, Juan Antonio; Guevara, Antonio

2014-01-01

We have developed the MC64-ClustalWP2 as a new implementation of the Clustal W algorithm, integrating a novel parallelization strategy and significantly increasing the performance when aligning long sequences in architectures with many cores. It must be stressed that in such a process, the detailed analysis of both the software and hardware features and peculiarities is of paramount importance to reveal key points to exploit and optimize the full potential of parallelism in many-core CPU systems. The new parallelization approach has focused into the most time-consuming stages of this algorithm. In particular, the so-called progressive alignment has drastically improved the performance, due to a fine-grained approach where the forward and backward loops were unrolled and parallelized. Another key approach has been the implementation of the new algorithm in a hybrid-computing system, integrating both an Intel Xeon multi-core CPU and a Tilera Tile64 many-core card. A comparison with other Clustal W implementations reveals the high-performance of the new algorithm and strategy in many-core CPU architectures, in a scenario where the sequences to align are relatively long (more than 10 kb) and, hence, a many-core GPU hardware cannot be used. Thus, the MC64-ClustalWP2 runs multiple alignments more than 18x than the original Clustal W algorithm, and more than 7x than the best x86 parallel implementation to date, being publicly available through a web service. Besides, these developments have been deployed in cost-effective personal computers and should be useful for life-science researchers, including the identification of identities and differences for mutation/polymorphism analyses, biodiversity and evolutionary studies and for the development of molecular markers for paternity testing, germplasm management and protection, to assist breeding, illegal traffic control, fraud prevention and for the protection of the intellectual property (identification/traceability), including the protected designation of origin, among other applications. PMID:24710354

Constructing DNA Barcode Sets Based on Particle Swarm Optimization.

PubMed

Wang, Bin; Zheng, Xuedong; Zhou, Shihua; Zhou, Changjun; Wei, Xiaopeng; Zhang, Qiang; Wei, Ziqi

2018-01-01

Following the completion of the human genome project, a large amount of high-throughput bio-data was generated. To analyze these data, massively parallel sequencing, namely next-generation sequencing, was rapidly developed. DNA barcodes are used to identify the ownership between sequences and samples when they are attached at the beginning or end of sequencing reads. Constructing DNA barcode sets provides the candidate DNA barcodes for this application. To increase the accuracy of DNA barcode sets, a particle swarm optimization (PSO) algorithm has been modified and used to construct the DNA barcode sets in this paper. Compared with the extant results, some lower bounds of DNA barcode sets are improved. The results show that the proposed algorithm is effective in constructing DNA barcode sets.

Next-generation sequencing in clinical virology: Discovery of new viruses.

PubMed

Datta, Sibnarayan; Budhauliya, Raghvendra; Das, Bidisha; Chatterjee, Soumya; Vanlalhmuaka; Veer, Vijay

2015-08-12

Viruses are a cause of significant health problem worldwide, especially in the developing nations. Due to different anthropological activities, human populations are exposed to different viral pathogens, many of which emerge as outbreaks. In such situations, discovery of novel viruses is utmost important for deciding prevention and treatment strategies. Since last century, a number of different virus discovery methods, based on cell culture inoculation, sequence-independent PCR have been used for identification of a variety of viruses. However, the recent emergence and commercial availability of next-generation sequencers (NGS) has entirely changed the field of virus discovery. These massively parallel sequencing platforms can sequence a mixture of genetic materials from a very heterogeneous mix, with high sensitivity. Moreover, these platforms work in a sequence-independent manner, making them ideal tools for virus discovery. However, for their application in clinics, sample preparation or enrichment is necessary to detect low abundance virus populations. A number of techniques have also been developed for enrichment or viral nucleic acids. In this manuscript, we review the evolution of sequencing; NGS technologies available today as well as widely used virus enrichment technologies. We also discuss the challenges associated with their applications in the clinical virus discovery.

Quantitative phenotyping via deep barcode sequencing

PubMed Central

Smith, Andrew M.; Heisler, Lawrence E.; Mellor, Joseph; Kaper, Fiona; Thompson, Michael J.; Chee, Mark; Roth, Frederick P.; Giaever, Guri; Nislow, Corey

2009-01-01

Next-generation DNA sequencing technologies have revolutionized diverse genomics applications, including de novo genome sequencing, SNP detection, chromatin immunoprecipitation, and transcriptome analysis. Here we apply deep sequencing to genome-scale fitness profiling to evaluate yeast strain collections in parallel. This method, Barcode analysis by Sequencing, or “Bar-seq,” outperforms the current benchmark barcode microarray assay in terms of both dynamic range and throughput. When applied to a complex chemogenomic assay, Bar-seq quantitatively identifies drug targets, with performance superior to the benchmark microarray assay. We also show that Bar-seq is well-suited for a multiplex format. We completely re-sequenced and re-annotated the yeast deletion collection using deep sequencing, found that ∼20% of the barcodes and common priming sequences varied from expectation, and used this revised list of barcode sequences to improve data quality. Together, this new assay and analysis routine provide a deep-sequencing-based toolkit for identifying gene–environment interactions on a genome-wide scale. PMID:19622793

The use of coded PCR primers enables high-throughput sequencing of multiple homolog amplification products by 454 parallel sequencing.

PubMed

Binladen, Jonas; Gilbert, M Thomas P; Bollback, Jonathan P; Panitz, Frank; Bendixen, Christian; Nielsen, Rasmus; Willerslev, Eske

2007-02-14

The invention of the Genome Sequence 20 DNA Sequencing System (454 parallel sequencing platform) has enabled the rapid and high-volume production of sequence data. Until now, however, individual emulsion PCR (emPCR) reactions and subsequent sequencing runs have been unable to combine template DNA from multiple individuals, as homologous sequences cannot be subsequently assigned to their original sources. We use conventional PCR with 5'-nucleotide tagged primers to generate homologous DNA amplification products from multiple specimens, followed by sequencing through the high-throughput Genome Sequence 20 DNA Sequencing System (GS20, Roche/454 Life Sciences). Each DNA sequence is subsequently traced back to its individual source through 5'tag-analysis. We demonstrate that this new approach enables the assignment of virtually all the generated DNA sequences to the correct source once sequencing anomalies are accounted for (miss-assignment rate<0.4%). Therefore, the method enables accurate sequencing and assignment of homologous DNA sequences from multiple sources in single high-throughput GS20 run. We observe a bias in the distribution of the differently tagged primers that is dependent on the 5' nucleotide of the tag. In particular, primers 5' labelled with a cytosine are heavily overrepresented among the final sequences, while those 5' labelled with a thymine are strongly underrepresented. A weaker bias also exists with regards to the distribution of the sequences as sorted by the second nucleotide of the dinucleotide tags. As the results are based on a single GS20 run, the general applicability of the approach requires confirmation. However, our experiments demonstrate that 5'primer tagging is a useful method in which the sequencing power of the GS20 can be applied to PCR-based assays of multiple homologous PCR products. The new approach will be of value to a broad range of research areas, such as those of comparative genomics, complete mitochondrial analyses, population genetics, and phylogenetics.

ATGC transcriptomics: a web-based application to integrate, explore and analyze de novo transcriptomic data.

PubMed

Gonzalez, Sergio; Clavijo, Bernardo; Rivarola, Máximo; Moreno, Patricio; Fernandez, Paula; Dopazo, Joaquín; Paniego, Norma

2017-02-22

In the last years, applications based on massively parallelized RNA sequencing (RNA-seq) have become valuable approaches for studying non-model species, e.g., without a fully sequenced genome. RNA-seq is a useful tool for detecting novel transcripts and genetic variations and for evaluating differential gene expression by digital measurements. The large and complex datasets resulting from functional genomic experiments represent a challenge in data processing, management, and analysis. This problem is especially significant for small research groups working with non-model species. We developed a web-based application, called ATGC transcriptomics, with a flexible and adaptable interface that allows users to work with new generation sequencing (NGS) transcriptomic analysis results using an ontology-driven database. This new application simplifies data exploration, visualization, and integration for a better comprehension of the results. ATGC transcriptomics provides access to non-expert computer users and small research groups to a scalable storage option and simple data integration, including database administration and management. The software is freely available under the terms of GNU public license at http://atgcinta.sourceforge.net .

ParDRe: faster parallel duplicated reads removal tool for sequencing studies.

PubMed

González-Domínguez, Jorge; Schmidt, Bertil

2016-05-15

Current next generation sequencing technologies often generate duplicated or near-duplicated reads that (depending on the application scenario) do not provide any interesting biological information but can increase memory requirements and computational time of downstream analysis. In this work we present ParDRe, a de novo parallel tool to remove duplicated and near-duplicated reads through the clustering of Single-End or Paired-End sequences from fasta or fastq files. It uses a novel bitwise approach to compare the suffixes of DNA strings and employs hybrid MPI/multithreading to reduce runtime on multicore systems. We show that ParDRe is up to 27.29 times faster than Fulcrum (a representative state-of-the-art tool) on a platform with two 8-core Sandy-Bridge processors. Source code in C ++ and MPI running on Linux systems as well as a reference manual are available at https://sourceforge.net/projects/pardre/ jgonzalezd@udc.es. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Neptune: a bioinformatics tool for rapid discovery of genomic variation in bacterial populations

PubMed Central

Marinier, Eric; Zaheer, Rahat; Berry, Chrystal; Weedmark, Kelly A.; Domaratzki, Michael; Mabon, Philip; Knox, Natalie C.; Reimer, Aleisha R.; Graham, Morag R.; Chui, Linda; Patterson-Fortin, Laura; Zhang, Jian; Pagotto, Franco; Farber, Jeff; Mahony, Jim; Seyer, Karine; Bekal, Sadjia; Tremblay, Cécile; Isaac-Renton, Judy; Prystajecky, Natalie; Chen, Jessica; Slade, Peter

2017-01-01

Abstract The ready availability of vast amounts of genomic sequence data has created the need to rethink comparative genomics algorithms using ‘big data’ approaches. Neptune is an efficient system for rapidly locating differentially abundant genomic content in bacterial populations using an exact k-mer matching strategy, while accommodating k-mer mismatches. Neptune’s loci discovery process identifies sequences that are sufficiently common to a group of target sequences and sufficiently absent from non-targets using probabilistic models. Neptune uses parallel computing to efficiently identify and extract these loci from draft genome assemblies without requiring multiple sequence alignments or other computationally expensive comparative sequence analyses. Tests on simulated and real datasets showed that Neptune rapidly identifies regions that are both sensitive and specific. We demonstrate that this system can identify trait-specific loci from different bacterial lineages. Neptune is broadly applicable for comparative bacterial analyses, yet will particularly benefit pathogenomic applications, owing to efficient and sensitive discovery of differentially abundant genomic loci. The software is available for download at: http://github.com/phac-nml/neptune. PMID:29048594

Katome: de novo DNA assembler implemented in rust

NASA Astrophysics Data System (ADS)

Neumann, Łukasz; Nowak, Robert M.; Kuśmirek, Wiktor

2017-08-01

Katome is a new de novo sequence assembler written in the Rust programming language, designed with respect to future parallelization of the algorithms, run time and memory usage optimization. The application uses new algorithms for the correct assembly of repetitive sequences. Performance and quality tests were performed on various data, comparing the new application to `dnaasm', `ABySS' and `Velvet' genome assemblers. Quality tests indicate that the new assembler creates more contigs than well-established solutions, but the contigs have better quality with regard to mismatches per 100kbp and indels per 100kbp. Additionally, benchmarks indicate that the Rust-based implementation outperforms `dnaasm', `ABySS' and `Velvet' assemblers, written in C++, in terms of assembly time. Lower memory usage in comparison to `dnaasm' is observed.

A Data Type for Efficient Representation of Other Data Types

NASA Technical Reports Server (NTRS)

James, Mark

2008-01-01

A self-organizing, monomorphic data type denoted a sequence has been conceived to address certain concerns that arise in programming parallel computers. A sequence in the present sense can be regarded abstractly as a vector, set, bag, queue, or other construct. Heretofore, in programming a parallel computer, it has been necessary for the programmer to state explicitly, at the outset, what parts of the program and the underlying data structures must be represented in parallel form. Not only is this requirement not optimal from the perspective of implementation; it entails an additional requirement that the programmer have intimate understanding of the underlying parallel structure. The present sequence data type overcomes both the implementation and parallel structure obstacles. In so doing, the sequence data type provides unified means by which the programmer can represent a data structure for natural and automatic decomposition to a parallel computing architecture. Sequences exhibit the behavioral and structural characteristics of vectors, but the underlying representations are automatically synthesized from combinations of programmers advice and execution use metrics. Sequences can vary bidirectionally between sparseness and density, making them excellent choices for many kinds of algorithms. The novelty and benefit of this behavior lies in the fact that it can relieve programmers of the details of implementations. The creation of a sequence enables decoupling of a conceptual representation from an implementation. The underlying representation of a sequence is a hybrid of representations composed of vectors, linked lists, connected blocks, and hash tables. The internal structure of a sequence can automatically change from time to time on the basis of how it is being used. Those portions of a sequence where elements have not been added or removed can be as efficient as vectors. As elements are inserted and removed in a given portion, then different methods are utilized to provide both an access and memory strategy that is optimized for that portion and the use to which it is put.

The history of MR imaging as seen through the pages of radiology.

PubMed

Edelman, Robert R

2014-11-01

The first reports in Radiology pertaining to magnetic resonance (MR) imaging were published in 1980, 7 years after Paul Lauterbur pioneered the first MR images and 9 years after the first human computed tomographic images were obtained. Historical advances in the research and clinical applications of MR imaging very much parallel the remarkable advances in MR imaging technology. These advances can be roughly classified into hardware (eg, magnets, gradients, radiofrequency [RF] coils, RF transmitter and receiver, MR imaging-compatible biopsy devices) and imaging techniques (eg, pulse sequences, parallel imaging, and so forth). Image quality has been dramatically improved with the introduction of high-field-strength superconducting magnets, digital RF systems, and phased-array coils. Hybrid systems, such as MR/positron emission tomography (PET), combine the superb anatomic and functional imaging capabilities of MR imaging with the unsurpassed capability of PET to demonstrate tissue metabolism. Supported by the improvements in hardware, advances in pulse sequence design and image reconstruction techniques have spurred dramatic improvements in imaging speed and the capability for studying tissue function. In this historical review, the history of MR imaging technology and developing research and clinical applications, as seen through the pages of Radiology, will be considered.

Highly multiplexed targeted DNA sequencing from single nuclei.

PubMed

Leung, Marco L; Wang, Yong; Kim, Charissa; Gao, Ruli; Jiang, Jerry; Sei, Emi; Navin, Nicholas E

2016-02-01

Single-cell DNA sequencing methods are challenged by poor physical coverage, high technical error rates and low throughput. To address these issues, we developed a single-cell DNA sequencing protocol that combines flow-sorting of single nuclei, time-limited multiple-displacement amplification (MDA), low-input library preparation, DNA barcoding, targeted capture and next-generation sequencing (NGS). This approach represents a major improvement over our previous single nucleus sequencing (SNS) Nature Protocols paper in terms of generating higher-coverage data (>90%), thereby enabling the detection of genome-wide variants in single mammalian cells at base-pair resolution. Furthermore, by pooling 48-96 single-cell libraries together for targeted capture, this approach can be used to sequence many single-cell libraries in parallel in a single reaction. This protocol greatly reduces the cost of single-cell DNA sequencing, and it can be completed in 5-6 d by advanced users. This single-cell DNA sequencing protocol has broad applications for studying rare cells and complex populations in diverse fields of biological research and medicine.

Enabling large-scale next-generation sequence assembly with Blacklight

PubMed Central

Couger, M. Brian; Pipes, Lenore; Squina, Fabio; Prade, Rolf; Siepel, Adam; Palermo, Robert; Katze, Michael G.; Mason, Christopher E.; Blood, Philip D.

2014-01-01

Summary A variety of extremely challenging biological sequence analyses were conducted on the XSEDE large shared memory resource Blacklight, using current bioinformatics tools and encompassing a wide range of scientific applications. These include genomic sequence assembly, very large metagenomic sequence assembly, transcriptome assembly, and sequencing error correction. The data sets used in these analyses included uncategorized fungal species, reference microbial data, very large soil and human gut microbiome sequence data, and primate transcriptomes, composed of both short-read and long-read sequence data. A new parallel command execution program was developed on the Blacklight resource to handle some of these analyses. These results, initially reported previously at XSEDE13 and expanded here, represent significant advances for their respective scientific communities. The breadth and depth of the results achieved demonstrate the ease of use, versatility, and unique capabilities of the Blacklight XSEDE resource for scientific analysis of genomic and transcriptomic sequence data, and the power of these resources, together with XSEDE support, in meeting the most challenging scientific problems. PMID:25294974

Targeted parallel sequencing of the Musa species: searching for an alternative model system for polyploidy studies

USDA-ARS?s Scientific Manuscript database

Modern day genomics holds the promise of solving the complexities of basic plant sciences, and of catalyzing practical advances in plant breeding. While contiguous, "base perfect" deep sequencing is a key module of any genome project, recent advances in parallel next generation sequencing technologi...

cljam: a library for handling DNA sequence alignment/map (SAM) with parallel processing.

PubMed

Takeuchi, Toshiki; Yamada, Atsuo; Aoki, Takashi; Nishimura, Kunihiro

2016-01-01

Next-generation sequencing can determine DNA bases and the results of sequence alignments are generally stored in files in the Sequence Alignment/Map (SAM) format and the compressed binary version (BAM) of it. SAMtools is a typical tool for dealing with files in the SAM/BAM format. SAMtools has various functions, including detection of variants, visualization of alignments, indexing, extraction of parts of the data and loci, and conversion of file formats. It is written in C and can execute fast. However, SAMtools requires an additional implementation to be used in parallel with, for example, OpenMP (Open Multi-Processing) libraries. For the accumulation of next-generation sequencing data, a simple parallelization program, which can support cloud and PC cluster environments, is required. We have developed cljam using the Clojure programming language, which simplifies parallel programming, to handle SAM/BAM data. Cljam can run in a Java runtime environment (e.g., Windows, Linux, Mac OS X) with Clojure. Cljam can process and analyze SAM/BAM files in parallel and at high speed. The execution time with cljam is almost the same as with SAMtools. The cljam code is written in Clojure and has fewer lines than other similar tools.

Genomes by design

PubMed Central

Haimovich, Adrian D.; Muir, Paul; Isaacs, Farren J.

2016-01-01

Next-generation DNA sequencing has revealed the complete genome sequences of numerous organisms, establishing a fundamental and growing understanding of genetic variation and phenotypic diversity. Engineering at the gene, network and whole-genome scale aims to introduce targeted genetic changes both to explore emergent phenotypes and to introduce new functionalities. Expansion of these approaches into massively parallel platforms establishes the ability to generate targeted genome modifications, elucidating causal links between genotype and phenotype, as well as the ability to design and reprogramme organisms. In this Review, we explore techniques and applications in genome engineering, outlining key advances and defining challenges. PMID:26260262

Parallel Algorithms for Switching Edges in Heterogeneous Graphs.

PubMed

Bhuiyan, Hasanuzzaman; Khan, Maleq; Chen, Jiangzhuo; Marathe, Madhav

2017-06-01

An edge switch is an operation on a graph (or network) where two edges are selected randomly and one of their end vertices are swapped with each other. Edge switch operations have important applications in graph theory and network analysis, such as in generating random networks with a given degree sequence, modeling and analyzing dynamic networks, and in studying various dynamic phenomena over a network. The recent growth of real-world networks motivates the need for efficient parallel algorithms. The dependencies among successive edge switch operations and the requirement to keep the graph simple (i.e., no self-loops or parallel edges) as the edges are switched lead to significant challenges in designing a parallel algorithm. Addressing these challenges requires complex synchronization and communication among the processors leading to difficulties in achieving a good speedup by parallelization. In this paper, we present distributed memory parallel algorithms for switching edges in massive networks. These algorithms provide good speedup and scale well to a large number of processors. A harmonic mean speedup of 73.25 is achieved on eight different networks with 1024 processors. One of the steps in our edge switch algorithms requires the computation of multinomial random variables in parallel. This paper presents the first non-trivial parallel algorithm for the problem, achieving a speedup of 925 using 1024 processors.

Parallel Algorithms for Switching Edges in Heterogeneous Graphs☆

PubMed Central

Khan, Maleq; Chen, Jiangzhuo; Marathe, Madhav

2017-01-01

An edge switch is an operation on a graph (or network) where two edges are selected randomly and one of their end vertices are swapped with each other. Edge switch operations have important applications in graph theory and network analysis, such as in generating random networks with a given degree sequence, modeling and analyzing dynamic networks, and in studying various dynamic phenomena over a network. The recent growth of real-world networks motivates the need for efficient parallel algorithms. The dependencies among successive edge switch operations and the requirement to keep the graph simple (i.e., no self-loops or parallel edges) as the edges are switched lead to significant challenges in designing a parallel algorithm. Addressing these challenges requires complex synchronization and communication among the processors leading to difficulties in achieving a good speedup by parallelization. In this paper, we present distributed memory parallel algorithms for switching edges in massive networks. These algorithms provide good speedup and scale well to a large number of processors. A harmonic mean speedup of 73.25 is achieved on eight different networks with 1024 processors. One of the steps in our edge switch algorithms requires the computation of multinomial random variables in parallel. This paper presents the first non-trivial parallel algorithm for the problem, achieving a speedup of 925 using 1024 processors. PMID:28757680

Bioinformatics algorithm based on a parallel implementation of a machine learning approach using transducers

NASA Astrophysics Data System (ADS)

Roche-Lima, Abiel; Thulasiram, Ruppa K.

2012-02-01

Finite automata, in which each transition is augmented with an output label in addition to the familiar input label, are considered finite-state transducers. Transducers have been used to analyze some fundamental issues in bioinformatics. Weighted finite-state transducers have been proposed to pairwise alignments of DNA and protein sequences; as well as to develop kernels for computational biology. Machine learning algorithms for conditional transducers have been implemented and used for DNA sequence analysis. Transducer learning algorithms are based on conditional probability computation. It is calculated by using techniques, such as pair-database creation, normalization (with Maximum-Likelihood normalization) and parameters optimization (with Expectation-Maximization - EM). These techniques are intrinsically costly for computation, even worse when are applied to bioinformatics, because the databases sizes are large. In this work, we describe a parallel implementation of an algorithm to learn conditional transducers using these techniques. The algorithm is oriented to bioinformatics applications, such as alignments, phylogenetic trees, and other genome evolution studies. Indeed, several experiences were developed using the parallel and sequential algorithm on Westgrid (specifically, on the Breeze cluster). As results, we obtain that our parallel algorithm is scalable, because execution times are reduced considerably when the data size parameter is increased. Another experience is developed by changing precision parameter. In this case, we obtain smaller execution times using the parallel algorithm. Finally, number of threads used to execute the parallel algorithm on the Breezy cluster is changed. In this last experience, we obtain as result that speedup is considerably increased when more threads are used; however there is a convergence for number of threads equal to or greater than 16.

Next generation sequencing (NGS): a golden tool in forensic toolkit.

PubMed

Aly, S M; Sabri, D M

The DNA analysis is a cornerstone in contemporary forensic sciences. DNA sequencing technologies are powerful tools that enrich molecular sciences in the past based on Sanger sequencing and continue to glowing these sciences based on Next generation sequencing (NGS). Next generation sequencing has excellent potential to flourish and increase the molecular applications in forensic sciences by jumping over the pitfalls of the conventional method of sequencing. The main advantages of NGS compared to conventional method that it utilizes simultaneously a large number of genetic markers with high-resolution of genetic data. These advantages will help in solving several challenges such as mixture analysis and dealing with minute degraded samples. Based on these new technologies, many markers could be examined to get important biological data such as age, geographical origins, tissue type determination, external visible traits and monozygotic twins identification. It also could get data related to microbes, insects, plants and soil which are of great medico-legal importance. Despite the dozens of forensic research involving NGS, there are requirements before using this technology routinely in forensic cases. Thus, there is a great need to more studies that address robustness of these techniques. Therefore, this work highlights the applications of forensic sciences in the era of massively parallel sequencing.

Evaluation of second-generation sequencing of 19 dilated cardiomyopathy genes for clinical applications.

PubMed

Gowrisankar, Sivakumar; Lerner-Ellis, Jordan P; Cox, Stephanie; White, Emily T; Manion, Megan; LeVan, Kevin; Liu, Jonathan; Farwell, Lisa M; Iartchouk, Oleg; Rehm, Heidi L; Funke, Birgit H

2010-11-01

Medical sequencing for diseases with locus and allelic heterogeneities has been limited by the high cost and low throughput of traditional sequencing technologies. "Second-generation" sequencing (SGS) technologies allow the parallel processing of a large number of genes and, therefore, offer great promise for medical sequencing; however, their use in clinical laboratories is still in its infancy. Our laboratory offers clinical resequencing for dilated cardiomyopathy (DCM) using an array-based platform that interrogates 19 of more than 30 genes known to cause DCM. We explored both the feasibility and cost effectiveness of using PCR amplification followed by SGS technology for sequencing these 19 genes in a set of five samples enriched for known sequence alterations (109 unique substitutions and 27 insertions and deletions). While the analytical sensitivity for substitutions was comparable to that of the DCM array (98%), SGS technology performed better than the DCM array for insertions and deletions (90.6% versus 58%). Overall, SGS performed substantially better than did the current array-based testing platform; however, the operational cost and projected turnaround time do not meet our current standards. Therefore, efficient capture methods and/or sample pooling strategies that shorten the turnaround time and decrease reagent and labor costs are needed before implementing this platform into routine clinical applications.

Accurate and exact CNV identification from targeted high-throughput sequence data.

PubMed

Nord, Alex S; Lee, Ming; King, Mary-Claire; Walsh, Tom

2011-04-12

Massively parallel sequencing of barcoded DNA samples significantly increases screening efficiency for clinically important genes. Short read aligners are well suited to single nucleotide and indel detection. However, methods for CNV detection from targeted enrichment are lacking. We present a method combining coverage with map information for the identification of deletions and duplications in targeted sequence data. Sequencing data is first scanned for gains and losses using a comparison of normalized coverage data between samples. CNV calls are confirmed by testing for a signature of sequences that span the CNV breakpoint. With our method, CNVs can be identified regardless of whether breakpoints are within regions targeted for sequencing. For CNVs where at least one breakpoint is within targeted sequence, exact CNV breakpoints can be identified. In a test data set of 96 subjects sequenced across ~1 Mb genomic sequence using multiplexing technology, our method detected mutations as small as 31 bp, predicted quantitative copy count, and had a low false-positive rate. Application of this method allows for identification of gains and losses in targeted sequence data, providing comprehensive mutation screening when combined with a short read aligner.

Churchill: an ultra-fast, deterministic, highly scalable and balanced parallelization strategy for the discovery of human genetic variation in clinical and population-scale genomics.

PubMed

Kelly, Benjamin J; Fitch, James R; Hu, Yangqiu; Corsmeier, Donald J; Zhong, Huachun; Wetzel, Amy N; Nordquist, Russell D; Newsom, David L; White, Peter

2015-01-20

While advances in genome sequencing technology make population-scale genomics a possibility, current approaches for analysis of these data rely upon parallelization strategies that have limited scalability, complex implementation and lack reproducibility. Churchill, a balanced regional parallelization strategy, overcomes these challenges, fully automating the multiple steps required to go from raw sequencing reads to variant discovery. Through implementation of novel deterministic parallelization techniques, Churchill allows computationally efficient analysis of a high-depth whole genome sample in less than two hours. The method is highly scalable, enabling full analysis of the 1000 Genomes raw sequence dataset in a week using cloud resources. http://churchill.nchri.org/.

100 Gbps Wireless System and Circuit Design Using Parallel Spread-Spectrum Sequencing

NASA Astrophysics Data System (ADS)

Scheytt, J. Christoph; Javed, Abdul Rehman; Bammidi, Eswara Rao; KrishneGowda, Karthik; Kallfass, Ingmar; Kraemer, Rolf

2017-09-01

In this article mixed analog/digital signal processing techniques based on parallel spread-spectrum sequencing (PSSS) and radio frequency (RF) carrier synchronization for ultra-broadband wireless communication are investigated on system and circuit level.

Parallel reduced-instruction-set-computer architecture for real-time symbolic pattern matching

NASA Astrophysics Data System (ADS)

Parson, Dale E.

1991-03-01

This report discusses ongoing work on a parallel reduced-instruction- set-computer (RISC) architecture for automatic production matching. The PRIOPS compiler takes advantage of the memoryless character of automatic processing by translating a program's collection of automatic production tests into an equivalent combinational circuit-a digital circuit without memory, whose outputs are immediate functions of its inputs. The circuit provides a highly parallel, fine-grain model of automatic matching. The compiler then maps the combinational circuit onto RISC hardware. The heart of the processor is an array of comparators capable of testing production conditions in parallel, Each comparator attaches to private memory that contains virtual circuit nodes-records of the current state of nodes and busses in the combinational circuit. All comparator memories hold identical information, allowing simultaneous update for a single changing circuit node and simultaneous retrieval of different circuit nodes by different comparators. Along with the comparator-based logic unit is a sequencer that determines the current combination of production-derived comparisons to try, based on the combined success and failure of previous combinations of comparisons. The memoryless nature of automatic matching allows the compiler to designate invariant memory addresses for virtual circuit nodes, and to generate the most effective sequences of comparison test combinations. The result is maximal utilization of parallel hardware, indicating speed increases and scalability beyond that found for course-grain, multiprocessor approaches to concurrent Rete matching. Future work will consider application of this RISC architecture to the standard (controlled) Rete algorithm, where search through memory dominates portions of matching.

A whole-genome shotgun approach for assembling and anchoring the hexaploid bread wheat genome

DOE PAGES

Chapman, Jarrod A.; Mascher, Martin; Buluc, Aydin; ...

2015-01-31

We report that polyploid species have long been thought to be recalcitrant to whole-genome assembly. By combining high-throughput sequencing, recent developments in parallel computing, and genetic mapping, we derive, de novo, a sequence assembly representing 9.1 Gbp of the highly repetitive 16 Gbp genome of hexaploid wheat, Triticum aestivum, and assign 7.1 Gb of this assembly to chromosomal locations. The genome representation and accuracy of our assembly is comparable or even exceeds that of a chromosome-by-chromosome shotgun assembly. Our assembly and mapping strategy uses only short read sequencing technology and is applicable to any species where it is possible tomore » construct a mapping population.« less

A whole-genome shotgun approach for assembling and anchoring the hexaploid bread wheat genome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Jarrod A.; Mascher, Martin; Buluc, Aydin

We report that polyploid species have long been thought to be recalcitrant to whole-genome assembly. By combining high-throughput sequencing, recent developments in parallel computing, and genetic mapping, we derive, de novo, a sequence assembly representing 9.1 Gbp of the highly repetitive 16 Gbp genome of hexaploid wheat, Triticum aestivum, and assign 7.1 Gb of this assembly to chromosomal locations. The genome representation and accuracy of our assembly is comparable or even exceeds that of a chromosome-by-chromosome shotgun assembly. Our assembly and mapping strategy uses only short read sequencing technology and is applicable to any species where it is possible tomore » construct a mapping population.« less

Detection and Evaluation of Spatio-Temporal Spike Patterns in Massively Parallel Spike Train Data with SPADE.

PubMed

Quaglio, Pietro; Yegenoglu, Alper; Torre, Emiliano; Endres, Dominik M; Grün, Sonja

2017-01-01

Repeated, precise sequences of spikes are largely considered a signature of activation of cell assemblies. These repeated sequences are commonly known under the name of spatio-temporal patterns (STPs). STPs are hypothesized to play a role in the communication of information in the computational process operated by the cerebral cortex. A variety of statistical methods for the detection of STPs have been developed and applied to electrophysiological recordings, but such methods scale poorly with the current size of available parallel spike train recordings (more than 100 neurons). In this work, we introduce a novel method capable of overcoming the computational and statistical limits of existing analysis techniques in detecting repeating STPs within massively parallel spike trains (MPST). We employ advanced data mining techniques to efficiently extract repeating sequences of spikes from the data. Then, we introduce and compare two alternative approaches to distinguish statistically significant patterns from chance sequences. The first approach uses a measure known as conceptual stability, of which we investigate a computationally cheap approximation for applications to such large data sets. The second approach is based on the evaluation of pattern statistical significance. In particular, we provide an extension to STPs of a method we recently introduced for the evaluation of statistical significance of synchronous spike patterns. The performance of the two approaches is evaluated in terms of computational load and statistical power on a variety of artificial data sets that replicate specific features of experimental data. Both methods provide an effective and robust procedure for detection of STPs in MPST data. The method based on significance evaluation shows the best overall performance, although at a higher computational cost. We name the novel procedure the spatio-temporal Spike PAttern Detection and Evaluation (SPADE) analysis.

Detection and Evaluation of Spatio-Temporal Spike Patterns in Massively Parallel Spike Train Data with SPADE

PubMed Central

Quaglio, Pietro; Yegenoglu, Alper; Torre, Emiliano; Endres, Dominik M.; Grün, Sonja

2017-01-01

Repeated, precise sequences of spikes are largely considered a signature of activation of cell assemblies. These repeated sequences are commonly known under the name of spatio-temporal patterns (STPs). STPs are hypothesized to play a role in the communication of information in the computational process operated by the cerebral cortex. A variety of statistical methods for the detection of STPs have been developed and applied to electrophysiological recordings, but such methods scale poorly with the current size of available parallel spike train recordings (more than 100 neurons). In this work, we introduce a novel method capable of overcoming the computational and statistical limits of existing analysis techniques in detecting repeating STPs within massively parallel spike trains (MPST). We employ advanced data mining techniques to efficiently extract repeating sequences of spikes from the data. Then, we introduce and compare two alternative approaches to distinguish statistically significant patterns from chance sequences. The first approach uses a measure known as conceptual stability, of which we investigate a computationally cheap approximation for applications to such large data sets. The second approach is based on the evaluation of pattern statistical significance. In particular, we provide an extension to STPs of a method we recently introduced for the evaluation of statistical significance of synchronous spike patterns. The performance of the two approaches is evaluated in terms of computational load and statistical power on a variety of artificial data sets that replicate specific features of experimental data. Both methods provide an effective and robust procedure for detection of STPs in MPST data. The method based on significance evaluation shows the best overall performance, although at a higher computational cost. We name the novel procedure the spatio-temporal Spike PAttern Detection and Evaluation (SPADE) analysis. PMID:28596729

Microfluidic integration of parallel solid-phase liquid chromatography.

PubMed

Huft, Jens; Haynes, Charles A; Hansen, Carl L

2013-03-05

We report the development of a fully integrated microfluidic chromatography system based on a recently developed column geometry that allows for robust packing of high-performance separation columns in poly(dimethylsiloxane) microfluidic devices having integrated valves made by multilayer soft lithography (MSL). The combination of parallel high-performance separation columns and on-chip plumbing was used to achieve a fully integrated system for on-chip chromatography, including all steps of automated sample loading, programmable gradient generation, separation, fluorescent detection, and sample recovery. We demonstrate this system in the separation of fluorescently labeled DNA and parallel purification of reverse transcription polymerase chain reaction (RT-PCR) amplified variable regions of mouse immunoglobulin genes using a strong anion exchange (AEX) resin. Parallel sample recovery in an immiscible oil stream offers the advantage of low sample dilution and high recovery rates. The ability to perform nucleic acid size selection and recovery on subnanogram samples of DNA holds promise for on-chip genomics applications including sequencing library preparation, cloning, and sample fractionation for diagnostics.

A rapid, generally applicable method to engineer zinc fingers illustrated by targeting the HIV-1 promoter.

PubMed

Isalan, M; Klug, A; Choo, Y

2001-07-01

DNA-binding domains with predetermined sequence specificity are engineered by selection of zinc finger modules using phage display, allowing the construction of customized transcription factors. Despite remarkable progress in this field, the available protein-engineering methods are deficient in many respects, thus hampering the applicability of the technique. Here we present a rapid and convenient method that can be used to design zinc finger proteins against a variety of DNA-binding sites. This is based on a pair of pre-made zinc finger phage-display libraries, which are used in parallel to select two DNA-binding domains each of which recognizes given 5 base pair sequences, and whose products are recombined to produce a single protein that recognizes a composite (9 base pair) site of predefined sequence. Engineering using this system can be completed in less than two weeks and yields proteins that bind sequence-specifically to DNA with Kd values in the nanomolar range. To illustrate the technique, we have selected seven different proteins to bind various regions of the human immunodeficiency virus 1 (HIV-1) promoter.

Using Massive Parallel Sequencing for the Development, Validation, and Application of Population Genetics Markers in the Invasive Bivalve Zebra Mussel (Dreissena polymorpha)

PubMed Central

Peñarrubia, Luis; Sanz, Nuria; Pla, Carles; Vidal, Oriol; Viñas, Jordi

2015-01-01

The zebra mussel (Dreissena polymorpha, Pallas, 1771) is one of the most invasive species of freshwater bivalves, due to a combination of biological and anthropogenic factors. Once this species has been introduced to a new area, individuals form dense aggregations that are very difficult to remove, leading to many adverse socioeconomic and ecological consequences. In this study, we identified, tested, and validated a new set of polymorphic microsatellite loci (also known as SSRs, Single Sequence Repeats) using a Massive Parallel Sequencing (MPS) platform. After several pruning steps, 93 SSRs could potentially be amplified. Out of these SSRs, 14 were polymorphic, producing a polymorphic yield of 15.05%. These 14 polymorphic microsatellites were fully validated in a first approximation of the genetic population structure of D. polymorpha in the Iberian Peninsula. Based on this polymorphic yield, we propose a criterion for establishing the number of SSRs that require validation in similar species, depending on the final use of the markers. These results could be used to optimize MPS approaches in the development of microsatellites as genetic markers, which would reduce the cost of this process. PMID:25780924

Multiplex single-molecule interaction profiling of DNA-barcoded proteins.

PubMed

Gu, Liangcai; Li, Chao; Aach, John; Hill, David E; Vidal, Marc; Church, George M

2014-11-27

In contrast with advances in massively parallel DNA sequencing, high-throughput protein analyses are often limited by ensemble measurements, individual analyte purification and hence compromised quality and cost-effectiveness. Single-molecule protein detection using optical methods is limited by the number of spectrally non-overlapping chromophores. Here we introduce a single-molecular-interaction sequencing (SMI-seq) technology for parallel protein interaction profiling leveraging single-molecule advantages. DNA barcodes are attached to proteins collectively via ribosome display or individually via enzymatic conjugation. Barcoded proteins are assayed en masse in aqueous solution and subsequently immobilized in a polyacrylamide thin film to construct a random single-molecule array, where barcoding DNAs are amplified into in situ polymerase colonies (polonies) and analysed by DNA sequencing. This method allows precise quantification of various proteins with a theoretical maximum array density of over one million polonies per square millimetre. Furthermore, protein interactions can be measured on the basis of the statistics of colocalized polonies arising from barcoding DNAs of interacting proteins. Two demanding applications, G-protein coupled receptor and antibody-binding profiling, are demonstrated. SMI-seq enables 'library versus library' screening in a one-pot assay, simultaneously interrogating molecular binding affinity and specificity.

Multiplex single-molecule interaction profiling of DNA barcoded proteins

PubMed Central

Gu, Liangcai; Li, Chao; Aach, John; Hill, David E.; Vidal, Marc; Church, George M.

2014-01-01

In contrast with advances in massively parallel DNA sequencing1, high-throughput protein analyses2-4 are often limited by ensemble measurements, individual analyte purification and hence compromised quality and cost-effectiveness. Single-molecule (SM) protein detection achieved using optical methods5 is limited by the number of spectrally nonoverlapping chromophores. Here, we introduce a single molecular interaction-sequencing (SMI-Seq) technology for parallel protein interaction profiling leveraging SM advantages. DNA barcodes are attached to proteins collectively via ribosome display6 or individually via enzymatic conjugation. Barcoded proteins are assayed en masse in aqueous solution and subsequently immobilized in a polyacrylamide (PAA) thin film to construct a random SM array, where barcoding DNAs are amplified into in situ polymerase colonies (polonies)7 and analyzed by DNA sequencing. This method allows precise quantification of various proteins with a theoretical maximum array density of over one million polonies per square millimeter. Furthermore, protein interactions can be measured based on the statistics of colocalized polonies arising from barcoding DNAs of interacting proteins. Two demanding applications, G-protein coupled receptor (GPCR) and antibody binding profiling, were demonstrated. SMI-Seq enables “library vs. library” screening in a one-pot assay, simultaneously interrogating molecular binding affinity and specificity. PMID:25252978

Cloud parallel processing of tandem mass spectrometry based proteomics data.

PubMed

Mohammed, Yassene; Mostovenko, Ekaterina; Henneman, Alex A; Marissen, Rob J; Deelder, André M; Palmblad, Magnus

2012-10-05

Data analysis in mass spectrometry based proteomics struggles to keep pace with the advances in instrumentation and the increasing rate of data acquisition. Analyzing this data involves multiple steps requiring diverse software, using different algorithms and data formats. Speed and performance of the mass spectral search engines are continuously improving, although not necessarily as needed to face the challenges of acquired big data. Improving and parallelizing the search algorithms is one possibility; data decomposition presents another, simpler strategy for introducing parallelism. We describe a general method for parallelizing identification of tandem mass spectra using data decomposition that keeps the search engine intact and wraps the parallelization around it. We introduce two algorithms for decomposing mzXML files and recomposing resulting pepXML files. This makes the approach applicable to different search engines, including those relying on sequence databases and those searching spectral libraries. We use cloud computing to deliver the computational power and scientific workflow engines to interface and automate the different processing steps. We show how to leverage these technologies to achieve faster data analysis in proteomics and present three scientific workflows for parallel database as well as spectral library search using our data decomposition programs, X!Tandem and SpectraST.

Bit error rate tester using fast parallel generation of linear recurring sequences

DOEpatents

Pierson, Lyndon G.; Witzke, Edward L.; Maestas, Joseph H.

2003-05-06

A fast method for generating linear recurring sequences by parallel linear recurring sequence generators (LRSGs) with a feedback circuit optimized to balance minimum propagation delay against maximal sequence period. Parallel generation of linear recurring sequences requires decimating the sequence (creating small contiguous sections of the sequence in each LRSG). A companion matrix form is selected depending on whether the LFSR is right-shifting or left-shifting. The companion matrix is completed by selecting a primitive irreducible polynomial with 1's most closely grouped in a corner of the companion matrix. A decimation matrix is created by raising the companion matrix to the (n*k).sup.th power, where k is the number of parallel LRSGs and n is the number of bits to be generated at a time by each LRSG. Companion matrices with 1's closely grouped in a corner will yield sparse decimation matrices. A feedback circuit comprised of XOR logic gates implements the decimation matrix in hardware. Sparse decimation matrices can be implemented with minimum number of XOR gates, and therefore a minimum propagation delay through the feedback circuit. The LRSG of the invention is particularly well suited to use as a bit error rate tester on high speed communication lines because it permits the receiver to synchronize to the transmitted pattern within 2n bits.

Pattern recognition of electronic bit-sequences using a semiconductor mode-locked laser and spatial light modulators

NASA Astrophysics Data System (ADS)

Bhooplapur, Sharad; Akbulut, Mehmetkan; Quinlan, Franklyn; Delfyett, Peter J.

2010-04-01

A novel scheme for recognition of electronic bit-sequences is demonstrated. Two electronic bit-sequences that are to be compared are each mapped to a unique code from a set of Walsh-Hadamard codes. The codes are then encoded in parallel on the spectral phase of the frequency comb lines from a frequency-stabilized mode-locked semiconductor laser. Phase encoding is achieved by using two independent spatial light modulators based on liquid crystal arrays. Encoded pulses are compared using interferometric pulse detection and differential balanced photodetection. Orthogonal codes eight bits long are compared, and matched codes are successfully distinguished from mismatched codes with very low error rates, of around 10-18. This technique has potential for high-speed, high accuracy recognition of bit-sequences, with applications in keyword searches and internet protocol packet routing.

Homopolymer tail-mediated ligation PCR: a streamlined and highly efficient method for DNA cloning and library construction.

PubMed

Lazinski, David W; Camilli, Andrew

2013-01-01

The amplification of DNA fragments, cloned between user-defined 5' and 3' end sequences, is a prerequisite step in the use of many current applications including massively parallel sequencing (MPS). Here we describe an improved method, called homopolymer tail-mediated ligation PCR (HTML-PCR), that requires very little starting template, minimal hands-on effort, is cost-effective, and is suited for use in high-throughput and robotic methodologies. HTML-PCR starts with the addition of homopolymer tails of controlled lengths to the 3' termini of a double-stranded genomic template. The homopolymer tails enable the annealing-assisted ligation of a hybrid oligonucleotide to the template's recessed 5' ends. The hybrid oligonucleotide has a user-defined sequence at its 5' end. This primer, together with a second primer composed of a longer region complementary to the homopolymer tail and fused to a second 5' user-defined sequence, are used in a PCR reaction to generate the final product. The user-defined sequences can be varied to enable compatibility with a wide variety of downstream applications. We demonstrate our new method by constructing MPS libraries starting from nanogram and sub-nanogram quantities of Vibrio cholerae and Streptococcus pneumoniae genomic DNA.

DNAAlignEditor: DNA alignment editor tool

PubMed Central

Sanchez-Villeda, Hector; Schroeder, Steven; Flint-Garcia, Sherry; Guill, Katherine E; Yamasaki, Masanori; McMullen, Michael D

2008-01-01

Background With advances in DNA re-sequencing methods and Next-Generation parallel sequencing approaches, there has been a large increase in genomic efforts to define and analyze the sequence variability present among individuals within a species. For very polymorphic species such as maize, this has lead to a need for intuitive, user-friendly software that aids the biologist, often with naïve programming capability, in tracking, editing, displaying, and exporting multiple individual sequence alignments. To fill this need we have developed a novel DNA alignment editor. Results We have generated a nucleotide sequence alignment editor (DNAAlignEditor) that provides an intuitive, user-friendly interface for manual editing of multiple sequence alignments with functions for input, editing, and output of sequence alignments. The color-coding of nucleotide identity and the display of associated quality score aids in the manual alignment editing process. DNAAlignEditor works as a client/server tool having two main components: a relational database that collects the processed alignments and a user interface connected to database through universal data access connectivity drivers. DNAAlignEditor can be used either as a stand-alone application or as a network application with multiple users concurrently connected. Conclusion We anticipate that this software will be of general interest to biologists and population genetics in editing DNA sequence alignments and analyzing natural sequence variation regardless of species, and will be particularly useful for manual alignment editing of sequences in species with high levels of polymorphism. PMID:18366684

Separation and parallel sequencing of the genomes and transcriptomes of single cells using G&T-seq.

PubMed

Macaulay, Iain C; Teng, Mabel J; Haerty, Wilfried; Kumar, Parveen; Ponting, Chris P; Voet, Thierry

2016-11-01

Parallel sequencing of a single cell's genome and transcriptome provides a powerful tool for dissecting genetic variation and its relationship with gene expression. Here we present a detailed protocol for G&T-seq, a method for separation and parallel sequencing of genomic DNA and full-length polyA(+) mRNA from single cells. We provide step-by-step instructions for the isolation and lysis of single cells; the physical separation of polyA(+) mRNA from genomic DNA using a modified oligo-dT bead capture and the respective whole-transcriptome and whole-genome amplifications; and library preparation and sequence analyses of these amplification products. The method allows the detection of thousands of transcripts in parallel with the genetic variants captured by the DNA-seq data from the same single cell. G&T-seq differs from other currently available methods for parallel DNA and RNA sequencing from single cells, as it involves physical separation of the DNA and RNA and does not require bespoke microfluidics platforms. The process can be implemented manually or through automation. When performed manually, paired genome and transcriptome sequencing libraries from eight single cells can be produced in ∼3 d by researchers experienced in molecular laboratory work. For users with experience in the programming and operation of liquid-handling robots, paired DNA and RNA libraries from 96 single cells can be produced in the same time frame. Sequence analysis and integration of single-cell G&T-seq DNA and RNA data requires a high level of bioinformatics expertise and familiarity with a wide range of informatics tools.

Massively parallel whole genome amplification for single-cell sequencing using droplet microfluidics.

PubMed

Hosokawa, Masahito; Nishikawa, Yohei; Kogawa, Masato; Takeyama, Haruko

2017-07-12

Massively parallel single-cell genome sequencing is required to further understand genetic diversities in complex biological systems. Whole genome amplification (WGA) is the first step for single-cell sequencing, but its throughput and accuracy are insufficient in conventional reaction platforms. Here, we introduce single droplet multiple displacement amplification (sd-MDA), a method that enables massively parallel amplification of single cell genomes while maintaining sequence accuracy and specificity. Tens of thousands of single cells are compartmentalized in millions of picoliter droplets and then subjected to lysis and WGA by passive droplet fusion in microfluidic channels. Because single cells are isolated in compartments, their genomes are amplified to saturation without contamination. This enables the high-throughput acquisition of contamination-free and cell specific sequence reads from single cells (21,000 single-cells/h), resulting in enhancement of the sequence data quality compared to conventional methods. This method allowed WGA of both single bacterial cells and human cancer cells. The obtained sequencing coverage rivals those of conventional techniques with superior sequence quality. In addition, we also demonstrate de novo assembly of uncultured soil bacteria and obtain draft genomes from single cell sequencing. This sd-MDA is promising for flexible and scalable use in single-cell sequencing.

Research on Parallel Three Phase PWM Converters base on RTDS

NASA Astrophysics Data System (ADS)

Xia, Yan; Zou, Jianxiao; Li, Kai; Liu, Jingbo; Tian, Jun

2018-01-01

Converters parallel operation can increase capacity of the system, but it may lead to potential zero-sequence circulating current, so the control of circulating current was an important goal in the design of parallel inverters. In this paper, the Real Time Digital Simulator (RTDS) is used to model the converters parallel system in real time and study the circulating current restraining. The equivalent model of two parallel converters and zero-sequence circulating current(ZSCC) were established and analyzed, then a strategy using variable zero vector control was proposed to suppress the circulating current. For two parallel modular converters, hardware-in-the-loop(HIL) study based on RTDS and practical experiment were implemented, results prove that the proposed control strategy is feasible and effective.

Reconstructing evolutionary trees in parallel for massive sequences.

PubMed

Zou, Quan; Wan, Shixiang; Zeng, Xiangxiang; Ma, Zhanshan Sam

2017-12-14

Building the evolutionary trees for massive unaligned DNA sequences is challenging and crucial. However, reconstructing evolutionary tree for ultra-large sequences is hard. Massive multiple sequence alignment is also challenging and time/space consuming. Hadoop and Spark are developed recently, which bring spring light for the classical computational biology problems. In this paper, we tried to solve the multiple sequence alignment and evolutionary reconstruction in parallel. HPTree, which is developed in this paper, can deal with big DNA sequence files quickly. It works well on the >1GB files, and gets better performance than other evolutionary reconstruction tools. Users could use HPTree for reonstructing evolutioanry trees on the computer clusters or cloud platform (eg. Amazon Cloud). HPTree could help on population evolution research and metagenomics analysis. In this paper, we employ the Hadoop and Spark platform and design an evolutionary tree reconstruction software tool for unaligned massive DNA sequences. Clustering and multiple sequence alignment are done in parallel. Neighbour-joining model was employed for the evolutionary tree building. We opened our software together with source codes via http://lab.malab.cn/soft/HPtree/ .

Designing deep sequencing experiments: detecting structural variation and estimating transcript abundance.

PubMed

Bashir, Ali; Bansal, Vikas; Bafna, Vineet

2010-06-18

Massively parallel DNA sequencing technologies have enabled the sequencing of several individual human genomes. These technologies are also being used in novel ways for mRNA expression profiling, genome-wide discovery of transcription-factor binding sites, small RNA discovery, etc. The multitude of sequencing platforms, each with their unique characteristics, pose a number of design challenges, regarding the technology to be used and the depth of sequencing required for a particular sequencing application. Here we describe a number of analytical and empirical results to address design questions for two applications: detection of structural variations from paired-end sequencing and estimating mRNA transcript abundance. For structural variation, our results provide explicit trade-offs between the detection and resolution of rearrangement breakpoints, and the optimal mix of paired-read insert lengths. Specifically, we prove that optimal detection and resolution of breakpoints is achieved using a mix of exactly two insert library lengths. Furthermore, we derive explicit formulae to determine these insert length combinations, enabling a 15% improvement in breakpoint detection at the same experimental cost. On empirical short read data, these predictions show good concordance with Illumina 200 bp and 2 Kbp insert length libraries. For transcriptome sequencing, we determine the sequencing depth needed to detect rare transcripts from a small pilot study. With only 1 Million reads, we derive corrections that enable almost perfect prediction of the underlying expression probability distribution, and use this to predict the sequencing depth required to detect low expressed genes with greater than 95% probability. Together, our results form a generic framework for many design considerations related to high-throughput sequencing. We provide software tools http://bix.ucsd.edu/projects/NGS-DesignTools to derive platform independent guidelines for designing sequencing experiments (amount of sequencing, choice of insert length, mix of libraries) for novel applications of next generation sequencing.

An overview of the Hadoop/MapReduce/HBase framework and its current applications in bioinformatics

PubMed Central

2010-01-01

Background Bioinformatics researchers are now confronted with analysis of ultra large-scale data sets, a problem that will only increase at an alarming rate in coming years. Recent developments in open source software, that is, the Hadoop project and associated software, provide a foundation for scaling to petabyte scale data warehouses on Linux clusters, providing fault-tolerant parallelized analysis on such data using a programming style named MapReduce. Description An overview is given of the current usage within the bioinformatics community of Hadoop, a top-level Apache Software Foundation project, and of associated open source software projects. The concepts behind Hadoop and the associated HBase project are defined, and current bioinformatics software that employ Hadoop is described. The focus is on next-generation sequencing, as the leading application area to date. Conclusions Hadoop and the MapReduce programming paradigm already have a substantial base in the bioinformatics community, especially in the field of next-generation sequencing analysis, and such use is increasing. This is due to the cost-effectiveness of Hadoop-based analysis on commodity Linux clusters, and in the cloud via data upload to cloud vendors who have implemented Hadoop/HBase; and due to the effectiveness and ease-of-use of the MapReduce method in parallelization of many data analysis algorithms. PMID:21210976

An overview of the Hadoop/MapReduce/HBase framework and its current applications in bioinformatics.

PubMed

Taylor, Ronald C

2010-12-21

Bioinformatics researchers are now confronted with analysis of ultra large-scale data sets, a problem that will only increase at an alarming rate in coming years. Recent developments in open source software, that is, the Hadoop project and associated software, provide a foundation for scaling to petabyte scale data warehouses on Linux clusters, providing fault-tolerant parallelized analysis on such data using a programming style named MapReduce. An overview is given of the current usage within the bioinformatics community of Hadoop, a top-level Apache Software Foundation project, and of associated open source software projects. The concepts behind Hadoop and the associated HBase project are defined, and current bioinformatics software that employ Hadoop is described. The focus is on next-generation sequencing, as the leading application area to date. Hadoop and the MapReduce programming paradigm already have a substantial base in the bioinformatics community, especially in the field of next-generation sequencing analysis, and such use is increasing. This is due to the cost-effectiveness of Hadoop-based analysis on commodity Linux clusters, and in the cloud via data upload to cloud vendors who have implemented Hadoop/HBase; and due to the effectiveness and ease-of-use of the MapReduce method in parallelization of many data analysis algorithms.

Magnetophoretic circuits for digital control of single particles and cells

NASA Astrophysics Data System (ADS)

Lim, Byeonghwa; Reddy, Venu; Hu, Xinghao; Kim, Kunwoo; Jadhav, Mital; Abedini-Nassab, Roozbeh; Noh, Young-Woock; Lim, Yong Taik; Yellen, Benjamin B.; Kim, Cheolgi

2014-05-01

The ability to manipulate small fluid droplets, colloidal particles and single cells with the precision and parallelization of modern-day computer hardware has profound applications for biochemical detection, gene sequencing, chemical synthesis and highly parallel analysis of single cells. Drawing inspiration from general circuit theory and magnetic bubble technology, here we demonstrate a class of integrated circuits for executing sequential and parallel, timed operations on an ensemble of single particles and cells. The integrated circuits are constructed from lithographically defined, overlaid patterns of magnetic film and current lines. The magnetic patterns passively control particles similar to electrical conductors, diodes and capacitors. The current lines actively switch particles between different tracks similar to gated electrical transistors. When combined into arrays and driven by a rotating magnetic field clock, these integrated circuits have general multiplexing properties and enable the precise control of magnetizable objects.

Massively Parallel Sequencing Detected a Mutation in the MFN2 Gene Missed by Sanger Sequencing Due to a Primer Mismatch on an SNP Site.

PubMed

Neupauerová, Jana; Grečmalová, Dagmar; Seeman, Pavel; Laššuthová, Petra

2016-05-01

We describe a patient with early onset severe axonal Charcot-Marie-Tooth disease (CMT2) with dominant inheritance, in whom Sanger sequencing failed to detect a mutation in the mitofusin 2 (MFN2) gene because of a single nucleotide polymorphism (rs2236057) under the PCR primer sequence. The severe early onset phenotype and the family history with severely affected mother (died after delivery) was very suggestive of CMT2A and this suspicion was finally confirmed by a MFN2 mutation. The mutation p.His361Tyr was later detected in the patient by massively parallel sequencing with a gene panel for hereditary neuropathies. According to this information, new primers for amplification and sequencing were designed which bind away from the polymorphic sites of the patient's DNA. Sanger sequencing with these new primers then confirmed the heterozygous mutation in the MFN2 gene in this patient. This case report shows that massively parallel sequencing may in some rare cases be more sensitive than Sanger sequencing and highlights the importance of accurate primer design which requires special attention. © 2016 John Wiley & Sons Ltd/University College London.

BarraCUDA - a fast short read sequence aligner using graphics processing units

PubMed Central

2012-01-01

Background With the maturation of next-generation DNA sequencing (NGS) technologies, the throughput of DNA sequencing reads has soared to over 600 gigabases from a single instrument run. General purpose computing on graphics processing units (GPGPU), extracts the computing power from hundreds of parallel stream processors within graphics processing cores and provides a cost-effective and energy efficient alternative to traditional high-performance computing (HPC) clusters. In this article, we describe the implementation of BarraCUDA, a GPGPU sequence alignment software that is based on BWA, to accelerate the alignment of sequencing reads generated by these instruments to a reference DNA sequence. Findings Using the NVIDIA Compute Unified Device Architecture (CUDA) software development environment, we ported the most computational-intensive alignment component of BWA to GPU to take advantage of the massive parallelism. As a result, BarraCUDA offers a magnitude of performance boost in alignment throughput when compared to a CPU core while delivering the same level of alignment fidelity. The software is also capable of supporting multiple CUDA devices in parallel to further accelerate the alignment throughput. Conclusions BarraCUDA is designed to take advantage of the parallelism of GPU to accelerate the alignment of millions of sequencing reads generated by NGS instruments. By doing this, we could, at least in part streamline the current bioinformatics pipeline such that the wider scientific community could benefit from the sequencing technology. BarraCUDA is currently available from http://seqbarracuda.sf.net PMID:22244497

Implementations of BLAST for parallel computers.

PubMed

Jülich, A

1995-02-01

The BLAST sequence comparison programs have been ported to a variety of parallel computers-the shared memory machine Cray Y-MP 8/864 and the distributed memory architectures Intel iPSC/860 and nCUBE. Additionally, the programs were ported to run on workstation clusters. We explain the parallelization techniques and consider the pros and cons of these methods. The BLAST programs are very well suited for parallelization for a moderate number of processors. We illustrate our results using the program blastp as an example. As input data for blastp, a 799 residue protein query sequence and the protein database PIR were used.

Control and protection system for paralleled modular static inverter-converter systems

NASA Technical Reports Server (NTRS)

Birchenough, A. G.; Gourash, F.

1973-01-01

A control and protection system was developed for use with a paralleled 2.5-kWe-per-module static inverter-converter system. The control and protection system senses internal and external fault parameters such as voltage, frequency, current, and paralleling current unbalance. A logic system controls contactors to isolate defective power conditioners or loads. The system sequences contactor operation to automatically control parallel operation, startup, and fault isolation. Transient overload protection and fault checking sequences are included. The operation and performance of a control and protection system, with detailed circuit descriptions, are presented.

BioPig: Developing Cloud Computing Applications for Next-Generation Sequence Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatia, Karan; Wang, Zhong

Next Generation sequencing is producing ever larger data sizes with a growth rate outpacing Moore's Law. The data deluge has made many of the current sequenceanalysis tools obsolete because they do not scale with data. Here we present BioPig, a collection of cloud computing tools to scale data analysis and management. Pig is aflexible data scripting language that uses Apache's Hadoop data structure and map reduce framework to process very large data files in parallel and combine the results.BioPig extends Pig with capability with sequence analysis. We will show the performance of BioPig on a variety of bioinformatics tasks, includingmore » screeningsequence contaminants, Illumina QA/QC, and gene discovery from metagenome data sets using the Rumen metagenome as an example.« less

[Personalized urooncology based on molecular uropathology: what is the future?].

PubMed

Dahl, E; Haller, F

2013-07-01

Targeted therapies and biomarker validation are key drivers in the advancement of personalized oncology which is a growing topic in all clinical areas. Compared with other professions, such as pulmonology and gynecology, development in urology has so far been retarded but has recently gained increasing momentum. A basis for this is the currently growing and in future accelerated application of new knowledge derived from molecular biology in the field of uropathology. The rapid gain of knowledge is driven by a whole new class of analytical methods, such as massively parallel sequencing (deep sequencing or next generation sequencing), which enables analysis of virtually a new universe of potential biomarkers. This article describes the emerging paradigm shift in molecular pathological diagnostics of urological tumors using the example of prostate cancer.

DIALIGN P: fast pair-wise and multiple sequence alignment using parallel processors.

PubMed

Schmollinger, Martin; Nieselt, Kay; Kaufmann, Michael; Morgenstern, Burkhard

2004-09-09

Parallel computing is frequently used to speed up computationally expensive tasks in Bioinformatics. Herein, a parallel version of the multi-alignment program DIALIGN is introduced. We propose two ways of dividing the program into independent sub-routines that can be run on different processors: (a) pair-wise sequence alignments that are used as a first step to multiple alignment account for most of the CPU time in DIALIGN. Since alignments of different sequence pairs are completely independent of each other, they can be distributed to multiple processors without any effect on the resulting output alignments. (b) For alignments of large genomic sequences, we use a heuristics by splitting up sequences into sub-sequences based on a previously introduced anchored alignment procedure. For our test sequences, this combined approach reduces the program running time of DIALIGN by up to 97%. By distributing sub-routines to multiple processors, the running time of DIALIGN can be crucially improved. With these improvements, it is possible to apply the program in large-scale genomics and proteomics projects that were previously beyond its scope.

Model-Based Systems Engineering in the Execution of Search and Rescue Operations

DTIC Science & Technology

2015-09-01

OSC can fulfill the duties of an ACO but it may make sense to split the duties if there are no communication links between the OSC and participating...parallel mode. This mode is the most powerful option because it 35 creates sequence diagrams that generate parallel “ swim lanes” for each asset...greater flexibility is desired, sequence mode generates diagrams based purely on sequential action and activity diagrams without the parallel “ swim lanes

Optimizing high performance computing workflow for protein functional annotation.

PubMed

Stanberry, Larissa; Rekepalli, Bhanu; Liu, Yuan; Giblock, Paul; Higdon, Roger; Montague, Elizabeth; Broomall, William; Kolker, Natali; Kolker, Eugene

2014-09-10

Functional annotation of newly sequenced genomes is one of the major challenges in modern biology. With modern sequencing technologies, the protein sequence universe is rapidly expanding. Newly sequenced bacterial genomes alone contain over 7.5 million proteins. The rate of data generation has far surpassed that of protein annotation. The volume of protein data makes manual curation infeasible, whereas a high compute cost limits the utility of existing automated approaches. In this work, we present an improved and optmized automated workflow to enable large-scale protein annotation. The workflow uses high performance computing architectures and a low complexity classification algorithm to assign proteins into existing clusters of orthologous groups of proteins. On the basis of the Position-Specific Iterative Basic Local Alignment Search Tool the algorithm ensures at least 80% specificity and sensitivity of the resulting classifications. The workflow utilizes highly scalable parallel applications for classification and sequence alignment. Using Extreme Science and Engineering Discovery Environment supercomputers, the workflow processed 1,200,000 newly sequenced bacterial proteins. With the rapid expansion of the protein sequence universe, the proposed workflow will enable scientists to annotate big genome data.

Optimizing high performance computing workflow for protein functional annotation

PubMed Central

Stanberry, Larissa; Rekepalli, Bhanu; Liu, Yuan; Giblock, Paul; Higdon, Roger; Montague, Elizabeth; Broomall, William; Kolker, Natali; Kolker, Eugene

2014-01-01

Functional annotation of newly sequenced genomes is one of the major challenges in modern biology. With modern sequencing technologies, the protein sequence universe is rapidly expanding. Newly sequenced bacterial genomes alone contain over 7.5 million proteins. The rate of data generation has far surpassed that of protein annotation. The volume of protein data makes manual curation infeasible, whereas a high compute cost limits the utility of existing automated approaches. In this work, we present an improved and optmized automated workflow to enable large-scale protein annotation. The workflow uses high performance computing architectures and a low complexity classification algorithm to assign proteins into existing clusters of orthologous groups of proteins. On the basis of the Position-Specific Iterative Basic Local Alignment Search Tool the algorithm ensures at least 80% specificity and sensitivity of the resulting classifications. The workflow utilizes highly scalable parallel applications for classification and sequence alignment. Using Extreme Science and Engineering Discovery Environment supercomputers, the workflow processed 1,200,000 newly sequenced bacterial proteins. With the rapid expansion of the protein sequence universe, the proposed workflow will enable scientists to annotate big genome data. PMID:25313296

The development of GPU-based parallel PRNG for Monte Carlo applications in CUDA Fortran

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kargaran, Hamed, E-mail: h-kargaran@sbu.ac.ir; Minuchehr, Abdolhamid; Zolfaghari, Ahmad

The implementation of Monte Carlo simulation on the CUDA Fortran requires a fast random number generation with good statistical properties on GPU. In this study, a GPU-based parallel pseudo random number generator (GPPRNG) have been proposed to use in high performance computing systems. According to the type of GPU memory usage, GPU scheme is divided into two work modes including GLOBAL-MODE and SHARED-MODE. To generate parallel random numbers based on the independent sequence method, the combination of middle-square method and chaotic map along with the Xorshift PRNG have been employed. Implementation of our developed PPRNG on a single GPU showedmore » a speedup of 150x and 470x (with respect to the speed of PRNG on a single CPU core) for GLOBAL-MODE and SHARED-MODE, respectively. To evaluate the accuracy of our developed GPPRNG, its performance was compared to that of some other commercially available PPRNGs such as MATLAB, FORTRAN and Miller-Park algorithm through employing the specific standard tests. The results of this comparison showed that the developed GPPRNG in this study can be used as a fast and accurate tool for computational science applications.« less

Optimal control design of turbo spin‐echo sequences with applications to parallel‐transmit systems

PubMed Central

Hoogduin, Hans; Hajnal, Joseph V.; van den Berg, Cornelis A. T.; Luijten, Peter R.; Malik, Shaihan J.

2016-01-01

Purpose The design of turbo spin‐echo sequences is modeled as a dynamic optimization problem which includes the case of inhomogeneous transmit radiofrequency fields. This problem is efficiently solved by optimal control techniques making it possible to design patient‐specific sequences online. Theory and Methods The extended phase graph formalism is employed to model the signal evolution. The design problem is cast as an optimal control problem and an efficient numerical procedure for its solution is given. The numerical and experimental tests address standard multiecho sequences and pTx configurations. Results Standard, analytically derived flip angle trains are recovered by the numerical optimal control approach. New sequences are designed where constraints on radiofrequency total and peak power are included. In the case of parallel transmit application, the method is able to calculate the optimal echo train for two‐dimensional and three‐dimensional turbo spin echo sequences in the order of 10 s with a single central processing unit (CPU) implementation. The image contrast is maintained through the whole field of view despite inhomogeneities of the radiofrequency fields. Conclusion The optimal control design sheds new light on the sequence design process and makes it possible to design sequences in an online, patient‐specific fashion. Magn Reson Med 77:361–373, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine PMID:26800383

De novo assembly of human genomes with massively parallel short read sequencing.

PubMed

Li, Ruiqiang; Zhu, Hongmei; Ruan, Jue; Qian, Wubin; Fang, Xiaodong; Shi, Zhongbin; Li, Yingrui; Li, Shengting; Shan, Gao; Kristiansen, Karsten; Li, Songgang; Yang, Huanming; Wang, Jian; Wang, Jun

2010-02-01

Next-generation massively parallel DNA sequencing technologies provide ultrahigh throughput at a substantially lower unit data cost; however, the data are very short read length sequences, making de novo assembly extremely challenging. Here, we describe a novel method for de novo assembly of large genomes from short read sequences. We successfully assembled both the Asian and African human genome sequences, achieving an N50 contig size of 7.4 and 5.9 kilobases (kb) and scaffold of 446.3 and 61.9 kb, respectively. The development of this de novo short read assembly method creates new opportunities for building reference sequences and carrying out accurate analyses of unexplored genomes in a cost-effective way.

High-Throughput, Data-Rich Cellular RNA Device Engineering

PubMed Central

Townshend, Brent; Kennedy, Andrew B.; Xiang, Joy S.; Smolke, Christina D.

2015-01-01

Methods for rapidly assessing sequence-structure-function landscapes and developing conditional gene-regulatory devices are critical to our ability to manipulate and interface with biology. We describe a framework for engineering RNA devices from preexisting aptamers that exhibit ligand-responsive ribozyme tertiary interactions. Our methodology utilizes cell sorting, high-throughput sequencing, and statistical data analyses to enable parallel measurements of the activities of hundreds of thousands of sequences from RNA device libraries in the absence and presence of ligands. Our tertiary interaction RNA devices exhibit improved performance in terms of gene silencing, activation ratio, and ligand sensitivity as compared to optimized RNA devices that rely on secondary structure changes. We apply our method to building biosensors for diverse ligands and determine consensus sequences that enable ligand-responsive tertiary interactions. These methods advance our ability to develop broadly applicable genetic tools and to elucidate understanding of the underlying sequence-structure-function relationships that empower rational design of complex biomolecules. PMID:26258292

BioPig: a Hadoop-based analytic toolkit for large-scale sequence data.

PubMed

Nordberg, Henrik; Bhatia, Karan; Wang, Kai; Wang, Zhong

2013-12-01

The recent revolution in sequencing technologies has led to an exponential growth of sequence data. As a result, most of the current bioinformatics tools become obsolete as they fail to scale with data. To tackle this 'data deluge', here we introduce the BioPig sequence analysis toolkit as one of the solutions that scale to data and computation. We built BioPig on the Apache's Hadoop MapReduce system and the Pig data flow language. Compared with traditional serial and MPI-based algorithms, BioPig has three major advantages: first, BioPig's programmability greatly reduces development time for parallel bioinformatics applications; second, testing BioPig with up to 500 Gb sequences demonstrates that it scales automatically with size of data; and finally, BioPig can be ported without modification on many Hadoop infrastructures, as tested with Magellan system at National Energy Research Scientific Computing Center and the Amazon Elastic Compute Cloud. In summary, BioPig represents a novel program framework with the potential to greatly accelerate data-intensive bioinformatics analysis.

Parallel gene analysis with allele-specific padlock probes and tag microarrays

PubMed Central

Banér, Johan; Isaksson, Anders; Waldenström, Erik; Jarvius, Jonas; Landegren, Ulf; Nilsson, Mats

2003-01-01

Parallel, highly specific analysis methods are required to take advantage of the extensive information about DNA sequence variation and of expressed sequences. We present a scalable laboratory technique suitable to analyze numerous target sequences in multiplexed assays. Sets of padlock probes were applied to analyze single nucleotide variation directly in total genomic DNA or cDNA for parallel genotyping or gene expression analysis. All reacted probes were then co-amplified and identified by hybridization to a standard tag oligonucleotide array. The technique was illustrated by analyzing normal and pathogenic variation within the Wilson disease-related ATP7B gene, both at the level of DNA and RNA, using allele-specific padlock probes. PMID:12930977

CloudAligner: A fast and full-featured MapReduce based tool for sequence mapping.

PubMed

Nguyen, Tung; Shi, Weisong; Ruden, Douglas

2011-06-06

Research in genetics has developed rapidly recently due to the aid of next generation sequencing (NGS). However, massively-parallel NGS produces enormous amounts of data, which leads to storage, compatibility, scalability, and performance issues. The Cloud Computing and MapReduce framework, which utilizes hundreds or thousands of shared computers to map sequencing reads quickly and efficiently to reference genome sequences, appears to be a very promising solution for these issues. Consequently, it has been adopted by many organizations recently, and the initial results are very promising. However, since these are only initial steps toward this trend, the developed software does not provide adequate primary functions like bisulfite, pair-end mapping, etc., in on-site software such as RMAP or BS Seeker. In addition, existing MapReduce-based applications were not designed to process the long reads produced by the most recent second-generation and third-generation NGS instruments and, therefore, are inefficient. Last, it is difficult for a majority of biologists untrained in programming skills to use these tools because most were developed on Linux with a command line interface. To urge the trend of using Cloud technologies in genomics and prepare for advances in second- and third-generation DNA sequencing, we have built a Hadoop MapReduce-based application, CloudAligner, which achieves higher performance, covers most primary features, is more accurate, and has a user-friendly interface. It was also designed to be able to deal with long sequences. The performance gain of CloudAligner over Cloud-based counterparts (35 to 80%) mainly comes from the omission of the reduce phase. In comparison to local-based approaches, the performance gain of CloudAligner is from the partition and parallel processing of the huge reference genome as well as the reads. The source code of CloudAligner is available at http://cloudaligner.sourceforge.net/ and its web version is at http://mine.cs.wayne.edu:8080/CloudAligner/. Our results show that CloudAligner is faster than CloudBurst, provides more accurate results than RMAP, and supports various input as well as output formats. In addition, with the web-based interface, it is easier to use than its counterparts.

Homopolymer tail-mediated ligation PCR: a streamlined and highly efficient method for DNA cloning and library construction

PubMed Central

Lazinski, David W.; Camilli, Andrew

2013-01-01

The amplification of DNA fragments, cloned between user-defined 5′ and 3′ end sequences, is a prerequisite step in the use of many current applications including massively parallel sequencing (MPS). Here we describe an improved method, called homopolymer tail-mediated ligation PCR (HTML-PCR), that requires very little starting template, minimal hands-on effort, is cost-effective, and is suited for use in high-throughput and robotic methodologies. HTML-PCR starts with the addition of homopolymer tails of controlled lengths to the 3′ termini of a double-stranded genomic template. The homopolymer tails enable the annealing-assisted ligation of a hybrid oligonucleotide to the template's recessed 5′ ends. The hybrid oligonucleotide has a user-defined sequence at its 5′ end. This primer, together with a second primer composed of a longer region complementary to the homopolymer tail and fused to a second 5′ user-defined sequence, are used in a PCR reaction to generate the final product. The user-defined sequences can be varied to enable compatibility with a wide variety of downstream applications. We demonstrate our new method by constructing MPS libraries starting from nanogram and sub-nanogram quantities of Vibrio cholerae and Streptococcus pneumoniae genomic DNA. PMID:23311318

Flexible CRISPR library construction using parallel oligonucleotide retrieval

PubMed Central

Read, Abigail; Gao, Shaojian; Batchelor, Eric

2017-01-01

Abstract CRISPR/Cas9-based gene knockout libraries have emerged as a powerful tool for functional screens. We present here a set of pre-designed human and mouse sgRNA sequences that are optimized for both high on-target potency and low off-target effect. To maximize the chance of target gene inactivation, sgRNAs were curated to target both 5΄ constitutive exons and exons that encode conserved protein domains. We describe here a robust and cost-effective method to construct multiple small sized CRISPR library from a single oligo pool generated by array synthesis using parallel oligonucleotide retrieval. Together, these resources provide a convenient means for individual labs to generate customized CRISPR libraries of variable size and coverage depth for functional genomics application. PMID:28334828

CUDAMPF: a multi-tiered parallel framework for accelerating protein sequence search in HMMER on CUDA-enabled GPU.

PubMed

Jiang, Hanyu; Ganesan, Narayan

2016-02-27

HMMER software suite is widely used for analysis of homologous protein and nucleotide sequences with high sensitivity. The latest version of hmmsearch in HMMER 3.x, utilizes heuristic-pipeline which consists of MSV/SSV (Multiple/Single ungapped Segment Viterbi) stage, P7Viterbi stage and the Forward scoring stage to accelerate homology detection. Since the latest version is highly optimized for performance on modern multi-core CPUs with SSE capabilities, only a few acceleration attempts report speedup. However, the most compute intensive tasks within the pipeline (viz., MSV/SSV and P7Viterbi stages) still stand to benefit from the computational capabilities of massively parallel processors. A Multi-Tiered Parallel Framework (CUDAMPF) implemented on CUDA-enabled GPUs presented here, offers a finer-grained parallelism for MSV/SSV and Viterbi algorithms. We couple SIMT (Single Instruction Multiple Threads) mechanism with SIMD (Single Instructions Multiple Data) video instructions with warp-synchronism to achieve high-throughput processing and eliminate thread idling. We also propose a hardware-aware optimal allocation scheme of scarce resources like on-chip memory and caches in order to boost performance and scalability of CUDAMPF. In addition, runtime compilation via NVRTC available with CUDA 7.0 is incorporated into the presented framework that not only helps unroll innermost loop to yield upto 2 to 3-fold speedup than static compilation but also enables dynamic loading and switching of kernels depending on the query model size, in order to achieve optimal performance. CUDAMPF is designed as a hardware-aware parallel framework for accelerating computational hotspots within the hmmsearch pipeline as well as other sequence alignment applications. It achieves significant speedup by exploiting hierarchical parallelism on single GPU and takes full advantage of limited resources based on their own performance features. In addition to exceeding performance of other acceleration attempts, comprehensive evaluations against high-end CPUs (Intel i5, i7 and Xeon) shows that CUDAMPF yields upto 440 GCUPS for SSV, 277 GCUPS for MSV and 14.3 GCUPS for P7Viterbi all with 100 % accuracy, which translates to a maximum speedup of 37.5, 23.1 and 11.6-fold for MSV, SSV and P7Viterbi respectively. The source code is available at https://github.com/Super-Hippo/CUDAMPF.

Increasing phylogenetic resolution at low taxonomic levels using massively parallel sequencing of chloroplast genomes

Treesearch

Matthew Parks; Richard Cronn; Aaron Liston

2009-01-01

We reconstruct the infrageneric phylogeny of Pinus from 37 nearly-complete chloroplast genomes (average 109 kilobases each of an approximately 120 kilobase genome) generated using multiplexed massively parallel sequencing. We found that 30/33 ingroup nodes resolved wlth > 95-percent bootstrap support; this is a substantial improvement relative...

Ordered fast fourier transforms on a massively parallel hypercube multiprocessor

NASA Technical Reports Server (NTRS)

Tong, Charles; Swarztrauber, Paul N.

1989-01-01

Design alternatives for ordered Fast Fourier Transformation (FFT) algorithms were examined on massively parallel hypercube multiprocessors such as the Connection Machine. Particular emphasis is placed on reducing communication which is known to dominate the overall computing time. To this end, the order and computational phases of the FFT were combined, and the sequence to processor maps that reduce communication were used. The class of ordered transforms is expanded to include any FFT in which the order of the transform is the same as that of the input sequence. Two such orderings are examined, namely, standard-order and A-order which can be implemented with equal ease on the Connection Machine where orderings are determined by geometries and priorities. If the sequence has N = 2 exp r elements and the hypercube has P = 2 exp d processors, then a standard-order FFT can be implemented with d + r/2 + 1 parallel transmissions. An A-order sequence can be transformed with 2d - r/2 parallel transmissions which is r - d + 1 fewer than the standard order. A parallel method for computing the trigonometric coefficients is presented that does not use trigonometric functions or interprocessor communication. A performance of 0.9 GFLOPS was obtained for an A-order transform on the Connection Machine.

FANSe2: a robust and cost-efficient alignment tool for quantitative next-generation sequencing applications.

PubMed

Xiao, Chuan-Le; Mai, Zhi-Biao; Lian, Xin-Lei; Zhong, Jia-Yong; Jin, Jing-Jie; He, Qing-Yu; Zhang, Gong

2014-01-01

Correct and bias-free interpretation of the deep sequencing data is inevitably dependent on the complete mapping of all mappable reads to the reference sequence, especially for quantitative RNA-seq applications. Seed-based algorithms are generally slow but robust, while Burrows-Wheeler Transform (BWT) based algorithms are fast but less robust. To have both advantages, we developed an algorithm FANSe2 with iterative mapping strategy based on the statistics of real-world sequencing error distribution to substantially accelerate the mapping without compromising the accuracy. Its sensitivity and accuracy are higher than the BWT-based algorithms in the tests using both prokaryotic and eukaryotic sequencing datasets. The gene identification results of FANSe2 is experimentally validated, while the previous algorithms have false positives and false negatives. FANSe2 showed remarkably better consistency to the microarray than most other algorithms in terms of gene expression quantifications. We implemented a scalable and almost maintenance-free parallelization method that can utilize the computational power of multiple office computers, a novel feature not present in any other mainstream algorithm. With three normal office computers, we demonstrated that FANSe2 mapped an RNA-seq dataset generated from an entire Illunima HiSeq 2000 flowcell (8 lanes, 608 M reads) to masked human genome within 4.1 hours with higher sensitivity than Bowtie/Bowtie2. FANSe2 thus provides robust accuracy, full indel sensitivity, fast speed, versatile compatibility and economical computational utilization, making it a useful and practical tool for deep sequencing applications. FANSe2 is freely available at http://bioinformatics.jnu.edu.cn/software/fanse2/.

Genome Evolution and Meiotic Maps by Massively Parallel DNA Sequencing: Spotted Gar, an Outgroup for the Teleost Genome Duplication

PubMed Central

Amores, Angel; Catchen, Julian; Ferrara, Allyse; Fontenot, Quenton; Postlethwait, John H.

2011-01-01

Genomic resources for hundreds of species of evolutionary, agricultural, economic, and medical importance are unavailable due to the expense of well-assembled genome sequences and difficulties with multigenerational studies. Teleost fish provide many models for human disease but possess anciently duplicated genomes that sometimes obfuscate connectivity. Genomic information representing a fish lineage that diverged before the teleost genome duplication (TGD) would provide an outgroup for exploring the mechanisms of evolution after whole-genome duplication. We exploited massively parallel DNA sequencing to develop meiotic maps with thrift and speed by genotyping F1 offspring of a single female and a single male spotted gar (Lepisosteus oculatus) collected directly from nature utilizing only polymorphisms existing in these two wild individuals. Using Stacks, software that automates the calling of genotypes from polymorphisms assayed by Illumina sequencing, we constructed a map containing 8406 markers. RNA-seq on two map-cross larvae provided a reference transcriptome that identified nearly 1000 mapped protein-coding markers and allowed genome-wide analysis of conserved synteny. Results showed that the gar lineage diverged from teleosts before the TGD and its genome is organized more similarly to that of humans than teleosts. Thus, spotted gar provides a critical link between medical models in teleost fish, to which gar is biologically similar, and humans, to which gar is genomically similar. Application of our F1 dense mapping strategy to species with no prior genome information promises to facilitate comparative genomics and provide a scaffold for ordering the numerous contigs arising from next generation genome sequencing. PMID:21828280

Swellix: a computational tool to explore RNA conformational space.

PubMed

Sloat, Nathan; Liu, Jui-Wen; Schroeder, Susan J

2017-11-21

The sequence of nucleotides in an RNA determines the possible base pairs for an RNA fold and thus also determines the overall shape and function of an RNA. The Swellix program presented here combines a helix abstraction with a combinatorial approach to the RNA folding problem in order to compute all possible non-pseudoknotted RNA structures for RNA sequences. The Swellix program builds on the Crumple program and can include experimental constraints on global RNA structures such as the minimum number and lengths of helices from crystallography, cryoelectron microscopy, or in vivo crosslinking and chemical probing methods. The conceptual advance in Swellix is to count helices and generate all possible combinations of helices rather than counting and combining base pairs. Swellix bundles similar helices and includes improvements in memory use and efficient parallelization. Biological applications of Swellix are demonstrated by computing the reduction in conformational space and entropy due to naturally modified nucleotides in tRNA sequences and by motif searches in Human Endogenous Retroviral (HERV) RNA sequences. The Swellix motif search reveals occurrences of protein and drug binding motifs in the HERV RNA ensemble that do not occur in minimum free energy or centroid predicted structures. Swellix presents significant improvements over Crumple in terms of efficiency and memory use. The efficient parallelization of Swellix enables the computation of sequences as long as 418 nucleotides with sufficient experimental constraints. Thus, Swellix provides a practical alternative to free energy minimization tools when multiple structures, kinetically determined structures, or complex RNA-RNA and RNA-protein interactions are present in an RNA folding problem.

miTRATA: a web-based tool for microRNA Truncation and Tailing Analysis.

PubMed

Patel, Parth; Ramachandruni, S Deepthi; Kakrana, Atul; Nakano, Mayumi; Meyers, Blake C

2016-02-01

We describe miTRATA, the first web-based tool for microRNA Truncation and Tailing Analysis--the analysis of 3' modifications of microRNAs including the loss or gain of nucleotides relative to the canonical sequence. miTRATA is implemented in Python (version 3) and employs parallel processing modules to enhance its scalability when analyzing multiple small RNA (sRNA) sequencing datasets. It utilizes miRBase, currently version 21, as a source of known microRNAs for analysis. miTRATA notifies user(s) via email to download as well as visualize the results online. miTRATA's strengths lie in (i) its biologist-focused web interface, (ii) improved scalability via parallel processing and (iii) its uniqueness as a webtool to perform microRNA truncation and tailing analysis. miTRATA is developed in Python and PHP. It is available as a web-based application from https://wasabi.dbi.udel.edu/∼apps/ta/. meyers@dbi.udel.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Human telomere sequence DNA in water-free and high-viscosity solvents: G-quadruplex folding governed by Kramers rate theory.

PubMed

Lannan, Ford M; Mamajanov, Irena; Hud, Nicholas V

2012-09-19

Structures formed by human telomere sequence (HTS) DNA are of interest due to the implication of telomeres in the aging process and cancer. We present studies of HTS DNA folding in an anhydrous, high viscosity deep eutectic solvent (DES) comprised of choline choride and urea. In this solvent, the HTS DNA forms a G-quadruplex with the parallel-stranded ("propeller") fold, consistent with observations that reduced water activity favors the parallel fold, whereas alternative folds are favored at high water activity. Surprisingly, adoption of the parallel structure by HTS DNA in the DES, after thermal denaturation and quick cooling to room temperature, requires several months, as opposed to less than 2 min in an aqueous solution. This extended folding time in the DES is, in part, due to HTS DNA becoming kinetically trapped in a folded state that is apparently not accessed in lower viscosity solvents. A comparison of times required for the G-quadruplex to convert from its aqueous-preferred folded state to its parallel fold also reveals a dependence on solvent viscosity that is consistent with Kramers rate theory, which predicts that diffusion-controlled transitions will slow proportionally with solvent friction. These results provide an enhanced view of a G-quadruplex folding funnel and highlight the necessity to consider solvent viscosity in studies of G-quadruplex formation in vitro and in vivo. Additionally, the solvents and analyses presented here should prove valuable for understanding the folding of many other nucleic acids and potentially have applications in DNA-based nanotechnology where time-dependent structures are desired.

Aerobraking Maneuver (ABM) Report Generator

NASA Technical Reports Server (NTRS)

Fisher, Forrest; Gladden, Roy; Khanampornpan, Teerapat

2008-01-01

abmREPORT Version 3.1 is a Perl script that extracts vital summarization information from the Mars Reconnaissance Orbiter (MRO) aerobraking ABM build process. This information facilitates sequence reviews, and provides a high-level summarization of the sequence for mission management. The script extracts information from the ENV, SSF, FRF, SCMFmax, and OPTG files and burn magnitude configuration files and presents them in a single, easy-to-check report that provides the majority of the parameters necessary for cross check and verification during the sequence review process. This means that needed information, formerly spread across a number of different files and each in a different format, is all available in this one application. This program is built on the capabilities developed in dragReport and then the scripts evolved as the two tools continued to be developed in parallel.

Probing the Proteome on Earth and Beyond

NASA Astrophysics Data System (ADS)

Ostrom, P.

2008-12-01

Less than a decade ago, protein sequencing was the bane of paleobiology. Since that time researchers have completely sequenced proteins in >50 Ka fossils, been dazzled by reports of collagen peptides in dinosaur bones, and witnessed the development of phylogenetic trees from ancient protein sequences. Enlisting proteomics as biosignature is now in our grasp. In this talk the pitfalls and challenges of mass spectrometric approaches to protein sequencing will be illustrated and phylogenetic applications will be discussed. Work on extinct organisms at Michigan State University, University of Michigan and York University will provide a vantage point to assess methodologies, explore diagenetic alterations, evaluate mass spectra and illustrate issues associated with data base searching. Challenges encountered in the study of paleoproteomics, such as the absence of sequences for extinct organisms in commercially available databases, protein diagenesis and low concentrations of target are parallel to those that will be encountered when protein sequencing is extended to extreme and extraterrestrial environments. Thus, lessons learned from interrogating the ancient proteome are important and necessary step in developing proteomics as a biosignature tools.

FDSTools: A software package for analysis of massively parallel sequencing data with the ability to recognise and correct STR stutter and other PCR or sequencing noise.

PubMed

Hoogenboom, Jerry; van der Gaag, Kristiaan J; de Leeuw, Rick H; Sijen, Titia; de Knijff, Peter; Laros, Jeroen F J

2017-03-01

Massively parallel sequencing (MPS) is on the advent of a broad scale application in forensic research and casework. The improved capabilities to analyse evidentiary traces representing unbalanced mixtures is often mentioned as one of the major advantages of this technique. However, most of the available software packages that analyse forensic short tandem repeat (STR) sequencing data are not well suited for high throughput analysis of such mixed traces. The largest challenge is the presence of stutter artefacts in STR amplifications, which are not readily discerned from minor contributions. FDSTools is an open-source software solution developed for this purpose. The level of stutter formation is influenced by various aspects of the sequence, such as the length of the longest uninterrupted stretch occurring in an STR. When MPS is used, STRs are evaluated as sequence variants that each have particular stutter characteristics which can be precisely determined. FDSTools uses a database of reference samples to determine stutter and other systemic PCR or sequencing artefacts for each individual allele. In addition, stutter models are created for each repeating element in order to predict stutter artefacts for alleles that are not included in the reference set. This information is subsequently used to recognise and compensate for the noise in a sequence profile. The result is a better representation of the true composition of a sample. Using Promega Powerseq™ Auto System data from 450 reference samples and 31 two-person mixtures, we show that the FDSTools correction module decreases stutter ratios above 20% to below 3%. Consequently, much lower levels of contributions in the mixed traces are detected. FDSTools contains modules to visualise the data in an interactive format allowing users to filter data with their own preferred thresholds. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Protein structure determination by exhaustive search of Protein Data Bank derived databases.

PubMed

Stokes-Rees, Ian; Sliz, Piotr

2010-12-14

Parallel sequence and structure alignment tools have become ubiquitous and invaluable at all levels in the study of biological systems. We demonstrate the application and utility of this same parallel search paradigm to the process of protein structure determination, benefitting from the large and growing corpus of known structures. Such searches were previously computationally intractable. Through the method of Wide Search Molecular Replacement, developed here, they can be completed in a few hours with the aide of national-scale federated cyberinfrastructure. By dramatically expanding the range of models considered for structure determination, we show that small (less than 12% structural coverage) and low sequence identity (less than 20% identity) template structures can be identified through multidimensional template scoring metrics and used for structure determination. Many new macromolecular complexes can benefit significantly from such a technique due to the lack of known homologous protein folds or sequences. We demonstrate the effectiveness of the method by determining the structure of a full-length p97 homologue from Trichoplusia ni. Example cases with the MHC/T-cell receptor complex and the EmoB protein provide systematic estimates of minimum sequence identity, structure coverage, and structural similarity required for this method to succeed. We describe how this structure-search approach and other novel computationally intensive workflows are made tractable through integration with the US national computational cyberinfrastructure, allowing, for example, rapid processing of the entire Structural Classification of Proteins protein fragment database.

High-Performance Integrated Virtual Environment (HIVE) Tools and Applications for Big Data Analysis.

PubMed

Simonyan, Vahan; Mazumder, Raja

2014-09-30

The High-performance Integrated Virtual Environment (HIVE) is a high-throughput cloud-based infrastructure developed for the storage and analysis of genomic and associated biological data. HIVE consists of a web-accessible interface for authorized users to deposit, retrieve, share, annotate, compute and visualize Next-generation Sequencing (NGS) data in a scalable and highly efficient fashion. The platform contains a distributed storage library and a distributed computational powerhouse linked seamlessly. Resources available through the interface include algorithms, tools and applications developed exclusively for the HIVE platform, as well as commonly used external tools adapted to operate within the parallel architecture of the system. HIVE is composed of a flexible infrastructure, which allows for simple implementation of new algorithms and tools. Currently, available HIVE tools include sequence alignment and nucleotide variation profiling tools, metagenomic analyzers, phylogenetic tree-building tools using NGS data, clone discovery algorithms, and recombination analysis algorithms. In addition to tools, HIVE also provides knowledgebases that can be used in conjunction with the tools for NGS sequence and metadata analysis.

High-Performance Integrated Virtual Environment (HIVE) Tools and Applications for Big Data Analysis

PubMed Central

Simonyan, Vahan; Mazumder, Raja

2014-01-01

The High-performance Integrated Virtual Environment (HIVE) is a high-throughput cloud-based infrastructure developed for the storage and analysis of genomic and associated biological data. HIVE consists of a web-accessible interface for authorized users to deposit, retrieve, share, annotate, compute and visualize Next-generation Sequencing (NGS) data in a scalable and highly efficient fashion. The platform contains a distributed storage library and a distributed computational powerhouse linked seamlessly. Resources available through the interface include algorithms, tools and applications developed exclusively for the HIVE platform, as well as commonly used external tools adapted to operate within the parallel architecture of the system. HIVE is composed of a flexible infrastructure, which allows for simple implementation of new algorithms and tools. Currently, available HIVE tools include sequence alignment and nucleotide variation profiling tools, metagenomic analyzers, phylogenetic tree-building tools using NGS data, clone discovery algorithms, and recombination analysis algorithms. In addition to tools, HIVE also provides knowledgebases that can be used in conjunction with the tools for NGS sequence and metadata analysis. PMID:25271953

Microtubule Actin Crosslinking Factor 1 Regulates the Balbiani Body and Animal-Vegetal Polarity of the Zebrafish Oocyte

PubMed Central

Gupta, Tripti; Marlow, Florence L.; Ferriola, Deborah; Mackiewicz, Katarzyna; Dapprich, Johannes; Monos, Dimitri; Mullins, Mary C.

2010-01-01

Although of fundamental importance in developmental biology, the genetic basis for the symmetry breaking events that polarize the vertebrate oocyte and egg are largely unknown. In vertebrates, the first morphological asymmetry in the oocyte is the Balbiani body, a highly conserved, transient structure found in vertebrates and invertebrates including Drosophila, Xenopus, human, and mouse. We report the identification of the zebrafish magellan (mgn) mutant, which exhibits a novel enlarged Balbiani body phenotype and a disruption of oocyte polarity. To determine the molecular identity of the mgn gene, we positionally cloned the gene, employing a novel DNA capture method to target region-specific genomic DNA of 600 kb for massively parallel sequencing. Using this technique, we were able to enrich for the genomic region linked to our mutation within one week and then identify the mutation in mgn using massively parallel sequencing. This is one of the first successful uses of genomic DNA enrichment combined with massively parallel sequencing to determine the molecular identity of a gene associated with a mutant phenotype. We anticipate that the combination of these technologies will have wide applicability for the efficient identification of mutant genes in all organisms. We identified the mutation in mgn as a deletion in the coding sequence of the zebrafish microtubule actin crosslinking factor 1 (macf1) gene. macf1 is a member of the highly conserved spectraplakin family of cytoskeletal linker proteins, which play diverse roles in polarized cells such as neurons, muscle cells, and epithelial cells. In mgn mutants, the oocyte nucleus is mislocalized; and the Balbiani body, localized mRNAs, and organelles are absent from the periphery of the oocyte, consistent with a function for macf1 in nuclear anchoring and cortical localization. These data provide the first evidence for a role for spectraplakins in polarization of the vertebrate oocyte and egg. PMID:20808893

Microtubule actin crosslinking factor 1 regulates the Balbiani body and animal-vegetal polarity of the zebrafish oocyte.

PubMed

Gupta, Tripti; Marlow, Florence L; Ferriola, Deborah; Mackiewicz, Katarzyna; Dapprich, Johannes; Monos, Dimitri; Mullins, Mary C

2010-08-19

Although of fundamental importance in developmental biology, the genetic basis for the symmetry breaking events that polarize the vertebrate oocyte and egg are largely unknown. In vertebrates, the first morphological asymmetry in the oocyte is the Balbiani body, a highly conserved, transient structure found in vertebrates and invertebrates including Drosophila, Xenopus, human, and mouse. We report the identification of the zebrafish magellan (mgn) mutant, which exhibits a novel enlarged Balbiani body phenotype and a disruption of oocyte polarity. To determine the molecular identity of the mgn gene, we positionally cloned the gene, employing a novel DNA capture method to target region-specific genomic DNA of 600 kb for massively parallel sequencing. Using this technique, we were able to enrich for the genomic region linked to our mutation within one week and then identify the mutation in mgn using massively parallel sequencing. This is one of the first successful uses of genomic DNA enrichment combined with massively parallel sequencing to determine the molecular identity of a gene associated with a mutant phenotype. We anticipate that the combination of these technologies will have wide applicability for the efficient identification of mutant genes in all organisms. We identified the mutation in mgn as a deletion in the coding sequence of the zebrafish microtubule actin crosslinking factor 1 (macf1) gene. macf1 is a member of the highly conserved spectraplakin family of cytoskeletal linker proteins, which play diverse roles in polarized cells such as neurons, muscle cells, and epithelial cells. In mgn mutants, the oocyte nucleus is mislocalized; and the Balbiani body, localized mRNAs, and organelles are absent from the periphery of the oocyte, consistent with a function for macf1 in nuclear anchoring and cortical localization. These data provide the first evidence for a role for spectraplakins in polarization of the vertebrate oocyte and egg.

Environmental Barcoding: A Next-Generation Sequencing Approach for Biomonitoring Applications Using River Benthos

PubMed Central

Hajibabaei, Mehrdad; Shokralla, Shadi; Zhou, Xin; Singer, Gregory A. C.; Baird, Donald J.

2011-01-01

Timely and accurate biodiversity analysis poses an ongoing challenge for the success of biomonitoring programs. Morphology-based identification of bioindicator taxa is time consuming, and rarely supports species-level resolution especially for immature life stages. Much work has been done in the past decade to develop alternative approaches for biodiversity analysis using DNA sequence-based approaches such as molecular phylogenetics and DNA barcoding. On-going assembly of DNA barcode reference libraries will provide the basis for a DNA-based identification system. The use of recently introduced next-generation sequencing (NGS) approaches in biodiversity science has the potential to further extend the application of DNA information for routine biomonitoring applications to an unprecedented scale. Here we demonstrate the feasibility of using 454 massively parallel pyrosequencing for species-level analysis of freshwater benthic macroinvertebrate taxa commonly used for biomonitoring. We designed our experiments in order to directly compare morphology-based, Sanger sequencing DNA barcoding, and next-generation environmental barcoding approaches. Our results show the ability of 454 pyrosequencing of mini-barcodes to accurately identify all species with more than 1% abundance in the pooled mixture. Although the approach failed to identify 6 rare species in the mixture, the presence of sequences from 9 species that were not represented by individuals in the mixture provides evidence that DNA based analysis may yet provide a valuable approach in finding rare species in bulk environmental samples. We further demonstrate the application of the environmental barcoding approach by comparing benthic macroinvertebrates from an urban region to those obtained from a conservation area. Although considerable effort will be required to robustly optimize NGS tools to identify species from bulk environmental samples, our results indicate the potential of an environmental barcoding approach for biomonitoring programs. PMID:21533287

Synthesizing parallel imaging applications using the CAP (computer-aided parallelization) tool

NASA Astrophysics Data System (ADS)

Gennart, Benoit A.; Mazzariol, Marc; Messerli, Vincent; Hersch, Roger D.

1997-12-01

Imaging applications such as filtering, image transforms and compression/decompression require vast amounts of computing power when applied to large data sets. These applications would potentially benefit from the use of parallel processing. However, dedicated parallel computers are expensive and their processing power per node lags behind that of the most recent commodity components. Furthermore, developing parallel applications remains a difficult task: writing and debugging the application is difficult (deadlocks), programs may not be portable from one parallel architecture to the other, and performance often comes short of expectations. In order to facilitate the development of parallel applications, we propose the CAP computer-aided parallelization tool which enables application programmers to specify at a high-level of abstraction the flow of data between pipelined-parallel operations. In addition, the CAP tool supports the programmer in developing parallel imaging and storage operations. CAP enables combining efficiently parallel storage access routines and image processing sequential operations. This paper shows how processing and I/O intensive imaging applications must be implemented to take advantage of parallelism and pipelining between data access and processing. This paper's contribution is (1) to show how such implementations can be compactly specified in CAP, and (2) to demonstrate that CAP specified applications achieve the performance of custom parallel code. The paper analyzes theoretically the performance of CAP specified applications and demonstrates the accuracy of the theoretical analysis through experimental measurements.

Design of multiple sequence alignment algorithms on parallel, distributed memory supercomputers.

PubMed

Church, Philip C; Goscinski, Andrzej; Holt, Kathryn; Inouye, Michael; Ghoting, Amol; Makarychev, Konstantin; Reumann, Matthias

2011-01-01

The challenge of comparing two or more genomes that have undergone recombination and substantial amounts of segmental loss and gain has recently been addressed for small numbers of genomes. However, datasets of hundreds of genomes are now common and their sizes will only increase in the future. Multiple sequence alignment of hundreds of genomes remains an intractable problem due to quadratic increases in compute time and memory footprint. To date, most alignment algorithms are designed for commodity clusters without parallelism. Hence, we propose the design of a multiple sequence alignment algorithm on massively parallel, distributed memory supercomputers to enable research into comparative genomics on large data sets. Following the methodology of the sequential progressiveMauve algorithm, we design data structures including sequences and sorted k-mer lists on the IBM Blue Gene/P supercomputer (BG/P). Preliminary results show that we can reduce the memory footprint so that we can potentially align over 250 bacterial genomes on a single BG/P compute node. We verify our results on a dataset of E.coli, Shigella and S.pneumoniae genomes. Our implementation returns results matching those of the original algorithm but in 1/2 the time and with 1/4 the memory footprint for scaffold building. In this study, we have laid the basis for multiple sequence alignment of large-scale datasets on a massively parallel, distributed memory supercomputer, thus enabling comparison of hundreds instead of a few genome sequences within reasonable time.

Assaying gene function by growth competition experiment.

PubMed

Merritt, Joshua; Edwards, Jeremy S

2004-07-01

High-throughput screening and analysis is one of the emerging paradigms in biotechnology. In particular, high-throughput methods are essential in the field of functional genomics because of the vast amount of data generated in recent and ongoing genome sequencing efforts. In this report we discuss integrated functional analysis methodologies which incorporate both a growth competition component and a highly parallel assay used to quantify results of the growth competition. Several applications of the two most widely used technologies in the field, i.e., transposon mutagenesis and deletion strain library growth competition, and individual applications of several developing or less widely reported technologies are presented.

Comparison of Acceleration Techniques for Selected Low-Level Bioinformatics Operations

PubMed Central

Langenkämper, Daniel; Jakobi, Tobias; Feld, Dustin; Jelonek, Lukas; Goesmann, Alexander; Nattkemper, Tim W.

2016-01-01

Within the recent years clock rates of modern processors stagnated while the demand for computing power continued to grow. This applied particularly for the fields of life sciences and bioinformatics, where new technologies keep on creating rapidly growing piles of raw data with increasing speed. The number of cores per processor increased in an attempt to compensate for slight increments of clock rates. This technological shift demands changes in software development, especially in the field of high performance computing where parallelization techniques are gaining in importance due to the pressing issue of large sized datasets generated by e.g., modern genomics. This paper presents an overview of state-of-the-art manual and automatic acceleration techniques and lists some applications employing these in different areas of sequence informatics. Furthermore, we provide examples for automatic acceleration of two use cases to show typical problems and gains of transforming a serial application to a parallel one. The paper should aid the reader in deciding for a certain techniques for the problem at hand. We compare four different state-of-the-art automatic acceleration approaches (OpenMP, PluTo-SICA, PPCG, and OpenACC). Their performance as well as their applicability for selected use cases is discussed. While optimizations targeting the CPU worked better in the complex k-mer use case, optimizers for Graphics Processing Units (GPUs) performed better in the matrix multiplication example. But performance is only superior at a certain problem size due to data migration overhead. We show that automatic code parallelization is feasible with current compiler software and yields significant increases in execution speed. Automatic optimizers for CPU are mature and usually no additional manual adjustment is required. In contrast, some automatic parallelizers targeting GPUs still lack maturity and are limited to simple statements and structures. PMID:26904094

Comparison of Acceleration Techniques for Selected Low-Level Bioinformatics Operations.

PubMed

Langenkämper, Daniel; Jakobi, Tobias; Feld, Dustin; Jelonek, Lukas; Goesmann, Alexander; Nattkemper, Tim W

2016-01-01

Within the recent years clock rates of modern processors stagnated while the demand for computing power continued to grow. This applied particularly for the fields of life sciences and bioinformatics, where new technologies keep on creating rapidly growing piles of raw data with increasing speed. The number of cores per processor increased in an attempt to compensate for slight increments of clock rates. This technological shift demands changes in software development, especially in the field of high performance computing where parallelization techniques are gaining in importance due to the pressing issue of large sized datasets generated by e.g., modern genomics. This paper presents an overview of state-of-the-art manual and automatic acceleration techniques and lists some applications employing these in different areas of sequence informatics. Furthermore, we provide examples for automatic acceleration of two use cases to show typical problems and gains of transforming a serial application to a parallel one. The paper should aid the reader in deciding for a certain techniques for the problem at hand. We compare four different state-of-the-art automatic acceleration approaches (OpenMP, PluTo-SICA, PPCG, and OpenACC). Their performance as well as their applicability for selected use cases is discussed. While optimizations targeting the CPU worked better in the complex k-mer use case, optimizers for Graphics Processing Units (GPUs) performed better in the matrix multiplication example. But performance is only superior at a certain problem size due to data migration overhead. We show that automatic code parallelization is feasible with current compiler software and yields significant increases in execution speed. Automatic optimizers for CPU are mature and usually no additional manual adjustment is required. In contrast, some automatic parallelizers targeting GPUs still lack maturity and are limited to simple statements and structures.

Special purpose parallel computer architecture for real-time control and simulation in robotic applications

NASA Technical Reports Server (NTRS)

Fijany, Amir (Inventor); Bejczy, Antal K. (Inventor)

1993-01-01

This is a real-time robotic controller and simulator which is a MIMD-SIMD parallel architecture for interfacing with an external host computer and providing a high degree of parallelism in computations for robotic control and simulation. It includes a host processor for receiving instructions from the external host computer and for transmitting answers to the external host computer. There are a plurality of SIMD microprocessors, each SIMD processor being a SIMD parallel processor capable of exploiting fine grain parallelism and further being able to operate asynchronously to form a MIMD architecture. Each SIMD processor comprises a SIMD architecture capable of performing two matrix-vector operations in parallel while fully exploiting parallelism in each operation. There is a system bus connecting the host processor to the plurality of SIMD microprocessors and a common clock providing a continuous sequence of clock pulses. There is also a ring structure interconnecting the plurality of SIMD microprocessors and connected to the clock for providing the clock pulses to the SIMD microprocessors and for providing a path for the flow of data and instructions between the SIMD microprocessors. The host processor includes logic for controlling the RRCS by interpreting instructions sent by the external host computer, decomposing the instructions into a series of computations to be performed by the SIMD microprocessors, using the system bus to distribute associated data among the SIMD microprocessors, and initiating activity of the SIMD microprocessors to perform the computations on the data by procedure call.

cuBLASTP: Fine-Grained Parallelization of Protein Sequence Search on CPU+GPU.

PubMed

Zhang, Jing; Wang, Hao; Feng, Wu-Chun

2017-01-01

BLAST, short for Basic Local Alignment Search Tool, is a ubiquitous tool used in the life sciences for pairwise sequence search. However, with the advent of next-generation sequencing (NGS), whether at the outset or downstream from NGS, the exponential growth of sequence databases is outstripping our ability to analyze the data. While recent studies have utilized the graphics processing unit (GPU) to speedup the BLAST algorithm for searching protein sequences (i.e., BLASTP), these studies use coarse-grained parallelism, where one sequence alignment is mapped to only one thread. Such an approach does not efficiently utilize the capabilities of a GPU, particularly due to the irregularity of BLASTP in both execution paths and memory-access patterns. To address the above shortcomings, we present a fine-grained approach to parallelize BLASTP, where each individual phase of sequence search is mapped to many threads on a GPU. This approach, which we refer to as cuBLASTP, reorders data-access patterns and reduces divergent branches of the most time-consuming phases (i.e., hit detection and ungapped extension). In addition, cuBLASTP optimizes the remaining phases (i.e., gapped extension and alignment with trace back) on a multicore CPU and overlaps their execution with the phases running on the GPU.

Fine-grained parallelism accelerating for RNA secondary structure prediction with pseudoknots based on FPGA.

PubMed

Xia, Fei; Jin, Guoqing

2014-06-01

PKNOTS is a most famous benchmark program and has been widely used to predict RNA secondary structure including pseudoknots. It adopts the standard four-dimensional (4D) dynamic programming (DP) method and is the basis of many variants and improved algorithms. Unfortunately, the O(N(6)) computing requirements and complicated data dependency greatly limits the usefulness of PKNOTS package with the explosion in gene database size. In this paper, we present a fine-grained parallel PKNOTS package and prototype system for accelerating RNA folding application based on FPGA chip. We adopted a series of storage optimization strategies to resolve the "Memory Wall" problem. We aggressively exploit parallel computing strategies to improve computational efficiency. We also propose several methods that collectively reduce the storage requirements for FPGA on-chip memory. To the best of our knowledge, our design is the first FPGA implementation for accelerating 4D DP problem for RNA folding application including pseudoknots. The experimental results show a factor of more than 50x average speedup over the PKNOTS-1.08 software running on a PC platform with Intel Core2 Q9400 Quad CPU for input RNA sequences. However, the power consumption of our FPGA accelerator is only about 50% of the general-purpose micro-processors.

Identification and characterization of Highlands J virus from a Mississippi sandhill crane using unbiased next-generation sequencing

USGS Publications Warehouse

Ip, Hon S.; Wiley, Michael R.; Long, Renee; Gustavo, Palacios; Shearn-Bochsler, Valerie; Whitehouse, Chris A.

2014-01-01

Advances in massively parallel DNA sequencing platforms, commonly termed next-generation sequencing (NGS) technologies, have greatly reduced time, labor, and cost associated with DNA sequencing. Thus, NGS has become a routine tool for new viral pathogen discovery and will likely become the standard for routine laboratory diagnostics of infectious diseases in the near future. This study demonstrated the application of NGS for the rapid identification and characterization of a virus isolated from the brain of an endangered Mississippi sandhill crane. This bird was part of a population restoration effort and was found in an emaciated state several days after Hurricane Isaac passed over the refuge in Mississippi in 2012. Post-mortem examination had identified trichostrongyliasis as the possible cause of death, but because a virus with morphology consistent with a togavirus was isolated from the brain of the bird, an arboviral etiology was strongly suspected. Because individual molecular assays for several known arboviruses were negative, unbiased NGS by Illumina MiSeq was used to definitively identify and characterize the causative viral agent. Whole genome sequencing and phylogenetic analysis revealed the viral isolate to be the Highlands J virus, a known avian pathogen. This study demonstrates the use of unbiased NGS for the rapid detection and characterization of an unidentified viral pathogen and the application of this technology to wildlife disease diagnostics and conservation medicine.

A programmable method for massively parallel targeted sequencing

PubMed Central

Hopmans, Erik S.; Natsoulis, Georges; Bell, John M.; Grimes, Susan M.; Sieh, Weiva; Ji, Hanlee P.

2014-01-01

We have developed a targeted resequencing approach referred to as Oligonucleotide-Selective Sequencing. In this study, we report a series of significant improvements and novel applications of this method whereby the surface of a sequencing flow cell is modified in situ to capture specific genomic regions of interest from a sample and then sequenced. These improvements include a fully automated targeted sequencing platform through the use of a standard Illumina cBot fluidics station. Targeting optimization increased the yield of total on-target sequencing data 2-fold compared to the previous iteration, while simultaneously increasing the percentage of reads that could be mapped to the human genome. The described assays cover up to 1421 genes with a total coverage of 5.5 Megabases (Mb). We demonstrate a 10-fold abundance uniformity of greater than 90% in 1 log distance from the median and a targeting rate of up to 95%. We also sequenced continuous genomic loci up to 1.5 Mb while simultaneously genotyping SNPs and genes. Variants with low minor allele fraction were sensitively detected at levels of 5%. Finally, we determined the exact breakpoint sequence of cancer rearrangements. Overall, this approach has high performance for selective sequencing of genome targets, configuration flexibility and variant calling accuracy. PMID:24782526

Whole-exome/genome sequencing and genomics.

PubMed

Grody, Wayne W; Thompson, Barry H; Hudgins, Louanne

2013-12-01

As medical genetics has progressed from a descriptive entity to one focused on the functional relationship between genes and clinical disorders, emphasis has been placed on genomics. Genomics, a subelement of genetics, is the study of the genome, the sum total of all the genes of an organism. The human genome, which is contained in the 23 pairs of nuclear chromosomes and in the mitochondrial DNA of each cell, comprises >6 billion nucleotides of genetic code. There are some 23,000 protein-coding genes, a surprisingly small fraction of the total genetic material, with the remainder composed of noncoding DNA, regulatory sequences, and introns. The Human Genome Project, launched in 1990, produced a draft of the genome in 2001 and then a finished sequence in 2003, on the 50th anniversary of the initial publication of Watson and Crick's paper on the double-helical structure of DNA. Since then, this mass of genetic information has been translated at an ever-increasing pace into useable knowledge applicable to clinical medicine. The recent advent of massively parallel DNA sequencing (also known as shotgun, high-throughput, and next-generation sequencing) has brought whole-genome analysis into the clinic for the first time, and most of the current applications are directed at children with congenital conditions that are undiagnosable by using standard genetic tests for single-gene disorders. Thus, pediatricians must become familiar with this technology, what it can and cannot offer, and its technical and ethical challenges. Here, we address the concepts of human genomic analysis and its clinical applicability for primary care providers.

Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation.

PubMed

Babak, Tomas; Garrett-Engele, Philip; Armour, Christopher D; Raymond, Christopher K; Keller, Mark P; Chen, Ronghua; Rohl, Carol A; Johnson, Jason M; Attie, Alan D; Fraser, Hunter B; Schadt, Eric E

2010-08-13

Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing.

The Galley Parallel File System

NASA Technical Reports Server (NTRS)

Nieuwejaar, Nils; Kotz, David

1996-01-01

As the I/O needs of parallel scientific applications increase, file systems for multiprocessors are being designed to provide applications with parallel access to multiple disks. Many parallel file systems present applications with a conventional Unix-like interface that allows the application to access multiple disks transparently. The interface conceals the parallelism within the file system, which increases the ease of programmability, but makes it difficult or impossible for sophisticated programmers and libraries to use knowledge about their I/O needs to exploit that parallelism. Furthermore, most current parallel file systems are optimized for a different workload than they are being asked to support. We introduce Galley, a new parallel file system that is intended to efficiently support realistic parallel workloads. We discuss Galley's file structure and application interface, as well as an application that has been implemented using that interface.

Long Read Alignment with Parallel MapReduce Cloud Platform

PubMed Central

Al-Absi, Ahmed Abdulhakim; Kang, Dae-Ki

2015-01-01

Genomic sequence alignment is an important technique to decode genome sequences in bioinformatics. Next-Generation Sequencing technologies produce genomic data of longer reads. Cloud platforms are adopted to address the problems arising from storage and analysis of large genomic data. Existing genes sequencing tools for cloud platforms predominantly consider short read gene sequences and adopt the Hadoop MapReduce framework for computation. However, serial execution of map and reduce phases is a problem in such systems. Therefore, in this paper, we introduce Burrows-Wheeler Aligner's Smith-Waterman Alignment on Parallel MapReduce (BWASW-PMR) cloud platform for long sequence alignment. The proposed cloud platform adopts a widely accepted and accurate BWA-SW algorithm for long sequence alignment. A custom MapReduce platform is developed to overcome the drawbacks of the Hadoop framework. A parallel execution strategy of the MapReduce phases and optimization of Smith-Waterman algorithm are considered. Performance evaluation results exhibit an average speed-up of 6.7 considering BWASW-PMR compared with the state-of-the-art Bwasw-Cloud. An average reduction of 30% in the map phase makespan is reported across all experiments comparing BWASW-PMR with Bwasw-Cloud. Optimization of Smith-Waterman results in reducing the execution time by 91.8%. The experimental study proves the efficiency of BWASW-PMR for aligning long genomic sequences on cloud platforms. PMID:26839887

Long Read Alignment with Parallel MapReduce Cloud Platform.

PubMed

Al-Absi, Ahmed Abdulhakim; Kang, Dae-Ki

2015-01-01

Genomic sequence alignment is an important technique to decode genome sequences in bioinformatics. Next-Generation Sequencing technologies produce genomic data of longer reads. Cloud platforms are adopted to address the problems arising from storage and analysis of large genomic data. Existing genes sequencing tools for cloud platforms predominantly consider short read gene sequences and adopt the Hadoop MapReduce framework for computation. However, serial execution of map and reduce phases is a problem in such systems. Therefore, in this paper, we introduce Burrows-Wheeler Aligner's Smith-Waterman Alignment on Parallel MapReduce (BWASW-PMR) cloud platform for long sequence alignment. The proposed cloud platform adopts a widely accepted and accurate BWA-SW algorithm for long sequence alignment. A custom MapReduce platform is developed to overcome the drawbacks of the Hadoop framework. A parallel execution strategy of the MapReduce phases and optimization of Smith-Waterman algorithm are considered. Performance evaluation results exhibit an average speed-up of 6.7 considering BWASW-PMR compared with the state-of-the-art Bwasw-Cloud. An average reduction of 30% in the map phase makespan is reported across all experiments comparing BWASW-PMR with Bwasw-Cloud. Optimization of Smith-Waterman results in reducing the execution time by 91.8%. The experimental study proves the efficiency of BWASW-PMR for aligning long genomic sequences on cloud platforms.

Survey of MapReduce frame operation in bioinformatics.

PubMed

Zou, Quan; Li, Xu-Bin; Jiang, Wen-Rui; Lin, Zi-Yu; Li, Gui-Lin; Chen, Ke

2014-07-01

Bioinformatics is challenged by the fact that traditional analysis tools have difficulty in processing large-scale data from high-throughput sequencing. The open source Apache Hadoop project, which adopts the MapReduce framework and a distributed file system, has recently given bioinformatics researchers an opportunity to achieve scalable, efficient and reliable computing performance on Linux clusters and on cloud computing services. In this article, we present MapReduce frame-based applications that can be employed in the next-generation sequencing and other biological domains. In addition, we discuss the challenges faced by this field as well as the future works on parallel computing in bioinformatics. © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

RNA-Seq Alignment to Individualized Genomes Improves Transcript Abundance Estimates in Multiparent Populations

PubMed Central

Munger, Steven C.; Raghupathy, Narayanan; Choi, Kwangbom; Simons, Allen K.; Gatti, Daniel M.; Hinerfeld, Douglas A.; Svenson, Karen L.; Keller, Mark P.; Attie, Alan D.; Hibbs, Matthew A.; Graber, Joel H.; Chesler, Elissa J.; Churchill, Gary A.

2014-01-01

Massively parallel RNA sequencing (RNA-seq) has yielded a wealth of new insights into transcriptional regulation. A first step in the analysis of RNA-seq data is the alignment of short sequence reads to a common reference genome or transcriptome. Genetic variants that distinguish individual genomes from the reference sequence can cause reads to be misaligned, resulting in biased estimates of transcript abundance. Fine-tuning of read alignment algorithms does not correct this problem. We have developed Seqnature software to construct individualized diploid genomes and transcriptomes for multiparent populations and have implemented a complete analysis pipeline that incorporates other existing software tools. We demonstrate in simulated and real data sets that alignment to individualized transcriptomes increases read mapping accuracy, improves estimation of transcript abundance, and enables the direct estimation of allele-specific expression. Moreover, when applied to expression QTL mapping we find that our individualized alignment strategy corrects false-positive linkage signals and unmasks hidden associations. We recommend the use of individualized diploid genomes over reference sequence alignment for all applications of high-throughput sequencing technology in genetically diverse populations. PMID:25236449

Meeting the challenges of non-referenced genome assembly from short-read sequence data

Treesearch

M. Parks; A. Liston; R. Cronn

2010-01-01

Massively parallel sequencing technologies (MPST) offer unprecedented opportunities for novel sequencing projects. MPST, while offering tremendous sequencing capacity, are typically most effective in resequencing projects (as opposed to the sequencing of novel genomes) due to the fact that sequence is returned in relatively short reads. Nonetheless, there is great...

Massively Parallel DNA Sequencing Facilitates Diagnosis of Patients with Usher Syndrome Type 1

PubMed Central

Yoshimura, Hidekane; Iwasaki, Satoshi; Nishio, Shin-ya; Kumakawa, Kozo; Tono, Tetsuya; Kobayashi, Yumiko; Sato, Hiroaki; Nagai, Kyoko; Ishikawa, Kotaro; Ikezono, Tetsuo; Naito, Yasushi; Fukushima, Kunihiro; Oshikawa, Chie; Kimitsuki, Takashi; Nakanishi, Hiroshi; Usami, Shin-ichi

2014-01-01

Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families. However, the conventional genetic techniques, such as direct sequence analysis, are both time-consuming and expensive. Targeted exon sequencing of selected genes using the massively parallel DNA sequencing technology will potentially enable us to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using this technique combined with direct sequence analysis, we screened 17 unrelated Usher syndrome type 1 patients and detected probable pathogenic variants in the 16 of them (94.1%) who carried at least one mutation. Seven patients had the MYO7A mutation (41.2%), which is the most common type in Japanese. Most of the mutations were detected by only the massively parallel DNA sequencing. We report here four patients, who had probable pathogenic mutations in two different Usher syndrome type 1 genes, and one case of MYO7A/PCDH15 digenic inheritance. This is the first report of Usher syndrome mutation analysis using massively parallel DNA sequencing and the frequency of Usher syndrome type 1 genes in Japanese. Mutation screening using this technique has the power to quickly identify mutations of many causative genes while maintaining cost-benefit performance. In addition, the simultaneous mutation analysis of large numbers of genes is useful for detecting mutations in different genes that are possibly disease modifiers or of digenic inheritance. PMID:24618850

Massively parallel DNA sequencing facilitates diagnosis of patients with Usher syndrome type 1.

PubMed

Yoshimura, Hidekane; Iwasaki, Satoshi; Nishio, Shin-Ya; Kumakawa, Kozo; Tono, Tetsuya; Kobayashi, Yumiko; Sato, Hiroaki; Nagai, Kyoko; Ishikawa, Kotaro; Ikezono, Tetsuo; Naito, Yasushi; Fukushima, Kunihiro; Oshikawa, Chie; Kimitsuki, Takashi; Nakanishi, Hiroshi; Usami, Shin-Ichi

2014-01-01

Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families. However, the conventional genetic techniques, such as direct sequence analysis, are both time-consuming and expensive. Targeted exon sequencing of selected genes using the massively parallel DNA sequencing technology will potentially enable us to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using this technique combined with direct sequence analysis, we screened 17 unrelated Usher syndrome type 1 patients and detected probable pathogenic variants in the 16 of them (94.1%) who carried at least one mutation. Seven patients had the MYO7A mutation (41.2%), which is the most common type in Japanese. Most of the mutations were detected by only the massively parallel DNA sequencing. We report here four patients, who had probable pathogenic mutations in two different Usher syndrome type 1 genes, and one case of MYO7A/PCDH15 digenic inheritance. This is the first report of Usher syndrome mutation analysis using massively parallel DNA sequencing and the frequency of Usher syndrome type 1 genes in Japanese. Mutation screening using this technique has the power to quickly identify mutations of many causative genes while maintaining cost-benefit performance. In addition, the simultaneous mutation analysis of large numbers of genes is useful for detecting mutations in different genes that are possibly disease modifiers or of digenic inheritance.

High throughput SNP discovery and genotyping in grapevine (Vitis vinifera L.) by combining a re-sequencing approach and SNPlex technology

PubMed Central

Lijavetzky, Diego; Cabezas, José Antonio; Ibáñez, Ana; Rodríguez, Virginia; Martínez-Zapater, José M

2007-01-01

Background Single-nucleotide polymorphisms (SNPs) are the most abundant type of DNA sequence polymorphisms. Their higher availability and stability when compared to simple sequence repeats (SSRs) provide enhanced possibilities for genetic and breeding applications such as cultivar identification, construction of genetic maps, the assessment of genetic diversity, the detection of genotype/phenotype associations, or marker-assisted breeding. In addition, the efficiency of these activities can be improved thanks to the ease with which SNP genotyping can be automated. Expressed sequence tags (EST) sequencing projects in grapevine are allowing for the in silico detection of multiple putative sequence polymorphisms within and among a reduced number of cultivars. In parallel, the sequence of the grapevine cultivar Pinot Noir is also providing thousands of polymorphisms present in this highly heterozygous genome. Still the general application of those SNPs requires further validation since their use could be restricted to those specific genotypes. Results In order to develop a large SNP set of wide application in grapevine we followed a systematic re-sequencing approach in a group of 11 grape genotypes corresponding to ancient unrelated cultivars as well as wild plants. Using this approach, we have sequenced 230 gene fragments, what represents the analysis of over 1 Mb of grape DNA sequence. This analysis has allowed the discovery of 1573 SNPs with an average of one SNP every 64 bp (one SNP every 47 bp in non-coding regions and every 69 bp in coding regions). Nucleotide diversity in grape (π = 0.0051) was found to be similar to values observed in highly polymorphic plant species such as maize. The average number of haplotypes per gene sequence was estimated as six, with three haplotypes representing over 83% of the analyzed sequences. Short-range linkage disequilibrium (LD) studies within the analyzed sequences indicate the existence of a rapid decay of LD within the selected grapevine genotypes. To validate the use of the detected polymorphisms in genetic mapping, cultivar identification and genetic diversity studies we have used the SNPlex™ genotyping technology in a sample of grapevine genotypes and segregating progenies. Conclusion These results provide accurate values for nucleotide diversity in coding sequences and a first estimate of short-range LD in grapevine. Using SNPlex™ genotyping we have shown the application of a set of discovered SNPs as molecular markers for cultivar identification, linkage mapping and genetic diversity studies. Thus, the combination a highly efficient re-sequencing approach and the SNPlex™ high throughput genotyping technology provide a powerful tool for grapevine genetic analysis. PMID:18021442

Collectively loading an application in a parallel computer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aho, Michael E.; Attinella, John E.; Gooding, Thomas M.

Collectively loading an application in a parallel computer, the parallel computer comprising a plurality of compute nodes, including: identifying, by a parallel computer control system, a subset of compute nodes in the parallel computer to execute a job; selecting, by the parallel computer control system, one of the subset of compute nodes in the parallel computer as a job leader compute node; retrieving, by the job leader compute node from computer memory, an application for executing the job; and broadcasting, by the job leader to the subset of compute nodes in the parallel computer, the application for executing the job.

Investigation into the sequence structure of 23 Y chromosomal STR loci using massively parallel sequencing.

PubMed

Kwon, So Yeun; Lee, Hwan Young; Kim, Eun Hye; Lee, Eun Young; Shin, Kyoung-Jin

2016-11-01

Next-generation sequencing (NGS) can produce massively parallel sequencing (MPS) data for many targeted regions with a high depth of coverage, suggesting its successful application to the amplicons of forensic genetic markers. In the present study, we evaluated the practical utility of MPS in Y-chromosome short tandem repeat (Y-STR) analysis using a multiplex polymerase chain reaction (PCR) system. The multiplex PCR system simultaneously amplified 24 Y-chromosomal markers, including the PowerPlex ® Y23 loci (DYS19, DYS385ab, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS481, DYS533, DYS549, DYS570, DYS576, DYS635, DYS643, and YGATAH4) and the M175 marker with the small-sized amplicons ranging from 85 to 253bp. The barcoded libraries for the amplicons of the 24 Y-chromosomal markers were produced using a simplified PCR-based library preparation method and successfully sequenced using MPS on a MiSeq ® System with samples from 250 unrelated Korean males. The genotyping concordance between MPS and the capillary electrophoresis (CE) method, as well as the sequence structure of the 23 Y-STRs, were investigated. Three samples exhibited discordance between the MPS and CE results at DYS385, DYS439, and DYS576. There were 12 Y-STR loci that showed sequence variations in the alleles by a fragment size determination, and the most varied alleles occurred in DYS389II with a different sequence structure in the repeat region. The largest increase in gene diversity between the CE and MPS results was in DYS437 at +34.41%. Single nucleotide polymorphisms (SNPs), insertions, and deletions (indels) were observed in the flanking regions of DYS481, DYS576, and DYS385, respectively. Stutter and noise ratios of the 23 Y-STRs using the developed MPS system were also investigated. Based on these results, the MPS analysis system used in this study could facilitate the investigation into the sequences of the 23 Y-STRs in forensic genetics laboratories. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing.

PubMed

Yu, Stephanie C Y; Chan, K C Allen; Zheng, Yama W L; Jiang, Peiyong; Liao, Gary J W; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y; Go, Attie T J I; van Vugt, John M G; Minekawa, Ryoko; Oudejans, Cees B M; Nicolaides, Kypros H; Chiu, Rossa W K; Lo, Y M Dennis

2014-06-10

Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring.

Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing

PubMed Central

Yu, Stephanie C. Y.; Chan, K. C. Allen; Zheng, Yama W. L.; Jiang, Peiyong; Liao, Gary J. W.; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y.; Go, Attie T. J. I.; van Vugt, John M. G.; Minekawa, Ryoko; Oudejans, Cees B. M.; Nicolaides, Kypros H.; Chiu, Rossa W. K.; Lo, Y. M. Dennis

2014-01-01

Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring. PMID:24843150

RAMICS: trainable, high-speed and biologically relevant alignment of high-throughput sequencing reads to coding DNA

PubMed Central

Wright, Imogen A.; Travers, Simon A.

2014-01-01

The challenge presented by high-throughput sequencing necessitates the development of novel tools for accurate alignment of reads to reference sequences. Current approaches focus on using heuristics to map reads quickly to large genomes, rather than generating highly accurate alignments in coding regions. Such approaches are, thus, unsuited for applications such as amplicon-based analysis and the realignment phase of exome sequencing and RNA-seq, where accurate and biologically relevant alignment of coding regions is critical. To facilitate such analyses, we have developed a novel tool, RAMICS, that is tailored to mapping large numbers of sequence reads to short lengths (<10 000 bp) of coding DNA. RAMICS utilizes profile hidden Markov models to discover the open reading frame of each sequence and aligns to the reference sequence in a biologically relevant manner, distinguishing between genuine codon-sized indels and frameshift mutations. This approach facilitates the generation of highly accurate alignments, accounting for the error biases of the sequencing machine used to generate reads, particularly at homopolymer regions. Performance improvements are gained through the use of graphics processing units, which increase the speed of mapping through parallelization. RAMICS substantially outperforms all other mapping approaches tested in terms of alignment quality while maintaining highly competitive speed performance. PMID:24861618

Role of APOE Isoforms in the Pathogenesis of TBI induced Alzheimer’s Disease

DTIC Science & Technology

2016-10-01

deletion, APOE targeted replacement, complex breeding, CCI model optimization, mRNA library generation, high throughput massive parallel sequencing...demonstrate that the lack of Abca1 increases amyloid plaques and decreased APOE protein levels in AD-model mice. In this proposal we will test the hypothesis...injury, inflammatory reaction, transcriptome, high throughput massive parallel sequencing, mRNA-seq., behavioral testing, memory impairment, recovery 3

High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing

DTIC Science & Technology

2010-10-14

High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing...Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV...Smith JM, Schmaljohn CS (2010) High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and

Representing and computing regular languages on massively parallel networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, M.I.; O'Sullivan, J.A.; Boysam, B.

1991-01-01

This paper proposes a general method for incorporating rule-based constraints corresponding to regular languages into stochastic inference problems, thereby allowing for a unified representation of stochastic and syntactic pattern constraints. The authors' approach first established the formal connection of rules to Chomsky grammars, and generalizes the original work of Shannon on the encoding of rule-based channel sequences to Markov chains of maximum entropy. This maximum entropy probabilistic view leads to Gibb's representations with potentials which have their number of minima growing at precisely the exponential rate that the language of deterministically constrained sequences grow. These representations are coupled to stochasticmore » diffusion algorithms, which sample the language-constrained sequences by visiting the energy minima according to the underlying Gibbs' probability law. The coupling to stochastic search methods yields the all-important practical result that fully parallel stochastic cellular automata may be derived to generate samples from the rule-based constraint sets. The production rules and neighborhood state structure of the language of sequences directly determines the necessary connection structures of the required parallel computing surface. Representations of this type have been mapped to the DAP-510 massively-parallel processor consisting of 1024 mesh-connected bit-serial processing elements for performing automated segmentation of electron-micrograph images.« less

Optimal Golomb Ruler Sequences Generation for Optical WDM Systems: A Novel Parallel Hybrid Multi-objective Bat Algorithm

NASA Astrophysics Data System (ADS)

Bansal, Shonak; Singh, Arun Kumar; Gupta, Neena

2017-02-01

In real-life, multi-objective engineering design problems are very tough and time consuming optimization problems due to their high degree of nonlinearities, complexities and inhomogeneity. Nature-inspired based multi-objective optimization algorithms are now becoming popular for solving multi-objective engineering design problems. This paper proposes original multi-objective Bat algorithm (MOBA) and its extended form, namely, novel parallel hybrid multi-objective Bat algorithm (PHMOBA) to generate shortest length Golomb ruler called optimal Golomb ruler (OGR) sequences at a reasonable computation time. The OGRs found their application in optical wavelength division multiplexing (WDM) systems as channel-allocation algorithm to reduce the four-wave mixing (FWM) crosstalk. The performances of both the proposed algorithms to generate OGRs as optical WDM channel-allocation is compared with other existing classical computing and nature-inspired algorithms, including extended quadratic congruence (EQC), search algorithm (SA), genetic algorithms (GAs), biogeography based optimization (BBO) and big bang-big crunch (BB-BC) optimization algorithms. Simulations conclude that the proposed parallel hybrid multi-objective Bat algorithm works efficiently as compared to original multi-objective Bat algorithm and other existing algorithms to generate OGRs for optical WDM systems. The algorithm PHMOBA to generate OGRs, has higher convergence and success rate than original MOBA. The efficiency improvement of proposed PHMOBA to generate OGRs up to 20-marks, in terms of ruler length and total optical channel bandwidth (TBW) is 100 %, whereas for original MOBA is 85 %. Finally the implications for further research are also discussed.

PoPLAR: Portal for Petascale Lifescience Applications and Research

PubMed Central

2013-01-01

Background We are focusing specifically on fast data analysis and retrieval in bioinformatics that will have a direct impact on the quality of human health and the environment. The exponential growth of data generated in biology research, from small atoms to big ecosystems, necessitates an increasingly large computational component to perform analyses. Novel DNA sequencing technologies and complementary high-throughput approaches--such as proteomics, genomics, metabolomics, and meta-genomics--drive data-intensive bioinformatics. While individual research centers or universities could once provide for these applications, this is no longer the case. Today, only specialized national centers can deliver the level of computing resources required to meet the challenges posed by rapid data growth and the resulting computational demand. Consequently, we are developing massively parallel applications to analyze the growing flood of biological data and contribute to the rapid discovery of novel knowledge. Methods The efforts of previous National Science Foundation (NSF) projects provided for the generation of parallel modules for widely used bioinformatics applications on the Kraken supercomputer. We have profiled and optimized the code of some of the scientific community's most widely used desktop and small-cluster-based applications, including BLAST from the National Center for Biotechnology Information (NCBI), HMMER, and MUSCLE; scaled them to tens of thousands of cores on high-performance computing (HPC) architectures; made them robust and portable to next-generation architectures; and incorporated these parallel applications in science gateways with a web-based portal. Results This paper will discuss the various developmental stages, challenges, and solutions involved in taking bioinformatics applications from the desktop to petascale with a front-end portal for very-large-scale data analysis in the life sciences. Conclusions This research will help to bridge the gap between the rate of data generation and the speed at which scientists can study this data. The ability to rapidly analyze data at such a large scale is having a significant, direct impact on science achieved by collaborators who are currently using these tools on supercomputers. PMID:23902523

3DScapeCS: application of three dimensional, parallel, dynamic network visualization in Cytoscape

PubMed Central

2013-01-01

Background The exponential growth of gigantic biological data from various sources, such as protein-protein interaction (PPI), genome sequences scaffolding, Mass spectrometry (MS) molecular networking and metabolic flux, demands an efficient way for better visualization and interpretation beyond the conventional, two-dimensional visualization tools. Results We developed a 3D Cytoscape Client/Server (3DScapeCS) plugin, which adopted Cytoscape in interpreting different types of data, and UbiGraph for three-dimensional visualization. The extra dimension is useful in accommodating, visualizing, and distinguishing large-scale networks with multiple crossed connections in five case studies. Conclusions Evaluation on several experimental data using 3DScapeCS and its special features, including multilevel graph layout, time-course data animation, and parallel visualization has proven its usefulness in visualizing complex data and help to make insightful conclusions. PMID:24225050

RY-Coding and Non-Homogeneous Models Can Ameliorate the Maximum-Likelihood Inferences From Nucleotide Sequence Data with Parallel Compositional Heterogeneity.

PubMed

Ishikawa, Sohta A; Inagaki, Yuji; Hashimoto, Tetsuo

2012-01-01

In phylogenetic analyses of nucleotide sequences, 'homogeneous' substitution models, which assume the stationarity of base composition across a tree, are widely used, albeit individual sequences may bear distinctive base frequencies. In the worst-case scenario, a homogeneous model-based analysis can yield an artifactual union of two distantly related sequences that achieved similar base frequencies in parallel. Such potential difficulty can be countered by two approaches, 'RY-coding' and 'non-homogeneous' models. The former approach converts four bases into purine and pyrimidine to normalize base frequencies across a tree, while the heterogeneity in base frequency is explicitly incorporated in the latter approach. The two approaches have been applied to real-world sequence data; however, their basic properties have not been fully examined by pioneering simulation studies. Here, we assessed the performances of the maximum-likelihood analyses incorporating RY-coding and a non-homogeneous model (RY-coding and non-homogeneous analyses) on simulated data with parallel convergence to similar base composition. Both RY-coding and non-homogeneous analyses showed superior performances compared with homogeneous model-based analyses. Curiously, the performance of RY-coding analysis appeared to be significantly affected by a setting of the substitution process for sequence simulation relative to that of non-homogeneous analysis. The performance of a non-homogeneous analysis was also validated by analyzing a real-world sequence data set with significant base heterogeneity.

PETSc Users Manual Revision 3.3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balay, S.; Brown, J.; Buschelman, K.

This manual describes the use of PETSc for the numerical solution of partial differential equations and related problems on high-performance computers. The Portable, Extensible Toolkit for Scientific Computation (PETSc) is a suite of data structures and routines that provide the building blocks for the implementation of large-scale application codes on parallel (and serial) computers. PETSc uses the MPI standard for all message-passing communication. PETSc includes an expanding suite of parallel linear, nonlinear equation solvers and time integrators that may be used in application codes written in Fortran, C, C++, Python, and MATLAB (sequential). PETSc provides many of the mechanisms neededmore » within parallel application codes, such as parallel matrix and vector assembly routines. The library is organized hierarchically, enabling users to employ the level of abstraction that is most appropriate for a particular problem. By using techniques of object-oriented programming, PETSc provides enormous flexibility for users. PETSc is a sophisticated set of software tools; as such, for some users it initially has a much steeper learning curve than a simple subroutine library. In particular, for individuals without some computer science background, experience programming in C, C++ or Fortran and experience using a debugger such as gdb or dbx, it may require a significant amount of time to take full advantage of the features that enable efficient software use. However, the power of the PETSc design and the algorithms it incorporates may make the efficient implementation of many application codes simpler than “rolling them” yourself; For many tasks a package such as MATLAB is often the best tool; PETSc is not intended for the classes of problems for which effective MATLAB code can be written. PETSc also has a MATLAB interface, so portions of your code can be written in MATLAB to “try out” the PETSc solvers. The resulting code will not be scalable however because currently MATLAB is inherently not scalable; and PETSc should not be used to attempt to provide a “parallel linear solver” in an otherwise sequential code. Certainly all parts of a previously sequential code need not be parallelized but the matrix generation portion must be parallelized to expect any kind of reasonable performance. Do not expect to generate your matrix sequentially and then “use PETSc” to solve the linear system in parallel. Since PETSc is under continued development, small changes in usage and calling sequences of routines will occur. PETSc is supported; see the web site http://www.mcs.anl.gov/petsc for information on contacting support. A http://www.mcs.anl.gov/petsc/publications may be found a list of publications and web sites that feature work involving PETSc. We welcome any reports of corrections for this document.« less

PETSc Users Manual Revision 3.4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balay, S.; Brown, J.; Buschelman, K.

This manual describes the use of PETSc for the numerical solution of partial differential equations and related problems on high-performance computers. The Portable, Extensible Toolkit for Scientific Computation (PETSc) is a suite of data structures and routines that provide the building blocks for the implementation of large-scale application codes on parallel (and serial) computers. PETSc uses the MPI standard for all message-passing communication. PETSc includes an expanding suite of parallel linear, nonlinear equation solvers and time integrators that may be used in application codes written in Fortran, C, C++, Python, and MATLAB (sequential). PETSc provides many of the mechanisms neededmore » within parallel application codes, such as parallel matrix and vector assembly routines. The library is organized hierarchically, enabling users to employ the level of abstraction that is most appropriate for a particular problem. By using techniques of object-oriented programming, PETSc provides enormous flexibility for users. PETSc is a sophisticated set of software tools; as such, for some users it initially has a much steeper learning curve than a simple subroutine library. In particular, for individuals without some computer science background, experience programming in C, C++ or Fortran and experience using a debugger such as gdb or dbx, it may require a significant amount of time to take full advantage of the features that enable efficient software use. However, the power of the PETSc design and the algorithms it incorporates may make the efficient implementation of many application codes simpler than “rolling them” yourself; For many tasks a package such as MATLAB is often the best tool; PETSc is not intended for the classes of problems for which effective MATLAB code can be written. PETSc also has a MATLAB interface, so portions of your code can be written in MATLAB to “try out” the PETSc solvers. The resulting code will not be scalable however because currently MATLAB is inherently not scalable; and PETSc should not be used to attempt to provide a “parallel linear solver” in an otherwise sequential code. Certainly all parts of a previously sequential code need not be parallelized but the matrix generation portion must be parallelized to expect any kind of reasonable performance. Do not expect to generate your matrix sequentially and then “use PETSc” to solve the linear system in parallel. Since PETSc is under continued development, small changes in usage and calling sequences of routines will occur. PETSc is supported; see the web site http://www.mcs.anl.gov/petsc for information on contacting support. A http://www.mcs.anl.gov/petsc/publications may be found a list of publications and web sites that feature work involving PETSc. We welcome any reports of corrections for this document.« less

PETSc Users Manual Revision 3.5

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balay, S.; Abhyankar, S.; Adams, M.

This manual describes the use of PETSc for the numerical solution of partial differential equations and related problems on high-performance computers. The Portable, Extensible Toolkit for Scientific Computation (PETSc) is a suite of data structures and routines that provide the building blocks for the implementation of large-scale application codes on parallel (and serial) computers. PETSc uses the MPI standard for all message-passing communication. PETSc includes an expanding suite of parallel linear, nonlinear equation solvers and time integrators that may be used in application codes written in Fortran, C, C++, Python, and MATLAB (sequential). PETSc provides many of the mechanisms neededmore » within parallel application codes, such as parallel matrix and vector assembly routines. The library is organized hierarchically, enabling users to employ the level of abstraction that is most appropriate for a particular problem. By using techniques of object-oriented programming, PETSc provides enormous flexibility for users. PETSc is a sophisticated set of software tools; as such, for some users it initially has a much steeper learning curve than a simple subroutine library. In particular, for individuals without some computer science background, experience programming in C, C++ or Fortran and experience using a debugger such as gdb or dbx, it may require a significant amount of time to take full advantage of the features that enable efficient software use. However, the power of the PETSc design and the algorithms it incorporates may make the efficient implementation of many application codes simpler than “rolling them” yourself. ;For many tasks a package such as MATLAB is often the best tool; PETSc is not intended for the classes of problems for which effective MATLAB code can be written. PETSc also has a MATLAB interface, so portions of your code can be written in MATLAB to “try out” the PETSc solvers. The resulting code will not be scalable however because currently MATLAB is inherently not scalable; and PETSc should not be used to attempt to provide a “parallel linear solver” in an otherwise sequential code. Certainly all parts of a previously sequential code need not be parallelized but the matrix generation portion must be parallelized to expect any kind of reasonable performance. Do not expect to generate your matrix sequentially and then “use PETSc” to solve the linear system in parallel. Since PETSc is under continued development, small changes in usage and calling sequences of routines will occur. PETSc is supported; see the web site http://www.mcs.anl.gov/petsc for information on contacting support. A http://www.mcs.anl.gov/petsc/publications may be found a list of publications and web sites that feature work involving PETSc. We welcome any reports of corrections for this document.« less

Application Portable Parallel Library

NASA Technical Reports Server (NTRS)

Cole, Gary L.; Blech, Richard A.; Quealy, Angela; Townsend, Scott

1995-01-01

Application Portable Parallel Library (APPL) computer program is subroutine-based message-passing software library intended to provide consistent interface to variety of multiprocessor computers on market today. Minimizes effort needed to move application program from one computer to another. User develops application program once and then easily moves application program from parallel computer on which created to another parallel computer. ("Parallel computer" also include heterogeneous collection of networked computers). Written in C language with one FORTRAN 77 subroutine for UNIX-based computers and callable from application programs written in C language or FORTRAN 77.

Simultaneous activation of parallel sensory pathways promotes a grooming sequence in Drosophila

PubMed Central

Hampel, Stefanie; McKellar, Claire E

2017-01-01

A central model that describes how behavioral sequences are produced features a neural architecture that readies different movements simultaneously, and a mechanism where prioritized suppression between the movements determines their sequential performance. We previously described a model whereby suppression drives a Drosophila grooming sequence that is induced by simultaneous activation of different sensory pathways that each elicit a distinct movement (Seeds et al., 2014). Here, we confirm this model using transgenic expression to identify and optogenetically activate sensory neurons that elicit specific grooming movements. Simultaneous activation of different sensory pathways elicits a grooming sequence that resembles the naturally induced sequence. Moreover, the sequence proceeds after the sensory excitation is terminated, indicating that a persistent trace of this excitation induces the next grooming movement once the previous one is performed. This reveals a mechanism whereby parallel sensory inputs can be integrated and stored to elicit a delayed and sequential grooming response. PMID:28887878

Bamgineer: Introduction of simulated allele-specific copy number variants into exome and targeted sequence data sets.

PubMed

Samadian, Soroush; Bruce, Jeff P; Pugh, Trevor J

2018-03-01

Somatic copy number variations (CNVs) play a crucial role in development of many human cancers. The broad availability of next-generation sequencing data has enabled the development of algorithms to computationally infer CNV profiles from a variety of data types including exome and targeted sequence data; currently the most prevalent types of cancer genomics data. However, systemic evaluation and comparison of these tools remains challenging due to a lack of ground truth reference sets. To address this need, we have developed Bamgineer, a tool written in Python to introduce user-defined haplotype-phased allele-specific copy number events into an existing Binary Alignment Mapping (BAM) file, with a focus on targeted and exome sequencing experiments. As input, this tool requires a read alignment file (BAM format), lists of non-overlapping genome coordinates for introduction of gains and losses (bed file), and an optional file defining known haplotypes (vcf format). To improve runtime performance, Bamgineer introduces the desired CNVs in parallel using queuing and parallel processing on a local machine or on a high-performance computing cluster. As proof-of-principle, we applied Bamgineer to a single high-coverage (mean: 220X) exome sequence file from a blood sample to simulate copy number profiles of 3 exemplar tumors from each of 10 tumor types at 5 tumor cellularity levels (20-100%, 150 BAM files in total). To demonstrate feasibility beyond exome data, we introduced read alignments to a targeted 5-gene cell-free DNA sequencing library to simulate EGFR amplifications at frequencies consistent with circulating tumor DNA (10, 1, 0.1 and 0.01%) while retaining the multimodal insert size distribution of the original data. We expect Bamgineer to be of use for development and systematic benchmarking of CNV calling algorithms by users using locally-generated data for a variety of applications. The source code is freely available at http://github.com/pughlab/bamgineer.

Big Data Application in Biomedical Research and Health Care: A Literature Review.

PubMed

Luo, Jake; Wu, Min; Gopukumar, Deepika; Zhao, Yiqing

2016-01-01

Big data technologies are increasingly used for biomedical and health-care informatics research. Large amounts of biological and clinical data have been generated and collected at an unprecedented speed and scale. For example, the new generation of sequencing technologies enables the processing of billions of DNA sequence data per day, and the application of electronic health records (EHRs) is documenting large amounts of patient data. The cost of acquiring and analyzing biomedical data is expected to decrease dramatically with the help of technology upgrades, such as the emergence of new sequencing machines, the development of novel hardware and software for parallel computing, and the extensive expansion of EHRs. Big data applications present new opportunities to discover new knowledge and create novel methods to improve the quality of health care. The application of big data in health care is a fast-growing field, with many new discoveries and methodologies published in the last five years. In this paper, we review and discuss big data application in four major biomedical subdisciplines: (1) bioinformatics, (2) clinical informatics, (3) imaging informatics, and (4) public health informatics. Specifically, in bioinformatics, high-throughput experiments facilitate the research of new genome-wide association studies of diseases, and with clinical informatics, the clinical field benefits from the vast amount of collected patient data for making intelligent decisions. Imaging informatics is now more rapidly integrated with cloud platforms to share medical image data and workflows, and public health informatics leverages big data techniques for predicting and monitoring infectious disease outbreaks, such as Ebola. In this paper, we review the recent progress and breakthroughs of big data applications in these health-care domains and summarize the challenges, gaps, and opportunities to improve and advance big data applications in health care.

Big Data Application in Biomedical Research and Health Care: A Literature Review

PubMed Central

Luo, Jake; Wu, Min; Gopukumar, Deepika; Zhao, Yiqing

2016-01-01

Big data technologies are increasingly used for biomedical and health-care informatics research. Large amounts of biological and clinical data have been generated and collected at an unprecedented speed and scale. For example, the new generation of sequencing technologies enables the processing of billions of DNA sequence data per day, and the application of electronic health records (EHRs) is documenting large amounts of patient data. The cost of acquiring and analyzing biomedical data is expected to decrease dramatically with the help of technology upgrades, such as the emergence of new sequencing machines, the development of novel hardware and software for parallel computing, and the extensive expansion of EHRs. Big data applications present new opportunities to discover new knowledge and create novel methods to improve the quality of health care. The application of big data in health care is a fast-growing field, with many new discoveries and methodologies published in the last five years. In this paper, we review and discuss big data application in four major biomedical subdisciplines: (1) bioinformatics, (2) clinical informatics, (3) imaging informatics, and (4) public health informatics. Specifically, in bioinformatics, high-throughput experiments facilitate the research of new genome-wide association studies of diseases, and with clinical informatics, the clinical field benefits from the vast amount of collected patient data for making intelligent decisions. Imaging informatics is now more rapidly integrated with cloud platforms to share medical image data and workflows, and public health informatics leverages big data techniques for predicting and monitoring infectious disease outbreaks, such as Ebola. In this paper, we review the recent progress and breakthroughs of big data applications in these health-care domains and summarize the challenges, gaps, and opportunities to improve and advance big data applications in health care. PMID:26843812

Evaluation of massively parallel sequencing for forensic DNA methylation profiling.

PubMed

Richards, Rebecca; Patel, Jayshree; Stevenson, Kate; Harbison, SallyAnn

2018-05-11

Epigenetics is an emerging area of interest in forensic science. DNA methylation, a type of epigenetic modification, can be applied to chronological age estimation, identical twin differentiation and body fluid identification. However, there is not yet an agreed, established methodology for targeted detection and analysis of DNA methylation markers in forensic research. Recently a massively parallel sequencing-based approach has been suggested. The use of massively parallel sequencing is well established in clinical epigenetics and is emerging as a new technology in the forensic field. This review investigates the potential benefits, limitations and considerations of this technique for the analysis of DNA methylation in a forensic context. The importance of a robust protocol, regardless of the methodology used, that minimises potential sources of bias is highlighted. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Convergent evolution of marine mammals is associated with distinct substitutions in common genes

PubMed Central

Zhou, Xuming; Seim, Inge; Gladyshev, Vadim N.

2015-01-01

Phenotypic convergence is thought to be driven by parallel substitutions coupled with natural selection at the sequence level. Multiple independent evolutionary transitions of mammals to an aquatic environment offer an opportunity to test this thesis. Here, whole genome alignment of coding sequences identified widespread parallel amino acid substitutions in marine mammals; however, the majority of these changes were not unique to these animals. Conversely, we report that candidate aquatic adaptation genes, identified by signatures of likelihood convergence and/or elevated ratio of nonsynonymous to synonymous nucleotide substitution rate, are characterized by very few parallel substitutions and exhibit distinct sequence changes in each group. Moreover, no significant positive correlation was found between likelihood convergence and positive selection in all three marine lineages. These results suggest that convergence in protein coding genes associated with aquatic lifestyle is mainly characterized by independent substitutions and relaxed negative selection. PMID:26549748

Parallel Mitogenome Sequencing Alleviates Random Rooting Effect in Phylogeography.

PubMed

Hirase, Shotaro; Takeshima, Hirohiko; Nishida, Mutsumi; Iwasaki, Wataru

2016-04-28

Reliably rooted phylogenetic trees play irreplaceable roles in clarifying diversification in the patterns of species and populations. However, such trees are often unavailable in phylogeographic studies, particularly when the focus is on rapidly expanded populations that exhibit star-like trees. A fundamental bottleneck is known as the random rooting effect, where a distant outgroup tends to root an unrooted tree "randomly." We investigated whether parallel mitochondrial genome (mitogenome) sequencing alleviates this effect in phylogeography using a case study on the Sea of Japan lineage of the intertidal goby Chaenogobius annularis Eighty-three C. annularis individuals were collected and their mitogenomes were determined by high-throughput and low-cost parallel sequencing. Phylogenetic analysis of these mitogenome sequences was conducted to root the Sea of Japan lineage, which has a star-like phylogeny and had not been reliably rooted. The topologies of the bootstrap trees were investigated to determine whether the use of mitogenomes alleviated the random rooting effect. The mitogenome data successfully rooted the Sea of Japan lineage by alleviating the effect, which hindered phylogenetic analysis that used specific gene sequences. The reliable rooting of the lineage led to the discovery of a novel, northern lineage that expanded during an interglacial period with high bootstrap support. Furthermore, the finding of this lineage suggested the existence of additional glacial refugia and provided a new recent calibration point that revised the divergence time estimation between the Sea of Japan and Pacific Ocean lineages. This study illustrates the effectiveness of parallel mitogenome sequencing for solving the random rooting problem in phylogeographic studies. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Aggregating job exit statuses of a plurality of compute nodes executing a parallel application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aho, Michael E.; Attinella, John E.; Gooding, Thomas M.

Aggregating job exit statuses of a plurality of compute nodes executing a parallel application, including: identifying a subset of compute nodes in the parallel computer to execute the parallel application; selecting one compute node in the subset of compute nodes in the parallel computer as a job leader compute node; initiating execution of the parallel application on the subset of compute nodes; receiving an exit status from each compute node in the subset of compute nodes, where the exit status for each compute node includes information describing execution of some portion of the parallel application by the compute node; aggregatingmore » each exit status from each compute node in the subset of compute nodes; and sending an aggregated exit status for the subset of compute nodes in the parallel computer.« less

A parallel row-based algorithm with error control for standard-cell replacement on a hypercube multiprocessor

NASA Technical Reports Server (NTRS)

Sargent, Jeff Scott

1988-01-01

A new row-based parallel algorithm for standard-cell placement targeted for execution on a hypercube multiprocessor is presented. Key features of this implementation include a dynamic simulated-annealing schedule, row-partitioning of the VLSI chip image, and two novel new approaches to controlling error in parallel cell-placement algorithms; Heuristic Cell-Coloring and Adaptive (Parallel Move) Sequence Control. Heuristic Cell-Coloring identifies sets of noninteracting cells that can be moved repeatedly, and in parallel, with no buildup of error in the placement cost. Adaptive Sequence Control allows multiple parallel cell moves to take place between global cell-position updates. This feedback mechanism is based on an error bound derived analytically from the traditional annealing move-acceptance profile. Placement results are presented for real industry circuits and the performance is summarized of an implementation on the Intel iPSC/2 Hypercube. The runtime of this algorithm is 5 to 16 times faster than a previous program developed for the Hypercube, while producing equivalent quality placement. An integrated place and route program for the Intel iPSC/2 Hypercube is currently being developed.

Flow cytometry for enrichment and titration in massively parallel DNA sequencing

PubMed Central

Sandberg, Julia; Ståhl, Patrik L.; Ahmadian, Afshin; Bjursell, Magnus K.; Lundeberg, Joakim

2009-01-01

Massively parallel DNA sequencing is revolutionizing genomics research throughout the life sciences. However, the reagent costs and labor requirements in current sequencing protocols are still substantial, although improvements are continuously being made. Here, we demonstrate an effective alternative to existing sample titration protocols for the Roche/454 system using Fluorescence Activated Cell Sorting (FACS) technology to determine the optimal DNA-to-bead ratio prior to large-scale sequencing. Our method, which eliminates the need for the costly pilot sequencing of samples during titration is capable of rapidly providing accurate DNA-to-bead ratios that are not biased by the quantification and sedimentation steps included in current protocols. Moreover, we demonstrate that FACS sorting can be readily used to highly enrich fractions of beads carrying template DNA, with near total elimination of empty beads and no downstream sacrifice of DNA sequencing quality. Automated enrichment by FACS is a simple approach to obtain pure samples for bead-based sequencing systems, and offers an efficient, low-cost alternative to current enrichment protocols. PMID:19304748

A safe an easy method for building consensus HIV sequences from 454 massively parallel sequencing data.

PubMed

Fernández-Caballero Rico, Jose Ángel; Chueca Porcuna, Natalia; Álvarez Estévez, Marta; Mosquera Gutiérrez, María Del Mar; Marcos Maeso, María Ángeles; García, Federico

2018-02-01

To show how to generate a consensus sequence from the information of massive parallel sequences data obtained from routine HIV anti-retroviral resistance studies, and that may be suitable for molecular epidemiology studies. Paired Sanger (Trugene-Siemens) and next-generation sequencing (NGS) (454 GSJunior-Roche) HIV RT and protease sequences from 62 patients were studied. NGS consensus sequences were generated using Mesquite, using 10%, 15%, and 20% thresholds. Molecular evolutionary genetics analysis (MEGA) was used for phylogenetic studies. At a 10% threshold, NGS-Sanger sequences from 17/62 patients were phylogenetically related, with a median bootstrap-value of 88% (IQR83.5-95.5). Association increased to 36/62 sequences, median bootstrap 94% (IQR85.5-98)], using a 15% threshold. Maximum association was at the 20% threshold, with 61/62 sequences associated, and a median bootstrap value of 99% (IQR98-100). A safe method is presented to generate consensus sequences from HIV-NGS data at 20% threshold, which will prove useful for molecular epidemiological studies. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

IOPA: I/O-aware parallelism adaption for parallel programs

PubMed Central

Liu, Tao; Liu, Yi; Qian, Chen; Qian, Depei

2017-01-01

With the development of multi-/many-core processors, applications need to be written as parallel programs to improve execution efficiency. For data-intensive applications that use multiple threads to read/write files simultaneously, an I/O sub-system can easily become a bottleneck when too many of these types of threads exist; on the contrary, too few threads will cause insufficient resource utilization and hurt performance. Therefore, programmers must pay much attention to parallelism control to find the appropriate number of I/O threads for an application. This paper proposes a parallelism control mechanism named IOPA that can adjust the parallelism of applications to adapt to the I/O capability of a system and balance computing resources and I/O bandwidth. The programming interface of IOPA is also provided to programmers to simplify parallel programming. IOPA is evaluated using multiple applications with both solid state and hard disk drives. The results show that the parallel applications using IOPA can achieve higher efficiency than those with a fixed number of threads. PMID:28278236

IOPA: I/O-aware parallelism adaption for parallel programs.

PubMed

Liu, Tao; Liu, Yi; Qian, Chen; Qian, Depei

2017-01-01

With the development of multi-/many-core processors, applications need to be written as parallel programs to improve execution efficiency. For data-intensive applications that use multiple threads to read/write files simultaneously, an I/O sub-system can easily become a bottleneck when too many of these types of threads exist; on the contrary, too few threads will cause insufficient resource utilization and hurt performance. Therefore, programmers must pay much attention to parallelism control to find the appropriate number of I/O threads for an application. This paper proposes a parallelism control mechanism named IOPA that can adjust the parallelism of applications to adapt to the I/O capability of a system and balance computing resources and I/O bandwidth. The programming interface of IOPA is also provided to programmers to simplify parallel programming. IOPA is evaluated using multiple applications with both solid state and hard disk drives. The results show that the parallel applications using IOPA can achieve higher efficiency than those with a fixed number of threads.

Performance of the Galley Parallel File System

NASA Technical Reports Server (NTRS)

Nieuwejaar, Nils; Kotz, David

1996-01-01

As the input/output (I/O) needs of parallel scientific applications increase, file systems for multiprocessors are being designed to provide applications with parallel access to multiple disks. Many parallel file systems present applications with a conventional Unix-like interface that allows the application to access multiple disks transparently. This interface conceals the parallism within the file system, which increases the ease of programmability, but makes it difficult or impossible for sophisticated programmers and libraries to use knowledge about their I/O needs to exploit that parallelism. Furthermore, most current parallel file systems are optimized for a different workload than they are being asked to support. We introduce Galley, a new parallel file system that is intended to efficiently support realistic parallel workloads. Initial experiments, reported in this paper, indicate that Galley is capable of providing high-performance 1/O to applications the applications that rely on them. In Section 3 we describe that access data in patterns that have been observed to be common.

Parallel Implementation of MAFFT on CUDA-Enabled Graphics Hardware.

PubMed

Zhu, Xiangyuan; Li, Kenli; Salah, Ahmad; Shi, Lin; Li, Keqin

2015-01-01

Multiple sequence alignment (MSA) constitutes an extremely powerful tool for many biological applications including phylogenetic tree estimation, secondary structure prediction, and critical residue identification. However, aligning large biological sequences with popular tools such as MAFFT requires long runtimes on sequential architectures. Due to the ever increasing sizes of sequence databases, there is increasing demand to accelerate this task. In this paper, we demonstrate how graphic processing units (GPUs), powered by the compute unified device architecture (CUDA), can be used as an efficient computational platform to accelerate the MAFFT algorithm. To fully exploit the GPU's capabilities for accelerating MAFFT, we have optimized the sequence data organization to eliminate the bandwidth bottleneck of memory access, designed a memory allocation and reuse strategy to make full use of limited memory of GPUs, proposed a new modified-run-length encoding (MRLE) scheme to reduce memory consumption, and used high-performance shared memory to speed up I/O operations. Our implementation tested in three NVIDIA GPUs achieves speedup up to 11.28 on a Tesla K20m GPU compared to the sequential MAFFT 7.015.

Competitive Genomic Screens of Barcoded Yeast Libraries

PubMed Central

Urbanus, Malene; Proctor, Michael; Heisler, Lawrence E.; Giaever, Guri; Nislow, Corey

2011-01-01

By virtue of advances in next generation sequencing technologies, we have access to new genome sequences almost daily. The tempo of these advances is accelerating, promising greater depth and breadth. In light of these extraordinary advances, the need for fast, parallel methods to define gene function becomes ever more important. Collections of genome-wide deletion mutants in yeasts and E. coli have served as workhorses for functional characterization of gene function, but this approach is not scalable, current gene-deletion approaches require each of the thousands of genes that comprise a genome to be deleted and verified. Only after this work is complete can we pursue high-throughput phenotyping. Over the past decade, our laboratory has refined a portfolio of competitive, miniaturized, high-throughput genome-wide assays that can be performed in parallel. This parallelization is possible because of the inclusion of DNA 'tags', or 'barcodes,' into each mutant, with the barcode serving as a proxy for the mutation and one can measure the barcode abundance to assess mutant fitness. In this study, we seek to fill the gap between DNA sequence and barcoded mutant collections. To accomplish this we introduce a combined transposon disruption-barcoding approach that opens up parallel barcode assays to newly sequenced, but poorly characterized microbes. To illustrate this approach we present a new Candida albicans barcoded disruption collection and describe how both microarray-based and next generation sequencing-based platforms can be used to collect 10,000 - 1,000,000 gene-gene and drug-gene interactions in a single experiment. PMID:21860376

Learning Quantitative Sequence-Function Relationships from Massively Parallel Experiments

NASA Astrophysics Data System (ADS)

Atwal, Gurinder S.; Kinney, Justin B.

2016-03-01

A fundamental aspect of biological information processing is the ubiquity of sequence-function relationships—functions that map the sequence of DNA, RNA, or protein to a biochemically relevant activity. Most sequence-function relationships in biology are quantitative, but only recently have experimental techniques for effectively measuring these relationships been developed. The advent of such "massively parallel" experiments presents an exciting opportunity for the concepts and methods of statistical physics to inform the study of biological systems. After reviewing these recent experimental advances, we focus on the problem of how to infer parametric models of sequence-function relationships from the data produced by these experiments. Specifically, we retrace and extend recent theoretical work showing that inference based on mutual information, not the standard likelihood-based approach, is often necessary for accurately learning the parameters of these models. Closely connected with this result is the emergence of "diffeomorphic modes"—directions in parameter space that are far less constrained by data than likelihood-based inference would suggest. Analogous to Goldstone modes in physics, diffeomorphic modes arise from an arbitrarily broken symmetry of the inference problem. An analytically tractable model of a massively parallel experiment is then described, providing an explicit demonstration of these fundamental aspects of statistical inference. This paper concludes with an outlook on the theoretical and computational challenges currently facing studies of quantitative sequence-function relationships.

A statistical approach to detection of copy number variations in PCR-enriched targeted sequencing data.

PubMed

Demidov, German; Simakova, Tamara; Vnuchkova, Julia; Bragin, Anton

2016-10-22

Multiplex polymerase chain reaction (PCR) is a common enrichment technique for targeted massive parallel sequencing (MPS) protocols. MPS is widely used in biomedical research and clinical diagnostics as the fast and accurate tool for the detection of short genetic variations. However, identification of larger variations such as structure variants and copy number variations (CNV) is still being a challenge for targeted MPS. Some approaches and tools for structural variants detection were proposed, but they have limitations and often require datasets of certain type, size and expected number of amplicons affected by CNVs. In the paper, we describe novel algorithm for high-resolution germinal CNV detection in the PCR-enriched targeted sequencing data and present accompanying tool. We have developed a machine learning algorithm for the detection of large duplications and deletions in the targeted sequencing data generated with PCR-based enrichment step. We have performed verification studies and established the algorithm's sensitivity and specificity. We have compared developed tool with other available methods applicable for the described data and revealed its higher performance. We showed that our method has high specificity and sensitivity for high-resolution copy number detection in targeted sequencing data using large cohort of samples.

Deep learning of the regulatory grammar of yeast 5′ untranslated regions from 500,000 random sequences

PubMed Central

Groves, Benjamin; Kuchina, Anna; Rosenberg, Alexander B.; Jojic, Nebojsa; Fields, Stanley; Seelig, Georg

2017-01-01

Our ability to predict protein expression from DNA sequence alone remains poor, reflecting our limited understanding of cis-regulatory grammar and hampering the design of engineered genes for synthetic biology applications. Here, we generate a model that predicts the protein expression of the 5′ untranslated region (UTR) of mRNAs in the yeast Saccharomyces cerevisiae. We constructed a library of half a million 50-nucleotide-long random 5′ UTRs and assayed their activity in a massively parallel growth selection experiment. The resulting data allow us to quantify the impact on protein expression of Kozak sequence composition, upstream open reading frames (uORFs), and secondary structure. We trained a convolutional neural network (CNN) on the random library and showed that it performs well at predicting the protein expression of both a held-out set of the random 5′ UTRs as well as native S. cerevisiae 5′ UTRs. The model additionally was used to computationally evolve highly active 5′ UTRs. We confirmed experimentally that the great majority of the evolved sequences led to higher protein expression rates than the starting sequences, demonstrating the predictive power of this model. PMID:29097404

Cohort analysis of a single nucleotide polymorphism on DNA chips.

PubMed

Schwonbeck, Susanne; Krause-Griep, Andrea; Gajovic-Eichelmann, Nenad; Ehrentreich-Förster, Eva; Meinl, Walter; Glatt, Hansrüdi; Bier, Frank F

2004-11-15

A method has been developed to determine SNPs on DNA chips by applying a flow-through bioscanner. As a practical application we demonstrated the fast and simple SNP analysis of 24 genotypes in an array of 96 spots with a single hybridisation and dissociation experiment. The main advantage of this methodical concept is the parallel and fast analysis without any need of enzymatic digestion. Additionally, the DNA chip format used is appropriate for parallel analysis up to 400 spots. The polymorphism in the gene of the human phenol sulfotransferase SULT1A1 was studied as a model SNP. Biotinylated PCR products containing the SNP (The SNP summary web site: ) (mutant) and those containing no mutation (wild-type) were brought onto the chips coated with NeutrAvidin using non-contact spotting. This was followed by an analysis which was carried out in a flow-through biochip scanner while constantly rinsing with buffer. After removing the non-biotinylated strand a fluorescent probe was hybridised, which is complementary to the wild-type sequence. If this probe binds to a mutant sequence, then one single base is not fully matching. Thereby, the mismatched hybrid (mutant) is less stable than the full-matched hybrid (wild-type). The final step after hybridisation on the chip involves rinsing with a buffer to start dissociation of the fluorescent probe from the immobilised DNA strand. The online measurement of the fluorescence intensity by the biochip scanner provides the possibility to follow the kinetics of the hybridisation and dissociation processes. According to the different stability of the full-match and the mismatch, either visual discrimination or kinetic analysis is possible to distinguish SNP-containing sequence from the wild-type sequence.

Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing.

PubMed

Wendt, Frank R; Warshauer, David H; Zeng, Xiangpei; Churchill, Jennifer D; Novroski, Nicole M M; Song, Bing; King, Jonathan L; LaRue, Bobby L; Budowle, Bruce

2016-11-01

Short tandem repeat (STR) loci are the traditional markers used for kinship, missing persons, and direct comparison human identity testing. These markers hold considerable value due to their highly polymorphic nature, amplicon size, and ability to be multiplexed. However, many STRs are still too large for use in analysis of highly degraded DNA. Small bi-allelic polymorphisms, such as insertions/deletions (INDELs), may be better suited for analyzing compromised samples, and their allele size differences are amenable to analysis by capillary electrophoresis. The INDEL marker allelic states range in size from 2 to 6 base pairs, enabling small amplicon size. In addition, heterozygote balance may be increased by minimizing preferential amplification of the smaller allele, as is more common with STR markers. Multiplexing a large number of INDELs allows for generating panels with high discrimination power. The Nextera™ Rapid Capture Custom Enrichment Kit (Illumina, Inc., San Diego, CA) and massively parallel sequencing (MPS) on the Illumina MiSeq were used to sequence 68 well-characterized INDELs in four major US population groups. In addition, the STR Allele Identification Tool: Razor (STRait Razor) was used in a novel way to analyze INDEL sequences and detect adjacent single nucleotide polymorphisms (SNPs) and other polymorphisms. This application enabled the discovery of unique allelic variants, which increased the discrimination power and decreased the single-locus random match probabilities (RMPs) of 22 of these well-characterized INDELs which can be considered as microhaplotypes. These findings suggest that additional microhaplotypes containing human identification (HID) INDELs may exist elsewhere in the genome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Vander Lugt correlation of DNA sequence data

NASA Astrophysics Data System (ADS)

Christens-Barry, William A.; Hawk, James F.; Martin, James C.

1990-12-01

DNA, the molecule containing the genetic code of an organism, is a linear chain of subunits. It is the sequence of subunits, of which there are four kinds, that constitutes the unique blueprint of an individual. This sequence is the focus of a large number of analyses performed by an army of geneticists, biologists, and computer scientists. Most of these analyses entail searches for specific subsequences within the larger set of sequence data. Thus, most analyses are essentially pattern recognition or correlation tasks. Yet, there are special features to such analysis that influence the strategy and methods of an optical pattern recognition approach. While the serial processing employed in digital electronic computers remains the main engine of sequence analyses, there is no fundamental reason that more efficient parallel methods cannot be used. We describe an approach using optical pattern recognition (OPR) techniques based on matched spatial filtering. This allows parallel comparison of large blocks of sequence data. In this study we have simulated a Vander Lugt1 architecture implementing our approach. Searches for specific target sequence strings within a block of DNA sequence from the Co/El plasmid2 are performed.

An integrated semiconductor device enabling non-optical genome sequencing.

PubMed

Rothberg, Jonathan M; Hinz, Wolfgang; Rearick, Todd M; Schultz, Jonathan; Mileski, William; Davey, Mel; Leamon, John H; Johnson, Kim; Milgrew, Mark J; Edwards, Matthew; Hoon, Jeremy; Simons, Jan F; Marran, David; Myers, Jason W; Davidson, John F; Branting, Annika; Nobile, John R; Puc, Bernard P; Light, David; Clark, Travis A; Huber, Martin; Branciforte, Jeffrey T; Stoner, Isaac B; Cawley, Simon E; Lyons, Michael; Fu, Yutao; Homer, Nils; Sedova, Marina; Miao, Xin; Reed, Brian; Sabina, Jeffrey; Feierstein, Erika; Schorn, Michelle; Alanjary, Mohammad; Dimalanta, Eileen; Dressman, Devin; Kasinskas, Rachel; Sokolsky, Tanya; Fidanza, Jacqueline A; Namsaraev, Eugeni; McKernan, Kevin J; Williams, Alan; Roth, G Thomas; Bustillo, James

2011-07-20

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.

Temporal Precedence Checking for Switched Models and its Application to a Parallel Landing Protocol

NASA Technical Reports Server (NTRS)

Duggirala, Parasara Sridhar; Wang, Le; Mitra, Sayan; Viswanathan, Mahesh; Munoz, Cesar A.

2014-01-01

This paper presents an algorithm for checking temporal precedence properties of nonlinear switched systems. This class of properties subsume bounded safety and capture requirements about visiting a sequence of predicates within given time intervals. The algorithm handles nonlinear predicates that arise from dynamics-based predictions used in alerting protocols for state-of-the-art transportation systems. It is sound and complete for nonlinear switch systems that robustly satisfy the given property. The algorithm is implemented in the Compare Execute Check Engine (C2E2) using validated simulations. As a case study, a simplified model of an alerting system for closely spaced parallel runways is considered. The proposed approach is applied to this model to check safety properties of the alerting logic for different operating conditions such as initial velocities, bank angles, aircraft longitudinal separation, and runway separation.

Sequence investigation of 34 forensic autosomal STRs with massively parallel sequencing.

PubMed

Zhang, Suhua; Niu, Yong; Bian, Yingnan; Dong, Rixia; Liu, Xiling; Bao, Yun; Jin, Chao; Zheng, Hancheng; Li, Chengtao

2018-05-01

STRs vary not only in the length of the repeat units and the number of repeats but also in the region with which they conform to an incremental repeat pattern. Massively parallel sequencing (MPS) offers new possibilities in the analysis of STRs since they can simultaneously sequence multiple targets in a single reaction and capture potential internal sequence variations. Here, we sequenced 34 STRs applied in the forensic community of China with a custom-designed panel. MPS performance were evaluated from sequencing reads analysis, concordance study and sensitivity testing. High coverage sequencing data were obtained to determine the constitute ratios and heterozygous balance. No actual inconsistent genotypes were observed between capillary electrophoresis (CE) and MPS, demonstrating the reliability of the panel and the MPS technology. With the sequencing data from the 200 investigated individuals, 346 and 418 alleles were obtained via CE and MPS technologies at the 34 STRs, indicating MPS technology provides higher discrimination than CE detection. The whole study demonstrated that STR genotyping with the custom panel and MPS technology has the potential not only to reveal length and sequence variations but also to satisfy the demands of high throughput and high multiplexing with acceptable sensitivity.

RAMICS: trainable, high-speed and biologically relevant alignment of high-throughput sequencing reads to coding DNA.

PubMed

Wright, Imogen A; Travers, Simon A

2014-07-01

The challenge presented by high-throughput sequencing necessitates the development of novel tools for accurate alignment of reads to reference sequences. Current approaches focus on using heuristics to map reads quickly to large genomes, rather than generating highly accurate alignments in coding regions. Such approaches are, thus, unsuited for applications such as amplicon-based analysis and the realignment phase of exome sequencing and RNA-seq, where accurate and biologically relevant alignment of coding regions is critical. To facilitate such analyses, we have developed a novel tool, RAMICS, that is tailored to mapping large numbers of sequence reads to short lengths (<10 000 bp) of coding DNA. RAMICS utilizes profile hidden Markov models to discover the open reading frame of each sequence and aligns to the reference sequence in a biologically relevant manner, distinguishing between genuine codon-sized indels and frameshift mutations. This approach facilitates the generation of highly accurate alignments, accounting for the error biases of the sequencing machine used to generate reads, particularly at homopolymer regions. Performance improvements are gained through the use of graphics processing units, which increase the speed of mapping through parallelization. RAMICS substantially outperforms all other mapping approaches tested in terms of alignment quality while maintaining highly competitive speed performance. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Integration of targeted sequencing and NIPT into clinical practice in a Chinese family with maple syrup urine disease.

PubMed

You, Yanqin; Sun, Yan; Li, Xuchao; Li, Yali; Wei, Xiaoming; Chen, Fang; Ge, Huijuan; Lan, Zhangzhang; Zhu, Qian; Tang, Ying; Wang, Shujuan; Gao, Ya; Jiang, Fuman; Song, Jiaping; Shi, Quan; Zhu, Xuan; Mu, Feng; Dong, Wei; Gao, Vince; Jiang, Hui; Yi, Xin; Wang, Wei; Gao, Zhiying

2014-08-01

This article demonstrates a prominent noninvasive prenatal approach to assist the clinical diagnosis of a single-gene disorder disease, maple syrup urine disease, using targeted sequencing knowledge from the affected family. The method reported here combines novel mutant discovery in known genes by targeted massively parallel sequencing with noninvasive prenatal testing. By applying this new strategy, we successfully revealed novel mutations in the gene BCKDHA (Ex2_4dup and c.392A>G) in this Chinese family and developed a prenatal haplotype-assisted approach to noninvasively detect the genotype of the fetus (transmitted from both parents). This is the first report of integration of targeted sequencing and noninvasive prenatal testing into clinical practice. Our study has demonstrated that this massively parallel sequencing-based strategy can potentially be used for single-gene disorder diagnosis in the future.

Simultaneous digital quantification and fluorescence-based size characterization of massively parallel sequencing libraries.

PubMed

Laurie, Matthew T; Bertout, Jessica A; Taylor, Sean D; Burton, Joshua N; Shendure, Jay A; Bielas, Jason H

2013-08-01

Due to the high cost of failed runs and suboptimal data yields, quantification and determination of fragment size range are crucial steps in the library preparation process for massively parallel sequencing (or next-generation sequencing). Current library quality control methods commonly involve quantification using real-time quantitative PCR and size determination using gel or capillary electrophoresis. These methods are laborious and subject to a number of significant limitations that can make library calibration unreliable. Herein, we propose and test an alternative method for quality control of sequencing libraries using droplet digital PCR (ddPCR). By exploiting a correlation we have discovered between droplet fluorescence and amplicon size, we achieve the joint quantification and size determination of target DNA with a single ddPCR assay. We demonstrate the accuracy and precision of applying this method to the preparation of sequencing libraries.

Extended RF shimming: Sequence-level parallel transmission optimization applied to steady-state free precession MRI of the heart.

PubMed

Beqiri, Arian; Price, Anthony N; Padormo, Francesco; Hajnal, Joseph V; Malik, Shaihan J

2017-06-01

Cardiac magnetic resonance imaging (MRI) at high field presents challenges because of the high specific absorption rate and significant transmit field (B 1 + ) inhomogeneities. Parallel transmission MRI offers the ability to correct for both issues at the level of individual radiofrequency (RF) pulses, but must operate within strict hardware and safety constraints. The constraints are themselves affected by sequence parameters, such as the RF pulse duration and TR, meaning that an overall optimal operating point exists for a given sequence. This work seeks to obtain optimal performance by performing a 'sequence-level' optimization in which pulse sequence parameters are included as part of an RF shimming calculation. The method is applied to balanced steady-state free precession cardiac MRI with the objective of minimizing TR, hence reducing the imaging duration. Results are demonstrated using an eight-channel parallel transmit system operating at 3 T, with an in vivo study carried out on seven male subjects of varying body mass index (BMI). Compared with single-channel operation, a mean-squared-error shimming approach leads to reduced imaging durations of 32 ± 3% with simultaneous improvement in flip angle homogeneity of 32 ± 8% within the myocardium. © 2017 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation

PubMed Central

2010-01-01

Background Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Results Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Conclusion Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing. PMID:20707912

Massively parallel cis-regulatory analysis in the mammalian central nervous system

PubMed Central

Shen, Susan Q.; Myers, Connie A.; Hughes, Andrew E.O.; Byrne, Leah C.; Flannery, John G.; Corbo, Joseph C.

2016-01-01

Cis-regulatory elements (CREs, e.g., promoters and enhancers) regulate gene expression, and variants within CREs can modulate disease risk. Next-generation sequencing has enabled the rapid generation of genomic data that predict the locations of CREs, but a bottleneck lies in functionally interpreting these data. To address this issue, massively parallel reporter assays (MPRAs) have emerged, in which barcoded reporter libraries are introduced into cells, and the resulting barcoded transcripts are quantified by next-generation sequencing. Thus far, MPRAs have been largely restricted to assaying short CREs in a limited repertoire of cultured cell types. Here, we present two advances that extend the biological relevance and applicability of MPRAs. First, we adapt exome capture technology to instead capture candidate CREs, thereby tiling across the targeted regions and markedly increasing the length of CREs that can be readily assayed. Second, we package the library into adeno-associated virus (AAV), thereby allowing delivery to target organs in vivo. As a proof of concept, we introduce a capture library of about 46,000 constructs, corresponding to roughly 3500 DNase I hypersensitive (DHS) sites, into the mouse retina by ex vivo plasmid electroporation and into the mouse cerebral cortex by in vivo AAV injection. We demonstrate tissue-specific cis-regulatory activity of DHSs and provide examples of high-resolution truncation mutation analysis for multiplex parsing of CREs. Our approach should enable massively parallel functional analysis of a wide range of CREs in any organ or species that can be infected by AAV, such as nonhuman primates and human stem cell–derived organoids. PMID:26576614

Activity Enhancement of G-Quadruplex/Hemin DNAzyme by Flanking d(CCC).

PubMed

Chang, Tianjun; Gong, Hongmei; Ding, Pi; Liu, Xiangjun; Li, Weiguo; Bing, Tao; Cao, Zehui; Shangguan, Dihua

2016-03-14

G-quadruplex (G4)/hemin DNAzymes have been extensively applied in bioanalysis and molecular devices. However, their catalytic activity is still much lower than that of proteinous enzymes. The G4/hemin DNAzyme activity is correlated with the G4 conformations and the solution conditions. However, little is known about the effect of the flanking sequences on the activity, though they are important parts of G4s. Here, we report sequences containing d(CCC), flanked on both ends of the G4-core sequences remarkably enhance their DNAzyme activity. By using circular dichroism and UV-visible spectroscopy, the d(CCC) flanking sequences were demonstrated to improve the hemin binding affinity to G4s instead of increasing the parallel G4 formation, which might explain the enhanced DNAzyme activity. Meanwhile, the increased hemin binding ability promoted the degradation of hemin within the DNAzyme by H2O2. Furthermore, the DNAzyme with d(CCC) flanking sequences showed strong tolerance to pH value changes, which makes it more suitable for applications requiring wide pH conditions. The results highlight the influence of the flanking sequences on the DNAzyme activity and provide insightful information for the design of highly active DNAzymes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Informational and linguistic analysis of large genomic sequence collections via efficient Hadoop cluster algorithms.

PubMed

Ferraro Petrillo, Umberto; Roscigno, Gianluca; Cattaneo, Giuseppe; Giancarlo, Raffaele

2018-06-01

Information theoretic and compositional/linguistic analysis of genomes have a central role in bioinformatics, even more so since the associated methodologies are becoming very valuable also for epigenomic and meta-genomic studies. The kernel of those methods is based on the collection of k-mer statistics, i.e. how many times each k-mer in {A,C,G,T}k occurs in a DNA sequence. Although this problem is computationally very simple and efficiently solvable on a conventional computer, the sheer amount of data available now in applications demands to resort to parallel and distributed computing. Indeed, those type of algorithms have been developed to collect k-mer statistics in the realm of genome assembly. However, they are so specialized to this domain that they do not extend easily to the computation of informational and linguistic indices, concurrently on sets of genomes. Following the well-established approach in many disciplines, and with a growing success also in bioinformatics, to resort to MapReduce and Hadoop to deal with 'Big Data' problems, we present KCH, the first set of MapReduce algorithms able to perform concurrently informational and linguistic analysis of large collections of genomic sequences on a Hadoop cluster. The benchmarking of KCH that we provide indicates that it is quite effective and versatile. It is also competitive with respect to the parallel and distributed algorithms highly specialized to k-mer statistics collection for genome assembly problems. In conclusion, KCH is a much needed addition to the growing number of algorithms and tools that use MapReduce for bioinformatics core applications. The software, including instructions for running it over Amazon AWS, as well as the datasets are available at http://www.di-srv.unisa.it/KCH. umberto.ferraro@uniroma1.it. Supplementary data are available at Bioinformatics online.

Parallel Algorithms and Patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robey, Robert W.

2016-06-16

This is a powerpoint presentation on parallel algorithms and patterns. A parallel algorithm is a well-defined, step-by-step computational procedure that emphasizes concurrency to solve a problem. Examples of problems include: Sorting, searching, optimization, matrix operations. A parallel pattern is a computational step in a sequence of independent, potentially concurrent operations that occurs in diverse scenarios with some frequency. Examples are: Reductions, prefix scans, ghost cell updates. We only touch on parallel patterns in this presentation. It really deserves its own detailed discussion which Gabe Rockefeller would like to develop.

HAlign-II: efficient ultra-large multiple sequence alignment and phylogenetic tree reconstruction with distributed and parallel computing.

PubMed

Wan, Shixiang; Zou, Quan

2017-01-01

Multiple sequence alignment (MSA) plays a key role in biological sequence analyses, especially in phylogenetic tree construction. Extreme increase in next-generation sequencing results in shortage of efficient ultra-large biological sequence alignment approaches for coping with different sequence types. Distributed and parallel computing represents a crucial technique for accelerating ultra-large (e.g. files more than 1 GB) sequence analyses. Based on HAlign and Spark distributed computing system, we implement a highly cost-efficient and time-efficient HAlign-II tool to address ultra-large multiple biological sequence alignment and phylogenetic tree construction. The experiments in the DNA and protein large scale data sets, which are more than 1GB files, showed that HAlign II could save time and space. It outperformed the current software tools. HAlign-II can efficiently carry out MSA and construct phylogenetic trees with ultra-large numbers of biological sequences. HAlign-II shows extremely high memory efficiency and scales well with increases in computing resource. THAlign-II provides a user-friendly web server based on our distributed computing infrastructure. HAlign-II with open-source codes and datasets was established at http://lab.malab.cn/soft/halign.

Accelerating next generation sequencing data analysis with system level optimizations.

PubMed

Kathiresan, Nagarajan; Temanni, Ramzi; Almabrazi, Hakeem; Syed, Najeeb; Jithesh, Puthen V; Al-Ali, Rashid

2017-08-22

Next generation sequencing (NGS) data analysis is highly compute intensive. In-memory computing, vectorization, bulk data transfer, CPU frequency scaling are some of the hardware features in the modern computing architectures. To get the best execution time and utilize these hardware features, it is necessary to tune the system level parameters before running the application. We studied the GATK-HaplotypeCaller which is part of common NGS workflows, that consume more than 43% of the total execution time. Multiple GATK 3.x versions were benchmarked and the execution time of HaplotypeCaller was optimized by various system level parameters which included: (i) tuning the parallel garbage collection and kernel shared memory to simulate in-memory computing, (ii) architecture-specific tuning in the PairHMM library for vectorization, (iii) including Java 1.8 features through GATK source code compilation and building a runtime environment for parallel sorting and bulk data transfer (iv) the default 'on-demand' mode of CPU frequency is over-clocked by using 'performance-mode' to accelerate the Java multi-threads. As a result, the HaplotypeCaller execution time was reduced by 82.66% in GATK 3.3 and 42.61% in GATK 3.7. Overall, the execution time of NGS pipeline was reduced to 70.60% and 34.14% for GATK 3.3 and GATK 3.7 respectively.

Forensic ancestry analysis in two Chinese minority populations using massively parallel sequencing of 165 ancestry-informative SNPs.

PubMed

He, Guanglin; Wang, Zheng; Wang, Mengge; Luo, Tao; Liu, Jing; Zhou, You; Gao, Bo; Hou, Yiping

2018-06-04

Ancestry inference based on single nucleotide polymorphism (SNP) with marked allele frequency differences in diverse populations (called ancestry-informative SNP, AISNP) is rapidly developed with the technology advancements of massively parallel sequencing (MPS). Despite the decade of exploration and broad public interest in the peopling of East-Asians, the genetic landscape of Chinese Silk Road populations based on the AISNPs is still little known. In this work, 206 unrelated individuals from Chinese Uyghur and Hui populations were firstly genotyped by 165 AISNPs (The Precision ID Ancestry Panel) using the Ion Torrent PGM system. The ethnic origin of two investigated populations and population structures and genetic relationships were subsequently investigated. The 165 AISNPs panel not only can differentiate Uyghur and Hui populations but also has potential applications in individual identification. Comprehensive population comparisons and admixture estimates demonstrated a predominantly higher European-related ancestry (36.30%) in Uyghurs than Huis (3.66%). Overall, the Precision ID Ancestry Panel can provide good resolution at the intercontinental level, but has limitations on the genetic homogeneous populations, such as the Hui and Han. Additional population-specific AISNPs remain necessary to get better-scale resolution within geographically proximate populations in East Asia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prediction of response to anti-EGFR antibody-based therapies by multigene sequencing in colorectal cancer patients.

PubMed

Lupini, Laura; Bassi, Cristian; Mlcochova, Jitka; Musa, Gentian; Russo, Marta; Vychytilova-Faltejskova, Petra; Svoboda, Marek; Sabbioni, Silvia; Nemecek, Radim; Slaby, Ondrej; Negrini, Massimo

2015-10-27

The anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (moAbs) cetuximab or panitumumab are administered to colorectal cancer (CRC) patients who harbor wild-type RAS proto-oncogenes. However, a percentage of patients do not respond to this treatment. In addition to mutations in the RAS genes, mutations in other genes, such as BRAF, PI3KCA, or PTEN, could be involved in the resistance to anti-EGFR moAb therapy. In order to develop a comprehensive approach for the detection of mutations and to eventually identify other genes responsible for resistance to anti-EGFR moAbs, we investigated a panel of 21 genes by parallel sequencing on the Ion Torrent Personal Genome Machine platform. We sequenced 65 CRCs that were treated with cetuximab or panitumumab. Among these, 37 samples were responsive and 28 were resistant. We confirmed that mutations in EGFR-pathway genes (KRAS, NRAS, BRAF, PI3KCA) were relevant for conferring resistance to therapy and could predict response (p = 0.001). After exclusion of KRAS, NRAS, BRAF and PI3KCA combined mutations could still significantly associate to resistant phenotype (p = 0.045, by Fisher exact test). In addition, mutations in FBXW7 and SMAD4 were prevalent in cases that were non-responsive to anti-EGFR moAb. After we combined the mutations of all genes (excluding KRAS), the ability to predict response to therapy improved significantly (p = 0.002, by Fisher exact test). The combination of mutations at KRAS and at the five gene panel demonstrates the usefulness and feasibility of multigene sequencing to assess response to anti-EGFR moAbs. The application of parallel sequencing technology in clinical practice, in addition to its innate ability to simultaneously examine the genetic status of several cancer genes, proved to be more accurate and sensitive than the presently in use traditional approaches.

Evaluation of targeted exome sequencing for 28 protein-based blood group systems, including the homologous gene systems, for blood group genotyping.

PubMed

Schoeman, Elizna M; Lopez, Genghis H; McGowan, Eunike C; Millard, Glenda M; O'Brien, Helen; Roulis, Eileen V; Liew, Yew-Wah; Martin, Jacqueline R; McGrath, Kelli A; Powley, Tanya; Flower, Robert L; Hyland, Catherine A

2017-04-01

Blood group single nucleotide polymorphism genotyping probes for a limited range of polymorphisms. This study investigated whether massively parallel sequencing (also known as next-generation sequencing), with a targeted exome strategy, provides an extended blood group genotype and the extent to which massively parallel sequencing correctly genotypes in homologous gene systems, such as RH and MNS. Donor samples (n = 28) that were extensively phenotyped and genotyped using single nucleotide polymorphism typing, were analyzed using the TruSight One Sequencing Panel and MiSeq platform. Genes for 28 protein-based blood group systems, GATA1, and KLF1 were analyzed. Copy number variation analysis was used to characterize complex structural variants in the GYPC and RH systems. The average sequencing depth per target region was 66.2 ± 39.8. Each sample harbored on average 43 ± 9 variants, of which 10 ± 3 were used for genotyping. For the 28 samples, massively parallel sequencing variant sequences correctly matched expected sequences based on single nucleotide polymorphism genotyping data. Copy number variation analysis defined the Rh C/c alleles and complex RHD hybrids. Hybrid RHD*D-CE-D variants were correctly identified, but copy number variation analysis did not confidently distinguish between D and CE exon deletion versus rearrangement. The targeted exome sequencing strategy employed extended the range of blood group genotypes detected compared with single nucleotide polymorphism typing. This single-test format included detection of complex MNS hybrid cases and, with copy number variation analysis, defined RH hybrid genes along with the RHCE*C allele hitherto difficult to resolve by variant detection. The approach is economical compared with whole-genome sequencing and is suitable for a red blood cell reference laboratory setting. © 2017 AABB.

Parallel-Connected Photovoltaic Inverters: Zero Frequency Sequence Harmonic Analysis and Solution

NASA Astrophysics Data System (ADS)

Carmeli, Maria Stefania; Mauri, Marco; Frosio, Luisa; Bezzolato, Alberto; Marchegiani, Gabriele

2013-05-01

High-power photovoltaic (PV) plants are usually constituted of the connection of different PV subfields, each of them with its interface transformer. Different solutions have been studied to improve the efficiency of the whole generation system. In particular, transformerless configurations are the more attractive one from efficiency and costs point of view. This paper focuses on transformerless PV configurations characterised by the parallel connection of interface inverters. The problem of zero sequence current due to both the parallel connection and the presence of undesirable parasitic earth capacitances is considered and a solution, which consists of the synchronisation of pulse-width modulation triangular carrier, is proposed and theoretically analysed. The theoretical analysis has been validated through simulation and experimental results.

Dubinett - Targeted Sequencing 2012 — EDRN Public Portal

Cancer.gov

we propose to use targeted massively parallel DNA sequencing to identify somatic alterations within mutational hotspots in matched sets of primary lung tumors, premalignant lesions, and adjacent,histologically normal lung tissue.

Bayesian mixture analysis for metagenomic community profiling.

PubMed

Morfopoulou, Sofia; Plagnol, Vincent

2015-09-15

Deep sequencing of clinical samples is now an established tool for the detection of infectious pathogens, with direct medical applications. The large amount of data generated produces an opportunity to detect species even at very low levels, provided that computational tools can effectively profile the relevant metagenomic communities. Data interpretation is complicated by the fact that short sequencing reads can match multiple organisms and by the lack of completeness of existing databases, in particular for viral pathogens. Here we present metaMix, a Bayesian mixture model framework for resolving complex metagenomic mixtures. We show that the use of parallel Monte Carlo Markov chains for the exploration of the species space enables the identification of the set of species most likely to contribute to the mixture. We demonstrate the greater accuracy of metaMix compared with relevant methods, particularly for profiling complex communities consisting of several related species. We designed metaMix specifically for the analysis of deep transcriptome sequencing datasets, with a focus on viral pathogen detection; however, the principles are generally applicable to all types of metagenomic mixtures. metaMix is implemented as a user friendly R package, freely available on CRAN: http://cran.r-project.org/web/packages/metaMix sofia.morfopoulou.10@ucl.ac.uk Supplementary data are available at Bionformatics online. © The Author 2015. Published by Oxford University Press.

ASSET: Analysis of Sequences of Synchronous Events in Massively Parallel Spike Trains

PubMed Central

Canova, Carlos; Denker, Michael; Gerstein, George; Helias, Moritz

2016-01-01

With the ability to observe the activity from large numbers of neurons simultaneously using modern recording technologies, the chance to identify sub-networks involved in coordinated processing increases. Sequences of synchronous spike events (SSEs) constitute one type of such coordinated spiking that propagates activity in a temporally precise manner. The synfire chain was proposed as one potential model for such network processing. Previous work introduced a method for visualization of SSEs in massively parallel spike trains, based on an intersection matrix that contains in each entry the degree of overlap of active neurons in two corresponding time bins. Repeated SSEs are reflected in the matrix as diagonal structures of high overlap values. The method as such, however, leaves the task of identifying these diagonal structures to visual inspection rather than to a quantitative analysis. Here we present ASSET (Analysis of Sequences of Synchronous EvenTs), an improved, fully automated method which determines diagonal structures in the intersection matrix by a robust mathematical procedure. The method consists of a sequence of steps that i) assess which entries in the matrix potentially belong to a diagonal structure, ii) cluster these entries into individual diagonal structures and iii) determine the neurons composing the associated SSEs. We employ parallel point processes generated by stochastic simulations as test data to demonstrate the performance of the method under a wide range of realistic scenarios, including different types of non-stationarity of the spiking activity and different correlation structures. Finally, the ability of the method to discover SSEs is demonstrated on complex data from large network simulations with embedded synfire chains. Thus, ASSET represents an effective and efficient tool to analyze massively parallel spike data for temporal sequences of synchronous activity. PMID:27420734

A pluggable framework for parallel pairwise sequence search.

PubMed

Archuleta, Jeremy; Feng, Wu-chun; Tilevich, Eli

2007-01-01

The current and near future of the computing industry is one of multi-core and multi-processor technology. Most existing sequence-search tools have been designed with a focus on single-core, single-processor systems. This discrepancy between software design and hardware architecture substantially hinders sequence-search performance by not allowing full utilization of the hardware. This paper presents a novel framework that will aid the conversion of serial sequence-search tools into a parallel version that can take full advantage of the available hardware. The framework, which is based on a software architecture called mixin layers with refined roles, enables modules to be plugged into the framework with minimal effort. The inherent modular design improves maintenance and extensibility, thus opening up a plethora of opportunities for advanced algorithmic features to be developed and incorporated while routine maintenance of the codebase persists.

BONSAI Garden: Parallel knowledge discovery system for amino acid sequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shoudai, T.; Miyano, S.; Shinohara, A.

1995-12-31

We have developed a machine discovery system BON-SAI which receives positive and negative examples as inputs and produces as a hypothesis a pair of a decision tree over regular patterns and an alphabet indexing. This system has succeeded in discovering reasonable knowledge on transmembrane domain sequences and signal peptide sequences by computer experiments. However, when several kinds of sequences axe mixed in the data, it does not seem reasonable for a single BONSAI system to find a hypothesis of a reasonably small size with high accuracy. For this purpose, we have designed a system BONSAI Garden, in which several BONSAI`smore » and a program called Gardener run over a network in parallel, to partition the data into some number of classes together with hypotheses explaining these classes accurately.« less

Multiplexed microsatellite recovery using massively parallel sequencing

USGS Publications Warehouse

Jennings, T.N.; Knaus, B.J.; Mullins, T.D.; Haig, S.M.; Cronn, R.C.

2011-01-01

Conservation and management of natural populations requires accurate and inexpensive genotyping methods. Traditional microsatellite, or simple sequence repeat (SSR), marker analysis remains a popular genotyping method because of the comparatively low cost of marker development, ease of analysis and high power of genotype discrimination. With the availability of massively parallel sequencing (MPS), it is now possible to sequence microsatellite-enriched genomic libraries in multiplex pools. To test this approach, we prepared seven microsatellite-enriched, barcoded genomic libraries from diverse taxa (two conifer trees, five birds) and sequenced these on one lane of the Illumina Genome Analyzer using paired-end 80-bp reads. In this experiment, we screened 6.1 million sequences and identified 356958 unique microreads that contained di- or trinucleotide microsatellites. Examination of four species shows that our conversion rate from raw sequences to polymorphic markers compares favourably to Sanger- and 454-based methods. The advantage of multiplexed MPS is that the staggering capacity of modern microread sequencing is spread across many libraries; this reduces sample preparation and sequencing costs to less than $400 (USD) per species. This price is sufficiently low that microsatellite libraries could be prepared and sequenced for all 1373 organisms listed as 'threatened' and 'endangered' in the United States for under $0.5M (USD).

Binocular video ophthalmoscope for simultaneous recording of sequences of the human retina to compare dynamic parameters

NASA Astrophysics Data System (ADS)

Tornow, Ralf P.; Milczarek, Aleksandra; Odstrcilik, Jan; Kolar, Radim

2017-07-01

A parallel video ophthalmoscope was developed to acquire short video sequences (25 fps, 250 frames) of both eyes simultaneously with exact synchronization. Video sequences were registered off-line to compensate for eye movements. From registered video sequences dynamic parameters like cardiac cycle induced reflection changes and eye movements can be calculated and compared between eyes.

Opinion: Why we need a centralized repository for isotopic data

USGS Publications Warehouse

Pauli, Jonathan N.; Newsome, Seth D.; Cook, Joseph A.; Harrod, Chris; Steffan, Shawn A.; Baker, Christopher J. O.; Ben-David, Merav; Bloom, David; Bowen, Gabriel J.; Cerling, Thure E.; Cicero, Carla; Cook, Craig; Dohm, Michelle; Dharampal, Prarthana S.; Graves, Gary; Gropp, Robert; Hobson, Keith A.; Jordan, Chris; MacFadden, Bruce; Pilaar Birch, Suzanne; Poelen, Jorrit; Ratnasingham, Sujeevan; Russell, Laura; Stricker, Craig A.; Uhen, Mark D.; Yarnes, Christopher T.; Hayden, Brian

2017-01-01

Stable isotopes encode and integrate the origin of matter; thus, their analysis offers tremendous potential to address questions across diverse scientific disciplines (1, 2). Indeed, the broad applicability of stable isotopes, coupled with advancements in high-throughput analysis, have created a scientific field that is growing exponentially, and generating data at a rate paralleling the explosive rise of DNA sequencing and genomics (3). Centralized data repositories, such as GenBank, have become increasingly important as a means for archiving information, and “Big Data” analytics of these resources are revolutionizing science and everyday life.

Parallel programming of industrial applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heroux, M; Koniges, A; Simon, H

1998-07-21

In the introductory material, we overview the typical MPP environment for real application computing and the special tools available such as parallel debuggers and performance analyzers. Next, we draw from a series of real applications codes and discuss the specific challenges and problems that are encountered in parallelizing these individual applications. The application areas drawn from include biomedical sciences, materials processing and design, plasma and fluid dynamics, and others. We show how it was possible to get a particular application to run efficiently and what steps were necessary. Finally we end with a summary of the lessons learned from thesemore » applications and predictions for the future of industrial parallel computing. This tutorial is based on material from a forthcoming book entitled: "Industrial Strength Parallel Computing" to be published by Morgan Kaufmann Publishers (ISBN l-55860-54).« less

Autoplan: A self-processing network model for an extended blocks world planning environment

NASA Technical Reports Server (NTRS)

Dautrechy, C. Lynne; Reggia, James A.; Mcfadden, Frank

1990-01-01

Self-processing network models (neural/connectionist models, marker passing/message passing networks, etc.) are currently undergoing intense investigation for a variety of information processing applications. These models are potentially very powerful in that they support a large amount of explicit parallel processing, and they cleanly integrate high level and low level information processing. However they are currently limited by a lack of understanding of how to apply them effectively in many application areas. The formulation of self-processing network methods for dynamic, reactive planning is studied. The long-term goal is to formulate robust, computationally effective information processing methods for the distributed control of semiautonomous exploration systems, e.g., the Mars Rover. The current research effort is focusing on hierarchical plan generation, execution and revision through local operations in an extended blocks world environment. This scenario involves many challenging features that would be encountered in a real planning and control environment: multiple simultaneous goals, parallel as well as sequential action execution, action sequencing determined not only by goals and their interactions but also by limited resources (e.g., three tasks, two acting agents), need to interpret unanticipated events and react appropriately through replanning, etc.

Exploiting Parallel R in the Cloud with SPRINT

PubMed Central

Piotrowski, M.; McGilvary, G.A.; Sloan, T. M.; Mewissen, M.; Lloyd, A.D.; Forster, T.; Mitchell, L.; Ghazal, P.; Hill, J.

2012-01-01

Background Advances in DNA Microarray devices and next-generation massively parallel DNA sequencing platforms have led to an exponential growth in data availability but the arising opportunities require adequate computing resources. High Performance Computing (HPC) in the Cloud offers an affordable way of meeting this need. Objectives Bioconductor, a popular tool for high-throughput genomic data analysis, is distributed as add-on modules for the R statistical programming language but R has no native capabilities for exploiting multi-processor architectures. SPRINT is an R package that enables easy access to HPC for genomics researchers. This paper investigates: setting up and running SPRINT-enabled genomic analyses on Amazon’s Elastic Compute Cloud (EC2), the advantages of submitting applications to EC2 from different parts of the world and, if resource underutilization can improve application performance. Methods The SPRINT parallel implementations of correlation, permutation testing, partitioning around medoids and the multi-purpose papply have been benchmarked on data sets of various size on Amazon EC2. Jobs have been submitted from both the UK and Thailand to investigate monetary differences. Results It is possible to obtain good, scalable performance but the level of improvement is dependent upon the nature of algorithm. Resource underutilization can further improve the time to result. End-user’s location impacts on costs due to factors such as local taxation. Conclusions: Although not designed to satisfy HPC requirements, Amazon EC2 and cloud computing in general provides an interesting alternative and provides new possibilities for smaller organisations with limited funds. PMID:23223611

Exploiting parallel R in the cloud with SPRINT.

PubMed

Piotrowski, M; McGilvary, G A; Sloan, T M; Mewissen, M; Lloyd, A D; Forster, T; Mitchell, L; Ghazal, P; Hill, J

2013-01-01

Advances in DNA Microarray devices and next-generation massively parallel DNA sequencing platforms have led to an exponential growth in data availability but the arising opportunities require adequate computing resources. High Performance Computing (HPC) in the Cloud offers an affordable way of meeting this need. Bioconductor, a popular tool for high-throughput genomic data analysis, is distributed as add-on modules for the R statistical programming language but R has no native capabilities for exploiting multi-processor architectures. SPRINT is an R package that enables easy access to HPC for genomics researchers. This paper investigates: setting up and running SPRINT-enabled genomic analyses on Amazon's Elastic Compute Cloud (EC2), the advantages of submitting applications to EC2 from different parts of the world and, if resource underutilization can improve application performance. The SPRINT parallel implementations of correlation, permutation testing, partitioning around medoids and the multi-purpose papply have been benchmarked on data sets of various size on Amazon EC2. Jobs have been submitted from both the UK and Thailand to investigate monetary differences. It is possible to obtain good, scalable performance but the level of improvement is dependent upon the nature of the algorithm. Resource underutilization can further improve the time to result. End-user's location impacts on costs due to factors such as local taxation. Although not designed to satisfy HPC requirements, Amazon EC2 and cloud computing in general provides an interesting alternative and provides new possibilities for smaller organisations with limited funds.

Performance Evaluation in Network-Based Parallel Computing

NASA Technical Reports Server (NTRS)

Dezhgosha, Kamyar

1996-01-01

Network-based parallel computing is emerging as a cost-effective alternative for solving many problems which require use of supercomputers or massively parallel computers. The primary objective of this project has been to conduct experimental research on performance evaluation for clustered parallel computing. First, a testbed was established by augmenting our existing SUNSPARCs' network with PVM (Parallel Virtual Machine) which is a software system for linking clusters of machines. Second, a set of three basic applications were selected. The applications consist of a parallel search, a parallel sort, a parallel matrix multiplication. These application programs were implemented in C programming language under PVM. Third, we conducted performance evaluation under various configurations and problem sizes. Alternative parallel computing models and workload allocations for application programs were explored. The performance metric was limited to elapsed time or response time which in the context of parallel computing can be expressed in terms of speedup. The results reveal that the overhead of communication latency between processes in many cases is the restricting factor to performance. That is, coarse-grain parallelism which requires less frequent communication between processes will result in higher performance in network-based computing. Finally, we are in the final stages of installing an Asynchronous Transfer Mode (ATM) switch and four ATM interfaces (each 155 Mbps) which will allow us to extend our study to newer applications, performance metrics, and configurations.

Use Massive Parallel Sequencing and Exome Capture Technology to Sequence the Exome of Fanconi Anemia Children and Their Patents

ClinicalTrials.gov

2013-11-21

Fanconi Anemia; Autosomal or Sex Linked Recessive Genetic Disease; Bone Marrow Hematopoiesis Failure, Multiple Congenital Abnormalities, and Susceptibility to Neoplastic Diseases.; Hematopoiesis Maintainance.

An algorithm of discovering signatures from DNA databases on a computer cluster.

PubMed

Lee, Hsiao Ping; Sheu, Tzu-Fang

2014-10-05

Signatures are short sequences that are unique and not similar to any other sequence in a database that can be used as the basis to identify different species. Even though several signature discovery algorithms have been proposed in the past, these algorithms require the entirety of databases to be loaded in the memory, thus restricting the amount of data that they can process. It makes those algorithms unable to process databases with large amounts of data. Also, those algorithms use sequential models and have slower discovery speeds, meaning that the efficiency can be improved. In this research, we are debuting the utilization of a divide-and-conquer strategy in signature discovery and have proposed a parallel signature discovery algorithm on a computer cluster. The algorithm applies the divide-and-conquer strategy to solve the problem posed to the existing algorithms where they are unable to process large databases and uses a parallel computing mechanism to effectively improve the efficiency of signature discovery. Even when run with just the memory of regular personal computers, the algorithm can still process large databases such as the human whole-genome EST database which were previously unable to be processed by the existing algorithms. The algorithm proposed in this research is not limited by the amount of usable memory and can rapidly find signatures in large databases, making it useful in applications such as Next Generation Sequencing and other large database analysis and processing. The implementation of the proposed algorithm is available at http://www.cs.pu.edu.tw/~fang/DDCSDPrograms/DDCSD.htm.

A Hybrid Parallel Strategy Based on String Graph Theory to Improve De Novo DNA Assembly on the TianHe-2 Supercomputer.

PubMed

Zhang, Feng; Liao, Xiangke; Peng, Shaoliang; Cui, Yingbo; Wang, Bingqiang; Zhu, Xiaoqian; Liu, Jie

2016-06-01

' The de novo assembly of DNA sequences is increasingly important for biological researches in the genomic era. After more than one decade since the Human Genome Project, some challenges still exist and new solutions are being explored to improve de novo assembly of genomes. String graph assembler (SGA), based on the string graph theory, is a new method/tool developed to address the challenges. In this paper, based on an in-depth analysis of SGA we prove that the SGA-based sequence de novo assembly is an NP-complete problem. According to our analysis, SGA outperforms other similar methods/tools in memory consumption, but costs much more time, of which 60-70 % is spent on the index construction. Upon this analysis, we introduce a hybrid parallel optimization algorithm and implement this algorithm in the TianHe-2's parallel framework. Simulations are performed with different datasets. For data of small size the optimized solution is 3.06 times faster than before, and for data of middle size it's 1.60 times. The results demonstrate an evident performance improvement, with the linear scalability for parallel FM-index construction. This results thus contribute significantly to improving the efficiency of de novo assembly of DNA sequences.

Nanopore arrays in a silicon membrane for parallel single-molecule detection: DNA translocation

NASA Astrophysics Data System (ADS)

Zhang, Miao; Schmidt, Torsten; Jemt, Anders; Sahlén, Pelin; Sychugov, Ilya; Lundeberg, Joakim; Linnros, Jan

2015-08-01

Optical nanopore sensing offers great potential in single-molecule detection, genotyping, or DNA sequencing for high-throughput applications. However, one of the bottle-necks for fluorophore-based biomolecule sensing is the lack of an optically optimized membrane with a large array of nanopores, which has large pore-to-pore distance, small variation in pore size and low background photoluminescence (PL). Here, we demonstrate parallel detection of single-fluorophore-labeled DNA strands (450 bps) translocating through an array of silicon nanopores that fulfills the above-mentioned requirements for optical sensing. The nanopore array was fabricated using electron beam lithography and anisotropic etching followed by electrochemical etching resulting in pore diameters down to ∼7 nm. The DNA translocation measurements were performed in a conventional wide-field microscope tailored for effective background PL control. The individual nanopore diameter was found to have a substantial effect on the translocation velocity, where smaller openings slow the translocation enough for the event to be clearly detectable in the fluorescence. Our results demonstrate that a uniform silicon nanopore array combined with wide-field optical detection is a promising alternative with which to realize massively-parallel single-molecule detection.

Microfluidic Pneumatic Logic Circuits and Digital Pneumatic Microprocessors for Integrated Microfluidic Systems

PubMed Central

Rhee, Minsoung

2010-01-01

We have developed pneumatic logic circuits and microprocessors built with microfluidic channels and valves in polydimethylsiloxane (PDMS). The pneumatic logic circuits perform various combinational and sequential logic calculations with binary pneumatic signals (atmosphere and vacuum), producing cascadable outputs based on Boolean operations. A complex microprocessor is constructed from combinations of various logic circuits and receives pneumatically encoded serial commands at a single input line. The device then decodes the temporal command sequence by spatial parallelization, computes necessary logic calculations between parallelized command bits, stores command information for signal transportation and maintenance, and finally executes the command for the target devices. Thus, such pneumatic microprocessors will function as a universal on-chip control platform to perform complex parallel operations for large-scale integrated microfluidic devices. To demonstrate the working principles, we have built 2-bit, 3-bit, 4-bit, and 8-bit microprecessors to control various target devices for applications such as four color dye mixing, and multiplexed channel fluidic control. By significantly reducing the need for external controllers, the digital pneumatic microprocessor can be used as a universal on-chip platform to autonomously manipulate microfluids in a high throughput manner. PMID:19823730

Parallelized direct execution simulation of message-passing parallel programs

NASA Technical Reports Server (NTRS)

Dickens, Phillip M.; Heidelberger, Philip; Nicol, David M.

1994-01-01

As massively parallel computers proliferate, there is growing interest in findings ways by which performance of massively parallel codes can be efficiently predicted. This problem arises in diverse contexts such as parallelizing computers, parallel performance monitoring, and parallel algorithm development. In this paper we describe one solution where one directly executes the application code, but uses a discrete-event simulator to model details of the presumed parallel machine such as operating system and communication network behavior. Because this approach is computationally expensive, we are interested in its own parallelization specifically the parallelization of the discrete-event simulator. We describe methods suitable for parallelized direct execution simulation of message-passing parallel programs, and report on the performance of such a system, Large Application Parallel Simulation Environment (LAPSE), we have built on the Intel Paragon. On all codes measured to date, LAPSE predicts performance well typically within 10 percent relative error. Depending on the nature of the application code, we have observed low slowdowns (relative to natively executing code) and high relative speedups using up to 64 processors.

MRUniNovo: an efficient tool for de novo peptide sequencing utilizing the hadoop distributed computing framework.

PubMed

Li, Chuang; Chen, Tao; He, Qiang; Zhu, Yunping; Li, Kenli

2017-03-15

Tandem mass spectrometry-based de novo peptide sequencing is a complex and time-consuming process. The current algorithms for de novo peptide sequencing cannot rapidly and thoroughly process large mass spectrometry datasets. In this paper, we propose MRUniNovo, a novel tool for parallel de novo peptide sequencing. MRUniNovo parallelizes UniNovo based on the Hadoop compute platform. Our experimental results demonstrate that MRUniNovo significantly reduces the computation time of de novo peptide sequencing without sacrificing the correctness and accuracy of the results, and thus can process very large datasets that UniNovo cannot. MRUniNovo is an open source software tool implemented in java. The source code and the parameter settings are available at http://bioinfo.hupo.org.cn/MRUniNovo/index.php. s131020002@hnu.edu.cn ; taochen1019@163.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Identification of the Bovine Arachnomelia Mutation by Massively Parallel Sequencing Implicates Sulfite Oxidase (SUOX) in Bone Development

PubMed Central

Drögemüller, Cord; Tetens, Jens; Sigurdsson, Snaevar; Gentile, Arcangelo; Testoni, Stefania; Lindblad-Toh, Kerstin; Leeb, Tosso

2010-01-01

Arachnomelia is a monogenic recessive defect of skeletal development in cattle. The causative mutation was previously mapped to a ∼7 Mb interval on chromosome 5. Here we show that array-based sequence capture and massively parallel sequencing technology, combined with the typical family structure in livestock populations, facilitates the identification of the causative mutation. We re-sequenced the entire critical interval in a healthy partially inbred cow carrying one copy of the critical chromosome segment in its ancestral state and one copy of the same segment with the arachnomelia mutation, and we detected a single heterozygous position. The genetic makeup of several partially inbred cattle provides extremely strong support for the causality of this mutation. The mutation represents a single base insertion leading to a premature stop codon in the coding sequence of the SUOX gene and is perfectly associated with the arachnomelia phenotype. Our findings suggest an important role for sulfite oxidase in bone development. PMID:20865119

FRESCO: Referential compression of highly similar sequences.

PubMed

Wandelt, Sebastian; Leser, Ulf

2013-01-01

In many applications, sets of similar texts or sequences are of high importance. Prominent examples are revision histories of documents or genomic sequences. Modern high-throughput sequencing technologies are able to generate DNA sequences at an ever-increasing rate. In parallel to the decreasing experimental time and cost necessary to produce DNA sequences, computational requirements for analysis and storage of the sequences are steeply increasing. Compression is a key technology to deal with this challenge. Recently, referential compression schemes, storing only the differences between a to-be-compressed input and a known reference sequence, gained a lot of interest in this field. In this paper, we propose a general open-source framework to compress large amounts of biological sequence data called Framework for REferential Sequence COmpression (FRESCO). Our basic compression algorithm is shown to be one to two orders of magnitudes faster than comparable related work, while achieving similar compression ratios. We also propose several techniques to further increase compression ratios, while still retaining the advantage in speed: 1) selecting a good reference sequence; and 2) rewriting a reference sequence to allow for better compression. In addition,we propose a new way of further boosting the compression ratios by applying referential compression to already referentially compressed files (second-order compression). This technique allows for compression ratios way beyond state of the art, for instance,4,000:1 and higher for human genomes. We evaluate our algorithms on a large data set from three different species (more than 1,000 genomes, more than 3 TB) and on a collection of versions of Wikipedia pages. Our results show that real-time compression of highly similar sequences at high compression ratios is possible on modern hardware.

Use of the melting curve assay as a means for high-throughput quantification of Illumina sequencing libraries.

PubMed

Shinozuka, Hiroshi; Forster, John W

2016-01-01

Background. Multiplexed sequencing is commonly performed on massively parallel short-read sequencing platforms such as Illumina, and the efficiency of library normalisation can affect the quality of the output dataset. Although several library normalisation approaches have been established, none are ideal for highly multiplexed sequencing due to issues of cost and/or processing time. Methods. An inexpensive and high-throughput library quantification method has been developed, based on an adaptation of the melting curve assay. Sequencing libraries were subjected to the assay using the Bio-Rad Laboratories CFX Connect(TM) Real-Time PCR Detection System. The library quantity was calculated through summation of reduction of relative fluorescence units between 86 and 95 °C. Results.PCR-enriched sequencing libraries are suitable for this quantification without pre-purification of DNA. Short DNA molecules, which ideally should be eliminated from the library for subsequent processing, were differentiated from the target DNA in a mixture on the basis of differences in melting temperature. Quantification results for long sequences targeted using the melting curve assay were correlated with those from existing methods (R (2) > 0.77), and that observed from MiSeq sequencing (R (2) = 0.82). Discussion.The results of multiplexed sequencing suggested that the normalisation performance of the described method is equivalent to that of another recently reported high-throughput bead-based method, BeNUS. However, costs for the melting curve assay are considerably lower and processing times shorter than those of other existing methods, suggesting greater suitability for highly multiplexed sequencing applications.

CisSERS: Customizable in silico sequence evaluation for restriction sites

DOE PAGES

Sharpe, Richard M.; Koepke, Tyson; Harper, Artemus; ...

2016-04-12

High-throughput sequencing continues to produce an immense volume of information that is processed and assembled into mature sequence data. Here, data analysis tools are urgently needed that leverage the embedded DNA sequence polymorphisms and consequent changes to restriction sites or sequence motifs in a high-throughput manner to enable biological experimentation. CisSERS was developed as a standalone open source tool to analyze sequence datasets and provide biologists with individual or comparative genome organization information in terms of presence and frequency of patterns or motifs such as restriction enzymes. Predicted agarose gel visualization of the custom analyses results was also integrated tomore » enhance the usefulness of the software. CisSERS offers several novel functionalities, such as handling of large and multiple datasets in parallel, multiple restriction enzyme site detection and custom motif detection features, which are seamlessly integrated with real time agarose gel visualization. Using a simple fasta-formatted file as input, CisSERS utilizes the REBASE enzyme database. Results from CisSERSenable the user to make decisions for designing genotyping by sequencing experiments, reduced representation sequencing, 3’UTR sequencing, and cleaved amplified polymorphic sequence (CAPS) molecular markers for large sample sets. CisSERS is a java based graphical user interface built around a perl backbone. Several of the applications of CisSERS including CAPS molecular marker development were successfully validated using wet-lab experimentation. Here, we present the tool CisSERSand results from in-silico and corresponding wet-lab analyses demonstrating that CisSERS is a technology platform solution that facilitates efficient data utilization in genomics and genetics studies.« less

CisSERS: Customizable in silico sequence evaluation for restriction sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharpe, Richard M.; Koepke, Tyson; Harper, Artemus

High-throughput sequencing continues to produce an immense volume of information that is processed and assembled into mature sequence data. Here, data analysis tools are urgently needed that leverage the embedded DNA sequence polymorphisms and consequent changes to restriction sites or sequence motifs in a high-throughput manner to enable biological experimentation. CisSERS was developed as a standalone open source tool to analyze sequence datasets and provide biologists with individual or comparative genome organization information in terms of presence and frequency of patterns or motifs such as restriction enzymes. Predicted agarose gel visualization of the custom analyses results was also integrated tomore » enhance the usefulness of the software. CisSERS offers several novel functionalities, such as handling of large and multiple datasets in parallel, multiple restriction enzyme site detection and custom motif detection features, which are seamlessly integrated with real time agarose gel visualization. Using a simple fasta-formatted file as input, CisSERS utilizes the REBASE enzyme database. Results from CisSERSenable the user to make decisions for designing genotyping by sequencing experiments, reduced representation sequencing, 3’UTR sequencing, and cleaved amplified polymorphic sequence (CAPS) molecular markers for large sample sets. CisSERS is a java based graphical user interface built around a perl backbone. Several of the applications of CisSERS including CAPS molecular marker development were successfully validated using wet-lab experimentation. Here, we present the tool CisSERSand results from in-silico and corresponding wet-lab analyses demonstrating that CisSERS is a technology platform solution that facilitates efficient data utilization in genomics and genetics studies.« less

Data communications in a parallel active messaging interface of a parallel computer

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2013-11-12

Data communications in a parallel active messaging interface (`PAMI`) of a parallel computer composed of compute nodes that execute a parallel application, each compute node including application processors that execute the parallel application and at least one management processor dedicated to gathering information regarding data communications. The PAMI is composed of data communications endpoints, each endpoint composed of a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes and the endpoints coupled for data communications through the PAMI and through data communications resources. Embodiments function by gathering call site statistics describing data communications resulting from execution of data communications instructions and identifying in dependence upon the call cite statistics a data communications algorithm for use in executing a data communications instruction at a call site in the parallel application.

Scalable Molecular Dynamics with NAMD

PubMed Central

Phillips, James C.; Braun, Rosemary; Wang, Wei; Gumbart, James; Tajkhorshid, Emad; Villa, Elizabeth; Chipot, Christophe; Skeel, Robert D.; Kalé, Laxmikant; Schulten, Klaus

2008-01-01

NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This paper, directed to novices as well as experts, first introduces concepts and methods used in the NAMD program, describing the classical molecular dynamics force field, equations of motion, and integration methods along with the efficient electrostatics evaluation algorithms employed and temperature and pressure controls used. Features for steering the simulation across barriers and for calculating both alchemical and conformational free energy differences are presented. The motivations for and a roadmap to the internal design of NAMD, implemented in C++ and based on Charm++ parallel objects, are outlined. The factors affecting the serial and parallel performance of a simulation are discussed. Next, typical NAMD use is illustrated with representative applications to a small, a medium, and a large biomolecular system, highlighting particular features of NAMD, e.g., the Tcl scripting language. Finally, the paper provides a list of the key features of NAMD and discusses the benefits of combining NAMD with the molecular graphics/sequence analysis software VMD and the grid computing/collaboratory software BioCoRE. NAMD is distributed free of charge with source code at www.ks.uiuc.edu. PMID:16222654

Combining Phase Identification and Statistic Modeling for Automated Parallel Benchmark Generation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Ye; Ma, Xiaosong; Liu, Qing Gary

2015-01-01

Parallel application benchmarks are indispensable for evaluating/optimizing HPC software and hardware. However, it is very challenging and costly to obtain high-fidelity benchmarks reflecting the scale and complexity of state-of-the-art parallel applications. Hand-extracted synthetic benchmarks are time-and labor-intensive to create. Real applications themselves, while offering most accurate performance evaluation, are expensive to compile, port, reconfigure, and often plainly inaccessible due to security or ownership concerns. This work contributes APPRIME, a novel tool for trace-based automatic parallel benchmark generation. Taking as input standard communication-I/O traces of an application's execution, it couples accurate automatic phase identification with statistical regeneration of event parameters tomore » create compact, portable, and to some degree reconfigurable parallel application benchmarks. Experiments with four NAS Parallel Benchmarks (NPB) and three real scientific simulation codes confirm the fidelity of APPRIME benchmarks. They retain the original applications' performance characteristics, in particular the relative performance across platforms.« less

Adaptive efficient compression of genomes

PubMed Central

2012-01-01

Modern high-throughput sequencing technologies are able to generate DNA sequences at an ever increasing rate. In parallel to the decreasing experimental time and cost necessary to produce DNA sequences, computational requirements for analysis and storage of the sequences are steeply increasing. Compression is a key technology to deal with this challenge. Recently, referential compression schemes, storing only the differences between a to-be-compressed input and a known reference sequence, gained a lot of interest in this field. However, memory requirements of the current algorithms are high and run times often are slow. In this paper, we propose an adaptive, parallel and highly efficient referential sequence compression method which allows fine-tuning of the trade-off between required memory and compression speed. When using 12 MB of memory, our method is for human genomes on-par with the best previous algorithms in terms of compression ratio (400:1) and compression speed. In contrast, it compresses a complete human genome in just 11 seconds when provided with 9 GB of main memory, which is almost three times faster than the best competitor while using less main memory. PMID:23146997

A novel process of viral vector barcoding and library preparation enables high-diversity library generation and recombination-free paired-end sequencing

PubMed Central

Davidsson, Marcus; Diaz-Fernandez, Paula; Schwich, Oliver D.; Torroba, Marcos; Wang, Gang; Björklund, Tomas

2016-01-01

Detailed characterization and mapping of oligonucleotide function in vivo is generally a very time consuming effort that only allows for hypothesis driven subsampling of the full sequence to be analysed. Recent advances in deep sequencing together with highly efficient parallel oligonucleotide synthesis and cloning techniques have, however, opened up for entirely new ways to map genetic function in vivo. Here we present a novel, optimized protocol for the generation of universally applicable, barcode labelled, plasmid libraries. The libraries are designed to enable the production of viral vector preparations assessing coding or non-coding RNA function in vivo. When generating high diversity libraries, it is a challenge to achieve efficient cloning, unambiguous barcoding and detailed characterization using low-cost sequencing technologies. With the presented protocol, diversity of above 3 million uniquely barcoded adeno-associated viral (AAV) plasmids can be achieved in a single reaction through a process achievable in any molecular biology laboratory. This approach opens up for a multitude of in vivo assessments from the evaluation of enhancer and promoter regions to the optimization of genome editing. The generated plasmid libraries are also useful for validation of sequencing clustering algorithms and we here validate the newly presented message passing clustering process named Starcode. PMID:27874090

SNP discovery by high-throughput sequencing in soybean

PubMed Central

2010-01-01

Background With the advance of new massively parallel genotyping technologies, quantitative trait loci (QTL) fine mapping and map-based cloning become more achievable in identifying genes for important and complex traits. Development of high-density genetic markers in the QTL regions of specific mapping populations is essential for fine-mapping and map-based cloning of economically important genes. Single nucleotide polymorphisms (SNPs) are the most abundant form of genetic variation existing between any diverse genotypes that are usually used for QTL mapping studies. The massively parallel sequencing technologies (Roche GS/454, Illumina GA/Solexa, and ABI/SOLiD), have been widely applied to identify genome-wide sequence variations. However, it is still remains unclear whether sequence data at a low sequencing depth are enough to detect the variations existing in any QTL regions of interest in a crop genome, and how to prepare sequencing samples for a complex genome such as soybean. Therefore, with the aims of identifying SNP markers in a cost effective way for fine-mapping several QTL regions, and testing the validation rate of the putative SNPs predicted with Solexa short sequence reads at a low sequencing depth, we evaluated a pooled DNA fragment reduced representation library and SNP detection methods applied to short read sequences generated by Solexa high-throughput sequencing technology. Results A total of 39,022 putative SNPs were identified by the Illumina/Solexa sequencing system using a reduced representation DNA library of two parental lines of a mapping population. The validation rates of these putative SNPs predicted with low and high stringency were 72% and 85%, respectively. One hundred sixty four SNP markers resulted from the validation of putative SNPs and have been selectively chosen to target a known QTL, thereby increasing the marker density of the targeted region to one marker per 42 K bp. Conclusions We have demonstrated how to quickly identify large numbers of SNPs for fine mapping of QTL regions by applying massively parallel sequencing combined with genome complexity reduction techniques. This SNP discovery approach is more efficient for targeting multiple QTL regions in a same genetic population, which can be applied to other crops. PMID:20701770

A Robust and Scalable Software Library for Parallel Adaptive Refinement on Unstructured Meshes

NASA Technical Reports Server (NTRS)

Lou, John Z.; Norton, Charles D.; Cwik, Thomas A.

1999-01-01

The design and implementation of Pyramid, a software library for performing parallel adaptive mesh refinement (PAMR) on unstructured meshes, is described. This software library can be easily used in a variety of unstructured parallel computational applications, including parallel finite element, parallel finite volume, and parallel visualization applications using triangular or tetrahedral meshes. The library contains a suite of well-designed and efficiently implemented modules that perform operations in a typical PAMR process. Among these are mesh quality control during successive parallel adaptive refinement (typically guided by a local-error estimator), parallel load-balancing, and parallel mesh partitioning using the ParMeTiS partitioner. The Pyramid library is implemented in Fortran 90 with an interface to the Message-Passing Interface (MPI) library, supporting code efficiency, modularity, and portability. An EM waveguide filter application, adaptively refined using the Pyramid library, is illustrated.

A genetic algorithm-based job scheduling model for big data analytics.

PubMed

Lu, Qinghua; Li, Shanshan; Zhang, Weishan; Zhang, Lei

Big data analytics (BDA) applications are a new category of software applications that process large amounts of data using scalable parallel processing infrastructure to obtain hidden value. Hadoop is the most mature open-source big data analytics framework, which implements the MapReduce programming model to process big data with MapReduce jobs. Big data analytics jobs are often continuous and not mutually separated. The existing work mainly focuses on executing jobs in sequence, which are often inefficient and consume high energy. In this paper, we propose a genetic algorithm-based job scheduling model for big data analytics applications to improve the efficiency of big data analytics. To implement the job scheduling model, we leverage an estimation module to predict the performance of clusters when executing analytics jobs. We have evaluated the proposed job scheduling model in terms of feasibility and accuracy.

Seismic stratigraphic characteristics of upper Louisiana continental slope: an area east of Green Canyon

USGS Publications Warehouse

Bouma, Arnold H.; Feeley, Mary H.; Kindinger, Jack G.; Stelting, Charles E.; Hilde, Thomas W.C.

1981-01-01

A high-resolution seismic reflection survey was conducted in a small area of the upper Louisiana Continental Slope known as Green Canyon Area. This area includes tracts 427, 428, 471, 472, 515, and 516, that will be offered for sale in March 1982 as part of Lease Sale 67.The sea floor of this region is, slightly hummocky and is underlain by salt diapirs that are mantled by early Tertiary shale. Most of the shale is overlain by younger Tertiary and Quaternary deposits, although locally some of the shale protrudes the sea floor. Because of proximity to older Mississippi River sources, the sediments are thick. The sediment cover shows an abundance of geologic phenomena such as horsts, grabens, growth faults, normal faults, and consolidation faults, zones with distinct and indistinct parallel reflections, semi-transparent zones, distorted zones, and angular unconformities.The major feature of this region is a N-S linear zone of uplifted and intruded sedimentary deposits formed due to diapiric intrusion.Small scale graben development over the crest of the structure can be attributed to extension and collapse. Large scale undulations of reflections well off the flanks of the uplifted structure suggest sediment creep and slumping. Dipping of parallel reflections show block faulting and tilting.Air gun (5 and 40 cubic inch) records reveal at least five major sequences that show masked onlap and slumping in their lower parts grading into more distinct parallel reflections in their upper parts. Such sequences can be related to local uplift and sea level changes. Minisparker records of this area show similar sequences but on a smaller scale. The distinct parallel reflections often onlap the diapir flanks. The highly reflective parts of these sequences may represent turbidite-type deposition, possibly at times of lower sea level. The acoustically more transparent parts of each sequence may represent deposits containing primarily hemipelagic and pelagic sediment.A complex ridge system is present along the west side of the area and distinct parallel reflections onlap onto this structure primarily from the east. Much of this deposition may be ascribed to sedimentation within a submarine canyon whose position is controlled by this ridge.

Divide and Conquer (DC) BLAST: fast and easy BLAST execution within HPC environments

DOE PAGES

Yim, Won Cheol; Cushman, John C.

2017-07-22

Bioinformatics is currently faced with very large-scale data sets that lead to computational jobs, especially sequence similarity searches, that can take absurdly long times to run. For example, the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST and BLAST+) suite, which is by far the most widely used tool for rapid similarity searching among nucleic acid or amino acid sequences, is highly central processing unit (CPU) intensive. While the BLAST suite of programs perform searches very rapidly, they have the potential to be accelerated. In recent years, distributed computing environments have become more widely accessible andmore » used due to the increasing availability of high-performance computing (HPC) systems. Therefore, simple solutions for data parallelization are needed to expedite BLAST and other sequence analysis tools. However, existing software for parallel sequence similarity searches often requires extensive computational experience and skill on the part of the user. In order to accelerate BLAST and other sequence analysis tools, Divide and Conquer BLAST (DCBLAST) was developed to perform NCBI BLAST searches within a cluster, grid, or HPC environment by using a query sequence distribution approach. Scaling from one (1) to 256 CPU cores resulted in significant improvements in processing speed. Thus, DCBLAST dramatically accelerates the execution of BLAST searches using a simple, accessible, robust, and parallel approach. DCBLAST works across multiple nodes automatically and it overcomes the speed limitation of single-node BLAST programs. DCBLAST can be used on any HPC system, can take advantage of hundreds of nodes, and has no output limitations. Thus, this freely available tool simplifies distributed computation pipelines to facilitate the rapid discovery of sequence similarities between very large data sets.« less

Divide and Conquer (DC) BLAST: fast and easy BLAST execution within HPC environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yim, Won Cheol; Cushman, John C.

Bioinformatics is currently faced with very large-scale data sets that lead to computational jobs, especially sequence similarity searches, that can take absurdly long times to run. For example, the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST and BLAST+) suite, which is by far the most widely used tool for rapid similarity searching among nucleic acid or amino acid sequences, is highly central processing unit (CPU) intensive. While the BLAST suite of programs perform searches very rapidly, they have the potential to be accelerated. In recent years, distributed computing environments have become more widely accessible andmore » used due to the increasing availability of high-performance computing (HPC) systems. Therefore, simple solutions for data parallelization are needed to expedite BLAST and other sequence analysis tools. However, existing software for parallel sequence similarity searches often requires extensive computational experience and skill on the part of the user. In order to accelerate BLAST and other sequence analysis tools, Divide and Conquer BLAST (DCBLAST) was developed to perform NCBI BLAST searches within a cluster, grid, or HPC environment by using a query sequence distribution approach. Scaling from one (1) to 256 CPU cores resulted in significant improvements in processing speed. Thus, DCBLAST dramatically accelerates the execution of BLAST searches using a simple, accessible, robust, and parallel approach. DCBLAST works across multiple nodes automatically and it overcomes the speed limitation of single-node BLAST programs. DCBLAST can be used on any HPC system, can take advantage of hundreds of nodes, and has no output limitations. Thus, this freely available tool simplifies distributed computation pipelines to facilitate the rapid discovery of sequence similarities between very large data sets.« less

String-averaging incremental subgradients for constrained convex optimization with applications to reconstruction of tomographic images

NASA Astrophysics Data System (ADS)

Massambone de Oliveira, Rafael; Salomão Helou, Elias; Fontoura Costa, Eduardo

2016-11-01

We present a method for non-smooth convex minimization which is based on subgradient directions and string-averaging techniques. In this approach, the set of available data is split into sequences (strings) and a given iterate is processed independently along each string, possibly in parallel, by an incremental subgradient method (ISM). The end-points of all strings are averaged to form the next iterate. The method is useful to solve sparse and large-scale non-smooth convex optimization problems, such as those arising in tomographic imaging. A convergence analysis is provided under realistic, standard conditions. Numerical tests are performed in a tomographic image reconstruction application, showing good performance for the convergence speed when measured as the decrease ratio of the objective function, in comparison to classical ISM.

Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry and tandem mass spectrometry for peptide de novo amino acid sequencing for a seven-protein mixture by paired single-residue transposed Lys-N and Lys-C digestion.

PubMed

Guan, Xiaoyan; Brownstein, Naomi C; Young, Nicolas L; Marshall, Alan G

2017-01-30

Bottom-up tandem mass spectrometry (MS/MS) is regularly used in proteomics to identify proteins from a sequence database. De novo sequencing is also available for sequencing peptides with relatively short sequence lengths. We recently showed that paired Lys-C and Lys-N proteases produce peptides of identical mass and similar retention time, but different tandem mass spectra. Such parallel experiments provide complementary information, and allow for up to 100% MS/MS sequence coverage. Here, we report digestion by paired Lys-C and Lys-N proteases of a seven-protein mixture: human hemoglobin alpha, bovine carbonic anhydrase 2, horse skeletal muscle myoglobin, hen egg white lysozyme, bovine pancreatic ribonuclease, bovine rhodanese, and bovine serum albumin, followed by reversed-phase nanoflow liquid chromatography, collision-induced dissociation, and 14.5 T Fourier transform ion cyclotron resonance mass spectrometry. Matched pairs of product peptide ions of equal precursor mass and similar retention times from each digestion are compared, leveraging single-residue transposed information with independent interferences to confidently identify fragment ion types, residues, and peptides. Selected pairs of product ion mass spectra for de novo sequenced protein segments from each member of the mixture are presented. Pairs of the transposed product ions as well as complementary information from the parallel experiments allow for both high MS/MS coverage for long peptide sequences and high confidence in the amino acid identification. Moreover, the parallel experiments in the de novo sequencing reduce false-positive matches of product ions from the single-residue transposed peptides from the same segment, and thereby further improve the confidence in protein identification. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Launching genomics into the cloud: deployment of Mercury, a next generation sequence analysis pipeline.

PubMed

Reid, Jeffrey G; Carroll, Andrew; Veeraraghavan, Narayanan; Dahdouli, Mahmoud; Sundquist, Andreas; English, Adam; Bainbridge, Matthew; White, Simon; Salerno, William; Buhay, Christian; Yu, Fuli; Muzny, Donna; Daly, Richard; Duyk, Geoff; Gibbs, Richard A; Boerwinkle, Eric

2014-01-29

Massively parallel DNA sequencing generates staggering amounts of data. Decreasing cost, increasing throughput, and improved annotation have expanded the diversity of genomics applications in research and clinical practice. This expanding scale creates analytical challenges: accommodating peak compute demand, coordinating secure access for multiple analysts, and sharing validated tools and results. To address these challenges, we have developed the Mercury analysis pipeline and deployed it in local hardware and the Amazon Web Services cloud via the DNAnexus platform. Mercury is an automated, flexible, and extensible analysis workflow that provides accurate and reproducible genomic results at scales ranging from individuals to large cohorts. By taking advantage of cloud computing and with Mercury implemented on the DNAnexus platform, we have demonstrated a powerful combination of a robust and fully validated software pipeline and a scalable computational resource that, to date, we have applied to more than 10,000 whole genome and whole exome samples.

TARGETED CAPTURE IN EVOLUTIONARY AND ECOLOGICAL GENOMICS

PubMed Central

Jones, Matthew R.; Good, Jeffrey M.

2016-01-01

The rapid expansion of next-generation sequencing has yielded a powerful array of tools to address fundamental biological questions at a scale that was inconceivable just a few years ago. Various genome partitioning strategies to sequence select subsets of the genome have emerged as powerful alternatives to whole genome sequencing in ecological and evolutionary genomic studies. High throughput targeted capture is one such strategy that involves the parallel enrichment of pre-selected genomic regions of interest. The growing use of targeted capture demonstrates its potential power to address a range of research questions, yet these approaches have yet to expand broadly across labs focused on evolutionary and ecological genomics. In part, the use of targeted capture has been hindered by the logistics of capture design and implementation in species without established reference genomes. Here we aim to 1) increase the accessibility of targeted capture to researchers working in non-model taxa by discussing capture methods that circumvent the need of a reference genome, 2) highlight the evolutionary and ecological applications where this approach is emerging as a powerful sequencing strategy, and 3) discuss the future of targeted capture and other genome partitioning approaches in light of the increasing accessibility of whole genome sequencing. Given the practical advantages and increasing feasibility of high-throughput targeted capture, we anticipate an ongoing expansion of capture-based approaches in evolutionary and ecological research, synergistic with an expansion of whole genome sequencing. PMID:26137993

A parallel approach of COFFEE objective function to multiple sequence alignment

NASA Astrophysics Data System (ADS)

Zafalon, G. F. D.; Visotaky, J. M. V.; Amorim, A. R.; Valêncio, C. R.; Neves, L. A.; de Souza, R. C. G.; Machado, J. M.

2015-09-01

The computational tools to assist genomic analyzes show even more necessary due to fast increasing of data amount available. With high computational costs of deterministic algorithms for sequence alignments, many works concentrate their efforts in the development of heuristic approaches to multiple sequence alignments. However, the selection of an approach, which offers solutions with good biological significance and feasible execution time, is a great challenge. Thus, this work aims to show the parallelization of the processing steps of MSA-GA tool using multithread paradigm in the execution of COFFEE objective function. The standard objective function implemented in the tool is the Weighted Sum of Pairs (WSP), which produces some distortions in the final alignments when sequences sets with low similarity are aligned. Then, in studies previously performed we implemented the COFFEE objective function in the tool to smooth these distortions. Although the nature of COFFEE objective function implies in the increasing of execution time, this approach presents points, which can be executed in parallel. With the improvements implemented in this work, we can verify the execution time of new approach is 24% faster than the sequential approach with COFFEE. Moreover, the COFFEE multithreaded approach is more efficient than WSP, because besides it is slightly fast, its biological results are better.

Integrated Task and Data Parallel Programming

NASA Technical Reports Server (NTRS)

Grimshaw, A. S.

1998-01-01

This research investigates the combination of task and data parallel language constructs within a single programming language. There are an number of applications that exhibit properties which would be well served by such an integrated language. Examples include global climate models, aircraft design problems, and multidisciplinary design optimization problems. Our approach incorporates data parallel language constructs into an existing, object oriented, task parallel language. The language will support creation and manipulation of parallel classes and objects of both types (task parallel and data parallel). Ultimately, the language will allow data parallel and task parallel classes to be used either as building blocks or managers of parallel objects of either type, thus allowing the development of single and multi-paradigm parallel applications. 1995 Research Accomplishments In February I presented a paper at Frontiers 1995 describing the design of the data parallel language subset. During the spring I wrote and defended my dissertation proposal. Since that time I have developed a runtime model for the language subset. I have begun implementing the model and hand-coding simple examples which demonstrate the language subset. I have identified an astrophysical fluid flow application which will validate the data parallel language subset. 1996 Research Agenda Milestones for the coming year include implementing a significant portion of the data parallel language subset over the Legion system. Using simple hand-coded methods, I plan to demonstrate (1) concurrent task and data parallel objects and (2) task parallel objects managing both task and data parallel objects. My next steps will focus on constructing a compiler and implementing the fluid flow application with the language. Concurrently, I will conduct a search for a real-world application exhibiting both task and data parallelism within the same program. Additional 1995 Activities During the fall I collaborated with Andrew Grimshaw and Adam Ferrari to write a book chapter which will be included in Parallel Processing in C++ edited by Gregory Wilson. I also finished two courses, Compilers and Advanced Compilers, in 1995. These courses complete my class requirements at the University of Virginia. I have only my dissertation research and defense to complete.

Integrated Task And Data Parallel Programming: Language Design

NASA Technical Reports Server (NTRS)

Grimshaw, Andrew S.; West, Emily A.

1998-01-01

his research investigates the combination of task and data parallel language constructs within a single programming language. There are an number of applications that exhibit properties which would be well served by such an integrated language. Examples include global climate models, aircraft design problems, and multidisciplinary design optimization problems. Our approach incorporates data parallel language constructs into an existing, object oriented, task parallel language. The language will support creation and manipulation of parallel classes and objects of both types (task parallel and data parallel). Ultimately, the language will allow data parallel and task parallel classes to be used either as building blocks or managers of parallel objects of either type, thus allowing the development of single and multi-paradigm parallel applications. 1995 Research Accomplishments In February I presented a paper at Frontiers '95 describing the design of the data parallel language subset. During the spring I wrote and defended my dissertation proposal. Since that time I have developed a runtime model for the language subset. I have begun implementing the model and hand-coding simple examples which demonstrate the language subset. I have identified an astrophysical fluid flow application which will validate the data parallel language subset. 1996 Research Agenda Milestones for the coming year include implementing a significant portion of the data parallel language subset over the Legion system. Using simple hand-coded methods, I plan to demonstrate (1) concurrent task and data parallel objects and (2) task parallel objects managing both task and data parallel objects. My next steps will focus on constructing a compiler and implementing the fluid flow application with the language. Concurrently, I will conduct a search for a real-world application exhibiting both task and data parallelism within the same program m. Additional 1995 Activities During the fall I collaborated with Andrew Grimshaw and Adam Ferrari to write a book chapter which will be included in Parallel Processing in C++ edited by Gregory Wilson. I also finished two courses, Compilers and Advanced Compilers, in 1995. These courses complete my class requirements at the University of Virginia. I have only my dissertation research and defense to complete.

Relationship of Individual and Group Change: Ontogeny and Phylogeny in Biology.

ERIC Educational Resources Information Center

Gould, Steven Jay

1984-01-01

Considers the issue of parallels between ontogeny and phylogeny from an historical perspective. Discusses such parallels in relationship to two ontogenetic principles concerning recapitulation and sequence of stages. Differentiates between Piaget's use of the idea of recapitulation and Haeckel's biogenetic law. (Author/RH)

Extending Automatic Parallelization to Optimize High-Level Abstractions for Multicore

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, C; Quinlan, D J; Willcock, J J

2008-12-12

Automatic introduction of OpenMP for sequential applications has attracted significant attention recently because of the proliferation of multicore processors and the simplicity of using OpenMP to express parallelism for shared-memory systems. However, most previous research has only focused on C and Fortran applications operating on primitive data types. C++ applications using high-level abstractions, such as STL containers and complex user-defined types, are largely ignored due to the lack of research compilers that are readily able to recognize high-level object-oriented abstractions and leverage their associated semantics. In this paper, we automatically parallelize C++ applications using ROSE, a multiple-language source-to-source compiler infrastructuremore » which preserves the high-level abstractions and gives us access to their semantics. Several representative parallelization candidate kernels are used to explore semantic-aware parallelization strategies for high-level abstractions, combined with extended compiler analyses. Those kernels include an array-base computation loop, a loop with task-level parallelism, and a domain-specific tree traversal. Our work extends the applicability of automatic parallelization to modern applications using high-level abstractions and exposes more opportunities to take advantage of multicore processors.« less

Parallel Signal Processing and System Simulation using aCe

NASA Technical Reports Server (NTRS)

Dorband, John E.; Aburdene, Maurice F.

2003-01-01

Recently, networked and cluster computation have become very popular for both signal processing and system simulation. A new language is ideally suited for parallel signal processing applications and system simulation since it allows the programmer to explicitly express the computations that can be performed concurrently. In addition, the new C based parallel language (ace C) for architecture-adaptive programming allows programmers to implement algorithms and system simulation applications on parallel architectures by providing them with the assurance that future parallel architectures will be able to run their applications with a minimum of modification. In this paper, we will focus on some fundamental features of ace C and present a signal processing application (FFT).

A parallelized binary search tree

USDA-ARS?s Scientific Manuscript database

PTTRNFNDR is an unsupervised statistical learning algorithm that detects patterns in DNA sequences, protein sequences, or any natural language texts that can be decomposed into letters of a finite alphabet. PTTRNFNDR performs complex mathematical computations and its processing time increases when i...

DNA looping by FokI: the impact of synapse geometry on loop topology at varied site orientations

PubMed Central

Rusling, David A.; Laurens, Niels; Pernstich, Christian; Wuite, Gijs J. L.; Halford, Stephen E.

2012-01-01

Most restriction endonucleases, including FokI, interact with two copies of their recognition sequence before cutting DNA. On DNA with two sites they act in cis looping out the intervening DNA. While many restriction enzymes operate symmetrically at palindromic sites, FokI acts asymmetrically at a non-palindromic site. The directionality of its sequence means that two FokI sites can be bridged in either parallel or anti-parallel alignments. Here we show by biochemical and single-molecule biophysical methods that FokI aligns two recognition sites on separate DNA molecules in parallel and that the parallel arrangement holds for sites in the same DNA regardless of whether they are in inverted or repeated orientations. The parallel arrangement dictates the topology of the loop trapped between sites in cis: the loop from inverted sites has a simple 180° bend, while that with repeated sites has a convoluted 360° turn. The ability of FokI to act at asymmetric sites thus enabled us to identify the synapse geometry for sites in trans and in cis, which in turn revealed the relationship between synapse geometry and loop topology. PMID:22362745

Tentacle: distributed quantification of genes in metagenomes.

PubMed

Boulund, Fredrik; Sjögren, Anders; Kristiansson, Erik

2015-01-01

In metagenomics, microbial communities are sequenced at increasingly high resolution, generating datasets with billions of DNA fragments. Novel methods that can efficiently process the growing volumes of sequence data are necessary for the accurate analysis and interpretation of existing and upcoming metagenomes. Here we present Tentacle, which is a novel framework that uses distributed computational resources for gene quantification in metagenomes. Tentacle is implemented using a dynamic master-worker approach in which DNA fragments are streamed via a network and processed in parallel on worker nodes. Tentacle is modular, extensible, and comes with support for six commonly used sequence aligners. It is easy to adapt Tentacle to different applications in metagenomics and easy to integrate into existing workflows. Evaluations show that Tentacle scales very well with increasing computing resources. We illustrate the versatility of Tentacle on three different use cases. Tentacle is written for Linux in Python 2.7 and is published as open source under the GNU General Public License (v3). Documentation, tutorials, installation instructions, and the source code are freely available online at: http://bioinformatics.math.chalmers.se/tentacle.

Evaluation of Viremia Frequencies of a Novel Human Pegivirus by Using Bioinformatic Screening and PCR

PubMed Central

Bonsall, David; Gregory, William F.; Ip, Camilla L.C.; Donfield, Sharyne; Iles, James; Ansari, M. Azim; Piazza, Paolo; Trebes, Amy; Brown, Anthony; Frater, John; Pybus, Oliver G.; Goulder, Phillip; Klenerman, Paul; Bowden, Rory; Gomperts, Edward D.; Barnes, Eleanor; Kapoor, Amit; Sharp, Colin P.

2016-01-01

Next-generation sequencing has critical applications in virus discovery, diagnostics, and environmental surveillance. We used metagenomic sequence libraries for retrospective screening of plasma samples for the recently discovered human hepegivirus 1 (HHpgV-1). From a cohort of 150 hepatitis C virus (HCV)–positive case-patients, we identified 2 persons with HHpgV-1 viremia and a high frequency of human pegivirus (HPgV) viremia (14%). Detection of HHpgV-1 and HPgV was concordant with parallel PCR-based screening using conserved primers matching groups 1 (HPgV) and 2 (HHPgV-1) nonstructural 3 region sequences. PCR identified 1 HHPgV-1–positive person with viremia from a group of 195 persons with hemophilia who had been exposed to nonvirally inactivated factor VII/IX; 18 (9%) were HPgV-positive. Relative to HCV and HPgV, active infections with HHpgV-1 were infrequently detected in blood, even in groups that had substantial parenteral exposure. Our findings are consistent with lower transmissibility or higher rates of virus clearance for HHpgV-1 than for other bloodborne human flaviviruses. PMID:26982117

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

PubMed Central

Brett, Maggie; McPherson, John; Zang, Zhi Jiang; Lai, Angeline; Tan, Ee-Shien; Ng, Ivy; Ong, Lai-Choo; Cham, Breana; Tan, Patrick; Rozen, Steve; Tan, Ene-Choo

2014-01-01

Developmental delay and/or intellectual disability (DD/ID) affects 1–3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81–84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism. PMID:24690944

Inter-laboratory evaluation of the EUROFORGEN Global ancestry-informative SNP panel by massively parallel sequencing using the Ion PGM™.

PubMed

Eduardoff, M; Gross, T E; Santos, C; de la Puente, M; Ballard, D; Strobl, C; Børsting, C; Morling, N; Fusco, L; Hussing, C; Egyed, B; Souto, L; Uacyisrael, J; Syndercombe Court, D; Carracedo, Á; Lareu, M V; Schneider, P M; Parson, W; Phillips, C; Parson, W; Phillips, C

2016-07-01

The EUROFORGEN Global ancestry-informative SNP (AIM-SNPs) panel is a forensic multiplex of 128 markers designed to differentiate an individual's ancestry from amongst the five continental population groups of Africa, Europe, East Asia, Native America, and Oceania. A custom multiplex of AmpliSeq™ PCR primers was designed for the Global AIM-SNPs to perform massively parallel sequencing using the Ion PGM™ system. This study assessed individual SNP genotyping precision using the Ion PGM™, the forensic sensitivity of the multiplex using dilution series, degraded DNA plus simple mixtures, and the ancestry differentiation power of the final panel design, which required substitution of three original ancestry-informative SNPs with alternatives. Fourteen populations that had not been previously analyzed were genotyped using the custom multiplex and these studies allowed assessment of genotyping performance by comparison of data across five laboratories. Results indicate a low level of genotyping error can still occur from sequence misalignment caused by homopolymeric tracts close to the target SNP, despite careful scrutiny of candidate SNPs at the design stage. Such sequence misalignment required the exclusion of component SNP rs2080161 from the Global AIM-SNPs panel. However, the overall genotyping precision and sensitivity of this custom multiplex indicates the Ion PGM™ assay for the Global AIM-SNPs is highly suitable for forensic ancestry analysis with massively parallel sequencing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Establishing use of crutches by a mentally retarded spina bifida child1

PubMed Central

Horner, R. Don

1971-01-01

A 5-yr-old mentally retarded spina bifida child was taught to walk with the aid of crutches. This behavior was developed through fading of physical prompting within a 10-step successive approximation sequence. Preliminary training to establish gait consisted of developing use of parallel bars through fading of physically modelled responses within a six-step successive approximation sequence. Use of parallel bars ceased during an extinction period and completely recovered upon being primed with one “free” reinforcement. Systematic use of natural reinforcers was employed as an aid in maintaining use of crutches. PMID:16795294

High-throughput microsatellite genotyping in ecology: improved accuracy, efficiency, standardization and success with low-quantity and degraded DNA.

PubMed

De Barba, M; Miquel, C; Lobréaux, S; Quenette, P Y; Swenson, J E; Taberlet, P

2017-05-01

Microsatellite markers have played a major role in ecological, evolutionary and conservation research during the past 20 years. However, technical constrains related to the use of capillary electrophoresis and a recent technological revolution that has impacted other marker types have brought to question the continued use of microsatellites for certain applications. We present a study for improving microsatellite genotyping in ecology using high-throughput sequencing (HTS). This approach entails selection of short markers suitable for HTS, sequencing PCR-amplified microsatellites on an Illumina platform and bioinformatic treatment of the sequence data to obtain multilocus genotypes. It takes advantage of the fact that HTS gives direct access to microsatellite sequences, allowing unambiguous allele identification and enabling automation of the genotyping process through bioinformatics. In addition, the massive parallel sequencing abilities expand the information content of single experimental runs far beyond capillary electrophoresis. We illustrated the method by genotyping brown bear samples amplified with a multiplex PCR of 13 new microsatellite markers and a sex marker. HTS of microsatellites provided accurate individual identification and parentage assignment and resulted in a significant improvement of genotyping success (84%) of faecal degraded DNA and costs reduction compared to capillary electrophoresis. The HTS approach holds vast potential for improving success, accuracy, efficiency and standardization of microsatellite genotyping in ecological and conservation applications, especially those that rely on profiling of low-quantity/quality DNA and on the construction of genetic databases. We discuss and give perspectives for the implementation of the method in the light of the challenges encountered in wildlife studies. © 2016 John Wiley & Sons Ltd.

Concurrent and Accurate Short Read Mapping on Multicore Processors.

PubMed

Martínez, Héctor; Tárraga, Joaquín; Medina, Ignacio; Barrachina, Sergio; Castillo, Maribel; Dopazo, Joaquín; Quintana-Ortí, Enrique S

2015-01-01

We 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, HPG Aligner SA (HPG Aligner SA 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 HPG Aligner SA, 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.

Nanomechanical DNA origami pH sensors.

PubMed

Kuzuya, Akinori; Watanabe, Ryosuke; Yamanaka, Yusei; Tamaki, Takuya; Kaino, Masafumi; Ohya, Yuichi

2014-10-16

Single-molecule pH sensors have been developed by utilizing molecular imaging of pH-responsive shape transition of nanomechanical DNA origami devices with atomic force microscopy (AFM). Short DNA fragments that can form i-motifs were introduced to nanomechanical DNA origami devices with pliers-like shape (DNA Origami Pliers), which consist of two levers of 170-nm long and 20-nm wide connected at a Holliday-junction fulcrum. DNA Origami Pliers can be observed as in three distinct forms; cross, antiparallel and parallel forms, and cross form is the dominant species when no additional interaction is introduced to DNA Origami Pliers. Introduction of nine pairs of 12-mer sequence (5'-AACCCCAACCCC-3'), which dimerize into i-motif quadruplexes upon protonation of cytosine, drives transition of DNA Origami Pliers from open cross form into closed parallel form under acidic conditions. Such pH-dependent transition was clearly imaged on mica in molecular resolution by AFM, showing potential application of the system to single-molecular pH sensors.

Genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia cell line

PubMed Central

STOCZYNSKA-FIDELUS, EWELINA; PIASKOWSKI, SYLWESTER; PAWLOWSKA, ROZA; SZYBKA, MALGORZATA; PECIAK, JOANNA; HULAS-BIGOSZEWSKA, KRYSTYNA; WINIECKA-KLIMEK, MARTA; RIESKE, PIOTR

2016-01-01

Thorough examination of genetic heterogeneity of cell lines is uncommon. In order to address this issue, the present study analyzed the genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia (T-ALL) cell line. For this purpose, traditional techniques such as fluorescence in situ hybridization and immunocytochemistry were used, in addition to more advanced techniques, including cell sorting, Sanger sequencing and massive parallel sequencing. The results indicated that the RPMI-8402 cell line consists of several genetically different cell subpopulations. Furthermore, massive parallel sequencing of RPMI-8402 provided insight into the evolution of T-ALL carcinogenesis, since this cell line exhibited the genetic heterogeneity typical of T-ALL. Therefore, the use of cell lines for drug testing in future studies may aid the progress of anticancer drug research. PMID:26870252

Report on noninvasive prenatal testing: classical and alternative approaches.

PubMed

Pantiukh, Kateryna S; Chekanov, Nikolay N; Zaigrin, Igor V; Zotov, Alexei M; Mazur, Alexander M; Prokhortchouk, Egor B

2016-01-01

Concerns of traditional prenatal aneuploidy testing methods, such as low accuracy of noninvasive and health risks associated with invasive procedures, were overcome with the introduction of novel noninvasive methods based on genetics (NIPT). These were rapidly adopted into clinical practice in many countries after a series of successful trials of various independent submethods. Here we present results of own NIPT trial carried out in Moscow, Russia. 1012 samples were subjected to the method aimed at measuring chromosome coverage by massive parallel sequencing. Two alternative approaches are ascertained: one based on maternal/fetal differential methylation and another based on allelic difference. While the former failed to provide stable results, the latter was found to be promising and worthy of conducting a large-scale trial. One critical point in any NIPT approach is the determination of fetal cell-free DNA fraction, which dictates the reliability of obtained results for a given sample. We show that two different chromosome Y representation measures-by real-time PCR and by whole-genome massive parallel sequencing-are practically interchangeable (r=0.94). We also propose a novel method based on maternal/fetal allelic difference which is applicable in pregnancies with fetuses of either sex. Even in its pilot form it correlates well with chromosome Y coverage estimates (r=0.74) and can be further improved by increasing the number of polymorphisms.

Acceleration techniques and their impact on arterial input function sampling: Non-accelerated versus view-sharing and compressed sensing sequences.

PubMed

Benz, Matthias R; Bongartz, Georg; Froehlich, Johannes M; Winkel, David; Boll, Daniel T; Heye, Tobias

2018-07-01

The aim was to investigate the variation of the arterial input function (AIF) within and between various DCE MRI sequences. A dynamic flow-phantom and steady signal reference were scanned on a 3T MRI using fast low angle shot (FLASH) 2d, FLASH3d (parallel imaging factor (P) = P0, P2, P4), volumetric interpolated breath-hold examination (VIBE) (P = P0, P3, P2 × 2, P2 × 3, P3 × 2), golden-angle radial sparse parallel imaging (GRASP), and time-resolved imaging with stochastic trajectories (TWIST). Signal over time curves were normalized and quantitatively analyzed by full width half maximum (FWHM) measurements to assess variation within and between sequences. The coefficient of variation (CV) for the steady signal reference ranged from 0.07-0.8%. The non-accelerated gradient echo FLASH2d, FLASH3d, and VIBE sequences showed low within sequence variation with 2.1%, 1.0%, and 1.6%. The maximum FWHM CV was 3.2% for parallel imaging acceleration (VIBE P2 × 3), 2.7% for GRASP and 9.1% for TWIST. The FWHM CV between sequences ranged from 8.5-14.4% for most non-accelerated/accelerated gradient echo sequences except 6.2% for FLASH3d P0 and 0.3% for FLASH3d P2; GRASP FWHM CV was 9.9% versus 28% for TWIST. MRI acceleration techniques vary in reproducibility and quantification of the AIF. Incomplete coverage of the k-space with TWIST as a representative of view-sharing techniques showed the highest variation within sequences and might be less suited for reproducible quantification of the AIF. Copyright © 2018 Elsevier B.V. All rights reserved.

Characterizing and Mitigating Work Time Inflation in Task Parallel Programs

DOE PAGES

Olivier, Stephen L.; de Supinski, Bronis R.; Schulz, Martin; ...

2013-01-01

Task parallelism raises the level of abstraction in shared memory parallel programming to simplify the development of complex applications. However, task parallel applications can exhibit poor performance due to thread idleness, scheduling overheads, and work time inflation – additional time spent by threads in a multithreaded computation beyond the time required to perform the same work in a sequential computation. We identify the contributions of each factor to lost efficiency in various task parallel OpenMP applications and diagnose the causes of work time inflation in those applications. Increased data access latency can cause significant work time inflation in NUMA systems.more » Our locality framework for task parallel OpenMP programs mitigates this cause of work time inflation. Our extensions to the Qthreads library demonstrate that locality-aware scheduling can improve performance up to 3X compared to the Intel OpenMP task scheduler.« less

The Galley Parallel File System

NASA Technical Reports Server (NTRS)

Nieuwejaar, Nils; Kotz, David

1996-01-01

Most current multiprocessor file systems are designed to use multiple disks in parallel, using the high aggregate bandwidth to meet the growing I/0 requirements of parallel scientific applications. Many multiprocessor file systems provide applications with a conventional Unix-like interface, allowing the application to access multiple disks transparently. This interface conceals the parallelism within the file system, increasing the ease of programmability, but making it difficult or impossible for sophisticated programmers and libraries to use knowledge about their I/O needs to exploit that parallelism. In addition to providing an insufficient interface, most current multiprocessor file systems are optimized for a different workload than they are being asked to support. We introduce Galley, a new parallel file system that is intended to efficiently support realistic scientific multiprocessor workloads. We discuss Galley's file structure and application interface, as well as the performance advantages offered by that interface.

By Hand or Not By-Hand: A Case Study of Alternative Approaches to Parallelize CFD Applications

NASA Technical Reports Server (NTRS)

Yan, Jerry C.; Bailey, David (Technical Monitor)

1997-01-01

While parallel processing promises to speed up applications by several orders of magnitude, the performance achieved still depends upon several factors, including the multiprocessor architecture, system software, data distribution and alignment, as well as the methods used for partitioning the application and mapping its components onto the architecture. The existence of the Gorden Bell Prize given out at Supercomputing every year suggests that while good performance can be attained for real applications on general purpose multiprocessors, the large investment in man-power and time still has to be repeated for each application-machine combination. As applications and machine architectures become more complex, the cost and time-delays for obtaining performance by hand will become prohibitive. Computer users today can turn to three possible avenues for help: parallel libraries, parallel languages and compilers, interactive parallelization tools. The success of these methodologies, in turn, depends on proper application of data dependency analysis, program structure recognition and transformation, performance prediction as well as exploitation of user supplied knowledge. NASA has been developing multidisciplinary applications on highly parallel architectures under the High Performance Computing and Communications Program. Over the past six years, the transition of underlying hardware and system software have forced the scientists to spend a large effort to migrate and recede their applications. Various attempts to exploit software tools to automate the parallelization process have not produced favorable results. In this paper, we report our most recent experience with CAPTOOL, a package developed at Greenwich University. We have chosen CAPTOOL for three reasons: 1. CAPTOOL accepts a FORTRAN 77 program as input. This suggests its potential applicability to a large collection of legacy codes currently in use. 2. CAPTOOL employs domain decomposition to obtain parallelism. Although the fact that not all kinds of parallelism are handled may seem unappealing, many NASA applications in computational aerosciences as well as earth and space sciences are amenable to domain decomposition. 3. CAPTOOL generates code for a large variety of environments employed across NASA centers: MPI/PVM on network of workstations to the IBS/SP2 and CRAY/T3D.

Expansion of Microbial Forensics

PubMed Central

Schmedes, Sarah E.; Sajantila, Antti

2016-01-01

Microbial forensics has been defined as the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes. Over the past 15 years, technology, particularly massively parallel sequencing, and bioinformatics advances now allow the characterization of microorganisms for a variety of human forensic applications, such as human identification, body fluid characterization, postmortem interval estimation, and biocrimes involving tracking of infectious agents. Thus, microbial forensics should be more broadly described as the discipline of applying scientific methods to the analysis of microbial evidence in criminal and civil cases for investigative purposes. PMID:26912746

My-Forensic-Loci-queries (MyFLq) framework for analysis of forensic STR data generated by massive parallel sequencing.

PubMed

Van Neste, Christophe; Vandewoestyne, Mado; Van Criekinge, Wim; Deforce, Dieter; Van Nieuwerburgh, Filip

2014-03-01

Forensic scientists are currently investigating how to transition from capillary electrophoresis (CE) to massive parallel sequencing (MPS) for analysis of forensic DNA profiles. MPS offers several advantages over CE such as virtually unlimited multiplexy of loci, combining both short tandem repeat (STR) and single nucleotide polymorphism (SNP) loci, small amplicons without constraints of size separation, more discrimination power, deep mixture resolution and sample multiplexing. We present our bioinformatic framework My-Forensic-Loci-queries (MyFLq) for analysis of MPS forensic data. For allele calling, the framework uses a MySQL reference allele database with automatically determined regions of interest (ROIs) by a generic maximal flanking algorithm which makes it possible to use any STR or SNP forensic locus. Python scripts were designed to automatically make allele calls starting from raw MPS data. We also present a method to assess the usefulness and overall performance of a forensic locus with respect to MPS, as well as methods to estimate whether an unknown allele, which sequence is not present in the MySQL database, is in fact a new allele or a sequencing error. The MyFLq framework was applied to an Illumina MiSeq dataset of a forensic Illumina amplicon library, generated from multilocus STR polymerase chain reaction (PCR) on both single contributor samples and multiple person DNA mixtures. Although the multilocus PCR was not yet optimized for MPS in terms of amplicon length or locus selection, the results show excellent results for most loci. The results show a high signal-to-noise ratio, correct allele calls, and a low limit of detection for minor DNA contributors in mixed DNA samples. Technically, forensic MPS affords great promise for routine implementation in forensic genomics. The method is also applicable to adjacent disciplines such as molecular autopsy in legal medicine and in mitochondrial DNA research. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Rapid whole-brain resting-state fMRI at 3 T: Efficiency-optimized three-dimensional EPI versus repetition time-matched simultaneous-multi-slice EPI.

PubMed

Stirnberg, Rüdiger; Huijbers, Willem; Brenner, Daniel; Poser, Benedikt A; Breteler, Monique; Stöcker, Tony

2017-12-01

State-of-the-art simultaneous-multi-slice (SMS-)EPI and 3D-EPI share several properties that benefit functional MRI acquisition. Both sequences employ equivalent parallel imaging undersampling with controlled aliasing to achieve high temporal sampling rates. As a volumetric imaging sequence, 3D-EPI offers additional means of acceleration complementary to 2D-CAIPIRINHA sampling, such as fast water excitation and elliptical sampling. We performed an application-oriented comparison between a tailored, six-fold CAIPIRINHA-accelerated 3D-EPI protocol at 530 ms temporal and 2.4 mm isotropic spatial resolution and an SMS-EPI protocol with identical spatial and temporal resolution for whole-brain resting-state fMRI at 3 T. The latter required eight-fold slice acceleration to compensate for the lack of elliptical sampling and fast water excitation. Both sequences used vendor-supplied on-line image reconstruction. We acquired test/retest resting-state fMRI scans in ten volunteers, with simultaneous acquisition of cardiac and respiration data, subsequently used for optional physiological noise removal (nuisance regression). We found that the 3D-EPI protocol has significantly increased temporal signal-to-noise ratio throughout the brain as compared to the SMS-EPI protocol, especially when employing motion and nuisance regression. Both sequence types reliably identified known functional networks with stronger functional connectivity values for the 3D-EPI protocol. We conclude that the more time-efficient 3D-EPI primarily benefits from reduced parallel imaging noise due to a higher, actual k-space sampling density compared to SMS-EPI. The resultant BOLD sensitivity increase makes 3D-EPI a valuable alternative to SMS-EPI for whole-brain fMRI at 3 T, with voxel sizes well below 3 mm isotropic and sampling rates high enough to separate dominant cardiac signals from BOLD signals in the frequency domain. Copyright © 2017 Elsevier Inc. All rights reserved.

From Bioengineering to CRISPR/Cas9 – A Personal Retrospective of 20 Years of Research in Programmable Genome Targeting

PubMed Central

Jeltsch, Albert

2018-01-01

Genome targeting of restriction enzymes and DNA methyltransferases has many important applications including genome and epigenome editing. 15–20 years ago, my group was involved in the development of approaches for programmable genome targeting, aiming to connect enzymes with an oligodeoxynucleotide (ODN), which could form a sequence-specific triple helix at the genomic target site. Importantly, the target site of such enzyme-ODN conjugate could be varied simply by altering the ODN sequence promising great applicative values. However, this approach was facing many problems including the preparation and purification of the enzyme-ODN conjugates, their efficient delivery into cells, slow kinetics of triple helix formation and the requirement of a poly-purine target site sequence. Hence, for several years genome and epigenome editing approaches mainly were based on Zinc fingers and TAL proteins as targeting devices. More recently, CRISPR/Cas systems were discovered, which use a bound RNA for genome targeting that forms an RNA/DNA duplex with one DNA strand of the target site. These systems combine all potential advantages of the once imagined enzyme-ODN conjugates and avoid all main disadvantageous. Consequently, the application of CRISPR/Cas in genome and epigenome editing has exploded in recent years. We can draw two important conclusions from this example of research history. First, evolution still is the better bioengineer than humans and, whenever tested in parallel, natural solutions outcompete engineered ones. Second, CRISPR/Cas system were discovered in pure, curiosity driven, basic research, highlighting that it is basic, bottom-up research paving the way for fundamental innovation. PMID:29434619

Big Data GPU-Driven Parallel Processing Spatial and Spatio-Temporal Clustering Algorithms

NASA Astrophysics Data System (ADS)

Konstantaras, Antonios; Skounakis, Emmanouil; Kilty, James-Alexander; Frantzeskakis, Theofanis; Maravelakis, Emmanuel

2016-04-01

Advances in graphics processing units' technology towards encompassing parallel architectures [1], comprised of thousands of cores and multiples of parallel threads, provide the foundation in terms of hardware for the rapid processing of various parallel applications regarding seismic big data analysis. Seismic data are normally stored as collections of vectors in massive matrices, growing rapidly in size as wider areas are covered, denser recording networks are being established and decades of data are being compiled together [2]. Yet, many processes regarding seismic data analysis are performed on each seismic event independently or as distinct tiles [3] of specific grouped seismic events within a much larger data set. Such processes, independent of one another can be performed in parallel narrowing down processing times drastically [1,3]. This research work presents the development and implementation of three parallel processing algorithms using Cuda C [4] for the investigation of potentially distinct seismic regions [5,6] present in the vicinity of the southern Hellenic seismic arc. The algorithms, programmed and executed in parallel comparatively, are the: fuzzy k-means clustering with expert knowledge [7] in assigning overall clusters' number; density-based clustering [8]; and a selves-developed spatio-temporal clustering algorithm encompassing expert [9] and empirical knowledge [10] for the specific area under investigation. Indexing terms: GPU parallel programming, Cuda C, heterogeneous processing, distinct seismic regions, parallel clustering algorithms, spatio-temporal clustering References [1] Kirk, D. and Hwu, W.: 'Programming massively parallel processors - A hands-on approach', 2nd Edition, Morgan Kaufman Publisher, 2013 [2] Konstantaras, A., Valianatos, F., Varley, M.R. and Makris, J.P.: 'Soft-Computing Modelling of Seismicity in the Southern Hellenic Arc', Geoscience and Remote Sensing Letters, vol. 5 (3), pp. 323-327, 2008 [3] Papadakis, S. and Diamantaras, K.: 'Programming and architecture of parallel processing systems', 1st Edition, Eds. Kleidarithmos, 2011 [4] NVIDIA.: 'NVidia CUDA C Programming Guide', version 5.0, NVidia (reference book) [5] Konstantaras, A.: 'Classification of Distinct Seismic Regions and Regional Temporal Modelling of Seismicity in the Vicinity of the Hellenic Seismic Arc', IEEE Selected Topics in Applied Earth Observations and Remote Sensing, vol. 6 (4), pp. 1857-1863, 2013 [6] Konstantaras, A. Varley, M.R.,. Valianatos, F., Collins, G. and Holifield, P.: 'Recognition of electric earthquake precursors using neuro-fuzzy models: methodology and simulation results', Proc. IASTED International Conference on Signal Processing Pattern Recognition and Applications (SPPRA 2002), Crete, Greece, 2002, pp 303-308, 2002 [7] Konstantaras, A., Katsifarakis, E., Maravelakis, E., Skounakis, E., Kokkinos, E. and Karapidakis, E.: 'Intelligent Spatial-Clustering of Seismicity in the Vicinity of the Hellenic Seismic Arc', Earth Science Research, vol. 1 (2), pp. 1-10, 2012 [8] Georgoulas, G., Konstantaras, A., Katsifarakis, E., Stylios, C.D., Maravelakis, E. and Vachtsevanos, G.: '"Seismic-Mass" Density-based Algorithm for Spatio-Temporal Clustering', Expert Systems with Applications, vol. 40 (10), pp. 4183-4189, 2013 [9] Konstantaras, A. J.: 'Expert knowledge-based algorithm for the dynamic discrimination of interactive natural clusters', Earth Science Informatics, 2015 (In Press, see: www.scopus.com) [10] Drakatos, G. and Latoussakis, J.: 'A catalog of aftershock sequences in Greece (1971-1997): Their spatial and temporal characteristics', Journal of Seismology, vol. 5, pp. 137-145, 2001

Application of CHAD hydrodynamics to shock-wave problems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trease, H.E.; O`Rourke, P.J.; Sahota, M.S.

1997-12-31

CHAD is the latest in a sequence of continually evolving computer codes written to effectively utilize massively parallel computer architectures and the latest grid generators for unstructured meshes. Its applications range from automotive design issues such as in-cylinder and manifold flows of internal combustion engines, vehicle aerodynamics, underhood cooling and passenger compartment heating, ventilation, and air conditioning to shock hydrodynamics and materials modeling. CHAD solves the full unsteady Navier-Stoke equations with the k-epsilon turbulence model in three space dimensions. The code has four major features that distinguish it from the earlier KIVA code, also developed at Los Alamos. First, itmore » is based on a node-centered, finite-volume method in which, like finite element methods, all fluid variables are located at computational nodes. The computational mesh efficiently and accurately handles all element shapes ranging from tetrahedra to hexahedra. Second, it is written in standard Fortran 90 and relies on automatic domain decomposition and a universal communication library written in standard C and MPI for unstructured grids to effectively exploit distributed-memory parallel architectures. Thus the code is fully portable to a variety of computing platforms such as uniprocessor workstations, symmetric multiprocessors, clusters of workstations, and massively parallel platforms. Third, CHAD utilizes a variable explicit/implicit upwind method for convection that improves computational efficiency in flows that have large velocity Courant number variations due to velocity of mesh size variations. Fourth, CHAD is designed to also simulate shock hydrodynamics involving multimaterial anisotropic behavior under high shear. The authors will discuss CHAD capabilities and show several sample calculations showing the strengths and weaknesses of CHAD.« less

Dual-task interference effects on cross-modal numerical order and sound intensity judgments: the more the louder?

PubMed

Alards-Tomalin, Doug; Walker, Alexander C; Nepon, Hillary; Leboe-McGowan, Launa C

2017-09-01

In the current study, cross-task interactions between number order and sound intensity judgments were assessed using a dual-task paradigm. Participants first categorized numerical sequences composed of Arabic digits as either ordered (ascending, descending) or non-ordered. Following each number sequence, participants then had to judge the intensity level of a target sound. Experiment 1 emphasized processing the two tasks independently (serial processing), while Experiments 2 and 3 emphasized processing the two tasks simultaneously (parallel processing). Cross-task interference occurred only when the task required parallel processing and was specific to ascending numerical sequences, which led to a higher proportion of louder sound intensity judgments. In Experiment 4 we examined whether this unidirectional interaction was the result of participants misattributing enhanced processing fluency experienced on ascending sequences as indicating a louder target sound. The unidirectional finding could not be entirely attributed to misattributed processing fluency, and may also be connected to experientially derived conceptual associations between ascending number sequences and greater magnitude, consistent with conceptual mapping theory.

A simple procedure for parallel sequence analysis of both strands of 5'-labeled DNA.

PubMed

Razvi, F; Gargiulo, G; Worcel, A

1983-08-01

Ligation of a 5'-labeled DNA restriction fragment results in a circular DNA molecule carrying the two 32Ps at the reformed restriction site. Double digestions of the circular DNA with the original enzyme and a second restriction enzyme cleavage near the labeled site allows direct chemical sequencing of one 5'-labeled DNA strand. Similar double digestions, using an isoschizomer that cleaves differently at the 32P-labeled site, allows direct sequencing of the now 3'-labeled complementary DNA strand. It is possible to directly sequence both strands of cloned DNA inserts by using the above protocol and a multiple cloning site vector that provides the necessary restriction sites. The simultaneous and parallel visualization of both DNA strands eliminates sequence ambiguities. In addition, the labeled circular molecules are particularly useful for single-hit DNA cleavage studies and DNA footprint analysis. As an example, we show here an analysis of the micrococcal nuclease-induced breaks on the two strands of the somatic 5S RNA gene of Xenopus borealis, which suggests that the enzyme may recognize and cleave small AT-containing palindromes along the DNA helix.

Faster Smith-Waterman database searches with inter-sequence SIMD parallelisation

PubMed Central

2011-01-01

Background The Smith-Waterman algorithm for local sequence alignment is more sensitive than heuristic methods for database searching, but also more time-consuming. The fastest approach to parallelisation with SIMD technology has previously been described by Farrar in 2007. The aim of this study was to explore whether further speed could be gained by other approaches to parallelisation. Results A faster approach and implementation is described and benchmarked. In the new tool SWIPE, residues from sixteen different database sequences are compared in parallel to one query residue. Using a 375 residue query sequence a speed of 106 billion cell updates per second (GCUPS) was achieved on a dual Intel Xeon X5650 six-core processor system, which is over six times more rapid than software based on Farrar's 'striped' approach. SWIPE was about 2.5 times faster when the programs used only a single thread. For shorter queries, the increase in speed was larger. SWIPE was about twice as fast as BLAST when using the BLOSUM50 score matrix, while BLAST was about twice as fast as SWIPE for the BLOSUM62 matrix. The software is designed for 64 bit Linux on processors with SSSE3. Source code is available from http://dna.uio.no/swipe/ under the GNU Affero General Public License. Conclusions Efficient parallelisation using SIMD on standard hardware makes it possible to run Smith-Waterman database searches more than six times faster than before. The approach described here could significantly widen the potential application of Smith-Waterman searches. Other applications that require optimal local alignment scores could also benefit from improved performance. PMID:21631914

Faster Smith-Waterman database searches with inter-sequence SIMD parallelisation.

PubMed

Rognes, Torbjørn

2011-06-01

The Smith-Waterman algorithm for local sequence alignment is more sensitive than heuristic methods for database searching, but also more time-consuming. The fastest approach to parallelisation with SIMD technology has previously been described by Farrar in 2007. The aim of this study was to explore whether further speed could be gained by other approaches to parallelisation. A faster approach and implementation is described and benchmarked. In the new tool SWIPE, residues from sixteen different database sequences are compared in parallel to one query residue. Using a 375 residue query sequence a speed of 106 billion cell updates per second (GCUPS) was achieved on a dual Intel Xeon X5650 six-core processor system, which is over six times more rapid than software based on Farrar's 'striped' approach. SWIPE was about 2.5 times faster when the programs used only a single thread. For shorter queries, the increase in speed was larger. SWIPE was about twice as fast as BLAST when using the BLOSUM50 score matrix, while BLAST was about twice as fast as SWIPE for the BLOSUM62 matrix. The software is designed for 64 bit Linux on processors with SSSE3. Source code is available from http://dna.uio.no/swipe/ under the GNU Affero General Public License. Efficient parallelisation using SIMD on standard hardware makes it possible to run Smith-Waterman database searches more than six times faster than before. The approach described here could significantly widen the potential application of Smith-Waterman searches. Other applications that require optimal local alignment scores could also benefit from improved performance.

Employing Nested OpenMP for the Parallelization of Multi-Zone Computational Fluid Dynamics Applications

NASA Technical Reports Server (NTRS)

Ayguade, Eduard; Gonzalez, Marc; Martorell, Xavier; Jost, Gabriele

2004-01-01

In this paper we describe the parallelization of the multi-zone code versions of the NAS Parallel Benchmarks employing multi-level OpenMP parallelism. For our study we use the NanosCompiler, which supports nesting of OpenMP directives and provides clauses to control the grouping of threads, load balancing, and synchronization. We report the benchmark results, compare the timings with those of different hybrid parallelization paradigms and discuss OpenMP implementation issues which effect the performance of multi-level parallel applications.

The development of a scalable parallel 3-D CFD algorithm for turbomachinery. M.S. Thesis Final Report

NASA Technical Reports Server (NTRS)

Luke, Edward Allen

1993-01-01

Two algorithms capable of computing a transonic 3-D inviscid flow field about rotating machines are considered for parallel implementation. During the study of these algorithms, a significant new method of measuring the performance of parallel algorithms is developed. The theory that supports this new method creates an empirical definition of scalable parallel algorithms that is used to produce quantifiable evidence that a scalable parallel application was developed. The implementation of the parallel application and an automated domain decomposition tool are also discussed.

Parallel algorithm for determining motion vectors in ice floe images by matching edge features

NASA Technical Reports Server (NTRS)

Manohar, M.; Ramapriyan, H. K.; Strong, J. P.

1988-01-01

A parallel algorithm is described to determine motion vectors of ice floes using time sequences of images of the Arctic ocean obtained from the Synthetic Aperture Radar (SAR) instrument flown on-board the SEASAT spacecraft. Researchers describe a parallel algorithm which is implemented on the MPP for locating corresponding objects based on their translationally and rotationally invariant features. The algorithm first approximates the edges in the images by polygons or sets of connected straight-line segments. Each such edge structure is then reduced to a seed point. Associated with each seed point are the descriptions (lengths, orientations and sequence numbers) of the lines constituting the corresponding edge structure. A parallel matching algorithm is used to match packed arrays of such descriptions to identify corresponding seed points in the two images. The matching algorithm is designed such that fragmentation and merging of ice floes are taken into account by accepting partial matches. The technique has been demonstrated to work on synthetic test patterns and real image pairs from SEASAT in times ranging from .5 to 0.7 seconds for 128 x 128 images.

Automated Generation of Message-Passing Programs: An Evaluation Using CAPTools

NASA Technical Reports Server (NTRS)

Hribar, Michelle R.; Jin, Haoqiang; Yan, Jerry C.; Saini, Subhash (Technical Monitor)

1998-01-01

Scientists at NASA Ames Research Center have been developing computational aeroscience applications on highly parallel architectures over the past ten years. During that same time period, a steady transition of hardware and system software also occurred, forcing us to expend great efforts into migrating and re-coding our applications. As applications and machine architectures become increasingly complex, the cost and time required for this process will become prohibitive. In this paper, we present the first set of results in our evaluation of interactive parallelization tools. In particular, we evaluate CAPTool's ability to parallelize computational aeroscience applications. CAPTools was tested on serial versions of the NAS Parallel Benchmarks and ARC3D, a computational fluid dynamics application, on two platforms: the SGI Origin 2000 and the Cray T3E. This evaluation includes performance, amount of user interaction required, limitations and portability. Based on these results, a discussion on the feasibility of computer aided parallelization of aerospace applications is presented along with suggestions for future work.

Applicability of the single equivalent point dipole model to represent a spatially distributed bio-electrical source

NASA Technical Reports Server (NTRS)

Armoundas, A. A.; Feldman, A. B.; Sherman, D. A.; Cohen, R. J.

2001-01-01

Although the single equivalent point dipole model has been used to represent well-localised bio-electrical sources, in realistic situations the source is distributed. Consequently, position estimates of point dipoles determined by inverse algorithms suffer from systematic error due to the non-exact applicability of the inverse model. In realistic situations, this systematic error cannot be avoided, a limitation that is independent of the complexity of the torso model used. This study quantitatively investigates the intrinsic limitations in the assignment of a location to the equivalent dipole due to distributed electrical source. To simulate arrhythmic activity in the heart, a model of a wave of depolarisation spreading from a focal source over the surface of a spherical shell is used. The activity is represented by a sequence of concentric belt sources (obtained by slicing the shell with a sequence of parallel plane pairs), with constant dipole moment per unit length (circumferentially) directed parallel to the propagation direction. The distributed source is represented by N dipoles at equal arc lengths along the belt. The sum of the dipole potentials is calculated at predefined electrode locations. The inverse problem involves finding a single equivalent point dipole that best reproduces the electrode potentials due to the distributed source. The inverse problem is implemented by minimising the chi2 per degree of freedom. It is found that the trajectory traced by the equivalent dipole is sensitive to the location of the spherical shell relative to the fixed electrodes. It is shown that this trajectory does not coincide with the sequence of geometrical centres of the consecutive belt sources. For distributed sources within a bounded spherical medium, displaced from the sphere's centre by 40% of the sphere's radius, it is found that the error in the equivalent dipole location varies from 3 to 20% for sources with size between 5 and 50% of the sphere's radius. Finally, a method is devised to obtain the size of the distributed source during the cardiac cycle.

Parallel processing spacecraft communication system

NASA Technical Reports Server (NTRS)

Bolotin, Gary S. (Inventor); Donaldson, James A. (Inventor); Luong, Huy H. (Inventor); Wood, Steven H. (Inventor)

1998-01-01

An uplink controlling assembly speeds data processing using a special parallel codeblock technique. A correct start sequence initiates processing of a frame. Two possible start sequences can be used; and the one which is used determines whether data polarity is inverted or non-inverted. Processing continues until uncorrectable errors are found. The frame ends by intentionally sending a block with an uncorrectable error. Each of the codeblocks in the frame has a channel ID. Each channel ID can be separately processed in parallel. This obviates the problem of waiting for error correction processing. If that channel number is zero, however, it indicates that the frame of data represents a critical command only. That data is handled in a special way, independent of the software. Otherwise, the processed data further handled using special double buffering techniques to avoid problems from overrun. When overrun does occur, the system takes action to lose only the oldest data.

Fast I/O for Massively Parallel Applications

NASA Technical Reports Server (NTRS)

OKeefe, Matthew T.

1996-01-01

The two primary goals for this report were the design, contruction and modeling of parallel disk arrays for scientific visualization and animation, and a study of the IO requirements of highly parallel applications. In addition, further work in parallel display systems required to project and animate the very high-resolution frames resulting from our supercomputing simulations in ocean circulation and compressible gas dynamics.

Simultaneous Multi-Slice fMRI using Spiral Trajectories

PubMed Central

Zahneisen, Benjamin; Poser, Benedikt A.; Ernst, Thomas; Stenger, V. Andrew

2014-01-01

Parallel imaging methods using multi-coil receiver arrays have been shown to be effective for increasing MRI acquisition speed. However parallel imaging methods for fMRI with 2D sequences show only limited improvements in temporal resolution because of the long echo times needed for BOLD contrast. Recently, Simultaneous Multi-Slice (SMS) imaging techniques have been shown to increase fMRI temporal resolution by factors of four and higher. In SMS fMRI multiple slices can be acquired simultaneously using Echo Planar Imaging (EPI) and the overlapping slices are un-aliased using a parallel imaging reconstruction with multiple receivers. The slice separation can be further improved using the “blipped-CAIPI” EPI sequence that provides a more efficient sampling of the SMS 3D k-space. In this paper a blipped-spiral SMS sequence for ultra-fast fMRI is presented. The blipped-spiral sequence combines the sampling efficiency of spiral trajectories with the SMS encoding concept used in blipped-CAIPI EPI. We show that blipped spiral acquisition can achieve almost whole brain coverage at 3 mm isotropic resolution in 168 ms. It is also demonstrated that the high temporal resolution allows for dynamic BOLD lag time measurement using visual/motor and retinotopic mapping paradigms. The local BOLD lag time within the visual cortex following the retinotopic mapping stimulation of expanding flickering rings is directly measured and easily translated into an eccentricity map of the cortex. PMID:24518259

Kmerind: A Flexible Parallel Library for K-mer Indexing of Biological Sequences on Distributed Memory Systems.

PubMed

Pan, Tony; Flick, Patrick; Jain, Chirag; Liu, Yongchao; Aluru, Srinivas

2017-10-09

Counting and indexing fixed length substrings, or k-mers, in biological sequences is a key step in many bioinformatics tasks including genome alignment and mapping, genome assembly, and error correction. While advances in next generation sequencing technologies have dramatically reduced the cost and improved latency and throughput, few bioinformatics tools can efficiently process the datasets at the current generation rate of 1.8 terabases every 3 days. We present Kmerind, a high performance parallel k-mer indexing library for distributed memory environments. The Kmerind library provides a set of simple and consistent APIs with sequential semantics and parallel implementations that are designed to be flexible and extensible. Kmerind's k-mer counter performs similarly or better than the best existing k-mer counting tools even on shared memory systems. In a distributed memory environment, Kmerind counts k-mers in a 120 GB sequence read dataset in less than 13 seconds on 1024 Xeon CPU cores, and fully indexes their positions in approximately 17 seconds. Querying for 1% of the k-mers in these indices can be completed in 0.23 seconds and 28 seconds, respectively. Kmerind is the first k-mer indexing library for distributed memory environments, and the first extensible library for general k-mer indexing and counting. Kmerind is available at https://github.com/ParBLiSS/kmerind.

An overview of the Hadoop/MapReduce/HBase framework and its current applications in bioinformatics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Ronald C.

Bioinformatics researchers are increasingly confronted with analysis of ultra large-scale data sets, a problem that will only increase at an alarming rate in coming years. Recent developments in open source software, that is, the Hadoop project and associated software, provide a foundation for scaling to petabyte scale data warehouses on Linux clusters, providing fault-tolerant parallelized analysis on such data using a programming style named MapReduce. An overview is given of the current usage within the bioinformatics community of Hadoop, a top-level Apache Software Foundation project, and of associated open source software projects. The concepts behind Hadoop and the associated HBasemore » project are defined, and current bioinformatics software that employ Hadoop is described. The focus is on next-generation sequencing, as the leading application area to date.« less

Phylo_dCor: distance correlation as a novel metric for phylogenetic profiling.

PubMed

Sferra, Gabriella; Fratini, Federica; Ponzi, Marta; Pizzi, Elisabetta

2017-09-05

Elaboration of powerful methods to predict functional and/or physical protein-protein interactions from genome sequence is one of the main tasks in the post-genomic era. Phylogenetic profiling allows the prediction of protein-protein interactions at a whole genome level in both Prokaryotes and Eukaryotes. For this reason it is considered one of the most promising methods. Here, we propose an improvement of phylogenetic profiling that enables handling of large genomic datasets and infer global protein-protein interactions. This method uses the distance correlation as a new measure of phylogenetic profile similarity. We constructed robust reference sets and developed Phylo-dCor, a parallelized version of the algorithm for calculating the distance correlation that makes it applicable to large genomic data. Using Saccharomyces cerevisiae and Escherichia coli genome datasets, we showed that Phylo-dCor outperforms phylogenetic profiling methods previously described based on the mutual information and Pearson's correlation as measures of profile similarity. In this work, we constructed and assessed robust reference sets and propose the distance correlation as a measure for comparing phylogenetic profiles. To make it applicable to large genomic data, we developed Phylo-dCor, a parallelized version of the algorithm for calculating the distance correlation. Two R scripts that can be run on a wide range of machines are available upon request.

A universal TagModule collection for parallel genetic analysis of microorganisms

PubMed Central

Oh, Julia; Fung, Eula; Price, Morgan N.; Dehal, Paramvir S.; Davis, Ronald W.; Giaever, Guri; Nislow, Corey; Arkin, Adam P.; Deutschbauer, Adam

2010-01-01

Systems-level analyses of non-model microorganisms are limited by the existence of numerous uncharacterized genes and a corresponding over-reliance on automated computational annotations. One solution to this challenge is to disrupt gene function using DNA tag technology, which has been highly successful in parallelizing reverse genetics in Saccharomyces cerevisiae and has led to discoveries in gene function, genetic interactions and drug mechanism of action. To extend the yeast DNA tag methodology to a wide variety of microorganisms and applications, we have created a universal, sequence-verified TagModule collection. A hallmark of the 4280 TagModules is that they are cloned into a Gateway entry vector, thus facilitating rapid transfer to any compatible genetic system. Here, we describe the application of the TagModules to rapidly generate tagged mutants by transposon mutagenesis in the metal-reducing bacterium Shewanella oneidensis MR-1 and the pathogenic yeast Candida albicans. Our results demonstrate the optimal hybridization properties of the TagModule collection, the flexibility in applying the strategy to diverse microorganisms and the biological insights that can be gained from fitness profiling tagged mutant collections. The publicly available TagModule collection is a platform-independent resource for the functional genomics of a wide range of microbial systems in the post-genome era. PMID:20494978

Application of the Linux cluster for exhaustive window haplotype analysis using the FBAT and Unphased programs.

PubMed

Mishima, Hiroyuki; Lidral, Andrew C; Ni, Jun

2008-05-28

Genetic association studies have been used to map disease-causing genes. A newly introduced statistical method, called exhaustive haplotype association study, analyzes genetic information consisting of different numbers and combinations of DNA sequence variations along a chromosome. Such studies involve a large number of statistical calculations and subsequently high computing power. It is possible to develop parallel algorithms and codes to perform the calculations on a high performance computing (HPC) system. However, most existing commonly-used statistic packages for genetic studies are non-parallel versions. Alternatively, one may use the cutting-edge technology of grid computing and its packages to conduct non-parallel genetic statistical packages on a centralized HPC system or distributed computing systems. In this paper, we report the utilization of a queuing scheduler built on the Grid Engine and run on a Rocks Linux cluster for our genetic statistical studies. Analysis of both consecutive and combinational window haplotypes was conducted by the FBAT (Laird et al., 2000) and Unphased (Dudbridge, 2003) programs. The dataset consisted of 26 loci from 277 extended families (1484 persons). Using the Rocks Linux cluster with 22 compute-nodes, FBAT jobs performed about 14.4-15.9 times faster, while Unphased jobs performed 1.1-18.6 times faster compared to the accumulated computation duration. Execution of exhaustive haplotype analysis using non-parallel software packages on a Linux-based system is an effective and efficient approach in terms of cost and performance.

Application of the Linux cluster for exhaustive window haplotype analysis using the FBAT and Unphased programs

PubMed Central

Mishima, Hiroyuki; Lidral, Andrew C; Ni, Jun

2008-01-01

Background Genetic association studies have been used to map disease-causing genes. A newly introduced statistical method, called exhaustive haplotype association study, analyzes genetic information consisting of different numbers and combinations of DNA sequence variations along a chromosome. Such studies involve a large number of statistical calculations and subsequently high computing power. It is possible to develop parallel algorithms and codes to perform the calculations on a high performance computing (HPC) system. However, most existing commonly-used statistic packages for genetic studies are non-parallel versions. Alternatively, one may use the cutting-edge technology of grid computing and its packages to conduct non-parallel genetic statistical packages on a centralized HPC system or distributed computing systems. In this paper, we report the utilization of a queuing scheduler built on the Grid Engine and run on a Rocks Linux cluster for our genetic statistical studies. Results Analysis of both consecutive and combinational window haplotypes was conducted by the FBAT (Laird et al., 2000) and Unphased (Dudbridge, 2003) programs. The dataset consisted of 26 loci from 277 extended families (1484 persons). Using the Rocks Linux cluster with 22 compute-nodes, FBAT jobs performed about 14.4–15.9 times faster, while Unphased jobs performed 1.1–18.6 times faster compared to the accumulated computation duration. Conclusion Execution of exhaustive haplotype analysis using non-parallel software packages on a Linux-based system is an effective and efficient approach in terms of cost and performance. PMID:18541045

Broadcasting collective operation contributions throughout a parallel computer

DOEpatents

Faraj, Ahmad [Rochester, MN

2012-02-21

Methods, systems, and products are disclosed for broadcasting collective operation contributions throughout a parallel computer. The parallel computer includes a plurality of compute nodes connected together through a data communications network. Each compute node has a plurality of processors for use in collective parallel operations on the parallel computer. Broadcasting collective operation contributions throughout a parallel computer according to embodiments of the present invention includes: transmitting, by each processor on each compute node, that processor's collective operation contribution to the other processors on that compute node using intra-node communications; and transmitting on a designated network link, by each processor on each compute node according to a serial processor transmission sequence, that processor's collective operation contribution to the other processors on the other compute nodes using inter-node communications.

An integrated runtime and compile-time approach for parallelizing structured and block structured applications

NASA Technical Reports Server (NTRS)

Agrawal, Gagan; Sussman, Alan; Saltz, Joel

1993-01-01

Scientific and engineering applications often involve structured meshes. These meshes may be nested (for multigrid codes) and/or irregularly coupled (called multiblock or irregularly coupled regular mesh problems). A combined runtime and compile-time approach for parallelizing these applications on distributed memory parallel machines in an efficient and machine-independent fashion was described. A runtime library which can be used to port these applications on distributed memory machines was designed and implemented. The library is currently implemented on several different systems. To further ease the task of application programmers, methods were developed for integrating this runtime library with compilers for HPK-like parallel programming languages. How this runtime library was integrated with the Fortran 90D compiler being developed at Syracuse University is discussed. Experimental results to demonstrate the efficacy of our approach are presented. A multiblock Navier-Stokes solver template and a multigrid code were experimented with. Our experimental results show that our primitives have low runtime communication overheads. Further, the compiler parallelized codes perform within 20 percent of the code parallelized by manually inserting calls to the runtime library.

Application of advanced geophysical logging methods in the characterization of a fractured-sedimentary bedrock aquifer, Ventura County, California

USGS Publications Warehouse

Williams, John H.; Lane, John W.; Singha, Kamini; Haeni, F. Peter

2002-01-01

An integrated suite of advanced geophysical logging methods was used to characterize the geology and hydrology of three boreholes completed in fractured-sedimentary bedrock in Ventura County, California. The geophysical methods included caliper, gamma, electromagnetic induction, borehole deviation, optical and acoustic televiewer, borehole radar, fluid resistivity, temperature, and electromagnetic flowmeter. The geophysical logging 1) provided insights useful for the overall geohydrologic characterization of the bedrock and 2) enhanced the value of information collected by other methods from the boreholes including core-sample analysis, multiple-level monitoring, and packer testing.The logged boreholes, which have open intervals of 100 to 200 feet, penetrate a sequence of interbedded sandstone and mudstone with bedding striking 220 to 250 degrees and dipping 15 to 40 degrees to the northwest. Fractures intersected by the boreholes include fractures parallel to bedding and fractures with variable strike that dip moderately to steeply. Two to three flow zones were detected in each borehole. The flow zones consist of bedding-parallel or steeply dipping fractures or a combination of bedding-parallel fractures and moderately to steeply dipping fractures. About 75 to more than 90 percent of the measured flow under pumped conditions was produced by only one of the flow zones in each borehole.

Advances in single-cell RNA sequencing and its applications in cancer research.

PubMed

Zhu, Sibo; Qing, Tao; Zheng, Yuanting; Jin, Li; Shi, Leming

2017-08-08

Unlike population-level approaches, single-cell RNA sequencing enables transcriptomic analysis of an individual cell. Through the combination of high-throughput sequencing and bioinformatic tools, single-cell RNA-seq can detect more than 10,000 transcripts in one cell to distinguish cell subsets and dynamic cellular changes. After several years' development, single-cell RNA-seq can now achieve massively parallel, full-length mRNA sequencing as well as in situ sequencing and even has potential for multi-omic detection. One appealing area of single-cell RNA-seq is cancer research, and it is regarded as a promising way to enhance prognosis and provide more precise target therapy by identifying druggable subclones. Indeed, progresses have been made regarding solid tumor analysis to reveal intratumoral heterogeneity, correlations between signaling pathways, stemness, drug resistance, and tumor architecture shaping the microenvironment. Furthermore, through investigation into circulating tumor cells, many genes have been shown to promote a propensity toward stemness and the epithelial-mesenchymal transition, to enhance anchoring and adhesion, and to be involved in mechanisms of anoikis resistance and drug resistance. This review focuses on advances and progresses of single-cell RNA-seq with regard to the following aspects: 1. Methodologies of single-cell RNA-seq 2. Single-cell isolation techniques 3. Single-cell RNA-seq in solid tumor research 4. Single-cell RNA-seq in circulating tumor cell research 5.

Advances in single-cell RNA sequencing and its applications in cancer research

PubMed Central

Zhu, Sibo; Qing, Tao; Zheng, Yuanting; Jin, Li; Shi, Leming

2017-01-01

Unlike population-level approaches, single-cell RNA sequencing enables transcriptomic analysis of an individual cell. Through the combination of high-throughput sequencing and bioinformatic tools, single-cell RNA-seq can detect more than 10,000 transcripts in one cell to distinguish cell subsets and dynamic cellular changes. After several years’ development, single-cell RNA-seq can now achieve massively parallel, full-length mRNA sequencing as well as in situ sequencing and even has potential for multi-omic detection. One appealing area of single-cell RNA-seq is cancer research, and it is regarded as a promising way to enhance prognosis and provide more precise target therapy by identifying druggable subclones. Indeed, progresses have been made regarding solid tumor analysis to reveal intratumoral heterogeneity, correlations between signaling pathways, stemness, drug resistance, and tumor architecture shaping the microenvironment. Furthermore, through investigation into circulating tumor cells, many genes have been shown to promote a propensity toward stemness and the epithelial-mesenchymal transition, to enhance anchoring and adhesion, and to be involved in mechanisms of anoikis resistance and drug resistance. This review focuses on advances and progresses of single-cell RNA-seq with regard to the following aspects: 1. Methodologies of single-cell RNA-seq 2. Single-cell isolation techniques 3. Single-cell RNA-seq in solid tumor research 4. Single-cell RNA-seq in circulating tumor cell research 5. Perspectives PMID:28881849

Parallel human genome analysis: microarray-based expression monitoring of 1000 genes.

PubMed Central

Schena, M; Shalon, D; Heller, R; Chai, A; Brown, P O; Davis, R W

1996-01-01

Microarrays containing 1046 human cDNAs of unknown sequence were printed on glass with high-speed robotics. These 1.0-cm2 DNA "chips" were used to quantitatively monitor differential expression of the cognate human genes using a highly sensitive two-color hybridization assay. Array elements that displayed differential expression patterns under given experimental conditions were characterized by sequencing. The identification of known and novel heat shock and phorbol ester-regulated genes in human T cells demonstrates the sensitivity of the assay. Parallel gene analysis with microarrays provides a rapid and efficient method for large-scale human gene discovery. Images Fig. 1 Fig. 2 Fig. 3 PMID:8855227

Portable programming on parallel/networked computers using the Application Portable Parallel Library (APPL)

NASA Technical Reports Server (NTRS)

Quealy, Angela; Cole, Gary L.; Blech, Richard A.

1993-01-01

The Application Portable Parallel Library (APPL) is a subroutine-based library of communication primitives that is callable from applications written in FORTRAN or C. APPL provides a consistent programmer interface to a variety of distributed and shared-memory multiprocessor MIMD machines. The objective of APPL is to minimize the effort required to move parallel applications from one machine to another, or to a network of homogeneous machines. APPL encompasses many of the message-passing primitives that are currently available on commercial multiprocessor systems. This paper describes APPL (version 2.3.1) and its usage, reports the status of the APPL project, and indicates possible directions for the future. Several applications using APPL are discussed, as well as performance and overhead results.

Competitive Dominance among Strains of Luminous Bacteria Provides an Unusual Form of Evidence for Parallel Evolution in Sepiolid Squid-Vibrio Symbioses

PubMed Central

Nishiguchi, Michele K.; Ruby, Edward G.; McFall-Ngai, Margaret J.

1998-01-01

One of the principal assumptions in symbiosis research is that associated partners have evolved in parallel. We report here experimental evidence for parallel speciation patterns among several partners of the sepiolid squid-luminous bacterial symbioses. Molecular phylogenies for 14 species of host squids were derived from sequences of both the nuclear internal transcribed spacer region and the mitochondrial cytochrome oxidase subunit I; the glyceraldehyde phosphate dehydrogenase locus was sequenced for phylogenetic determinations of 7 strains of bacterial symbionts. Comparisons of trees constructed for each of the three loci revealed a parallel phylogeny between the sepiolids and their respective symbionts. Because both the squids and their bacterial partners can be easily cultured independently in the laboratory, we were able to couple these phylogenetic analyses with experiments to examine the ability of the different symbiont strains to compete with each other during the colonization of one of the host species. Our results not only indicate a pronounced dominance of native symbiont strains over nonnative strains, but also reveal a hierarchy of symbiont competency that reflects the phylogenetic relationships of the partners. For the first time, molecular systematics has been coupled with experimental colonization assays to provide evidence for the existence of parallel speciation among a set of animal-bacterial associations. PMID:9726861

High Resolution Size Analysis of Fetal DNA in the Urine of Pregnant Women by Paired-End Massively Parallel Sequencing

PubMed Central

Tsui, Nancy B. Y.; Jiang, Peiyong; Chow, Katherine C. K.; Su, Xiaoxi; Leung, Tak Y.; Sun, Hao; Chan, K. C. Allen; Chiu, Rossa W. K.; Lo, Y. M. Dennis

2012-01-01

Background Fetal DNA in maternal urine, if present, would be a valuable source of fetal genetic material for noninvasive prenatal diagnosis. However, the existence of fetal DNA in maternal urine has remained controversial. The issue is due to the lack of appropriate technology to robustly detect the potentially highly degraded fetal DNA in maternal urine. Methodology We have used massively parallel paired-end sequencing to investigate cell-free DNA molecules in maternal urine. Catheterized urine samples were collected from seven pregnant women during the third trimester of pregnancies. We detected fetal DNA by identifying sequenced reads that contained fetal-specific alleles of the single nucleotide polymorphisms. The sizes of individual urinary DNA fragments were deduced from the alignment positions of the paired reads. We measured the fractional fetal DNA concentration as well as the size distributions of fetal and maternal DNA in maternal urine. Principal Findings Cell-free fetal DNA was detected in five of the seven maternal urine samples, with the fractional fetal DNA concentrations ranged from 1.92% to 4.73%. Fetal DNA became undetectable in maternal urine after delivery. The total urinary cell-free DNA molecules were less intact when compared with plasma DNA. Urinary fetal DNA fragments were very short, and the most dominant fetal sequences were between 29 bp and 45 bp in length. Conclusions With the use of massively parallel sequencing, we have confirmed the existence of transrenal fetal DNA in maternal urine, and have shown that urinary fetal DNA was heavily degraded. PMID:23118982

Molecular characterization of colorectal cancer patients and concomitant patient-derived tumor cell establishment

PubMed Central

Kim, Seung Tae; Kim, Sun Young; Kim, Nayoung K.D.; Jang, Jiryeon; Kang, Mihyun; Jang, Hyojin; Ahn, Soomin; Kim, Seok Hyeong; Park, Yoona; Cho, Yong Beom; Heo, Jeong Wook; Lee, Woo Yong; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Park, Woong-Yang; Lee, Jeeyun; Kim, Hee Cheol

2016-01-01

Background We aimed to establish a prospectively enrolled colorectal cancer (CRC) cohort for targeted sequencing of primary tumors from CRC patients. In parallel, we established collateral PDC models from the matched primary tumor tissues, which may be later used as preclinical models for genome-directed targeted therapy experiments. Results In all, we identified 27 SNVs in the 6 genes such as PIK3CA (N = 16), BRAF (N = 6), NRAS (N = 2), and CTNNB1 (N = 1), PTEN (N = 1), and ERBB2 (N = 1). RET-NCOA4 translocation was observed in one out of 105 patients (0.9%). PDC models were successfully established from 62 (55.4%) of the 112 samples. To confirm the genomic features of various tumor cells, we compared variant allele frequency results of the primary tumor and progeny PDCs. The Pearson correlation coefficient between the variants from primary tumor cells and PDCs was 0.881. Methods Between April 2014 and June 2015, 112 patients with CRC who underwent resection of the primary tumor were enrolled in the SMC Oncology Biomarker study. The PDC culture protocol was performed for all eligible patients. All of the primary tumors from the 112 patients who provided written informed consent were genomically sequenced with targeted sequencing. In parallel, PDC establishment was attempted for all sequenced tumors. Conclusions We have prospectively sequenced a CRC cohort of 105 patients and successfully established 62 PDC in parallel. Each genomically characterized PDCs can be used as a preclinical model especially in rare genomic alteration event. PMID:26909603

The Einstein Genome Gateway using WASP - a high throughput multi-layered life sciences portal for XSEDE.

PubMed

Golden, Aaron; McLellan, Andrew S; Dubin, Robert A; Jing, Qiang; O Broin, Pilib; Moskowitz, David; Zhang, Zhengdong; Suzuki, Masako; Hargitai, Joseph; Calder, R Brent; Greally, John M

2012-01-01

Massively-parallel sequencing (MPS) technologies and their diverse applications in genomics and epigenomics research have yielded enormous new insights into the physiology and pathophysiology of the human genome. The biggest hurdle remains the magnitude and diversity of the datasets generated, compromising our ability to manage, organize, process and ultimately analyse data. The Wiki-based Automated Sequence Processor (WASP), developed at the Albert Einstein College of Medicine (hereafter Einstein), uniquely manages to tightly couple the sequencing platform, the sequencing assay, sample metadata and the automated workflows deployed on a heterogeneous high performance computing cluster infrastructure that yield sequenced, quality-controlled and 'mapped' sequence data, all within the one operating environment accessible by a web-based GUI interface. WASP at Einstein processes 4-6 TB of data per week and since its production cycle commenced it has processed ~ 1 PB of data overall and has revolutionized user interactivity with these new genomic technologies, who remain blissfully unaware of the data storage, management and most importantly processing services they request. The abstraction of such computational complexity for the user in effect makes WASP an ideal middleware solution, and an appropriate basis for the development of a grid-enabled resource - the Einstein Genome Gateway - as part of the Extreme Science and Engineering Discovery Environment (XSEDE) program. In this paper we discuss the existing WASP system, its proposed middleware role, and its planned interaction with XSEDE to form the Einstein Genome Gateway.

RISC RNA sequencing for context-specific identification of in vivo microRNA targets.

PubMed

Matkovich, Scot J; Van Booven, Derek J; Eschenbacher, William H; Dorn, Gerald W

2011-01-07

MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo. To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs). We optimized techniques for expression profiling small amounts of RNA without introducing amplification bias and applied this to anti-Argonaute 2 immunoprecipitated RISCs (RISC-Seq) from mouse hearts. By comparing RNA-sequencing results of cardiac RISC and transcriptome from the same individual hearts, we defined 1645 mRNAs consistently targeted to mouse cardiac RISCs. We used this approach in hearts overexpressing miRs from Myh6 promoter-driven precursors (programmed RISC-Seq) to identify 209 in vivo targets of miR-133a and 81 in vivo targets of miR-499. Consistent with the fact that miR-133a and miR-499 have widely differing "seed" sequences and belong to different miR families, only 6 targets were common to miR-133a- and miR-499-programmed hearts. RISC-sequencing is a highly sensitive method for general RISC profiling and individual miR target identification in biological context and is applicable to any tissue and any disease state.

Accelerating parallel transmit array B1 mapping in high field MRI with slice undersampling and interpolation by kriging.

PubMed

Ferrand, Guillaume; Luong, Michel; Cloos, Martijn A; Amadon, Alexis; Wackernagel, Hans

2014-08-01

Transmit arrays have been developed to mitigate the RF field inhomogeneity commonly observed in high field magnetic resonance imaging (MRI), typically above 3T. To this end, the knowledge of the RF complex-valued B1 transmit-sensitivities of each independent radiating element has become essential. This paper details a method to speed up a currently available B1-calibration method. The principle relies on slice undersampling, slice and channel interleaving and kriging, an interpolation method developed in geostatistics and applicable in many domains. It has been demonstrated that, under certain conditions, kriging gives the best estimator of a field in a region of interest. The resulting accelerated sequence allows mapping a complete set of eight volumetric field maps of the human head in about 1 min. For validation, the accuracy of kriging is first evaluated against a well-known interpolation technique based on Fourier transform as well as to a B1-maps interpolation method presented in the literature. This analysis is carried out on simulated and decimated experimental B1 maps. Finally, the accelerated sequence is compared to the standard sequence on a phantom and a volunteer. The new sequence provides B1 maps three times faster with a loss of accuracy limited potentially to about 5%.

Suitability and setup of next-generation sequencing-based method for taxonomic characterization of aquatic microbial biofilm.

PubMed

Bakal, Tomas; Janata, Jiri; Sabova, Lenka; Grabic, Roman; Zlabek, Vladimir; Najmanova, Lucie

2018-06-16

A robust and widely applicable method for sampling of aquatic microbial biofilm and further sample processing is presented. The method is based on next-generation sequencing of V4-V5 variable regions of 16S rRNA gene and further statistical analysis of sequencing data, which could be useful not only to investigate taxonomic composition of biofilm bacterial consortia but also to assess aquatic ecosystem health. Five artificial materials commonly used for biofilm growth (glass, stainless steel, aluminum, polypropylene, polyethylene) were tested to determine the one giving most robust and reproducible results. The effect of used sampler material on total microbial composition was not statistically significant; however, the non-plastic materials (glass, metal) gave more stable outputs without irregularities among sample parallels. The bias of the method is assessed with respect to the employment of a non-quantitative step (PCR amplification) to obtain quantitative results (relative abundance of identified taxa). This aspect is often overlooked in ecological and medical studies. We document that sequencing of a mixture of three merged primary PCR reactions for each sample and further evaluation of median values from three technical replicates for each sample enables to overcome this bias and gives robust and repeatable results well distinguishing among sampling localities and seasons.

Multiplexed microsatellite recovery using massively parallel sequencing

Treesearch

T.N. Jennings; B.J. Knaus; T.D. Mullins; S.M. Haig; R.C. Cronn

2011-01-01

Conservation and management of natural populations requires accurate and inexpensive genotyping methods. Traditional microsatellite, or simple sequence repeat (SSR), marker analysis remains a popular genotyping method because of the comparatively low cost of marker development, ease of analysis and high power of genotype discrimination. With the availability of...

Parallelization and checkpointing of GPU applications through program transformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solano-Quinde, Lizandro Damian

2012-01-01

GPUs have emerged as a powerful tool for accelerating general-purpose applications. The availability of programming languages that makes writing general-purpose applications for running on GPUs tractable have consolidated GPUs as an alternative for accelerating general purpose applications. Among the areas that have benefited from GPU acceleration are: signal and image processing, computational fluid dynamics, quantum chemistry, and, in general, the High Performance Computing (HPC) Industry. In order to continue to exploit higher levels of parallelism with GPUs, multi-GPU systems are gaining popularity. In this context, single-GPU applications are parallelized for running in multi-GPU systems. Furthermore, multi-GPU systems help to solvemore » the GPU memory limitation for applications with large application memory footprint. Parallelizing single-GPU applications has been approached by libraries that distribute the workload at runtime, however, they impose execution overhead and are not portable. On the other hand, on traditional CPU systems, parallelization has been approached through application transformation at pre-compile time, which enhances the application to distribute the workload at application level and does not have the issues of library-based approaches. Hence, a parallelization scheme for GPU systems based on application transformation is needed. Like any computing engine of today, reliability is also a concern in GPUs. GPUs are vulnerable to transient and permanent failures. Current checkpoint/restart techniques are not suitable for systems with GPUs. Checkpointing for GPU systems present new and interesting challenges, primarily due to the natural differences imposed by the hardware design, the memory subsystem architecture, the massive number of threads, and the limited amount of synchronization among threads. Therefore, a checkpoint/restart technique suitable for GPU systems is needed. The goal of this work is to exploit higher levels of parallelism and to develop support for application-level fault tolerance in applications using multiple GPUs. Our techniques reduce the burden of enhancing single-GPU applications to support these features. To achieve our goal, this work designs and implements a framework for enhancing a single-GPU OpenCL application through application transformation.« less

High Performance Parallel Computational Nanotechnology

NASA Technical Reports Server (NTRS)

Saini, Subhash; Craw, James M. (Technical Monitor)

1995-01-01

At a recent press conference, NASA Administrator Dan Goldin encouraged NASA Ames Research Center to take a lead role in promoting research and development of advanced, high-performance computer technology, including nanotechnology. Manufacturers of leading-edge microprocessors currently perform large-scale simulations in the design and verification of semiconductor devices and microprocessors. Recently, the need for this intensive simulation and modeling analysis has greatly increased, due in part to the ever-increasing complexity of these devices, as well as the lessons of experiences such as the Pentium fiasco. Simulation, modeling, testing, and validation will be even more important for designing molecular computers because of the complex specification of millions of atoms, thousands of assembly steps, as well as the simulation and modeling needed to ensure reliable, robust and efficient fabrication of the molecular devices. The software for this capacity does not exist today, but it can be extrapolated from the software currently used in molecular modeling for other applications: semi-empirical methods, ab initio methods, self-consistent field methods, Hartree-Fock methods, molecular mechanics; and simulation methods for diamondoid structures. In as much as it seems clear that the application of such methods in nanotechnology will require powerful, highly powerful systems, this talk will discuss techniques and issues for performing these types of computations on parallel systems. We will describe system design issues (memory, I/O, mass storage, operating system requirements, special user interface issues, interconnects, bandwidths, and programming languages) involved in parallel methods for scalable classical, semiclassical, quantum, molecular mechanics, and continuum models; molecular nanotechnology computer-aided designs (NanoCAD) techniques; visualization using virtual reality techniques of structural models and assembly sequences; software required to control mini robotic manipulators for positional control; scalable numerical algorithms for reliability, verifications and testability. There appears no fundamental obstacle to simulating molecular compilers and molecular computers on high performance parallel computers, just as the Boeing 777 was simulated on a computer before manufacturing it.

A Debugger for Computational Grid Applications

NASA Technical Reports Server (NTRS)

Hood, Robert; Jost, Gabriele; Biegel, Bryan (Technical Monitor)

2001-01-01

This viewgraph presentation gives an overview of a debugger for computational grid applications. Details are given on NAS parallel tools groups (including parallelization support tools, evaluation of various parallelization strategies, and distributed and aggregated computing), debugger dependencies, scalability, initial implementation, the process grid, and information on Globus.

Opus: A Coordination Language for Multidisciplinary Applications

NASA Technical Reports Server (NTRS)

Chapman, Barbara; Haines, Matthew; Mehrotra, Piyush; Zima, Hans; vanRosendale, John

1997-01-01

Data parallel languages, such as High Performance fortran, can be successfully applied to a wide range of numerical applications. However, many advanced scientific and engineering applications are multidisciplinary and heterogeneous in nature, and thus do not fit well into the data parallel paradigm. In this paper we present Opus, a language designed to fill this gap. The central concept of Opus is a mechanism called ShareD Abstractions (SDA). An SDA can be used as a computation server, i.e., a locus of computational activity, or as a data repository for sharing data between asynchronous tasks. SDAs can be internally data parallel, providing support for the integration of data and task parallelism as well as nested task parallelism. They can thus be used to express multidisciplinary applications in a natural and efficient way. In this paper we describe the features of the language through a series of examples and give an overview of the runtime support required to implement these concepts in parallel and distributed environments.

Parallel Selection Revealed by Population Sequencing in Chicken.

PubMed

Qanbari, Saber; Seidel, Michael; Strom, Tim-Mathias; Mayer, Klaus F X; Preisinger, Ruedi; Simianer, Henner

2015-11-13

Human-driven selection during domestication and subsequent breed formation has likely left detectable signatures within the genome of modern chicken. The elucidation of these signatures of selection is of interest from the perspective of evolutionary biology, and for identifying genes relevant to domestication and improvement that ultimately may help to further genetically improve this economically important animal. We used whole genome sequence data from 50 hens of commercial white (WL) and brown (BL) egg-laying chicken along with pool sequences of three meat-type chicken to perform a systematic screening of past selection in modern chicken. Evidence of positive selection was investigated in two steps. First, we explored evidence of parallel fixation in regions with overlapping elevated allele frequencies in replicated populations of layers and broilers, suggestive of selection during domestication or preimprovement ages. We confirmed parallel fixation in BCDO2 and TSHR genes and found four candidates including AGTR2, a gene heavily involved in "Ascites" in commercial birds. Next, we explored differentiated loci between layers and broilers suggestive of selection during improvement in chicken. This analysis revealed evidence of parallel differentiation in genes relevant to appearance and production traits exemplified with the candidate gene OPG, implicated in Osteoporosis, a disorder related to overconsumption of calcium in egg-laying hens. Our results illustrate the potential for population genetic techniques to identify genomic regions relevant to the phenotypes of importance to breeders. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

MerCat: a versatile k-mer counter and diversity estimator for database-independent property analysis obtained from metagenomic and/or metatranscriptomic sequencing data

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, Richard A.; Panyala, Ajay R.; Glass, Kevin A.

MerCat is a parallel, highly scalable and modular property software package for robust analysis of features in next-generation sequencing data. MerCat inputs include assembled contigs and raw sequence reads from any platform resulting in feature abundance counts tables. MerCat allows for direct analysis of data properties without reference sequence database dependency commonly used by search tools such as BLAST and/or DIAMOND for compositional analysis of whole community shotgun sequencing (e.g. metagenomes and metatranscriptomes).

A novel approach to multiple sequence alignment using hadoop data grids.

PubMed

Sudha Sadasivam, G; Baktavatchalam, G

2010-01-01

Multiple alignment of protein sequences helps to determine evolutionary linkage and to predict molecular structures. The factors to be considered while aligning multiple sequences are speed and accuracy of alignment. Although dynamic programming algorithms produce accurate alignments, they are computation intensive. In this paper we propose a time efficient approach to sequence alignment that also produces quality alignment. The dynamic nature of the algorithm coupled with data and computational parallelism of hadoop data grids improves the accuracy and speed of sequence alignment. The principle of block splitting in hadoop coupled with its scalability facilitates alignment of very large sequences.

Targeted Capture and High-Throughput Sequencing Using Molecular Inversion Probes (MIPs).

PubMed

Cantsilieris, Stuart; Stessman, Holly A; Shendure, Jay; Eichler, Evan E

2017-01-01

Molecular inversion probes (MIPs) in combination with massively parallel DNA sequencing represent a versatile, yet economical tool for targeted sequencing of genomic DNA. Several thousand genomic targets can be selectively captured using long oligonucleotides containing unique targeting arms and universal linkers. The ability to append sequencing adaptors and sample-specific barcodes allows large-scale pooling and subsequent high-throughput sequencing at relatively low cost per sample. Here, we describe a "wet bench" protocol detailing the capture and subsequent sequencing of >2000 genomic targets from 192 samples, representative of a single lane on the Illumina HiSeq 2000 platform.

Genome Analysis of the Domestic Dog (Korean Jindo) by Massively Parallel Sequencing

PubMed Central

Kim, Ryong Nam; Kim, Dae-Soo; Choi, Sang-Haeng; Yoon, Byoung-Ha; Kang, Aram; Nam, Seong-Hyeuk; Kim, Dong-Wook; Kim, Jong-Joo; Ha, Ji-Hong; Toyoda, Atsushi; Fujiyama, Asao; Kim, Aeri; Kim, Min-Young; Park, Kun-Hyang; Lee, Kang Seon; Park, Hong-Seog

2012-01-01

Although pioneering sequencing projects have shed light on the boxer and poodle genomes, a number of challenges need to be met before the sequencing and annotation of the dog genome can be considered complete. Here, we present the DNA sequence of the Jindo dog genome, sequenced to 45-fold average coverage using Illumina massively parallel sequencing technology. A comparison of the sequence to the reference boxer genome led to the identification of 4 675 437 single nucleotide polymorphisms (SNPs, including 3 346 058 novel SNPs), 71 642 indels and 8131 structural variations. Of these, 339 non-synonymous SNPs and 3 indels are located within coding sequences (CDS). In particular, 3 non-synonymous SNPs and a 26-bp deletion occur in the TCOF1 locus, implying that the difference observed in cranial facial morphology between Jindo and boxer dogs might be influenced by those variations. Through the annotation of the Jindo olfactory receptor gene family, we found 2 unique olfactory receptor genes and 236 olfactory receptor genes harbouring non-synonymous homozygous SNPs that are likely to affect smelling capability. In addition, we determined the DNA sequence of the Jindo dog mitochondrial genome and identified Jindo dog-specific mtDNA genotypes. This Jindo genome data upgrade our understanding of dog genomic architecture and will be a very valuable resource for investigating not only dog genetics and genomics but also human and dog disease genetics and comparative genomics. PMID:22474061

Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing.

PubMed

Vega, Ana I; Medrano, Celia; Navarrete, Rosa; Desviat, Lourdes R; Merinero, Begoña; Rodríguez-Pombo, Pilar; Vitoria, Isidro; Ugarte, Magdalena; Pérez-Cerdá, Celia; Pérez, Belen

2016-10-01

Glycogen storage disease (GSD) is an umbrella term for a group of genetic disorders that involve the abnormal metabolism of glycogen; to date, 23 types of GSD have been identified. The nonspecific clinical presentation of GSD and the lack of specific biomarkers mean that Sanger sequencing is now widely relied on for making a diagnosis. However, this gene-by-gene sequencing technique is both laborious and costly, which is a consequence of the number of genes to be sequenced and the large size of some genes. This work reports the use of massive parallel sequencing to diagnose patients at our laboratory in Spain using either a customized gene panel (targeted exome sequencing) or the Illumina Clinical-Exome TruSight One Gene Panel (clinical exome sequencing (CES)). Sequence variants were matched against biochemical and clinical hallmarks. Pathogenic mutations were detected in 23 patients. Twenty-two mutations were recognized (mostly loss-of-function mutations), including 11 that were novel in GSD-associated genes. In addition, CES detected five patients with mutations in ALDOB, LIPA, NKX2-5, CPT2, or ANO5. Although these genes are not involved in GSD, they are associated with overlapping phenotypic characteristics such as hepatic, muscular, and cardiac dysfunction. These results show that next-generation sequencing, in combination with the detection of biochemical and clinical hallmarks, provides an accurate, high-throughput means of making genetic diagnoses of GSD and related diseases.Genet Med 18 10, 1037-1043.

Rapid code acquisition algorithms employing PN matched filters

NASA Technical Reports Server (NTRS)

Su, Yu T.

1988-01-01

The performance of four algorithms using pseudonoise matched filters (PNMFs), for direct-sequence spread-spectrum systems, is analyzed. They are: parallel search with fix dwell detector (PL-FDD), parallel search with sequential detector (PL-SD), parallel-serial search with fix dwell detector (PS-FDD), and parallel-serial search with sequential detector (PS-SD). The operation characteristic for each detector and the mean acquisition time for each algorithm are derived. All the algorithms are studied in conjunction with the noncoherent integration technique, which enables the system to operate in the presence of data modulation. Several previous proposals using PNMF are seen as special cases of the present algorithms.

Stimulus-Dependent Flexibility in Non-Human Auditory Pitch Processing

ERIC Educational Resources Information Center

Bregman, Micah R.; Patel, Aniruddh D.; Gentner, Timothy Q.

2012-01-01

Songbirds and humans share many parallels in vocal learning and auditory sequence processing. However, the two groups differ notably in their abilities to recognize acoustic sequences shifted in absolute pitch (pitch height). Whereas humans maintain accurate recognition of words or melodies over large pitch height changes, songbirds are…

The Design and Evaluation of "CAPTools"--A Computer Aided Parallelization Toolkit

NASA Technical Reports Server (NTRS)

Yan, Jerry; Frumkin, Michael; Hribar, Michelle; Jin, Haoqiang; Waheed, Abdul; Johnson, Steve; Cross, Jark; Evans, Emyr; Ierotheou, Constantinos; Leggett, Pete;

Evaluation of Novel Broad-Range Real-Time PCR Assay for Rapid Detection of Human Pathogenic Fungi in Various Clinical Specimens▿

PubMed Central

Vollmer, Tanja; Störmer, Melanie; Kleesiek, Knut; Dreier, Jens

2008-01-01

In the present study, a novel broad-range real-time PCR was developed for the rapid detection of human pathogenic fungi. The assay targets a part of the 28S large-subunit ribosomal RNA (rDNA) gene. We investigated its application for the most important human pathogenic fungal genera, including Aspergillus, Candida, Cryptococcus, Mucor, Penicillium, Pichia, Microsporum, Trichophyton, and Scopulariopsis. Species were identified in PCR-positive reactions by direct DNA sequencing. A noncompetitive internal control was applied to prevent false-negative results due to PCR inhibition. The minimum detection limit for the PCR was determined to be one 28S rDNA copy per PCR, and the 95% detection limit was calculated to 15 copies per PCR. To assess the clinical applicability of the PCR method, intensive-care patients with artificial respiration and patients with infective endocarditis were investigated. For this purpose, 76 tracheal secretion samples and 70 heart valve tissues were analyzed in parallel by real-time PCR and cultivation. No discrepancies in results were observed between PCR analysis and cultivation methods. Furthermore, the application of the PCR method was investigated for other clinical specimens, including cervical swabs, nail and horny skin scrapings, and serum, blood, and urine samples. The combination of a broad-range real-time PCR and direct sequencing facilitates rapid screening for fungal infection in various clinical specimens. PMID:18385440

Evaluation of novel broad-range real-time PCR assay for rapid detection of human pathogenic fungi in various clinical specimens.

PubMed

Vollmer, Tanja; Störmer, Melanie; Kleesiek, Knut; Dreier, Jens

2008-06-01

In the present study, a novel broad-range real-time PCR was developed for the rapid detection of human pathogenic fungi. The assay targets a part of the 28S large-subunit ribosomal RNA (rDNA) gene. We investigated its application for the most important human pathogenic fungal genera, including Aspergillus, Candida, Cryptococcus, Mucor, Penicillium, Pichia, Microsporum, Trichophyton, and Scopulariopsis. Species were identified in PCR-positive reactions by direct DNA sequencing. A noncompetitive internal control was applied to prevent false-negative results due to PCR inhibition. The minimum detection limit for the PCR was determined to be one 28S rDNA copy per PCR, and the 95% detection limit was calculated to 15 copies per PCR. To assess the clinical applicability of the PCR method, intensive-care patients with artificial respiration and patients with infective endocarditis were investigated. For this purpose, 76 tracheal secretion samples and 70 heart valve tissues were analyzed in parallel by real-time PCR and cultivation. No discrepancies in results were observed between PCR analysis and cultivation methods. Furthermore, the application of the PCR method was investigated for other clinical specimens, including cervical swabs, nail and horny skin scrapings, and serum, blood, and urine samples. The combination of a broad-range real-time PCR and direct sequencing facilitates rapid screening for fungal infection in various clinical specimens.

Multi-threading: A new dimension to massively parallel scientific computation

NASA Astrophysics Data System (ADS)

Nielsen, Ida M. B.; Janssen, Curtis L.

2000-06-01

Multi-threading is becoming widely available for Unix-like operating systems, and the application of multi-threading opens new ways for performing parallel computations with greater efficiency. We here briefly discuss the principles of multi-threading and illustrate the application of multi-threading for a massively parallel direct four-index transformation of electron repulsion integrals. Finally, other potential applications of multi-threading in scientific computing are outlined.

Implementation of DFT application on ternary optical computer

NASA Astrophysics Data System (ADS)

Junjie, Peng; Youyi, Fu; Xiaofeng, Zhang; Shuai, Kong; Xinyu, Wei

2018-03-01

As its characteristics of huge number of data bits and low energy consumption, optical computing may be used in the applications such as DFT etc. which needs a lot of computation and can be implemented in parallel. According to this, DFT implementation methods in full parallel as well as in partial parallel are presented. Based on resources ternary optical computer (TOC), extensive experiments were carried out. Experimental results show that the proposed schemes are correct and feasible. They provide a foundation for further exploration of the applications on TOC that needs a large amount calculation and can be processed in parallel.

FPGA-based protein sequence alignment : A review

NASA Astrophysics Data System (ADS)

Isa, Mohd. Nazrin Md.; Muhsen, Ku Noor Dhaniah Ku; Saiful Nurdin, Dayana; Ahmad, Muhammad Imran; Anuar Zainol Murad, Sohiful; Nizam Mohyar, Shaiful; Harun, Azizi; Hussin, Razaidi

2017-11-01

Sequence alignment have been optimized using several techniques in order to accelerate the computation time to obtain the optimal score by implementing DP-based algorithm into hardware such as FPGA-based platform. During hardware implementation, there will be performance challenges such as the frequent memory access and highly data dependent in computation process. Therefore, investigation in processing element (PE) configuration where involves more on memory access in load or access the data (substitution matrix, query sequence character) and the PE configuration time will be the main focus in this paper. There are various approaches to enhance the PE configuration performance that have been done in previous works such as by using serial configuration chain and parallel configuration chain i.e. the configuration data will be loaded into each PEs sequentially and simultaneously respectively. Some researchers have proven that the performance using parallel configuration chain has optimized both the configuration time and area.

A software architecture for multidisciplinary applications: Integrating task and data parallelism

NASA Technical Reports Server (NTRS)

Chapman, Barbara; Mehrotra, Piyush; Vanrosendale, John; Zima, Hans

1994-01-01

Data parallel languages such as Vienna Fortran and HPF can be successfully applied to a wide range of numerical applications. However, many advanced scientific and engineering applications are of a multidisciplinary and heterogeneous nature and thus do not fit well into the data parallel paradigm. In this paper we present new Fortran 90 language extensions to fill this gap. Tasks can be spawned as asynchronous activities in a homogeneous or heterogeneous computing environment; they interact by sharing access to Shared Data Abstractions (SDA's). SDA's are an extension of Fortran 90 modules, representing a pool of common data, together with a set of Methods for controlled access to these data and a mechanism for providing persistent storage. Our language supports the integration of data and task parallelism as well as nested task parallelism and thus can be used to express multidisciplinary applications in a natural and efficient way.

RISC RNA sequencing for context-specific identification of in vivo miR targets

PubMed Central

Matkovich, Scot J; Van Booven, Derek J; Eschenbacher, William H; Dorn, Gerald W

2010-01-01

Rationale MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo. Objective To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs). Methods and Results We optimized techniques for expression profiling small amounts of RNA without introducing amplification bias, and applied this to anti-Argonaute 2 immunoprecipitated RISCs (RISC-Seq) from mouse hearts. By comparing RNA-sequencing results of cardiac RISC and transcriptome from the same individual hearts, we defined 1,645 mRNAs consistently targeted to mouse cardiac RISCs. We employed this approach in hearts overexpressing miRs from Myh6 promoter-driven precursors (programmed RISC-Seq) to identify 209 in vivo targets of miR-133a and 81 in vivo targets of miR-499. Consistent with the fact that miR-133a and miR-499 have widely differing ‘seed’ sequences and belong to different miR families, only 6 targets were common to miR-133a- and miR-499-programmed hearts. Conclusions RISC-sequencing is a highly sensitive method for general RISC profiling and individual miR target identification in biological context, and is applicable to any tissue and any disease state. Summary MicroRNAs (miRs) are key regulators of mRNA translation in health and disease. While bioinformatic predictions suggest that a single miR may target hundreds of mRNAs, the number of experimentally verified targets of miRs is low. To enable comprehensive, unbiased examination of miR targets, we have performed deep RNA sequencing of cardiac transcriptomes in parallel with cardiac RNA-induced silencing complex (RISC)-associated RNAs (the RISCome), called RISC sequencing. We developed methods that did not require cross-linking of RNAs to RISCs or amplification of mRNA prior to sequencing, making it possible to rapidly perform RISC sequencing from intact tissue while avoiding amplification bias. Comparison of RISCome with transcriptome expression defined the degree of RISC enrichment for each mRNA. The majority of the mRNAs enriched in wild-type cardiac RISComes compared to transcriptomes were bioinformatically predicted to be targets of at least 1 of 139 cardiac-expressed miRs. Programming cardiomyocyte RISCs via transgenic overexpression in adult hearts of miR-133a or miR-499, two miRs that contain entirely different ‘seed’ sequences, elicited differing profiles of RISC-targeted mRNAs. Thus, RISC sequencing represents a highly sensitive method for general RISC profiling and individual miR target identification in biological context. PMID:21030712

Solid-phase proximity ligation assays for individual or parallel protein analyses with readout via real-time PCR or sequencing.

PubMed

Nong, Rachel Yuan; Wu, Di; Yan, Junhong; Hammond, Maria; Gu, Gucci Jijuan; Kamali-Moghaddam, Masood; Landegren, Ulf; Darmanis, Spyros

2013-06-01

Solid-phase proximity ligation assays share properties with the classical sandwich immunoassays for protein detection. The proteins captured via antibodies on solid supports are, however, detected not by single antibodies with detectable functions, but by pairs of antibodies with attached DNA strands. Upon recognition by these sets of three antibodies, pairs of DNA strands brought in proximity are joined by ligation. The ligated reporter DNA strands are then detected via methods such as real-time PCR or next-generation sequencing (NGS). We describe how to construct assays that can offer improved detection specificity by virtue of recognition by three antibodies, as well as enhanced sensitivity owing to reduced background and amplified detection. Finally, we also illustrate how the assays can be applied for parallel detection of proteins, taking advantage of the oligonucleotide ligation step to avoid background problems that might arise with multiplexing. The protocol for the singleplex solid-phase proximity ligation assay takes ~5 h. The multiplex version of the assay takes 7-8 h depending on whether quantitative PCR (qPCR) or sequencing is used as the readout. The time for the sequencing-based protocol includes the library preparation but not the actual sequencing, as times may vary based on the choice of sequencing platform.

A massive parallel sequencing workflow for diagnostic genetic testing of mismatch repair genes

PubMed Central

Hansen, Maren F; Neckmann, Ulrike; Lavik, Liss A S; Vold, Trine; Gilde, Bodil; Toft, Ragnhild K; Sjursen, Wenche

2014-01-01

The purpose of this study was to develop a massive parallel sequencing (MPS) workflow for diagnostic analysis of mismatch repair (MMR) genes using the GS Junior system (Roche). A pathogenic variant in one of four MMR genes, (MLH1, PMS2, MSH6, and MSH2), is the cause of Lynch Syndrome (LS), which mainly predispose to colorectal cancer. We used an amplicon-based sequencing method allowing specific and preferential amplification of the MMR genes including PMS2, of which several pseudogenes exist. The amplicons were pooled at different ratios to obtain coverage uniformity and maximize the throughput of a single-GS Junior run. In total, 60 previously identified and distinct variants (substitutions and indels), were sequenced by MPS and successfully detected. The heterozygote detection range was from 19% to 63% and dependent on sequence context and coverage. We were able to distinguish between false-positive and true-positive calls in homopolymeric regions by cross-sample comparison and evaluation of flow signal distributions. In addition, we filtered variants according to a predefined status, which facilitated variant annotation. Our study shows that implementation of MPS in routine diagnostics of LS can accelerate sample throughput and reduce costs without compromising sensitivity, compared to Sanger sequencing. PMID:24689082

Tracking the roots of cellulase hyperproduction by the fungus Trichoderma reesei using massively parallel DNA sequencing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le Crom, Stphane; Schackwitz, Wendy; Pennacchiod, Len

2009-09-22

Trichoderma reesei (teleomorph Hypocrea jecorina) is the main industrial source of cellulases and hemicellulases harnessed for the hydrolysis of biomass to simple sugars, which can then be converted to biofuels, such as ethanol, and other chemicals. The highly productive strains in use today were generated by classical mutagenesis. To learn how cellulase production was improved by these techniques, we performed massively parallel sequencing to identify mutations in the genomes of two hyperproducing strains (NG14, and its direct improved descendant, RUT C30). We detected a surprisingly high number of mutagenic events: 223 single nucleotides variants, 15 small deletions or insertions andmore » 18 larger deletions leading to the loss of more than 100 kb of genomic DNA. From these events we report previously undocumented non-synonymous mutations in 43 genes that are mainly involved in nuclear transport, mRNA stability, transcription, secretion/vacuolar targeting, and metabolism. This homogeneity of functional categories suggests that multiple changes are necessary to improve cellulase production and not simply a few clear-cut mutagenic events. Phenotype microarrays show that some of these mutations result in strong changes in the carbon assimilation pattern of the two mutants with respect to the wild type strain QM6a. Our analysis provides the first genome-wide insights into the changes induced by classical mutagenesis in a filamentous fungus, and suggests new areas for the generation of enhanced T. reesei strains for industrial applications such as biofuel production.« less

Diversity arrays technology: a generic genome profiling technology on open platforms.

PubMed

Kilian, Andrzej; Wenzl, Peter; Huttner, Eric; Carling, Jason; Xia, Ling; Blois, Hélène; Caig, Vanessa; Heller-Uszynska, Katarzyna; Jaccoud, Damian; Hopper, Colleen; Aschenbrenner-Kilian, Malgorzata; Evers, Margaret; Peng, Kaiman; Cayla, Cyril; Hok, Puthick; Uszynski, Grzegorz

2012-01-01

In the last 20 years, we have observed an exponential growth of the DNA sequence data and simular increase in the volume of DNA polymorphism data generated by numerous molecular marker technologies. Most of the investment, and therefore progress, concentrated on human genome and genomes of selected model species. Diversity Arrays Technology (DArT), developed over a decade ago, was among the first "democratizing" genotyping technologies, as its performance was primarily driven by the level of DNA sequence variation in the species rather than by the level of financial investment. DArT also proved more robust to genome size and ploidy-level differences among approximately 60 organisms for which DArT was developed to date compared to other high-throughput genotyping technologies. The success of DArT in a number of organisms, including a wide range of "orphan crops," can be attributed to the simplicity of underlying concepts: DArT combines genome complexity reduction methods enriching for genic regions with a highly parallel assay readout on a number of "open-access" microarray platforms. The quantitative nature of the assay enabled a number of applications in which allelic frequencies can be estimated from DArT arrays. A typical DArT assay tests for polymorphism tens of thousands of genomic loci with the final number of markers reported (hundreds to thousands) reflecting the level of DNA sequence variation in the tested loci. Detailed DArT methods, protocols, and a range of their application examples as well as DArT's evolution path are presented.

Scheduling with genetic algorithms

NASA Technical Reports Server (NTRS)

Fennel, Theron R.; Underbrink, A. J., Jr.; Williams, George P. W., Jr.

1994-01-01

In many domains, scheduling a sequence of jobs is an important function contributing to the overall efficiency of the operation. At Boeing, we develop schedules for many different domains, including assembly of military and commercial aircraft, weapons systems, and space vehicles. Boeing is under contract to develop scheduling systems for the Space Station Payload Planning System (PPS) and Payload Operations and Integration Center (POIC). These applications require that we respect certain sequencing restrictions among the jobs to be scheduled while at the same time assigning resources to the jobs. We call this general problem scheduling and resource allocation. Genetic algorithms (GA's) offer a search method that uses a population of solutions and benefits from intrinsic parallelism to search the problem space rapidly, producing near-optimal solutions. Good intermediate solutions are probabalistically recombined to produce better offspring (based upon some application specific measure of solution fitness, e.g., minimum flowtime, or schedule completeness). Also, at any point in the search, any intermediate solution can be accepted as a final solution; allowing the search to proceed longer usually produces a better solution while terminating the search at virtually any time may yield an acceptable solution. Many processes are constrained by restrictions of sequence among the individual jobs. For a specific job, other jobs must be completed beforehand. While there are obviously many other constraints on processes, it is these on which we focussed for this research: how to allocate crews to jobs while satisfying job precedence requirements and personnel, and tooling and fixture (or, more generally, resource) requirements.

Non-invasive prenatal testing using massively parallel sequencing of maternal plasma DNA: from molecular karyotyping to fetal whole-genome sequencing.

PubMed

Lo, Y M Dennis

2013-12-01

The discovery of cell-free fetal DNA in maternal plasma in 1997 has stimulated a rapid development of non-invasive prenatal testing. The recent advent of massively parallel sequencing has allowed the analysis of circulating cell-free fetal DNA to be performed with unprecedented sensitivity and precision. Fetal trisomies 21, 18 and 13 are now robustly detectable in maternal plasma and such analyses have been available clinically since 2011. Fetal genome-wide molecular karyotyping and whole-genome sequencing have now been demonstrated in a number of proof-of-concept studies. Genome-wide and targeted sequencing of maternal plasma has been shown to allow the non-invasive prenatal testing of β-thalassaemia and can potentially be generalized to other monogenic diseases. It is thus expected that plasma DNA-based non-invasive prenatal testing will play an increasingly important role in future obstetric care. It is thus timely and important that the ethical, social and legal issues of non-invasive prenatal testing be discussed actively by all parties involved in prenatal care. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma DNA in twin pregnancies.

PubMed

Huang, Xuan; Zheng, Jing; Chen, Min; Zhao, Yangyu; Zhang, Chunlei; Liu, Lifu; Xie, Weiwei; Shi, Shuqiong; Wei, Yuan; Lei, Dongzhu; Xu, Chenming; Wu, Qichang; Guo, Xiaoling; Shi, Xiaomei; Zhou, Yi; Liu, Qiufang; Gao, Ya; Jiang, Fuman; Zhang, Hongyun; Su, Fengxia; Ge, Huijuan; Li, Xuchao; Pan, Xiaoyu; Chen, Shengpei; Chen, Fang; Fang, Qun; Jiang, Hui; Lau, Tze Kin; Wang, Wei

2014-04-01

The objective of this study is to assess the performance of noninvasive prenatal testing for trisomies 21 and 18 on the basis of massively parallel sequencing of cell-free DNA from maternal plasma in twin pregnancies. A double-blind study was performed over 12 months. A total of 189 pregnant women carrying twins were recruited from seven hospitals. Maternal plasma DNA sequencing was performed to detect trisomies 21 and 18. The fetal karyotype was used as gold standard to estimate the sensitivity and specificity of sequencing-based noninvasive prenatal test. There were nine cases of trisomy 21 and two cases of trisomy 18 confirmed by karyotyping. Plasma DNA sequencing correctly identified nine cases of trisomy 21 and one case of trisomy 18. The discordant case of trisomy 18 was an unusual case of monozygotic twin with discordant fetal karyotype (one normal and the other trisomy 18). The sensitivity and specificity of maternal plasma DNA sequencing for fetal trisomy 21 were both 100% and for fetal trisomy 18 were 50% and 100%, respectively. Our study further supported that sequencing-based noninvasive prenatal testing of trisomy 21 in twin pregnancies could be achieved with a high accuracy, which could effectively avoid almost 95% of invasive prenatal diagnosis procedures. © 2013 John Wiley & Sons, Ltd.

Launching genomics into the cloud: deployment of Mercury, a next generation sequence analysis pipeline

PubMed Central

2014-01-01

Background Massively parallel DNA sequencing generates staggering amounts of data. Decreasing cost, increasing throughput, and improved annotation have expanded the diversity of genomics applications in research and clinical practice. This expanding scale creates analytical challenges: accommodating peak compute demand, coordinating secure access for multiple analysts, and sharing validated tools and results. Results To address these challenges, we have developed the Mercury analysis pipeline and deployed it in local hardware and the Amazon Web Services cloud via the DNAnexus platform. Mercury is an automated, flexible, and extensible analysis workflow that provides accurate and reproducible genomic results at scales ranging from individuals to large cohorts. Conclusions By taking advantage of cloud computing and with Mercury implemented on the DNAnexus platform, we have demonstrated a powerful combination of a robust and fully validated software pipeline and a scalable computational resource that, to date, we have applied to more than 10,000 whole genome and whole exome samples. PMID:24475911

Genome sequence and plasmid transformation of the model high-yield bacterial cellulose producer Gluconacetobacter hansenii ATCC 53582

NASA Astrophysics Data System (ADS)

Florea, Michael; Reeve, Benjamin; Abbott, James; Freemont, Paul S.; Ellis, Tom

2016-03-01

Bacterial cellulose is a strong, highly pure form of cellulose that is used in a range of applications in industry, consumer goods and medicine. Gluconacetobacter hansenii ATCC 53582 is one of the highest reported bacterial cellulose producing strains and has been used as a model organism in numerous studies of bacterial cellulose production and studies aiming to increased cellulose productivity. Here we present a high-quality draft genome sequence for G. hansenii ATCC 53582 and find that in addition to the previously described cellulose synthase operon, ATCC 53582 contains two additional cellulose synthase operons and several previously undescribed genes associated with cellulose production. In parallel, we also develop optimized protocols and identify plasmid backbones suitable for transformation of ATCC 53582, albeit with low efficiencies. Together, these results provide important information for further studies into cellulose synthesis and for future studies aiming to genetically engineer G. hansenii ATCC 53582 for increased cellulose productivity.

Expansion of Microbial Forensics.

PubMed

Schmedes, Sarah E; Sajantila, Antti; Budowle, Bruce

2016-08-01

Microbial forensics has been defined as the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes. Over the past 15 years, technology, particularly massively parallel sequencing, and bioinformatics advances now allow the characterization of microorganisms for a variety of human forensic applications, such as human identification, body fluid characterization, postmortem interval estimation, and biocrimes involving tracking of infectious agents. Thus, microbial forensics should be more broadly described as the discipline of applying scientific methods to the analysis of microbial evidence in criminal and civil cases for investigative purposes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Commerce and genetic diagnostics.

PubMed

Silverman, Paul H

1995-01-01

The revolution in molecular biology and molecular genetics has begun to reveal the sequence of events that links genes and disease. As a result of activities such as the Human Genome Project, a parallel revolution in technology is bringing nearer to hand the possibility of readily available genetic diagnostics. Genetic testing services have begun to move out of the academic medical centers and into the private enterprise arena. Under these circumstances it is important to understand the factors affecting the availability and application of this powerful predictive tool in a for-profit mode. How does the marketplace encourage or discourage genetic testing? Will the same market influences that generate pharmaceutical sales be operating to "sell" genetic tests?

Methods for design and evaluation of parallel computating systems (The PISCES project)

NASA Technical Reports Server (NTRS)

Pratt, Terrence W.; Wise, Robert; Haught, Mary JO

1989-01-01

The PISCES project started in 1984 under the sponsorship of the NASA Computational Structural Mechanics (CSM) program. A PISCES 1 programming environment and parallel FORTRAN were implemented in 1984 for the DEC VAX (using UNIX processes to simulate parallel processes). This system was used for experimentation with parallel programs for scientific applications and AI (dynamic scene analysis) applications. PISCES 1 was ported to a network of Apollo workstations by N. Fitzgerald.

Parallelizing serial code for a distributed processing environment with an application to high frequency electromagnetic scattering

NASA Astrophysics Data System (ADS)

Work, Paul R.

1991-12-01

This thesis investigates the parallelization of existing serial programs in computational electromagnetics for use in a parallel environment. Existing algorithms for calculating the radar cross section of an object are covered, and a ray-tracing code is chosen for implementation on a parallel machine. Current parallel architectures are introduced and a suitable parallel machine is selected for the implementation of the chosen ray-tracing algorithm. The standard techniques for the parallelization of serial codes are discussed, including load balancing and decomposition considerations, and appropriate methods for the parallelization effort are selected. A load balancing algorithm is modified to increase the efficiency of the application, and a high level design of the structure of the serial program is presented. A detailed design of the modifications for the parallel implementation is also included, with both the high level and the detailed design specified in a high level design language called UNITY. The correctness of the design is proven using UNITY and standard logic operations. The theoretical and empirical results show that it is possible to achieve an efficient parallel application for a serial computational electromagnetic program where the characteristics of the algorithm and the target architecture critically influence the development of such an implementation.

A general method to eliminate laboratory induced recombinants during massive, parallel sequencing of cDNA library.

PubMed

Waugh, Caryll; Cromer, Deborah; Grimm, Andrew; Chopra, Abha; Mallal, Simon; Davenport, Miles; Mak, Johnson

2015-04-09

Massive, parallel sequencing is a potent tool for dissecting the regulation of biological processes by revealing the dynamics of the cellular RNA profile under different conditions. Similarly, massive, parallel sequencing can be used to reveal the complexity of viral quasispecies that are often found in the RNA virus infected host. However, the production of cDNA libraries for next-generation sequencing (NGS) necessitates the reverse transcription of RNA into cDNA and the amplification of the cDNA template using PCR, which may introduce artefact in the form of phantom nucleic acids species that can bias the composition and interpretation of original RNA profiles. Using HIV as a model we have characterised the major sources of error during the conversion of viral RNA to cDNA, namely excess RNA template and the RNaseH activity of the polymerase enzyme, reverse transcriptase. In addition we have analysed the effect of PCR cycle on detection of recombinants and assessed the contribution of transfection of highly similar plasmid DNA to the formation of recombinant species during the production of our control viruses. We have identified RNA template concentrations, RNaseH activity of reverse transcriptase, and PCR conditions as key parameters that must be carefully optimised to minimise chimeric artefacts. Using our optimised RT-PCR conditions, in combination with our modified PCR amplification procedure, we have developed a reliable technique for accurate determination of RNA species using NGS technology.

A scalable geometric multigrid solver for nonsymmetric elliptic systems with application to variable-density flows

NASA Astrophysics Data System (ADS)

Esmaily, M.; Jofre, L.; Mani, A.; Iaccarino, G.

2018-03-01

A geometric multigrid algorithm is introduced for solving nonsymmetric linear systems resulting from the discretization of the variable density Navier-Stokes equations on nonuniform structured rectilinear grids and high-Reynolds number flows. The restriction operation is defined such that the resulting system on the coarser grids is symmetric, thereby allowing for the use of efficient smoother algorithms. To achieve an optimal rate of convergence, the sequence of interpolation and restriction operations are determined through a dynamic procedure. A parallel partitioning strategy is introduced to minimize communication while maintaining the load balance between all processors. To test the proposed algorithm, we consider two cases: 1) homogeneous isotropic turbulence discretized on uniform grids and 2) turbulent duct flow discretized on stretched grids. Testing the algorithm on systems with up to a billion unknowns shows that the cost varies linearly with the number of unknowns. This O (N) behavior confirms the robustness of the proposed multigrid method regarding ill-conditioning of large systems characteristic of multiscale high-Reynolds number turbulent flows. The robustness of our method to density variations is established by considering cases where density varies sharply in space by a factor of up to 104, showing its applicability to two-phase flow problems. Strong and weak scalability studies are carried out, employing up to 30,000 processors, to examine the parallel performance of our implementation. Excellent scalability of our solver is shown for a granularity as low as 104 to 105 unknowns per processor. At its tested peak throughput, it solves approximately 4 billion unknowns per second employing over 16,000 processors with a parallel efficiency higher than 50%.

Water Selective Imaging and bSSFP Banding Artifact Correction in Humans and Small Animals at 3T and 7T, Respectively

PubMed Central

Ribot, Emeline J.; Wecker, Didier; Trotier, Aurélien J.; Dallaudière, Benjamin; Lefrançois, William; Thiaudière, Eric; Franconi, Jean-Michel; Miraux, Sylvain

2015-01-01

Introduction The purpose of this paper is to develop an easy method to generate both fat signal and banding artifact free 3D balanced Steady State Free Precession (bSSFP) images at high magnetic field. Methods In order to suppress fat signal and bSSFP banding artifacts, two or four images were acquired with the excitation frequency of the water-selective binomial radiofrequency pulse set On Resonance or shifted by a maximum of 3/4TR. Mice and human volunteers were imaged at 7T and 3T, respectively to perform whole-body and musculoskeletal imaging. “Sum-Of-Square” reconstruction was performed and combined or not with parallel imaging. Results The frequency selectivity of 1-2-3-2-1 or 1-3-3-1 binomial pulses was preserved after (3/4TR) frequency shifting. Consequently, whole body small animal 3D imaging was performed at 7T and enabled visualization of small structures within adipose tissue like lymph nodes. In parallel, this method allowed 3D musculoskeletal imaging in humans with high spatial resolution at 3T. The combination with parallel imaging allowed the acquisition of knee images with ~500μm resolution images in less than 2min. In addition, ankles, full head coverage and legs of volunteers were imaged, demonstrating the possible application of the method also for large FOV. Conclusion In conclusion, this robust method can be applied in small animals and humans at high magnetic fields. The high SNR and tissue contrast obtained in short acquisition times allows to prescribe bSSFP sequence for several preclinical and clinical applications. PMID:26426849

Recent developments in genetics and medically assisted reproduction: from research to clinical applications.

PubMed

Harper, J C; Aittomäki, K; Borry, P; Cornel, M C; de Wert, G; Dondorp, W; Geraedts, J; Gianaroli, L; Ketterson, K; Liebaers, I; Lundin, K; Mertes, H; Morris, M; Pennings, G; Sermon, K; Spits, C; Soini, S; van Montfoort, A P A; Veiga, A; Vermeesch, J R; Viville, S; Macek, M

2018-01-01

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

Coarse-grained simulation of DNA using LAMMPS : An implementation of the oxDNA model and its applications.

PubMed

Henrich, Oliver; Gutiérrez Fosado, Yair Augusto; Curk, Tine; Ouldridge, Thomas E

2018-05-10

During the last decade coarse-grained nucleotide models have emerged that allow us to study DNA and RNA on unprecedented time and length scales. Among them is oxDNA, a coarse-grained, sequence-specific model that captures the hybridisation transition of DNA and many structural properties of single- and double-stranded DNA. oxDNA was previously only available as standalone software, but has now been implemented into the popular LAMMPS molecular dynamics code. This article describes the new implementation and analyses its parallel performance. Practical applications are presented that focus on single-stranded DNA, an area of research which has been so far under-investigated. The LAMMPS implementation of oxDNA lowers the entry barrier for using the oxDNA model significantly, facilitates future code development and interfacing with existing LAMMPS functionality as well as other coarse-grained and atomistic DNA models.

Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder.

PubMed

Steinberg, Karyn Meltz; Ramachandran, Dhanya; Patel, Viren C; Shetty, Amol C; Cutler, David J; Zwick, Michael E

2012-09-28

Autism spectrum disorder (ASD) is highly heritable, but the genetic risk factors for it remain largely unknown. Although structural variants with large effect sizes may explain up to 15% ASD, genome-wide association studies have failed to uncover common single nucleotide variants with large effects on phenotype. The focus within ASD genetics is now shifting to the examination of rare sequence variants of modest effect, which is most often achieved via exome selection and sequencing. This strategy has indeed identified some rare candidate variants; however, the approach does not capture the full spectrum of genetic variation that might contribute to the phenotype. We surveyed two loci with known rare variants that contribute to ASD, the X-linked neuroligin genes by performing massively parallel Illumina sequencing of the coding and noncoding regions from these genes in males from families with multiplex autism. We annotated all variant sites and functionally tested a subset to identify other rare mutations contributing to ASD susceptibility. We found seven rare variants at evolutionary conserved sites in our study population. Functional analyses of the three 3' UTR variants did not show statistically significant effects on the expression of NLGN3 and NLGN4X. In addition, we identified two NLGN3 intronic variants located within conserved transcription factor binding sites that could potentially affect gene regulation. These data demonstrate the power of massively parallel, targeted sequencing studies of affected individuals for identifying rare, potentially disease-contributing variation. However, they also point out the challenges and limitations of current methods of direct functional testing of rare variants and the difficulties of identifying alleles with modest effects.

Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder

PubMed Central

2012-01-01

Background Autism spectrum disorder (ASD) is highly heritable, but the genetic risk factors for it remain largely unknown. Although structural variants with large effect sizes may explain up to 15% ASD, genome-wide association studies have failed to uncover common single nucleotide variants with large effects on phenotype. The focus within ASD genetics is now shifting to the examination of rare sequence variants of modest effect, which is most often achieved via exome selection and sequencing. This strategy has indeed identified some rare candidate variants; however, the approach does not capture the full spectrum of genetic variation that might contribute to the phenotype. Methods We surveyed two loci with known rare variants that contribute to ASD, the X-linked neuroligin genes by performing massively parallel Illumina sequencing of the coding and noncoding regions from these genes in males from families with multiplex autism. We annotated all variant sites and functionally tested a subset to identify other rare mutations contributing to ASD susceptibility. Results We found seven rare variants at evolutionary conserved sites in our study population. Functional analyses of the three 3’ UTR variants did not show statistically significant effects on the expression of NLGN3 and NLGN4X. In addition, we identified two NLGN3 intronic variants located within conserved transcription factor binding sites that could potentially affect gene regulation. Conclusions These data demonstrate the power of massively parallel, targeted sequencing studies of affected individuals for identifying rare, potentially disease-contributing variation. However, they also point out the challenges and limitations of current methods of direct functional testing of rare variants and the difficulties of identifying alleles with modest effects. PMID:23020841

Parallel metatranscriptome analyses of host and symbiont gene expression in the gut of the termite Reticulitermes flavipes

PubMed Central

Tartar, Aurélien; Wheeler, Marsha M; Zhou, Xuguo; Coy, Monique R; Boucias, Drion G; Scharf, Michael E

2009-01-01

Background Termite lignocellulose digestion is achieved through a collaboration of host plus prokaryotic and eukaryotic symbionts. In the present work, we took a combined host and symbiont metatranscriptomic approach for investigating the digestive contributions of host and symbiont in the lower termite Reticulitermes flavipes. Our approach consisted of parallel high-throughput sequencing from (i) a host gut cDNA library and (ii) a hindgut symbiont cDNA library. Subsequently, we undertook functional analyses of newly identified phenoloxidases with potential importance as pretreatment enzymes in industrial lignocellulose processing. Results Over 10,000 expressed sequence tags (ESTs) were sequenced from the 2 libraries that aligned into 6,555 putative transcripts, including 171 putative lignocellulase genes. Sequence analyses provided insights in two areas. First, a non-overlapping complement of host and symbiont (prokaryotic plus protist) glycohydrolase gene families known to participate in cellulose, hemicellulose, alpha carbohydrate, and chitin degradation were identified. Of these, cellulases are contributed by host plus symbiont genomes, whereas hemicellulases are contributed exclusively by symbiont genomes. Second, a diverse complement of previously unknown genes that encode proteins with homology to lignase, antioxidant, and detoxification enzymes were identified exclusively from the host library (laccase, catalase, peroxidase, superoxide dismutase, carboxylesterase, cytochrome P450). Subsequently, functional analyses of phenoloxidase activity provided results that were strongly consistent with patterns of laccase gene expression. In particular, phenoloxidase activity and laccase gene expression are mostly restricted to symbiont-free foregut plus salivary gland tissues, and phenoloxidase activity is inducible by lignin feeding. Conclusion To our knowledge, this is the first time that a dual host-symbiont transcriptome sequencing effort has been conducted in a single termite species. This sequence database represents an important new genomic resource for use in further studies of collaborative host-symbiont termite digestion, as well as development of coevolved host and symbiont-derived biocatalysts for use in industrial biomass-to-bioethanol applications. Additionally, this study demonstrates that: (i) phenoloxidase activities are prominent in the R. flavipes gut and are not symbiont derived, (ii) expands the known number of host and symbiont glycosyl hydrolase families in Reticulitermes, and (iii) supports previous models of lignin degradation and host-symbiont collaboration in cellulose/hemicellulose digestion in the termite gut. All sequences in this paper are available publicly with the accession numbers FL634956-FL640828 (Termite Gut library) and FL641015-FL645753 (Symbiont library). PMID:19832970

An improved non-uniformity correction algorithm and its GPU parallel implementation

NASA Astrophysics Data System (ADS)

Cheng, Kuanhong; Zhou, Huixin; Qin, Hanlin; Zhao, Dong; Qian, Kun; Rong, Shenghui

2018-05-01

The performance of SLP-THP based non-uniformity correction algorithm is seriously affected by the result of SLP filter, which always leads to image blurring and ghosting artifacts. To address this problem, an improved SLP-THP based non-uniformity correction method with curvature constraint was proposed. Here we put forward a new way to estimate spatial low frequency component. First, the details and contours of input image were obtained respectively by minimizing local Gaussian curvature and mean curvature of image surface. Then, the guided filter was utilized to combine these two parts together to get the estimate of spatial low frequency component. Finally, we brought this SLP component into SLP-THP method to achieve non-uniformity correction. The performance of proposed algorithm was verified by several real and simulated infrared image sequences. The experimental results indicated that the proposed algorithm can reduce the non-uniformity without detail losing. After that, a GPU based parallel implementation that runs 150 times faster than CPU was presented, which showed the proposed algorithm has great potential for real time application.

Whole-body nonenhanced PET/MR versus PET/CT in the staging and restaging of cancers: preliminary observations.

PubMed

Huellner, Martin W; Appenzeller, Philippe; Kuhn, Félix P; Husmann, Lars; Pietsch, Carsten M; Burger, Irene A; Porto, Miguel; Delso, Gaspar; von Schulthess, Gustav K; Veit-Haibach, Patrick

2014-12-01

To assess the diagnostic performance of whole-body non-contrast material-enhanced positron emission tomography (PET)/magnetic resonance (MR) imaging and PET/computed tomography (CT) for staging and restaging of cancers and provide guidance for modality and sequence selection. This study was approved by the institutional review board and national government authorities. One hundred six consecutive patients (median age, 68 years; 46 female and 60 male patients) referred for staging or restaging of oncologic malignancies underwent whole-body imaging with a sequential trimodality PET/CT/MR system. The MR protocol included short inversion time inversion-recovery ( STIR short inversion time inversion-recovery ), Dixon-type liver accelerated volume acquisition ( LAVA liver accelerated volume acquisition ; GE Healthcare, Waukesha, Wis), and respiratory-gated periodically rotated overlapping parallel lines with enhanced reconstruction ( PROPELLER periodically rotated overlapping parallel lines with enhanced reconstruction ; GE Healthcare) sequences. Primary tumors (n = 43), local lymph node metastases (n = 74), and distant metastases (n = 66) were evaluated for conspicuity (scored 0-4), artifacts (scored 0-2), and reader confidence on PET/CT and PET/MR images. Subanalysis for lung lesions (n = 46) was also performed. Relevant incidental findings with both modalities were compared. Interreader agreement was analyzed with intraclass correlation coefficients and κ statistics. Lesion conspicuity, image artifacts, and incidental findings were analyzed with nonparametric tests. Primary tumors were less conspicuous on STIR short inversion time inversion-recovery (3.08, P = .016) and LAVA liver accelerated volume acquisition (2.64, P = .002) images than on CT images (3.49), while findings with the PROPELLER periodically rotated overlapping parallel lines with enhanced reconstruction sequence (3.70, P = .436) were comparable to those at CT. In distant metastases, the PROPELLER periodically rotated overlapping parallel lines with enhanced reconstruction sequence (3.84) yielded better results than CT (2.88, P < .001). Subanalysis for lung lesions yielded similar results (primary lung tumors: CT, 3.71; STIR short inversion time inversion-recovery , 3.32 [P = .014]; LAVA liver accelerated volume acquisition , 2.52 [P = .002]; PROPELLER periodically rotated overlapping parallel lines with enhanced reconstruction , 3.64 [P = .546]). Readers classified lesions more confidently with PET/MR than PET/CT. However, PET/CT showed more incidental findings than PET/MR (P = .039), especially in the lung (P < .001). MR images had more artifacts than CT images. PET/MR performs comparably to PET/CT in whole-body oncology and neoplastic lung disease, with the use of appropriate sequences. Further studies are needed to define regionalized PET/MR protocols with sequences tailored to specific tumor entities. © RSNA, 2014 Online supplemental material is available for this article.

Using video-oriented instructions to speed up sequence comparison.

PubMed

Wozniak, A

1997-04-01

This document presents an implementation of the well-known Smith-Waterman algorithm for comparison of proteic and nucleic sequences, using specialized video instructions. These instructions, SIMD-like in their design, make possible parallelization of the algorithm at the instruction level. Benchmarks on an ULTRA SPARC running at 167 MHz show a speed-up factor of two compared to the same algorithm implemented with integer instructions on the same machine. Performance reaches over 18 million matrix cells per second on a single processor, giving to our knowledge the fastest implementation of the Smith-Waterman algorithm on a workstation. The accelerated procedure was introduced in LASSAP--a LArge Scale Sequence compArison Package software developed at INRIA--which handles parallelism at higher level. On a SUN Enterprise 6000 server with 12 processors, a speed of nearly 200 million matrix cells per second has been obtained. A sequence of length 300 amino acids is scanned against SWISSPROT R33 (1,8531,385 residues) in 29 s. This procedure is not restricted to databank scanning. It applies to all cases handled by LASSAP (intra- and inter-bank comparisons, Z-score computation, etc.

Familial retinoblastoma due to intronic LINE-1 insertion causes aberrant and noncanonical mRNA splicing of the RB1 gene.

PubMed

Rodríguez-Martín, Carlos; Cidre, Florencia; Fernández-Teijeiro, Ana; Gómez-Mariano, Gema; de la Vega, Leticia; Ramos, Patricia; Zaballos, Ángel; Monzón, Sara; Alonso, Javier

2016-05-01

Retinoblastoma (RB, MIM 180200) is the paradigm of hereditary cancer. Individuals harboring a constitutional mutation in one allele of the RB1 gene have a high predisposition to develop RB. Here, we present the first case of familial RB caused by a de novo insertion of a full-length long interspersed element-1 (LINE-1) into intron 14 of the RB1 gene that caused a highly heterogeneous splicing pattern of RB1 mRNA. LINE-1 insertion was inferred by mRNA studies and full-length sequenced by massive parallel sequencing. Some of the aberrant mRNAs were produced by noncanonical acceptor splice sites, a new finding that up to date has not been described to occur upon LINE-1 retrotransposition. Our results clearly show that RNA-based strategies have the potential to detect disease-causing transposon insertions. It also confirms that the incorporation of new genetic approaches, such as massive parallel sequencing, contributes to characterize at the sequence level these unique and exceptional genetic alterations.

Discounting of reward sequences: a test of competing formal models of hyperbolic discounting

PubMed Central

Zarr, Noah; Alexander, William H.; Brown, Joshua W.

2014-01-01

Humans are known to discount future rewards hyperbolically in time. Nevertheless, a formal recursive model of hyperbolic discounting has been elusive until recently, with the introduction of the hyperbolically discounted temporal difference (HDTD) model. Prior to that, models of learning (especially reinforcement learning) have relied on exponential discounting, which generally provides poorer fits to behavioral data. Recently, it has been shown that hyperbolic discounting can also be approximated by a summed distribution of exponentially discounted values, instantiated in the μAgents model. The HDTD model and the μAgents model differ in one key respect, namely how they treat sequences of rewards. The μAgents model is a particular implementation of a Parallel discounting model, which values sequences based on the summed value of the individual rewards whereas the HDTD model contains a non-linear interaction. To discriminate among these models, we observed how subjects discounted a sequence of three rewards, and then we tested how well each candidate model fit the subject data. The results show that the Parallel model generally provides a better fit to the human data. PMID:24639662

IFRD1 Is a Candidate Gene for SMNA on Chromosome 7q22-q23

PubMed Central

Brkanac, Zoran; Spencer, David; Shendure, Jay; Robertson, Peggy D.; Matsushita, Mark; Vu, Tiffany; Bird, Thomas D.; Olson, Maynard V.; Raskind, Wendy H.

2009-01-01

We have established strong linkage evidence that supports mapping autosomal-dominant sensory/motor neuropathy with ataxia (SMNA) to chromosome 7q22-q32. SMNA is a rare neurological disorder whose phenotype encompasses both the central and the peripheral nervous system. In order to identify a gene responsible for SMNA, we have undertaken a comprehensive genomic evaluation of the region of linkage, including evaluation for repeat expansion and small deletions or duplications, capillary sequencing of candidate genes, and massively parallel sequencing of all coding exons. We excluded repeat expansion and small deletions or duplications as causative, and through microarray-based hybrid capture and massively parallel short-read sequencing, we identified a nonsynonymous variant in the human interferon-related developmental regulator gene 1 (IFRD1) as a disease-causing candidate. Sequence conservation, animal models, and protein structure evaluation support the involvement of IFRD1 in SMNA. Mutation analysis of IFRD1 in additional patients with similar phenotypes is needed for demonstration of causality and further evaluation of its importance in neurological diseases. PMID:19409521

Access and visualization using clusters and other parallel computers

NASA Technical Reports Server (NTRS)

Katz, Daniel S.; Bergou, Attila; Berriman, Bruce; Block, Gary; Collier, Jim; Curkendall, Dave; Good, John; Husman, Laura; Jacob, Joe; Laity, Anastasia;

Extended RF shimming: Sequence‐level parallel transmission optimization applied to steady‐state free precession MRI of the heart

PubMed Central

Price, Anthony N.; Padormo, Francesco; Hajnal, Joseph V.; Malik, Shaihan J.

2017-01-01

Cardiac magnetic resonance imaging (MRI) at high field presents challenges because of the high specific absorption rate and significant transmit field (B 1 +) inhomogeneities. Parallel transmission MRI offers the ability to correct for both issues at the level of individual radiofrequency (RF) pulses, but must operate within strict hardware and safety constraints. The constraints are themselves affected by sequence parameters, such as the RF pulse duration and TR, meaning that an overall optimal operating point exists for a given sequence. This work seeks to obtain optimal performance by performing a ‘sequence‐level’ optimization in which pulse sequence parameters are included as part of an RF shimming calculation. The method is applied to balanced steady‐state free precession cardiac MRI with the objective of minimizing TR, hence reducing the imaging duration. Results are demonstrated using an eight‐channel parallel transmit system operating at 3 T, with an in vivo study carried out on seven male subjects of varying body mass index (BMI). Compared with single‐channel operation, a mean‐squared‐error shimming approach leads to reduced imaging durations of 32 ± 3% with simultaneous improvement in flip angle homogeneity of 32 ± 8% within the myocardium. PMID:28195684

Fast parallel tandem mass spectral library searching using GPU hardware acceleration.

PubMed

Baumgardner, Lydia Ashleigh; Shanmugam, Avinash Kumar; Lam, Henry; Eng, Jimmy K; Martin, Daniel B

2011-06-03

Mass spectrometry-based proteomics is a maturing discipline of biologic research that is experiencing substantial growth. Instrumentation has steadily improved over time with the advent of faster and more sensitive instruments collecting ever larger data files. Consequently, the computational process of matching a peptide fragmentation pattern to its sequence, traditionally accomplished by sequence database searching and more recently also by spectral library searching, has become a bottleneck in many mass spectrometry experiments. In both of these methods, the main rate-limiting step is the comparison of an acquired spectrum with all potential matches from a spectral library or sequence database. This is a highly parallelizable process because the core computational element can be represented as a simple but arithmetically intense multiplication of two vectors. In this paper, we present a proof of concept project taking advantage of the massively parallel computing available on graphics processing units (GPUs) to distribute and accelerate the process of spectral assignment using spectral library searching. This program, which we have named FastPaSS (for Fast Parallelized Spectral Searching), is implemented in CUDA (Compute Unified Device Architecture) from NVIDIA, which allows direct access to the processors in an NVIDIA GPU. Our efforts demonstrate the feasibility of GPU computing for spectral assignment, through implementation of the validated spectral searching algorithm SpectraST in the CUDA environment.

The binding modes of carbazole derivatives with telomere G-quadruplex

NASA Astrophysics Data System (ADS)

Zhang, Xiu-feng; Zhang, Hui-juan; Xiang, Jun-feng; Li, Qian; Yang, Qian-fan; Shang, Qian; Zhang, Yan-xia; Tang, Ya-lin

2010-10-01

It is reported that carbazole derivatives can stabilize G-quadruplex DNA structure formed by human telomeric sequence, and therefore, they have the potential to serve as anti-cancer agents. In this present study, in order to further explore the binding mode between carbazole derivatives and G-quadruplex formed by human telomeric sequence, two carbazole iodides (BMVEC, MVEC) molecules were synthesized and used to investigate the interaction with the human telomeric parallel and antiparallel G-quadruplex structures by NMR, CD and molecular modeling study. Interestingly, it is the pivotal the cationic charge pendant groups of pyridinium rings of carbazole that plays an essential role in the stabilizing and binding mode of the human telomeric sequences G-quadruplex structure. It was found that BMVEC with two cationic charge pendant groups of pyridinium rings of 9-ethylcarbazole cannot only stabilize parallel G-quadruple of Hum6 by groove binding and G-tetrad stacking modes and antiparallel G-quadruplex of Hum22 by groove binding, but also induce the formation of mixed G-quadruplex of Hum22. While MVEC with one cationic charge pendant groups of pyridinium ring only can bind with the parallel G-quadruplex of Hum6 by the stacking onto the G4 G-tetrad and could not interact with the G-quadruplex of Hum22.

Terrain types and local-scale stratigraphy of grooved terrain on ganymede

NASA Technical Reports Server (NTRS)

Murchie, Scott L.; Head, James W.; Helfenstein, Paul; Plescia, Jeffrey B.

1986-01-01

Grooved terrain is subdivided on the basis of pervasive morphology into: (1) groove lanes - elongate parallel groove bands, (2) grooved polygons - polygonal domains of parallel grooves, (3) reticulate terrain - polygonal domains of orthogonal grooves, and (4) complex grooved terrain - polygons with several complexly cross-cutting groove sets. Detailed geologic mapping of select areas, employing previously established conventions for determining relative age relations, reveals a general three-stage sequence of grooved terrain emplacement: first, dissection of the lithosphere by throughgoing grooves, and pervasive deformation of intervening blocks; second, extensive flooding and continued deformation of the intervening blocks; third, repeated superposition of groove lanes concentrated at sites of initial throughgoing grooves. This sequence is corroborated by crater-density measurements. Dominant orientations of groove sets are parallel to relict zones of weakness that probably were reactivated during grooved terrain formation. Groove lane morphology and development consistent with that predicted for passive rifts suggests a major role of global expansion in grooved terrain formation.

An object-oriented approach for parallel self adaptive mesh refinement on block structured grids

NASA Technical Reports Server (NTRS)

Lemke, Max; Witsch, Kristian; Quinlan, Daniel

1993-01-01

Self-adaptive mesh refinement dynamically matches the computational demands of a solver for partial differential equations to the activity in the application's domain. In this paper we present two C++ class libraries, P++ and AMR++, which significantly simplify the development of sophisticated adaptive mesh refinement codes on (massively) parallel distributed memory architectures. The development is based on our previous research in this area. The C++ class libraries provide abstractions to separate the issues of developing parallel adaptive mesh refinement applications into those of parallelism, abstracted by P++, and adaptive mesh refinement, abstracted by AMR++. P++ is a parallel array class library to permit efficient development of architecture independent codes for structured grid applications, and AMR++ provides support for self-adaptive mesh refinement on block-structured grids of rectangular non-overlapping blocks. Using these libraries, the application programmers' work is greatly simplified to primarily specifying the serial single grid application and obtaining the parallel and self-adaptive mesh refinement code with minimal effort. Initial results for simple singular perturbation problems solved by self-adaptive multilevel techniques (FAC, AFAC), being implemented on the basis of prototypes of the P++/AMR++ environment, are presented. Singular perturbation problems frequently arise in large applications, e.g. in the area of computational fluid dynamics. They usually have solutions with layers which require adaptive mesh refinement and fast basic solvers in order to be resolved efficiently.

Language Classification using N-grams Accelerated by FPGA-based Bloom Filters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacob, A; Gokhale, M

N-Gram (n-character sequences in text documents) counting is a well-established technique used in classifying the language of text in a document. In this paper, n-gram processing is accelerated through the use of reconfigurable hardware on the XtremeData XD1000 system. Our design employs parallelism at multiple levels, with parallel Bloom Filters accessing on-chip RAM, parallel language classifiers, and parallel document processing. In contrast to another hardware implementation (HAIL algorithm) that uses off-chip SRAM for lookup, our highly scalable implementation uses only on-chip memory blocks. Our implementation of end-to-end language classification runs at 85x comparable software and 1.45x the competing hardware design.

Creation of parallel algorithms for the solution of problems of gas dynamics on multi-core computers and GPU

NASA Astrophysics Data System (ADS)

Rybakin, B.; Bogatencov, P.; Secrieru, G.; Iliuha, N.

2013-10-01

The paper deals with a parallel algorithm for calculations on multiprocessor computers and GPU accelerators. The calculations of shock waves interaction with low-density bubble results and the problem of the gas flow with the forces of gravity are presented. This algorithm combines a possibility to capture a high resolution of shock waves, the second-order accuracy for TVD schemes, and a possibility to observe a low-level diffusion of the advection scheme. Many complex problems of continuum mechanics are numerically solved on structured or unstructured grids. To improve the accuracy of the calculations is necessary to choose a sufficiently small grid (with a small cell size). This leads to the drawback of a substantial increase of computation time. Therefore, for the calculations of complex problems it is reasonable to use the method of Adaptive Mesh Refinement. That is, the grid refinement is performed only in the areas of interest of the structure, where, e.g., the shock waves are generated, or a complex geometry or other such features exist. Thus, the computing time is greatly reduced. In addition, the execution of the application on the resulting sequence of nested, decreasing nets can be parallelized. Proposed algorithm is based on the AMR method. Utilization of AMR method can significantly improve the resolution of the difference grid in areas of high interest, and from other side to accelerate the processes of the multi-dimensional problems calculating. Parallel algorithms of the analyzed difference models realized for the purpose of calculations on graphic processors using the CUDA technology [1].

Parallel multiphase microflows: fundamental physics, stabilization methods and applications.

PubMed

Aota, Arata; Mawatari, Kazuma; Kitamori, Takehiko

2009-09-07

Parallel multiphase microflows, which can integrate unit operations in a microchip under continuous flow conditions, are discussed. Fundamental physics, stabilization methods and some applications are shown.

Efficient parallel and out of core algorithms for constructing large bi-directed de Bruijn graphs.

PubMed

Kundeti, Vamsi K; Rajasekaran, Sanguthevar; Dinh, Hieu; Vaughn, Matthew; Thapar, Vishal

2010-11-15

Assembling genomic sequences from a set of overlapping reads is one of the most fundamental problems in computational biology. Algorithms addressing the assembly problem fall into two broad categories - based on the data structures which they employ. The first class uses an overlap/string graph and the second type uses a de Bruijn graph. However with the recent advances in short read sequencing technology, de Bruijn graph based algorithms seem to play a vital role in practice. Efficient algorithms for building these massive de Bruijn graphs are very essential in large sequencing projects based on short reads. In an earlier work, an O(n/p) time parallel algorithm has been given for this problem. Here n is the size of the input and p is the number of processors. This algorithm enumerates all possible bi-directed edges which can overlap with a node and ends up generating Θ(nΣ) messages (Σ being the size of the alphabet). In this paper we present a Θ(n/p) time parallel algorithm with a communication complexity that is equal to that of parallel sorting and is not sensitive to Σ. The generality of our algorithm makes it very easy to extend it even to the out-of-core model and in this case it has an optimal I/O complexity of Θ(nlog(n/B)Blog(M/B)) (M being the main memory size and B being the size of the disk block). We demonstrate the scalability of our parallel algorithm on a SGI/Altix computer. A comparison of our algorithm with the previous approaches reveals that our algorithm is faster--both asymptotically and practically. We demonstrate the scalability of our sequential out-of-core algorithm by comparing it with the algorithm used by VELVET to build the bi-directed de Bruijn graph. Our experiments reveal that our algorithm can build the graph with a constant amount of memory, which clearly outperforms VELVET. We also provide efficient algorithms for the bi-directed chain compaction problem. The bi-directed de Bruijn graph is a fundamental data structure for any sequence assembly program based on Eulerian approach. Our algorithms for constructing Bi-directed de Bruijn graphs are efficient in parallel and out of core settings. These algorithms can be used in building large scale bi-directed de Bruijn graphs. Furthermore, our algorithms do not employ any all-to-all communications in a parallel setting and perform better than the prior algorithms. Finally our out-of-core algorithm is extremely memory efficient and can replace the existing graph construction algorithm in VELVET.

YAPPA: a Compiler-Based Parallelization Framework for Irregular Applications on MPSoCs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lovergine, Silvia; Tumeo, Antonino; Villa, Oreste

Modern embedded systems include hundreds of cores. Because of the difficulty in providing a fast, coherent memory architecture, these systems usually rely on non-coherent, non-uniform memory architectures with private memories for each core. However, programming these systems poses significant challenges. The developer must extract large amounts of parallelism, while orchestrating communication among cores to optimize application performance. These issues become even more significant with irregular applications, which present data sets difficult to partition, unpredictable memory accesses, unbalanced control flow and fine grained communication. Hand-optimizing every single aspect is hard and time-consuming, and it often does not lead to the expectedmore » performance. There is a growing gap between such complex and highly-parallel architectures and the high level languages used to describe the specification, which were designed for simpler systems and do not consider these new issues. In this paper we introduce YAPPA (Yet Another Parallel Programming Approach), a compilation framework for the automatic parallelization of irregular applications on modern MPSoCs based on LLVM. We start by considering an efficient parallel programming approach for irregular applications on distributed memory systems. We then propose a set of transformations that can reduce the development and optimization effort. The results of our initial prototype confirm the correctness of the proposed approach.« less

Code Parallelization with CAPO: A User Manual

NASA Technical Reports Server (NTRS)

Jin, Hao-Qiang; Frumkin, Michael; Yan, Jerry; Biegel, Bryan (Technical Monitor)

2001-01-01

A software tool has been developed to assist the parallelization of scientific codes. This tool, CAPO, extends an existing parallelization toolkit, CAPTools developed at the University of Greenwich, to generate OpenMP parallel codes for shared memory architectures. This is an interactive toolkit to transform a serial Fortran application code to an equivalent parallel version of the software - in a small fraction of the time normally required for a manual parallelization. We first discuss the way in which loop types are categorized and how efficient OpenMP directives can be defined and inserted into the existing code using the in-depth interprocedural analysis. The use of the toolkit on a number of application codes ranging from benchmark to real-world application codes is presented. This will demonstrate the great potential of using the toolkit to quickly parallelize serial programs as well as the good performance achievable on a large number of toolkit to quickly parallelize serial programs as well as the good performance achievable on a large number of processors. The second part of the document gives references to the parameters and the graphic user interface implemented in the toolkit. Finally a set of tutorials is included for hands-on experiences with this toolkit.

Niche and neutral processes both shape community structure in parallelized, aerobic, single carbon-source enrichments

DOE Data Explorer

Flynn, Theodore M.; Koval, Jason C.; Greenwald, Stephanie M.; Owens, Sarah M.; Kemner, Kenneth M.; Antonopoulos, Dionysios A.

2017-01-01

We present DNA sequence data in FASTA-formatted files from aerobic environmental microcosms inoculated with a sole carbon source. DNA sequences are of 16S rRNA genes present in DNA extracted from each microcosm along with the environmental samples (soil, water) used to inoculate them. These samples were sequenced using the Illumina MiSeq platform at the Environmental Sample Preparation and Sequencing Facility at Argonne National Laboratory. This data is compatible with standard microbiome analysis pipelines (e.g., QIIME, mothur, etc.).

Modern Computational Techniques for the HMMER Sequence Analysis

PubMed Central

2013-01-01

This paper focuses on the latest research and critical reviews on modern computing architectures, software and hardware accelerated algorithms for bioinformatics data analysis with an emphasis on one of the most important sequence analysis applications—hidden Markov models (HMM). We show the detailed performance comparison of sequence analysis tools on various computing platforms recently developed in the bioinformatics society. The characteristics of the sequence analysis, such as data and compute-intensive natures, make it very attractive to optimize and parallelize by using both traditional software approach and innovated hardware acceleration technologies. PMID:25937944

NAS Requirements Checklist for Job Queuing/Scheduling Software

NASA Technical Reports Server (NTRS)

Jones, James Patton

1996-01-01

The increasing reliability of parallel systems and clusters of computers has resulted in these systems becoming more attractive for true production workloads. Today, the primary obstacle to production use of clusters of computers is the lack of a functional and robust Job Management System for parallel applications. This document provides a checklist of NAS requirements for job queuing and scheduling in order to make most efficient use of parallel systems and clusters for parallel applications. Future requirements are also identified to assist software vendors with design planning.

The NAS parallel benchmarks

NASA Technical Reports Server (NTRS)

Bailey, David (Editor); Barton, John (Editor); Lasinski, Thomas (Editor); Simon, Horst (Editor)

1993-01-01

A new set of benchmarks was developed for the performance evaluation of highly parallel supercomputers. These benchmarks consist of a set of kernels, the 'Parallel Kernels,' and a simulated application benchmark. Together they mimic the computation and data movement characteristics of large scale computational fluid dynamics (CFD) applications. The principal distinguishing feature of these benchmarks is their 'pencil and paper' specification - all details of these benchmarks are specified only algorithmically. In this way many of the difficulties associated with conventional benchmarking approaches on highly parallel systems are avoided.

State Transition Matrix for Perturbed Orbital Motion Using Modified Chebyshev Picard Iteration

NASA Astrophysics Data System (ADS)

Read, Julie L.; Younes, Ahmad Bani; Macomber, Brent; Turner, James; Junkins, John L.

2015-06-01

The Modified Chebyshev Picard Iteration (MCPI) method has recently proven to be highly efficient for a given accuracy compared to several commonly adopted numerical integration methods, as a means to solve for perturbed orbital motion. This method utilizes Picard iteration, which generates a sequence of path approximations, and Chebyshev Polynomials, which are orthogonal and also enable both efficient and accurate function approximation. The nodes consistent with discrete Chebyshev orthogonality are generated using cosine sampling; this strategy also reduces the Runge effect and as a consequence of orthogonality, there is no matrix inversion required to find the basis function coefficients. The MCPI algorithms considered herein are parallel-structured so that they are immediately well-suited for massively parallel implementation with additional speedup. MCPI has a wide range of applications beyond ephemeris propagation, including the propagation of the State Transition Matrix (STM) for perturbed two-body motion. A solution is achieved for a spherical harmonic series representation of earth gravity (EGM2008), although the methodology is suitable for application to any gravity model. Included in this representation the normalized, Associated Legendre Functions are given and verified numerically. Modifications of the classical algorithm techniques, such as rewriting the STM equations in a second-order cascade formulation, gives rise to additional speedup. Timing results for the baseline formulation and this second-order formulation are given.

INVITED TOPICAL REVIEW: Parallel magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Larkman, David J.; Nunes, Rita G.

2007-04-01

Parallel imaging has been the single biggest innovation in magnetic resonance imaging in the last decade. The use of multiple receiver coils to augment the time consuming Fourier encoding has reduced acquisition times significantly. This increase in speed comes at a time when other approaches to acquisition time reduction were reaching engineering and human limits. A brief summary of spatial encoding in MRI is followed by an introduction to the problem parallel imaging is designed to solve. There are a large number of parallel reconstruction algorithms; this article reviews a cross-section, SENSE, SMASH, g-SMASH and GRAPPA, selected to demonstrate the different approaches. Theoretical (the g-factor) and practical (coil design) limits to acquisition speed are reviewed. The practical implementation of parallel imaging is also discussed, in particular coil calibration. How to recognize potential failure modes and their associated artefacts are shown. Well-established applications including angiography, cardiac imaging and applications using echo planar imaging are reviewed and we discuss what makes a good application for parallel imaging. Finally, active research areas where parallel imaging is being used to improve data quality by repairing artefacted images are also reviewed.

Geospatial Applications on Different Parallel and Distributed Systems in enviroGRIDS Project

NASA Astrophysics Data System (ADS)

Rodila, D.; Bacu, V.; Gorgan, D.

2012-04-01

The execution of Earth Science applications and services on parallel and distributed systems has become a necessity especially due to the large amounts of Geospatial data these applications require and the large geographical areas they cover. The parallelization of these applications comes to solve important performance issues and can spread from task parallelism to data parallelism as well. Parallel and distributed architectures such as Grid, Cloud, Multicore, etc. seem to offer the necessary functionalities to solve important problems in the Earth Science domain: storing, distribution, management, processing and security of Geospatial data, execution of complex processing through task and data parallelism, etc. A main goal of the FP7-funded project enviroGRIDS (Black Sea Catchment Observation and Assessment System supporting Sustainable Development) [1] is the development of a Spatial Data Infrastructure targeting this catchment region but also the development of standardized and specialized tools for storing, analyzing, processing and visualizing the Geospatial data concerning this area. For achieving these objectives, the enviroGRIDS deals with the execution of different Earth Science applications, such as hydrological models, Geospatial Web services standardized by the Open Geospatial Consortium (OGC) and others, on parallel and distributed architecture to maximize the obtained performance. This presentation analysis the integration and execution of Geospatial applications on different parallel and distributed architectures and the possibility of choosing among these architectures based on application characteristics and user requirements through a specialized component. Versions of the proposed platform have been used in enviroGRIDS project on different use cases such as: the execution of Geospatial Web services both on Web and Grid infrastructures [2] and the execution of SWAT hydrological models both on Grid and Multicore architectures [3]. The current focus is to integrate in the proposed platform the Cloud infrastructure, which is still a paradigm with critical problems to be solved despite the great efforts and investments. Cloud computing comes as a new way of delivering resources while using a large set of old as well as new technologies and tools for providing the necessary functionalities. The main challenges in the Cloud computing, most of them identified also in the Open Cloud Manifesto 2009, address resource management and monitoring, data and application interoperability and portability, security, scalability, software licensing, etc. We propose a platform able to execute different Geospatial applications on different parallel and distributed architectures such as Grid, Cloud, Multicore, etc. with the possibility of choosing among these architectures based on application characteristics and complexity, user requirements, necessary performances, cost support, etc. The execution redirection on a selected architecture is realized through a specialized component and has the purpose of offering a flexible way in achieving the best performances considering the existing restrictions.

Parallel Analysis of 124 Universal SNPs for Human Identification by Targeted Semiconductor Sequencing

PubMed Central

Zhang, Suhua; Bian, Yingnan; Zhang, Zheren; Zheng, Hancheng; Wang, Zheng; Zha, Lagabaiyila; Cai, Jifeng; Gao, Yuzhen; Ji, Chaoneng; Hou, Yiping; Li, Chengtao

2015-01-01

SNPs, abundant in human genome with lower mutation rate, are attractive to genetic application like forensic, anthropological and evolutionary studies. Universal SNPs showing little allelic frequency variation among populations while remaining highly informative for human identification were obtained from previous studies. However, genotyping tools target only dozens of markers simultaneously, limiting their applications. Here, 124 SNPs were simultaneous tested using Ampliseq technology with Ion Torrent PGM platform. Concordance study was performed with 2 reference samples of 9947A and 9948 between NGS and Sanger sequencing. Full concordance were obtained except genotype of rs576261 with 9947A. Parameter of FMAR (%) was introduced for NGS data analysis for the first time, evaluating allelic performance, sensitivity testing and mixture testing. FMAR values for accurate heterozygotes should be range from 50% to 60%, for homozygotes or Y-SNP should be above 90%. SNPs of rs7520386, rs4530059, rs214955, rs1523537, rs2342747, rs576261 and rs12997453 were recognized as poorly performing loci, either with allelic imbalance or with lower coverage. Sensitivity testing demonstrated that with DNA range from 10 ng-0.5 ng, all correct genotypes were obtained. For mixture testing, a clear linear correlation (R2 = 0.9429) between the excepted FMAR and observed FMAR values of mixtures was observed. PMID:26691610

ProperCAD: A portable object-oriented parallel environment for VLSI CAD

NASA Technical Reports Server (NTRS)

Ramkumar, Balkrishna; Banerjee, Prithviraj

1993-01-01

Most parallel algorithms for VLSI CAD proposed to date have one important drawback: they work efficiently only on machines that they were designed for. As a result, algorithms designed to date are dependent on the architecture for which they are developed and do not port easily to other parallel architectures. A new project under way to address this problem is described. A Portable object-oriented parallel environment for CAD algorithms (ProperCAD) is being developed. The objectives of this research are (1) to develop new parallel algorithms that run in a portable object-oriented environment (CAD algorithms using a general purpose platform for portable parallel programming called CARM is being developed and a C++ environment that is truly object-oriented and specialized for CAD applications is also being developed); and (2) to design the parallel algorithms around a good sequential algorithm with a well-defined parallel-sequential interface (permitting the parallel algorithm to benefit from future developments in sequential algorithms). One CAD application that has been implemented as part of the ProperCAD project, flat VLSI circuit extraction, is described. The algorithm, its implementation, and its performance on a range of parallel machines are discussed in detail. It currently runs on an Encore Multimax, a Sequent Symmetry, Intel iPSC/2 and i860 hypercubes, a NCUBE 2 hypercube, and a network of Sun Sparc workstations. Performance data for other applications that were developed are provided: namely test pattern generation for sequential circuits, parallel logic synthesis, and standard cell placement.

Efficient Parallel Kernel Solvers for Computational Fluid Dynamics Applications

NASA Technical Reports Server (NTRS)

Sun, Xian-He

1997-01-01

Distributed-memory parallel computers dominate today's parallel computing arena. These machines, such as Intel Paragon, IBM SP2, and Cray Origin2OO, have successfully delivered high performance computing power for solving some of the so-called "grand-challenge" problems. Despite initial success, parallel machines have not been widely accepted in production engineering environments due to the complexity of parallel programming. On a parallel computing system, a task has to be partitioned and distributed appropriately among processors to reduce communication cost and to attain load balance. More importantly, even with careful partitioning and mapping, the performance of an algorithm may still be unsatisfactory, since conventional sequential algorithms may be serial in nature and may not be implemented efficiently on parallel machines. In many cases, new algorithms have to be introduced to increase parallel performance. In order to achieve optimal performance, in addition to partitioning and mapping, a careful performance study should be conducted for a given application to find a good algorithm-machine combination. This process, however, is usually painful and elusive. The goal of this project is to design and develop efficient parallel algorithms for highly accurate Computational Fluid Dynamics (CFD) simulations and other engineering applications. The work plan is 1) developing highly accurate parallel numerical algorithms, 2) conduct preliminary testing to verify the effectiveness and potential of these algorithms, 3) incorporate newly developed algorithms into actual simulation packages. The work plan has well achieved. Two highly accurate, efficient Poisson solvers have been developed and tested based on two different approaches: (1) Adopting a mathematical geometry which has a better capacity to describe the fluid, (2) Using compact scheme to gain high order accuracy in numerical discretization. The previously developed Parallel Diagonal Dominant (PDD) algorithm and Reduced Parallel Diagonal Dominant (RPDD) algorithm have been carefully studied on different parallel platforms for different applications, and a NASA simulation code developed by Man M. Rai and his colleagues has been parallelized and implemented based on data dependency analysis. These achievements are addressed in detail in the paper.

Fast inner-volume imaging of the lumbar spine with a spatially focused excitation using a 3D-TSE sequence.

PubMed

Riffel, Philipp; Michaely, Henrik J; Morelli, John N; Paul, Dominik; Kannengiesser, Stephan; Schoenberg, Stefan O; Haneder, Stefan

2015-04-01

The purpose of this study was to evaluate the feasibility and technical quality of a zoomed three-dimensional (3D) turbo spin-echo (TSE) sampling perfection with application optimized contrasts using different flip-angle evolutions (SPACE) sequence of the lumbar spine. In this prospective feasibility study, nine volunteers underwent a 3-T magnetic resonance examination of the lumbar spine including 1) a conventional 3D T2-weighted (T2w) SPACE sequence with generalized autocalibrating partially parallel acquisition technique acceleration factor 2 and 2) a zoomed 3D T2w SPACE sequence with a reduced field of view (reduction factor 2). Images were evaluated with regard to image sharpness, signal homogeneity, and the presence of artifacts by two experienced radiologists. For quantitative analysis, signal-to-noise ratio (SNR) values were calculated. Image sharpness of anatomic structures was statistically significantly greater with zoomed SPACE (P < .0001), whereas the signal homogeneity was statistically significantly greater with conventional SPACE (cSPACE; P = .0003). There were no statistically significant differences in extent of artifacts. Acquisition times were 8:20 minutes for cSPACE and 6:30 minutes for zoomed SPACE. Readers 1 and 2 selected zSPACE as the preferred sequence in five of nine cases. In two of nine cases, both sequences were rated as equally preferred by both the readers. SNR values were statistically significantly greater with cSPACE. In comparison to a cSPACE sequences, zoomed SPACE imaging of the lumbar spine provides sharper images in conjunction with a 25% reduction in acquisition time. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

Performance Analysis of Multilevel Parallel Applications on Shared Memory Architectures

NASA Technical Reports Server (NTRS)

Biegel, Bryan A. (Technical Monitor); Jost, G.; Jin, H.; Labarta J.; Gimenez, J.; Caubet, J.

2003-01-01

Parallel programming paradigms include process level parallelism, thread level parallelization, and multilevel parallelism. This viewgraph presentation describes a detailed performance analysis of these paradigms for Shared Memory Architecture (SMA). This analysis uses the Paraver Performance Analysis System. The presentation includes diagrams of a flow of useful computations.

Antibody performance in ChIP-sequencing assays: From quality scores of public data sets to quantitative certification.

PubMed

Mendoza-Parra, Marco-Antonio; Saravaki, Vincent; Cholley, Pierre-Etienne; Blum, Matthias; Billoré, Benjamin; Gronemeyer, Hinrich

2016-01-01

We have established a certification system for antibodies to be used in chromatin immunoprecipitation assays coupled to massive parallel sequencing (ChIP-seq). This certification comprises a standardized ChIP procedure and the attribution of a numerical quality control indicator (QCi) to biological replicate experiments. The QCi computation is based on a universally applicable quality assessment that quantitates the global deviation of randomly sampled subsets of ChIP-seq dataset with the original genome-aligned sequence reads. Comparison with a QCi database for >28,000 ChIP-seq assays were used to attribute quality grades (ranging from 'AAA' to 'DDD') to a given dataset. In the present report we used the numerical QC system to assess the factors influencing the quality of ChIP-seq assays, including the nature of the target, the sequencing depth and the commercial source of the antibody.  We have used this approach specifically to certify mono and polyclonal antibodies obtained from Active Motif directed against the histone modification marks H3K4me3, H3K27ac and H3K9ac for ChIP-seq. The antibodies received the grades AAA to BBC ( www.ngs-qc.org). We propose to attribute such quantitative grading of all antibodies attributed with the label "ChIP-seq grade".

Phosphoenolpyruvate carboxykinase 1 gene (Pck1) displays parallel evolution between Old World and New World fruit bats.

PubMed

Zhu, Lei; Yin, Qiuyuan; Irwin, David M; Zhang, Shuyi

2015-01-01

Bats are an ideal mammalian group for exploring adaptations to fasting due to their large variety of diets and because fasting is a regular part of their life cycle. Mammals fed on a carbohydrate-rich diet experience a rapid decrease in blood glucose levels during a fast, thus, the development of mechanisms to resist the consequences of regular fasts, experienced on a daily basis, must have been crucial in the evolution of frugivorous bats. Phosphoenolpyruvate carboxykinase 1 (PEPCK1, encoded by the Pck1 gene) is the rate-limiting enzyme in gluconeogenesis and is largely responsible for the maintenance of glucose homeostasis during fasting in fruit-eating bats. To test whether Pck1 has experienced adaptive evolution in frugivorous bats, we obtained Pck1 coding sequence from 20 species of bats, including five Old World fruit bats (OWFBs) (Pteropodidae) and two New World fruit bats (NWFBs) (Phyllostomidae). Our molecular evolutionary analyses of these sequences revealed that Pck1 was under purifying selection in both Old World and New World fruit bats with no evidence of positive selection detected in either ancestral branch leading to fruit bats. Interestingly, however, six specific amino acid substitutions were detected on the ancestral lineage of OWFBs. In addition, we found considerable evidence for parallel evolution, at the amino acid level, between the PEPCK1 sequences of Old World fruit bats and New World fruit bats. Test for parallel evolution showed that four parallel substitutions (Q276R, R503H, I558V and Q593R) were driven by natural selection. Our study provides evidence that Pck1 underwent parallel evolution between Old World and New World fruit bats, two lineages of mammals that feed on a carbohydrate-rich diet and experience regular periods of fasting as part of their life cycle.

Phosphoenolpyruvate Carboxykinase 1 Gene (Pck1) Displays Parallel Evolution between Old World and New World Fruit Bats

PubMed Central

Irwin, David M.; Zhang, Shuyi

2015-01-01

Bats are an ideal mammalian group for exploring adaptations to fasting due to their large variety of diets and because fasting is a regular part of their life cycle. Mammals fed on a carbohydrate-rich diet experience a rapid decrease in blood glucose levels during a fast, thus, the development of mechanisms to resist the consequences of regular fasts, experienced on a daily basis, must have been crucial in the evolution of frugivorous bats. Phosphoenolpyruvate carboxykinase 1 (PEPCK1, encoded by the Pck1 gene) is the rate-limiting enzyme in gluconeogenesis and is largely responsible for the maintenance of glucose homeostasis during fasting in fruit-eating bats. To test whether Pck1 has experienced adaptive evolution in frugivorous bats, we obtained Pck1 coding sequence from 20 species of bats, including five Old World fruit bats (OWFBs) (Pteropodidae) and two New World fruit bats (NWFBs) (Phyllostomidae). Our molecular evolutionary analyses of these sequences revealed that Pck1 was under purifying selection in both Old World and New World fruit bats with no evidence of positive selection detected in either ancestral branch leading to fruit bats. Interestingly, however, six specific amino acid substitutions were detected on the ancestral lineage of OWFBs. In addition, we found considerable evidence for parallel evolution, at the amino acid level, between the PEPCK1 sequences of Old World fruit bats and New World fruit bats. Test for parallel evolution showed that four parallel substitutions (Q276R, R503H, I558V and Q593R) were driven by natural selection. Our study provides evidence that Pck1 underwent parallel evolution between Old World and New World fruit bats, two lineages of mammals that feed on a carbohydrate-rich diet and experience regular periods of fasting as part of their life cycle. PMID:25807515

3D hyperpolarized C-13 EPI with calibrationless parallel imaging

NASA Astrophysics Data System (ADS)

Gordon, Jeremy W.; Hansen, Rie B.; Shin, Peter J.; Feng, Yesu; Vigneron, Daniel B.; Larson, Peder E. Z.

2018-04-01

With the translation of metabolic MRI with hyperpolarized 13C agents into the clinic, imaging approaches will require large volumetric FOVs to support clinical applications. Parallel imaging techniques will be crucial to increasing volumetric scan coverage while minimizing RF requirements and temporal resolution. Calibrationless parallel imaging approaches are well-suited for this application because they eliminate the need to acquire coil profile maps or auto-calibration data. In this work, we explored the utility of a calibrationless parallel imaging method (SAKE) and corresponding sampling strategies to accelerate and undersample hyperpolarized 13C data using 3D blipped EPI acquisitions and multichannel receive coils, and demonstrated its application in a human study of [1-13C]pyruvate metabolism.

Fault trees and sequence dependencies

NASA Technical Reports Server (NTRS)

Dugan, Joanne Bechta; Boyd, Mark A.; Bavuso, Salvatore J.

1990-01-01

One of the frequently cited shortcomings of fault-tree models, their inability to model so-called sequence dependencies, is discussed. Several sources of such sequence dependencies are discussed, and new fault-tree gates to capture this behavior are defined. These complex behaviors can be included in present fault-tree models because they utilize a Markov solution. The utility of the new gates is demonstrated by presenting several models of the fault-tolerant parallel processor, which include both hot and cold spares.

Identification and Resolution of Microdiversity through Metagenomic Sequencing of Parallel Consortia

PubMed Central

Maezato, Yukari; Wu, Yu-Wei; Romine, Margaret F.; Lindemann, Stephen R.

2015-01-01

To gain a predictive understanding of the interspecies interactions within microbial communities that govern community function, the genomic complement of every member population must be determined. Although metagenomic sequencing has enabled the de novo reconstruction of some microbial genomes from environmental communities, microdiversity confounds current genome reconstruction techniques. To overcome this issue, we performed short-read metagenomic sequencing on parallel consortia, defined as consortia cultivated under the same conditions from the same natural community with overlapping species composition. The differences in species abundance between the two consortia allowed reconstruction of near-complete (at an estimated >85% of gene complement) genome sequences for 17 of the 20 detected member species. Two Halomonas spp. indistinguishable by amplicon analysis were found to be present within the community. In addition, comparison of metagenomic reads against the consensus scaffolds revealed within-species variation for one of the Halomonas populations, one of the Rhodobacteraceae populations, and the Rhizobiales population. Genomic comparison of these representative instances of inter- and intraspecies microdiversity suggests differences in functional potential that may result in the expression of distinct roles in the community. In addition, isolation and complete genome sequence determination of six member species allowed an investigation into the sensitivity and specificity of genome reconstruction processes, demonstrating robustness across a wide range of sequence coverage (9× to 2,700×) within the metagenomic data set. PMID:26497460

Identification and Resolution of Microdiversity through Metagenomic Sequencing of Parallel Consortia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, William C.; Maezato, Yukari; Wu, Yu-Wei

2015-10-23

To gain a predictive understanding of the interspecies interactions within microbial communities that govern community function, the genomic complement of every member population must be determined. Although metagenomic sequencing has enabled thede novoreconstruction of some microbial genomes from environmental communities, microdiversity confounds current genome reconstruction techniques. To overcome this issue, we performed short-read metagenomic sequencing on parallel consortia, defined as consortia cultivated under the same conditions from the same natural community with overlapping species composition. The differences in species abundance between the two consortia allowed reconstruction of near-complete (at an estimated >85% of gene complement) genome sequences for 17 ofmore » the 20 detected member species. TwoHalomonasspp. indistinguishable by amplicon analysis were found to be present within the community. In addition, comparison of metagenomic reads against the consensus scaffolds revealed within-species variation for one of theHalomonaspopulations, one of theRhodobacteraceaepopulations, and theRhizobialespopulation. Genomic comparison of these representative instances of inter- and intraspecies microdiversity suggests differences in functional potential that may result in the expression of distinct roles in the community. In addition, isolation and complete genome sequence determination of six member species allowed an investigation into the sensitivity and specificity of genome reconstruction processes, demonstrating robustness across a wide range of sequence coverage (9× to 2,700×) within the metagenomic data set.« less

Equalizer: a scalable parallel rendering framework.

PubMed

Eilemann, Stefan; Makhinya, Maxim; Pajarola, Renato

2009-01-01

Continuing improvements in CPU and GPU performances as well as increasing multi-core processor and cluster-based parallelism demand for flexible and scalable parallel rendering solutions that can exploit multipipe hardware accelerated graphics. In fact, to achieve interactive visualization, scalable rendering systems are essential to cope with the rapid growth of data sets. However, parallel rendering systems are non-trivial to develop and often only application specific implementations have been proposed. The task of developing a scalable parallel rendering framework is even more difficult if it should be generic to support various types of data and visualization applications, and at the same time work efficiently on a cluster with distributed graphics cards. In this paper we introduce a novel system called Equalizer, a toolkit for scalable parallel rendering based on OpenGL which provides an application programming interface (API) to develop scalable graphics applications for a wide range of systems ranging from large distributed visualization clusters and multi-processor multipipe graphics systems to single-processor single-pipe desktop machines. We describe the system architecture, the basic API, discuss its advantages over previous approaches, present example configurations and usage scenarios as well as scalability results.

Parallel Computing Strategies for Irregular Algorithms

NASA Technical Reports Server (NTRS)

Biswas, Rupak; Oliker, Leonid; Shan, Hongzhang; Biegel, Bryan (Technical Monitor)

2002-01-01

Parallel computing promises several orders of magnitude increase in our ability to solve realistic computationally-intensive problems, but relies on their efficient mapping and execution on large-scale multiprocessor architectures. Unfortunately, many important applications are irregular and dynamic in nature, making their effective parallel implementation a daunting task. Moreover, with the proliferation of parallel architectures and programming paradigms, the typical scientist is faced with a plethora of questions that must be answered in order to obtain an acceptable parallel implementation of the solution algorithm. In this paper, we consider three representative irregular applications: unstructured remeshing, sparse matrix computations, and N-body problems, and parallelize them using various popular programming paradigms on a wide spectrum of computer platforms ranging from state-of-the-art supercomputers to PC clusters. We present the underlying problems, the solution algorithms, and the parallel implementation strategies. Smart load-balancing, partitioning, and ordering techniques are used to enhance parallel performance. Overall results demonstrate the complexity of efficiently parallelizing irregular algorithms.

Parallelization of NAS Benchmarks for Shared Memory Multiprocessors

NASA Technical Reports Server (NTRS)

Waheed, Abdul; Yan, Jerry C.; Saini, Subhash (Technical Monitor)

1998-01-01

This paper presents our experiences of parallelizing the sequential implementation of NAS benchmarks using compiler directives on SGI Origin2000 distributed shared memory (DSM) system. Porting existing applications to new high performance parallel and distributed computing platforms is a challenging task. Ideally, a user develops a sequential version of the application, leaving the task of porting to new generations of high performance computing systems to parallelization tools and compilers. Due to the simplicity of programming shared-memory multiprocessors, compiler developers have provided various facilities to allow the users to exploit parallelism. Native compilers on SGI Origin2000 support multiprocessing directives to allow users to exploit loop-level parallelism in their programs. Additionally, supporting tools can accomplish this process automatically and present the results of parallelization to the users. We experimented with these compiler directives and supporting tools by parallelizing sequential implementation of NAS benchmarks. Results reported in this paper indicate that with minimal effort, the performance gain is comparable with the hand-parallelized, carefully optimized, message-passing implementations of the same benchmarks.

F-Nets and Software Cabling: Deriving a Formal Model and Language for Portable Parallel Programming

NASA Technical Reports Server (NTRS)

DiNucci, David C.; Saini, Subhash (Technical Monitor)

1998-01-01

Parallel programming is still being based upon antiquated sequence-based definitions of the terms "algorithm" and "computation", resulting in programs which are architecture dependent and difficult to design and analyze. By focusing on obstacles inherent in existing practice, a more portable model is derived here, which is then formalized into a model called Soviets which utilizes a combination of imperative and functional styles. This formalization suggests more general notions of algorithm and computation, as well as insights into the meaning of structured programming in a parallel setting. To illustrate how these principles can be applied, a very-high-level graphical architecture-independent parallel language, called Software Cabling, is described, with many of the features normally expected from today's computer languages (e.g. data abstraction, data parallelism, and object-based programming constructs).

TIA: algorithms for development of identity-linked SNP islands for analysis by massively parallel DNA sequencing.

PubMed

Farris, M Heath; Scott, Andrew R; Texter, Pamela A; Bartlett, Marta; Coleman, Patricia; Masters, David

2018-04-11

Single nucleotide polymorphisms (SNPs) located within the human genome have been shown to have utility as markers of identity in the differentiation of DNA from individual contributors. Massively parallel DNA sequencing (MPS) technologies and human genome SNP databases allow for the design of suites of identity-linked target regions, amenable to sequencing in a multiplexed and massively parallel manner. Therefore, tools are needed for leveraging the genotypic information found within SNP databases for the discovery of genomic targets that can be evaluated on MPS platforms. The SNP island target identification algorithm (TIA) was developed as a user-tunable system to leverage SNP information within databases. Using data within the 1000 Genomes Project SNP database, human genome regions were identified that contain globally ubiquitous identity-linked SNPs and that were responsive to targeted resequencing on MPS platforms. Algorithmic filters were used to exclude target regions that did not conform to user-tunable SNP island target characteristics. To validate the accuracy of TIA for discovering these identity-linked SNP islands within the human genome, SNP island target regions were amplified from 70 contributor genomic DNA samples using the polymerase chain reaction. Multiplexed amplicons were sequenced using the Illumina MiSeq platform, and the resulting sequences were analyzed for SNP variations. 166 putative identity-linked SNPs were targeted in the identified genomic regions. Of the 309 SNPs that provided discerning power across individual SNP profiles, 74 previously undefined SNPs were identified during evaluation of targets from individual genomes. Overall, DNA samples of 70 individuals were uniquely identified using a subset of the suite of identity-linked SNP islands. TIA offers a tunable genome search tool for the discovery of targeted genomic regions that are scalable in the population frequency and numbers of SNPs contained within the SNP island regions. It also allows the definition of sequence length and sequence variability of the target region as well as the less variable flanking regions for tailoring to MPS platforms. As shown in this study, TIA can be used to discover identity-linked SNP islands within the human genome, useful for differentiating individuals by targeted resequencing on MPS technologies.

Automatic Generation of OpenMP Directives and Its Application to Computational Fluid Dynamics Codes

NASA Technical Reports Server (NTRS)

Yan, Jerry; Jin, Haoqiang; Frumkin, Michael; Yan, Jerry (Technical Monitor)

2000-01-01

The shared-memory programming model is a very effective way to achieve parallelism on shared memory parallel computers. As great progress was made in hardware and software technologies, performance of parallel programs with compiler directives has demonstrated large improvement. The introduction of OpenMP directives, the industrial standard for shared-memory programming, has minimized the issue of portability. In this study, we have extended CAPTools, a computer-aided parallelization toolkit, to automatically generate OpenMP-based parallel programs with nominal user assistance. We outline techniques used in the implementation of the tool and discuss the application of this tool on the NAS Parallel Benchmarks and several computational fluid dynamics codes. This work demonstrates the great potential of using the tool to quickly port parallel programs and also achieve good performance that exceeds some of the commercial tools.

Explicit pre-training instruction does not improve implicit perceptual-motor sequence learning

PubMed Central

Sanchez, Daniel J.; Reber, Paul J.

2012-01-01

Memory systems theory argues for separate neural systems supporting implicit and explicit memory in the human brain. Neuropsychological studies support this dissociation, but empirical studies of cognitively healthy participants generally observe that both kinds of memory are acquired to at least some extent, even in implicit learning tasks. A key question is whether this observation reflects parallel intact memory systems or an integrated representation of memory in healthy participants. Learning of complex tasks in which both explicit instruction and practice is used depends on both kinds of memory, and how these systems interact will be an important component of the learning process. Theories that posit an integrated, or single, memory system for both types of memory predict that explicit instruction should contribute directly to strengthening task knowledge. In contrast, if the two types of memory are independent and acquired in parallel, explicit knowledge should have no direct impact and may serve in a “scaffolding” role in complex learning. Using an implicit perceptual-motor sequence learning task, the effect of explicit pre-training instruction on skill learning and performance was assessed. Explicit pre-training instruction led to robust explicit knowledge, but sequence learning did not benefit from the contribution of pre-training sequence memorization. The lack of an instruction benefit suggests that during skill learning, implicit and explicit memory operate independently. While healthy participants will generally accrue parallel implicit and explicit knowledge in complex tasks, these types of information appear to be separately represented in the human brain consistent with multiple memory systems theory. PMID:23280147

Methods for operating parallel computing systems employing sequenced communications

DOEpatents

Benner, R.E.; Gustafson, J.L.; Montry, G.R.

1999-08-10

A parallel computing system and method are disclosed having improved performance where a program is concurrently run on a plurality of nodes for reducing total processing time, each node having a processor, a memory, and a predetermined number of communication channels connected to the node and independently connected directly to other nodes. The present invention improves performance of the parallel computing system by providing a system which can provide efficient communication between the processors and between the system and input and output devices. A method is also disclosed which can locate defective nodes with the computing system. 15 figs.

Methods for operating parallel computing systems employing sequenced communications

DOEpatents

Benner, Robert E.; Gustafson, John L.; Montry, Gary R.

1999-01-01

A parallel computing system and method having improved performance where a program is concurrently run on a plurality of nodes for reducing total processing time, each node having a processor, a memory, and a predetermined number of communication channels connected to the node and independently connected directly to other nodes. The present invention improves performance of performance of the parallel computing system by providing a system which can provide efficient communication between the processors and between the system and input and output devices. A method is also disclosed which can locate defective nodes with the computing system.

Targeted next-generation sequencing in steroid-resistant nephrotic syndrome: mutations in multiple glomerular genes may influence disease severity.

PubMed

Bullich, Gemma; Trujillano, Daniel; Santín, Sheila; Ossowski, Stephan; Mendizábal, Santiago; Fraga, Gloria; Madrid, Álvaro; Ariceta, Gema; Ballarín, José; Torra, Roser; Estivill, Xavier; Ars, Elisabet

2015-09-01

Genetic diagnosis of steroid-resistant nephrotic syndrome (SRNS) using Sanger sequencing is complicated by the high genetic heterogeneity and phenotypic variability of this disease. We aimed to improve the genetic diagnosis of SRNS by simultaneously sequencing 26 glomerular genes using massive parallel sequencing and to study whether mutations in multiple genes increase disease severity. High-throughput mutation analysis was performed in 50 SRNS and/or focal segmental glomerulosclerosis (FSGS) patients, a validation cohort of 25 patients with known pathogenic mutations, and a discovery cohort of 25 uncharacterized patients with probable genetic etiology. In the validation cohort, we identified the 42 previously known pathogenic mutations across NPHS1, NPHS2, WT1, TRPC6, and INF2 genes. In the discovery cohort, disease-causing mutations in SRNS/FSGS genes were found in nine patients. We detected three patients with mutations in an SRNS/FSGS gene and COL4A3. Two of them were familial cases and presented a more severe phenotype than family members with mutation in only one gene. In conclusion, our results show that massive parallel sequencing is feasible and robust for genetic diagnosis of SRNS/FSGS. Our results indicate that patients carrying mutations in an SRNS/FSGS gene and also in COL4A3 gene have increased disease severity.

DeNovoGUI: An Open Source Graphical User Interface for de Novo Sequencing of Tandem Mass Spectra

PubMed Central

2013-01-01

De novo sequencing is a popular technique in proteomics for identifying peptides from tandem mass spectra without having to rely on a protein sequence database. Despite the strong potential of de novo sequencing algorithms, their adoption threshold remains quite high. We here present a user-friendly and lightweight graphical user interface called DeNovoGUI for running parallelized versions of the freely available de novo sequencing software PepNovo+, greatly simplifying the use of de novo sequencing in proteomics. Our platform-independent software is freely available under the permissible Apache2 open source license. Source code, binaries, and additional documentation are available at http://denovogui.googlecode.com. PMID:24295440

DeNovoGUI: an open source graphical user interface for de novo sequencing of tandem mass spectra.

PubMed

Muth, Thilo; Weilnböck, Lisa; Rapp, Erdmann; Huber, Christian G; Martens, Lennart; Vaudel, Marc; Barsnes, Harald

2014-02-07

De novo sequencing is a popular technique in proteomics for identifying peptides from tandem mass spectra without having to rely on a protein sequence database. Despite the strong potential of de novo sequencing algorithms, their adoption threshold remains quite high. We here present a user-friendly and lightweight graphical user interface called DeNovoGUI for running parallelized versions of the freely available de novo sequencing software PepNovo+, greatly simplifying the use of de novo sequencing in proteomics. Our platform-independent software is freely available under the permissible Apache2 open source license. Source code, binaries, and additional documentation are available at http://denovogui.googlecode.com .

An Integrated Approach to Locality-Conscious Processor Allocation and Scheduling of Mixed-Parallel Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vydyanathan, Naga; Krishnamoorthy, Sriram; Sabin, Gerald M.

2009-08-01

Complex parallel applications can often be modeled as directed acyclic graphs of coarse-grained application-tasks with dependences. These applications exhibit both task- and data-parallelism, and combining these two (also called mixedparallelism), has been shown to be an effective model for their execution. In this paper, we present an algorithm to compute the appropriate mix of task- and data-parallelism required to minimize the parallel completion time (makespan) of these applications. In other words, our algorithm determines the set of tasks that should be run concurrently and the number of processors to be allocated to each task. The processor allocation and scheduling decisionsmore » are made in an integrated manner and are based on several factors such as the structure of the taskgraph, the runtime estimates and scalability characteristics of the tasks and the inter-task data communication volumes. A locality conscious scheduling strategy is used to improve inter-task data reuse. Evaluation through simulations and actual executions of task graphs derived from real applications as well as synthetic graphs shows that our algorithm consistently generates schedules with lower makespan as compared to CPR and CPA, two previously proposed scheduling algorithms. Our algorithm also produces schedules that have lower makespan than pure taskand data-parallel schedules. For task graphs with known optimal schedules or lower bounds on the makespan, our algorithm generates schedules that are closer to the optima than other scheduling approaches.« less

Parallel evolution of the glycogen synthase 1 (muscle) gene Gys1 between Old World and New World fruit bats (Order: Chiroptera).

PubMed

Fang, Lu; Shen, Bin; Irwin, David M; Zhang, Shuyi

2014-10-01

Glycogen synthase, which catalyzes the synthesis of glycogen, is especially important for Old World (Pteropodidae) and New World (Phyllostomidae) fruit bats that ingest high-carbohydrate diets. Glycogen synthase 1, encoded by the Gys1 gene, is the glycogen synthase isozyme that functions in muscles. To determine whether Gys1 has undergone adaptive evolution in bats with carbohydrate-rich diets, in comparison to insect-eating sister bat taxa, we sequenced the coding region of the Gys1 gene from 10 species of bats, including two Old World fruit bats (Pteropodidae) and a New World fruit bat (Phyllostomidae). Our results show no evidence for positive selection in the Gys1 coding sequence on the ancestral Old World and the New World Artibeus lituratus branches. Tests for convergent evolution indicated convergence of the sequences and one parallel amino acid substitution (T395A) was detected on these branches, which was likely driven by natural selection.

A parallel implementation of the Wuchty algorithm with additional experimental filters to more thoroughly explore RNA conformational space.

PubMed

Stone, Jonathan W; Bleckley, Samuel; Lavelle, Sean; Schroeder, Susan J

2015-01-01

We present new modifications to the Wuchty algorithm in order to better define and explore possible conformations for an RNA sequence. The new features, including parallelization, energy-independent lonely pair constraints, context-dependent chemical probing constraints, helix filters, and optional multibranch loops, provide useful tools for exploring the landscape of RNA folding. Chemical probing alone may not necessarily define a single unique structure. The helix filters and optional multibranch loops are global constraints on RNA structure that are an especially useful tool for generating models of encapsidated viral RNA for which cryoelectron microscopy or crystallography data may be available. The computations generate a combinatorially complete set of structures near a free energy minimum and thus provide data on the density and diversity of structures near the bottom of a folding funnel for an RNA sequence. The conformational landscapes for some RNA sequences may resemble a low, wide basin rather than a steep funnel that converges to a single structure.

How challenges in auditory fMRI led to general advancements for the field.

PubMed

Talavage, Thomas M; Hall, Deborah A

2012-08-15

In the early years of fMRI research, the auditory neuroscience community sought to expand its knowledge of the underlying physiology of hearing, while also seeking to come to grips with the inherent acoustic disadvantages of working in the fMRI environment. Early collaborative efforts between prominent auditory research laboratories and prominent fMRI centers led to development of a number of key technical advances that have subsequently been widely used to elucidate principles of auditory neurophysiology. Perhaps the key imaging advance was the simultaneous and parallel development of strategies to use pulse sequences in which the volume acquisitions were "clustered," providing gaps in which stimuli could be presented without direct masking. Such sequences have become widespread in fMRI studies using auditory stimuli and also in a range of translational research domains. This review presents the parallel stories of the people and the auditory neurophysiology research that led to these sequences. Copyright © 2011 Elsevier Inc. All rights reserved.

Quantitative analysis of RNA-protein interactions on a massively parallel array for mapping biophysical and evolutionary landscapes

PubMed Central

Buenrostro, Jason D.; Chircus, Lauren M.; Araya, Carlos L.; Layton, Curtis J.; Chang, Howard Y.; Snyder, Michael P.; Greenleaf, William J.

2015-01-01

RNA-protein interactions drive fundamental biological processes and are targets for molecular engineering, yet quantitative and comprehensive understanding of the sequence determinants of affinity remains limited. Here we repurpose a high-throughput sequencing instrument to quantitatively measure binding and dissociation of MS2 coat protein to >107 RNA targets generated on a flow-cell surface by in situ transcription and inter-molecular tethering of RNA to DNA. We decompose the binding energy contributions from primary and secondary RNA structure, finding that differences in affinity are often driven by sequence-specific changes in association rates. By analyzing the biophysical constraints and modeling mutational paths describing the molecular evolution of MS2 from low- to high-affinity hairpins, we quantify widespread molecular epistasis, and a long-hypothesized structure-dependent preference for G:U base pairs over C:A intermediates in evolutionary trajectories. Our results suggest that quantitative analysis of RNA on a massively parallel array (RNAMaP) relationships across molecular variants. PMID:24727714

Cache-Oblivious parallel SIMD Viterbi decoding for sequence search in HMMER.

PubMed

Ferreira, Miguel; Roma, Nuno; Russo, Luis M S

2014-05-30

HMMER is a commonly used bioinformatics tool based on Hidden Markov Models (HMMs) to analyze and process biological sequences. One of its main homology engines is based on the Viterbi decoding algorithm, which was already highly parallelized and optimized using Farrar's striped processing pattern with Intel SSE2 instruction set extension. A new SIMD vectorization of the Viterbi decoding algorithm is proposed, based on an SSE2 inter-task parallelization approach similar to the DNA alignment algorithm proposed by Rognes. Besides this alternative vectorization scheme, the proposed implementation also introduces a new partitioning of the Markov model that allows a significantly more efficient exploitation of the cache locality. Such optimization, together with an improved loading of the emission scores, allows the achievement of a constant processing throughput, regardless of the innermost-cache size and of the dimension of the considered model. The proposed optimized vectorization of the Viterbi decoding algorithm was extensively evaluated and compared with the HMMER3 decoder to process DNA and protein datasets, proving to be a rather competitive alternative implementation. Being always faster than the already highly optimized ViterbiFilter implementation of HMMER3, the proposed Cache-Oblivious Parallel SIMD Viterbi (COPS) implementation provides a constant throughput and offers a processing speedup as high as two times faster, depending on the model's size.

pWeb: A High-Performance, Parallel-Computing Framework for Web-Browser-Based Medical Simulation.

PubMed

Halic, Tansel; Ahn, Woojin; De, Suvranu

2014-01-01

This work presents a pWeb - a new language and compiler for parallelization of client-side compute intensive web applications such as surgical simulations. The recently introduced HTML5 standard has enabled creating unprecedented applications on the web. Low performance of the web browser, however, remains the bottleneck of computationally intensive applications including visualization of complex scenes, real time physical simulations and image processing compared to native ones. The new proposed language is built upon web workers for multithreaded programming in HTML5. The language provides fundamental functionalities of parallel programming languages as well as the fork/join parallel model which is not supported by web workers. The language compiler automatically generates an equivalent parallel script that complies with the HTML5 standard. A case study on realistic rendering for surgical simulations demonstrates enhanced performance with a compact set of instructions.

The glycogen synthase 2 gene (Gys2) displays parallel evolution between Old World and New World fruit bats.

PubMed

Qian, Yamin; Fang, Tao; Shen, Bin; Zhang, Shuyi

2014-01-01

Frugivorous and nectarivorous bats rely largely on hepatic glycogenesis and glycogenolysis for postprandial blood glucose disposal and maintenance of glucose homeostasis during short time starvation, respectively. The glycogen synthase 2 encoded by the Gys2 gene plays a critical role in liver glycogen synthesis. To test whether the Gys2 gene has undergone adaptive evolution in bats with carbohydrate-rich diets in relation to their insect-eating sister taxa, we sequenced the coding region of the Gys2 gene in a number of bat species, including three Old World fruit bats (OWFBs) (Pteropodidae) and two New World fruit bats (NWFBs) (Phyllostomidae). Our results showed that the Gys2 coding sequences are highly conserved across all bat species we examined, and no evidence of positive selection was detected in the ancestral branches leading to OWFBs and NWFBs. Our explicit convergence test showed that posterior probabilities of convergence between several branches of OWFBs, and the NWFBs were markedly higher than that of divergence. Three parallel amino acid substitutions (Q72H, K371Q, and E666D) were detected among branches of OWFBs and NWFBs. Tests for parallel evolution showed that two parallel substitutions (Q72H and E666D) were driven by natural selection, while the K371Q was more likely to be fixed randomly. Thus, our results suggested that the Gys2 gene has undergone parallel evolution on amino acid level between OWFBs and NWFBs in relation to their carbohydrate metabolism.

The NAS parallel benchmarks

NASA Technical Reports Server (NTRS)

Bailey, D. H.; Barszcz, E.; Barton, J. T.; Carter, R. L.; Lasinski, T. A.; Browning, D. S.; Dagum, L.; Fatoohi, R. A.; Frederickson, P. O.; Schreiber, R. S.

1991-01-01

A new set of benchmarks has been developed for the performance evaluation of highly parallel supercomputers in the framework of the NASA Ames Numerical Aerodynamic Simulation (NAS) Program. These consist of five 'parallel kernel' benchmarks and three 'simulated application' benchmarks. Together they mimic the computation and data movement characteristics of large-scale computational fluid dynamics applications. The principal distinguishing feature of these benchmarks is their 'pencil and paper' specification-all details of these benchmarks are specified only algorithmically. In this way many of the difficulties associated with conventional benchmarking approaches on highly parallel systems are avoided.

Representing motion in a static image: constraints and parallels in art, science, and popular culture.

PubMed

Cutting, James E

2002-01-01

Representing motion in a picture is a challenge to artists, scientists, and all other imagemakers. Moreover, it presents a problem that will not go away with electronic and digital media, because often the pedagogical purpose of the representation of motion is more important than the motion itself. All satisfactory solutions evoke motion-for example, dynamic balance (or broken symmetry), stroboscopic sequences, affine shear (or forward lean), and photographic blur-but they also typically sacrifice the accuracy of the motion represented, a solution often unsuitable for science. Vector representations superimposed on static images allow for accuracy, but are not applicable to all situations. Workable solutions are almost certainly case specific and subject to continual evolution through exploration by imagemakers.

The Automatic Parallelisation of Scientific Application Codes Using a Computer Aided Parallelisation Toolkit

NASA Technical Reports Server (NTRS)

Ierotheou, C.; Johnson, S.; Leggett, P.; Cross, M.; Evans, E.; Jin, Hao-Qiang; Frumkin, M.; Yan, J.; Biegel, Bryan (Technical Monitor)

2001-01-01

The shared-memory programming model is a very effective way to achieve parallelism on shared memory parallel computers. Historically, the lack of a programming standard for using directives and the rather limited performance due to scalability have affected the take-up of this programming model approach. Significant progress has been made in hardware and software technologies, as a result the performance of parallel programs with compiler directives has also made improvements. The introduction of an industrial standard for shared-memory programming with directives, OpenMP, has also addressed the issue of portability. In this study, we have extended the computer aided parallelization toolkit (developed at the University of Greenwich), to automatically generate OpenMP based parallel programs with nominal user assistance. We outline the way in which loop types are categorized and how efficient OpenMP directives can be defined and placed using the in-depth interprocedural analysis that is carried out by the toolkit. We also discuss the application of the toolkit on the NAS Parallel Benchmarks and a number of real-world application codes. This work not only demonstrates the great potential of using the toolkit to quickly parallelize serial programs but also the good performance achievable on up to 300 processors for hybrid message passing and directive-based parallelizations.

Optimizing Illumina next-generation sequencing library preparation for extremely AT-biased genomes.

PubMed

Oyola, Samuel O; Otto, Thomas D; Gu, Yong; Maslen, Gareth; Manske, Magnus; Campino, Susana; Turner, Daniel J; Macinnis, Bronwyn; Kwiatkowski, Dominic P; Swerdlow, Harold P; Quail, Michael A

2012-01-03

Massively parallel sequencing technology is revolutionizing approaches to genomic and genetic research. Since its advent, the scale and efficiency of Next-Generation Sequencing (NGS) has rapidly improved. In spite of this success, sequencing genomes or genomic regions with extremely biased base composition is still a great challenge to the currently available NGS platforms. The genomes of some important pathogenic organisms like Plasmodium falciparum (high AT content) and Mycobacterium tuberculosis (high GC content) display extremes of base composition. The standard library preparation procedures that employ PCR amplification have been shown to cause uneven read coverage particularly across AT and GC rich regions, leading to problems in genome assembly and variation analyses. Alternative library-preparation approaches that omit PCR amplification require large quantities of starting material and hence are not suitable for small amounts of DNA/RNA such as those from clinical isolates. We have developed and optimized library-preparation procedures suitable for low quantity starting material and tolerant to extremely high AT content sequences. We have used our optimized conditions in parallel with standard methods to prepare Illumina sequencing libraries from a non-clinical and a clinical isolate (containing ~53% host contamination). By analyzing and comparing the quality of sequence data generated, we show that our optimized conditions that involve a PCR additive (TMAC), produces amplified libraries with improved coverage of extremely AT-rich regions and reduced bias toward GC neutral templates. We have developed a robust and optimized Next-Generation Sequencing library amplification method suitable for extremely AT-rich genomes. The new amplification conditions significantly reduce bias and retain the complexity of either extremes of base composition. This development will greatly benefit sequencing clinical samples that often require amplification due to low mass of DNA starting material.

Automatic Management of Parallel and Distributed System Resources

NASA Technical Reports Server (NTRS)

Yan, Jerry; Ngai, Tin Fook; Lundstrom, Stephen F.

1990-01-01

Viewgraphs on automatic management of parallel and distributed system resources are presented. Topics covered include: parallel applications; intelligent management of multiprocessing systems; performance evaluation of parallel architecture; dynamic concurrent programs; compiler-directed system approach; lattice gaseous cellular automata; and sparse matrix Cholesky factorization.

Design of universal parallel-transmit refocusing kT -point pulses and application to 3D T2 -weighted imaging at 7T.

PubMed

Gras, Vincent; Mauconduit, Franck; Vignaud, Alexandre; Amadon, Alexis; Le Bihan, Denis; Stöcker, Tony; Boulant, Nicolas

2018-07-01

T 2 -weighted sequences are particularly sensitive to the radiofrequency (RF) field inhomogeneity problem at ultra-high-field because of the errors accumulated by the imperfections of the train of refocusing pulses. As parallel transmission (pTx) has proved particularly useful to counteract RF heterogeneities, universal pulses were recently demonstrated to save precious time and computational efforts by skipping B 1 calibration and online RF pulse tailoring. Here, we report a universal RF pulse design for non-selective refocusing pulses to mitigate the RF inhomogeneity problem at 7T in turbo spin-echo sequences with variable flip angles. Average Hamiltonian theory was used to synthetize a single non-selective refocusing pulse with pTx while optimizing its scaling properties in the presence of static field offsets. The design was performed under explicit power and specific absorption rate constraints on a database of 10 subjects using a 8Tx-32Rx commercial coil at 7T. To validate the proposed design, the RF pulses were tested in simulation and applied in vivo on 5 additional test subjects. The root-mean-square rotation angle error (RA-NRMSE) evaluation and experimental data demonstrated great improvement with the proposed universal pulses (RA-NRMSE ∼8%) compared to the standard circularly polarized mode of excitation (RA-NRMSE ∼26%). This work further completes the spectrum of 3D universal pulses to mitigate RF field inhomogeneity throughout all 3D MRI sequences without any pTx calibration. The approach returns a single pulse that can be scaled to match the desired flip angle train, thereby increasing the modularity of the proposed plug and play approach. Magn Reson Med 80:53-65, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Adaptive MCMC in Bayesian phylogenetics: an application to analyzing partitioned data in BEAST.

PubMed

Baele, Guy; Lemey, Philippe; Rambaut, Andrew; Suchard, Marc A

2017-06-15

Advances in sequencing technology continue to deliver increasingly large molecular sequence datasets that are often heavily partitioned in order to accurately model the underlying evolutionary processes. In phylogenetic analyses, partitioning strategies involve estimating conditionally independent models of molecular evolution for different genes and different positions within those genes, requiring a large number of evolutionary parameters that have to be estimated, leading to an increased computational burden for such analyses. The past two decades have also seen the rise of multi-core processors, both in the central processing unit (CPU) and Graphics processing unit processor markets, enabling massively parallel computations that are not yet fully exploited by many software packages for multipartite analyses. We here propose a Markov chain Monte Carlo (MCMC) approach using an adaptive multivariate transition kernel to estimate in parallel a large number of parameters, split across partitioned data, by exploiting multi-core processing. Across several real-world examples, we demonstrate that our approach enables the estimation of these multipartite parameters more efficiently than standard approaches that typically use a mixture of univariate transition kernels. In one case, when estimating the relative rate parameter of the non-coding partition in a heterochronous dataset, MCMC integration efficiency improves by > 14-fold. Our implementation is part of the BEAST code base, a widely used open source software package to perform Bayesian phylogenetic inference. guy.baele@kuleuven.be. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

FPGA accelerator for protein secondary structure prediction based on the GOR algorithm

PubMed Central

2011-01-01

Background Protein is an important molecule that performs a wide range of functions in biological systems. Recently, the protein folding attracts much more attention since the function of protein can be generally derived from its molecular structure. The GOR algorithm is one of the most successful computational methods and has been widely used as an efficient analysis tool to predict secondary structure from protein sequence. However, the execution time is still intolerable with the steep growth in protein database. Recently, FPGA chips have emerged as one promising application accelerator to accelerate bioinformatics algorithms by exploiting fine-grained custom design. Results In this paper, we propose a complete fine-grained parallel hardware implementation on FPGA to accelerate the GOR-IV package for 2D protein structure prediction. To improve computing efficiency, we partition the parameter table into small segments and access them in parallel. We aggressively exploit data reuse schemes to minimize the need for loading data from external memory. The whole computation structure is carefully pipelined to overlap the sequence loading, computing and back-writing operations as much as possible. We implemented a complete GOR desktop system based on an FPGA chip XC5VLX330. Conclusions The experimental results show a speedup factor of more than 430x over the original GOR-IV version and 110x speedup over the optimized version with multi-thread SIMD implementation running on a PC platform with AMD Phenom 9650 Quad CPU for 2D protein structure prediction. However, the power consumption is only about 30% of that of current general-propose CPUs. PMID:21342582

Scaling bioinformatics applications on HPC.

PubMed

Mikailov, Mike; Luo, Fu-Jyh; Barkley, Stuart; Valleru, Lohit; Whitney, Stephen; Liu, Zhichao; Thakkar, Shraddha; Tong, Weida; Petrick, Nicholas

2017-12-28

Recent breakthroughs in molecular biology and next generation sequencing technologies have led to the expenential growh of the sequence databases. Researchrs use BLAST for processing these sequences. However traditional software parallelization techniques (threads, message passing interface) applied in newer versios of BLAST are not adequate for processing these sequences in timely manner. A new method for array job parallelization has been developed which offers O(T) theoretical speed-up in comparison to multi-threading and MPI techniques. Here T is the number of array job tasks. (The number of CPUs that will be used to complete the job equals the product of T multiplied by the number of CPUs used by a single task.) The approach is based on segmentation of both input datasets to the BLAST process, combining partial solutions published earlier (Dhanker and Gupta, Int J Comput Sci Inf Technol_5:4818-4820, 2014), (Grant et al., Bioinformatics_18:765-766, 2002), (Mathog, Bioinformatics_19:1865-1866, 2003). It is accordingly referred to as a "dual segmentation" method. In order to implement the new method, the BLAST source code was modified to allow the researcher to pass to the program the number of records (effective number of sequences) in the original database. The team also developed methods to manage and consolidate the large number of partial results that get produced. Dual segmentation allows for massive parallelization, which lifts the scaling ceiling in exciting ways. BLAST jobs that hitherto failed or slogged inefficiently to completion now finish with speeds that characteristically reduce wallclock time from 27 days on 40 CPUs to a single day using 4104 tasks, each task utilizing eight CPUs and taking less than 7 minutes to complete. The massive increase in the number of tasks when running an analysis job with dual segmentation reduces the size, scope and execution time of each task. Besides significant speed of completion, additional benefits include fine-grained checkpointing and increased flexibility of job submission. "Trickling in" a swarm of individual small tasks tempers competition for CPU time in the shared HPC environment, and jobs submitted during quiet periods can complete in extraordinarily short time frames. The smaller task size also allows the use of older and less powerful hardware. The CDRH workhorse cluster was commissioned in 2010, yet its eight-core CPUs with only 24GB RAM work well in 2017 for these dual segmentation jobs. Finally, these techniques are excitingly friendly to budget conscious scientific research organizations where probabilistic algorithms such as BLAST might discourage attempts at greater certainty because single runs represent a major resource drain. If a job that used to take 24 days can now be completed in less than an hour or on a space available basis (which is the case at CDRH), repeated runs for more exhaustive analyses can be usefully contemplated.

Execution of parallel algorithms on a heterogeneous multicomputer

NASA Astrophysics Data System (ADS)

Isenstein, Barry S.; Greene, Jonathon

1995-04-01

Many aerospace/defense sensing and dual-use applications require high-performance computing, extensive high-bandwidth interconnect and realtime deterministic operation. This paper will describe the architecture of a scalable multicomputer that includes DSP and RISC processors. A single chassis implementation is capable of delivering in excess of 10 GFLOPS of DSP processing power with 2 Gbytes/s of realtime sensor I/O. A software approach to implementing parallel algorithms called the Parallel Application System (PAS) is also presented. An example of applying PAS to a DSP application is shown.

Dynamic load balancing of applications

DOEpatents

Wheat, Stephen R.

1997-01-01

An application-level method for dynamically maintaining global load balance on a parallel computer, particularly on massively parallel MIMD computers. Global load balancing is achieved by overlapping neighborhoods of processors, where each neighborhood performs local load balancing. The method supports a large class of finite element and finite difference based applications and provides an automatic element management system to which applications are easily integrated.

Characterizing parallel file-access patterns on a large-scale multiprocessor

NASA Technical Reports Server (NTRS)

Purakayastha, A.; Ellis, Carla; Kotz, David; Nieuwejaar, Nils; Best, Michael L.

1995-01-01

High-performance parallel file systems are needed to satisfy tremendous I/O requirements of parallel scientific applications. The design of such high-performance parallel file systems depends on a comprehensive understanding of the expected workload, but so far there have been very few usage studies of multiprocessor file systems. This paper is part of the CHARISMA project, which intends to fill this void by measuring real file-system workloads on various production parallel machines. In particular, we present results from the CM-5 at the National Center for Supercomputing Applications. Our results are unique because we collect information about nearly every individual I/O request from the mix of jobs running on the machine. Analysis of the traces leads to various recommendations for parallel file-system design.

Architecture-Adaptive Computing Environment: A Tool for Teaching Parallel Programming

NASA Technical Reports Server (NTRS)

Dorband, John E.; Aburdene, Maurice F.

2002-01-01

Recently, networked and cluster computation have become very popular. This paper is an introduction to a new C based parallel language for architecture-adaptive programming, aCe C. The primary purpose of aCe (Architecture-adaptive Computing Environment) is to encourage programmers to implement applications on parallel architectures by providing them the assurance that future architectures will be able to run their applications with a minimum of modification. A secondary purpose is to encourage computer architects to develop new types of architectures by providing an easily implemented software development environment and a library of test applications. This new language should be an ideal tool to teach parallel programming. In this paper, we will focus on some fundamental features of aCe C.

Parallel Computation of the Jacobian Matrix for Nonlinear Equation Solvers Using MATLAB

NASA Technical Reports Server (NTRS)

Rose, Geoffrey K.; Nguyen, Duc T.; Newman, Brett A.

2017-01-01

Demonstrating speedup for parallel code on a multicore shared memory PC can be challenging in MATLAB due to underlying parallel operations that are often opaque to the user. This can limit potential for improvement of serial code even for the so-called embarrassingly parallel applications. One such application is the computation of the Jacobian matrix inherent to most nonlinear equation solvers. Computation of this matrix represents the primary bottleneck in nonlinear solver speed such that commercial finite element (FE) and multi-body-dynamic (MBD) codes attempt to minimize computations. A timing study using MATLAB's Parallel Computing Toolbox was performed for numerical computation of the Jacobian. Several approaches for implementing parallel code were investigated while only the single program multiple data (spmd) method using composite objects provided positive results. Parallel code speedup is demonstrated but the goal of linear speedup through the addition of processors was not achieved due to PC architecture.

Parallelization of ARC3D with Computer-Aided Tools

NASA Technical Reports Server (NTRS)

Jin, Haoqiang; Hribar, Michelle; Yan, Jerry; Saini, Subhash (Technical Monitor)

1998-01-01

A series of efforts have been devoted to investigating methods of porting and parallelizing applications quickly and efficiently for new architectures, such as the SCSI Origin 2000 and Cray T3E. This report presents the parallelization of a CFD application, ARC3D, using the computer-aided tools, Cesspools. Steps of parallelizing this code and requirements of achieving better performance are discussed. The generated parallel version has achieved reasonably well performance, for example, having a speedup of 30 for 36 Cray T3E processors. However, this performance could not be obtained without modification of the original serial code. It is suggested that in many cases improving serial code and performing necessary code transformations are important parts for the automated parallelization process although user intervention in many of these parts are still necessary. Nevertheless, development and improvement of useful software tools, such as Cesspools, can help trim down many tedious parallelization details and improve the processing efficiency.

A massively parallel strategy for STR marker development, capture, and genotyping.

PubMed

Kistler, Logan; Johnson, Stephen M; Irwin, Mitchell T; Louis, Edward E; Ratan, Aakrosh; Perry, George H

2017-09-06

Short tandem repeat (STR) variants are highly polymorphic markers that facilitate powerful population genetic analyses. STRs are especially valuable in conservation and ecological genetic research, yielding detailed information on population structure and short-term demographic fluctuations. Massively parallel sequencing has not previously been leveraged for scalable, efficient STR recovery. Here, we present a pipeline for developing STR markers directly from high-throughput shotgun sequencing data without a reference genome, and an approach for highly parallel target STR recovery. We employed our approach to capture a panel of 5000 STRs from a test group of diademed sifakas (Propithecus diadema, n = 3), endangered Malagasy rainforest lemurs, and we report extremely efficient recovery of targeted loci-97.3-99.6% of STRs characterized with ≥10x non-redundant sequence coverage. We then tested our STR capture strategy on P. diadema fecal DNA, and report robust initial results and suggestions for future implementations. In addition to STR targets, this approach also generates large, genome-wide single nucleotide polymorphism (SNP) panels from flanking regions. Our method provides a cost-effective and scalable solution for rapid recovery of large STR and SNP datasets in any species without needing a reference genome, and can be used even with suboptimal DNA more easily acquired in conservation and ecological studies. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

Parallel tagged next-generation sequencing on pooled samples - a new approach for population genetics in ecology and conservation.

PubMed

Zavodna, Monika; Grueber, Catherine E; Gemmell, Neil J

2013-01-01

Next-generation sequencing (NGS) on pooled samples has already been broadly applied in human medical diagnostics and plant and animal breeding. However, thus far it has been only sparingly employed in ecology and conservation, where it may serve as a useful diagnostic tool for rapid assessment of species genetic diversity and structure at the population level. Here we undertake a comprehensive evaluation of the accuracy, practicality and limitations of parallel tagged amplicon NGS on pooled population samples for estimating species population diversity and structure. We obtained 16S and Cyt b data from 20 populations of Leiopelma hochstetteri, a frog species of conservation concern in New Zealand, using two approaches - parallel tagged NGS on pooled population samples and individual Sanger sequenced samples. Data from each approach were then used to estimate two standard population genetic parameters, nucleotide diversity (π) and population differentiation (FST), that enable population genetic inference in a species conservation context. We found a positive correlation between our two approaches for population genetic estimates, showing that the pooled population NGS approach is a reliable, rapid and appropriate method for population genetic inference in an ecological and conservation context. Our experimental design also allowed us to identify both the strengths and weaknesses of the pooled population NGS approach and outline some guidelines and suggestions that might be considered when planning future projects.

Population genomics of parallel hybrid zones in the mimetic butterflies, H. melpomene and H. erato

PubMed Central

Ruiz, Mayté; Salazar, Patricio; Counterman, Brian; Medina, Jose Alejandro; Ortiz-Zuazaga, Humberto; Morrison, Anna; Papa, Riccardo

2014-01-01

Hybrid zones can be valuable tools for studying evolution and identifying genomic regions responsible for adaptive divergence and underlying phenotypic variation. Hybrid zones between subspecies of Heliconius butterflies can be very narrow and are maintained by strong selection acting on color pattern. The comimetic species, H. erato and H. melpomene, have parallel hybrid zones in which both species undergo a change from one color pattern form to another. We use restriction-associated DNA sequencing to obtain several thousand genome-wide sequence markers and use these to analyze patterns of population divergence across two pairs of parallel hybrid zones in Peru and Ecuador. We compare two approaches for analysis of this type of data—alignment to a reference genome and de novo assembly—and find that alignment gives the best results for species both closely (H. melpomene) and distantly (H. erato, ∼15% divergent) related to the reference sequence. Our results confirm that the color pattern controlling loci account for the majority of divergent regions across the genome, but we also detect other divergent regions apparently unlinked to color pattern differences. We also use association mapping to identify previously unmapped color pattern loci, in particular the Ro locus. Finally, we identify a new cryptic population of H. timareta in Ecuador, which occurs at relatively low altitude and is mimetic with H. melpomene malleti. PMID:24823669

Fast parallel tandem mass spectral library searching using GPU hardware acceleration

PubMed Central

Baumgardner, Lydia Ashleigh; Shanmugam, Avinash Kumar; Lam, Henry; Eng, Jimmy K.; Martin, Daniel B.

2011-01-01

Mass spectrometry-based proteomics is a maturing discipline of biologic research that is experiencing substantial growth. Instrumentation has steadily improved over time with the advent of faster and more sensitive instruments collecting ever larger data files. Consequently, the computational process of matching a peptide fragmentation pattern to its sequence, traditionally accomplished by sequence database searching and more recently also by spectral library searching, has become a bottleneck in many mass spectrometry experiments. In both of these methods, the main rate limiting step is the comparison of an acquired spectrum with all potential matches from a spectral library or sequence database. This is a highly parallelizable process because the core computational element can be represented as a simple but arithmetically intense multiplication of two vectors. In this paper we present a proof of concept project taking advantage of the massively parallel computing available on graphics processing units (GPUs) to distribute and accelerate the process of spectral assignment using spectral library searching. This program, which we have named FastPaSS (for Fast Parallelized Spectral Searching) is implemented in CUDA (Compute Unified Device Architecture) from NVIDIA which allows direct access to the processors in an NVIDIA GPU. Our efforts demonstrate the feasibility of GPU computing for spectral assignment, through implementation of the validated spectral searching algorithm SpectraST in the CUDA environment. PMID:21545112

Application of a hybrid MPI/OpenMP approach for parallel groundwater model calibration using multi-core computers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Guoping; D'Azevedo, Ed F; Zhang, Fan

2010-01-01

Calibration of groundwater models involves hundreds to thousands of forward solutions, each of which may solve many transient coupled nonlinear partial differential equations, resulting in a computationally intensive problem. We describe a hybrid MPI/OpenMP approach to exploit two levels of parallelisms in software and hardware to reduce calibration time on multi-core computers. HydroGeoChem 5.0 (HGC5) is parallelized using OpenMP for direct solutions for a reactive transport model application, and a field-scale coupled flow and transport model application. In the reactive transport model, a single parallelizable loop is identified to account for over 97% of the total computational time using GPROF.more » Addition of a few lines of OpenMP compiler directives to the loop yields a speedup of about 10 on a 16-core compute node. For the field-scale model, parallelizable loops in 14 of 174 HGC5 subroutines that require 99% of the execution time are identified. As these loops are parallelized incrementally, the scalability is found to be limited by a loop where Cray PAT detects over 90% cache missing rates. With this loop rewritten, similar speedup as the first application is achieved. The OpenMP-parallelized code can be run efficiently on multiple workstations in a network or multiple compute nodes on a cluster as slaves using parallel PEST to speedup model calibration. To run calibration on clusters as a single task, the Levenberg Marquardt algorithm is added to HGC5 with the Jacobian calculation and lambda search parallelized using MPI. With this hybrid approach, 100 200 compute cores are used to reduce the calibration time from weeks to a few hours for these two applications. This approach is applicable to most of the existing groundwater model codes for many applications.« less

Parallel sites implicate functional convergence of the hearing gene prestin among echolocating mammals.

PubMed

Liu, Zhen; Qi, Fei-Yan; Zhou, Xin; Ren, Hai-Qing; Shi, Peng

2014-09-01

Echolocation is a sensory system whereby certain mammals navigate and forage using sound waves, usually in environments where visibility is limited. Curiously, echolocation has evolved independently in bats and whales, which occupy entirely different environments. Based on this phenotypic convergence, recent studies identified several echolocation-related genes with parallel sites at the protein sequence level among different echolocating mammals, and among these, prestin seems the most promising. Although previous studies analyzed the evolutionary mechanism of prestin, the functional roles of the parallel sites in the evolution of mammalian echolocation are not clear. By functional assays, we show that a key parameter of prestin function, 1/α, is increased in all echolocating mammals and that the N7T parallel substitution accounted for this functional convergence. Moreover, another parameter, V1/2, was shifted toward the depolarization direction in a toothed whale, the bottlenose dolphin (Tursiops truncatus) and a constant-frequency (CF) bat, the Stoliczka's trident bat (Aselliscus stoliczkanus). The parallel site of I384T between toothed whales and CF bats was responsible for this functional convergence. Furthermore, the two parameters (1/α and V1/2) were correlated with mammalian high-frequency hearing, suggesting that the convergent changes of the prestin function in echolocating mammals may play important roles in mammalian echolocation. To our knowledge, these findings present the functional patterns of echolocation-related genes in echolocating mammals for the first time and rigorously demonstrate adaptive parallel evolution at the protein sequence level, paving the way to insights into the molecular mechanism underlying mammalian echolocation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficient Synthesis of γ-Lactams by a Tandem Reductive Amination/Lactamization Sequence

PubMed Central

Nöth, Julica; Frankowski, Kevin J.; Neuenswander, Benjamin; Aubé, Jeffrey; Reiser, Oliver

2009-01-01

A three-component method for synthesizing highly-substituted γ-lactams from readily available maleimides, aldehydes and amines is described. A new reductive amination/intramolecular lactamization sequence provides a straightforward route to the lactam products in a single manipulation. The general utility of this method is demonstrated by the parallel synthesis of a γ-lactam library. PMID:18338857

Efficient synthesis of gamma-lactams by a tandem reductive amination/lactamization sequence.

PubMed

Nöth, Julica; Frankowski, Kevin J; Neuenswander, Benjamin; Aubé, Jeffrey; Reiser, Oliver

2008-01-01

A three-component method for the synthesis of highly substituted gamma-lactams from readily available maleimides, aldehydes, and amines is described. A new reductive amination/intramolecular lactamization sequence provides a straightforward route to the lactam products in a single manipulation. The general utility of this method is demonstrated by the parallel synthesis of a gamma-lactam library.

Efficient Machine Learning Approach for Optimizing Scientific Computing Applications on Emerging HPC Architectures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arumugam, Kamesh

Efficient parallel implementations of scientific applications on multi-core CPUs with accelerators such as GPUs and Xeon Phis is challenging. This requires - exploiting the data parallel architecture of the accelerator along with the vector pipelines of modern x86 CPU architectures, load balancing, and efficient memory transfer between different devices. It is relatively easy to meet these requirements for highly structured scientific applications. In contrast, a number of scientific and engineering applications are unstructured. Getting performance on accelerators for these applications is extremely challenging because many of these applications employ irregular algorithms which exhibit data-dependent control-ow and irregular memory accesses. Furthermore,more » these applications are often iterative with dependency between steps, and thus making it hard to parallelize across steps. As a result, parallelism in these applications is often limited to a single step. Numerical simulation of charged particles beam dynamics is one such application where the distribution of work and memory access pattern at each time step is irregular. Applications with these properties tend to present significant branch and memory divergence, load imbalance between different processor cores, and poor compute and memory utilization. Prior research on parallelizing such irregular applications have been focused around optimizing the irregular, data-dependent memory accesses and control-ow during a single step of the application independent of the other steps, with the assumption that these patterns are completely unpredictable. We observed that the structure of computation leading to control-ow divergence and irregular memory accesses in one step is similar to that in the next step. It is possible to predict this structure in the current step by observing the computation structure of previous steps. In this dissertation, we present novel machine learning based optimization techniques to address the parallel implementation challenges of such irregular applications on different HPC architectures. In particular, we use supervised learning to predict the computation structure and use it to address the control-ow and memory access irregularities in the parallel implementation of such applications on GPUs, Xeon Phis, and heterogeneous architectures composed of multi-core CPUs with GPUs or Xeon Phis. We use numerical simulation of charged particles beam dynamics simulation as a motivating example throughout the dissertation to present our new approach, though they should be equally applicable to a wide range of irregular applications. The machine learning approach presented here use predictive analytics and forecasting techniques to adaptively model and track the irregular memory access pattern at each time step of the simulation to anticipate the future memory access pattern. Access pattern forecasts can then be used to formulate optimization decisions during application execution which improves the performance of the application at a future time step based on the observations from earlier time steps. In heterogeneous architectures, forecasts can also be used to improve the memory performance and resource utilization of all the processing units to deliver a good aggregate performance. We used these optimization techniques and anticipation strategy to design a cache-aware, memory efficient parallel algorithm to address the irregularities in the parallel implementation of charged particles beam dynamics simulation on different HPC architectures. Experimental result using a diverse mix of HPC architectures shows that our approach in using anticipation strategy is effective in maximizing data reuse, ensuring workload balance, minimizing branch and memory divergence, and in improving resource utilization.« less

Massively parallel sequencing-enabled mixture analysis of mitochondrial DNA samples.

PubMed

Churchill, Jennifer D; Stoljarova, Monika; King, Jonathan L; Budowle, Bruce

2018-02-22

The mitochondrial genome has a number of characteristics that provide useful information to forensic investigations. Massively parallel sequencing (MPS) technologies offer improvements to the quantitative analysis of the mitochondrial genome, specifically the interpretation of mixed mitochondrial samples. Two-person mixtures with nuclear DNA ratios of 1:1, 5:1, 10:1, and 20:1 of individuals from different and similar phylogenetic backgrounds and three-person mixtures with nuclear DNA ratios of 1:1:1 and 5:1:1 were prepared using the Precision ID mtDNA Whole Genome Panel and Ion Chef, and sequenced on the Ion PGM or Ion S5 sequencer (Thermo Fisher Scientific, Waltham, MA, USA). These data were used to evaluate whether and to what degree MPS mixtures could be deconvolved. Analysis was effective in identifying the major contributor in each instance, while SNPs from the minor contributor's haplotype only were identified in the 1:1, 5:1, and 10:1 two-person mixtures. While the major contributor was identified from the 5:1:1 mixture, analysis of the three-person mixtures was more complex, and the mixed haplotypes could not be completely parsed. These results indicate that mixed mitochondrial DNA samples may be interpreted with the use of MPS technologies.

Massively parallel rRNA gene sequencing exacerbates the potential for biased community diversity comparisons due to variable library sizes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gihring, Thomas; Green, Stefan; Schadt, Christopher Warren

2011-01-01

Technologies for massively parallel sequencing are revolutionizing microbial ecology and are vastly increasing the scale of ribosomal RNA (rRNA) gene studies. Although pyrosequencing has increased the breadth and depth of possible rRNA gene sampling, one drawback is that the number of reads obtained per sample is difficult to control. Pyrosequencing libraries typically vary widely in the number of sequences per sample, even within individual studies, and there is a need to revisit the behaviour of richness estimators and diversity indices with variable gene sequence library sizes. Multiple reports and review papers have demonstrated the bias in non-parametric richness estimators (e.g.more » Chao1 and ACE) and diversity indices when using clone libraries. However, we found that biased community comparisons are accumulating in the literature. Here we demonstrate the effects of sample size on Chao1, ACE, CatchAll, Shannon, Chao-Shen and Simpson's estimations specifically using pyrosequencing libraries. The need to equalize the number of reads being compared across libraries is reiterated, and investigators are directed towards available tools for making unbiased diversity comparisons.« less

Applications of New Surrogate Global Optimization Algorithms including Efficient Synchronous and Asynchronous Parallelism for Calibration of Expensive Nonlinear Geophysical Simulation Models.

NASA Astrophysics Data System (ADS)

Shoemaker, C. A.; Pang, M.; Akhtar, T.; Bindel, D.

2016-12-01

New parallel surrogate global optimization algorithms are developed and applied to objective functions that are expensive simulations (possibly with multiple local minima). The algorithms can be applied to most geophysical simulations, including those with nonlinear partial differential equations. The optimization does not require simulations be parallelized. Asynchronous (and synchronous) parallel execution is available in the optimization toolbox "pySOT". The parallel algorithms are modified from serial to eliminate fine grained parallelism. The optimization is computed with open source software pySOT, a Surrogate Global Optimization Toolbox that allows user to pick the type of surrogate (or ensembles), the search procedure on surrogate, and the type of parallelism (synchronous or asynchronous). pySOT also allows the user to develop new algorithms by modifying parts of the code. In the applications here, the objective function takes up to 30 minutes for one simulation, and serial optimization can take over 200 hours. Results from Yellowstone (NSF) and NCSS (Singapore) supercomputers are given for groundwater contaminant hydrology simulations with applications to model parameter estimation and decontamination management. All results are compared with alternatives. The first results are for optimization of pumping at many wells to reduce cost for decontamination of groundwater at a superfund site. The optimization runs with up to 128 processors. Superlinear speed up is obtained for up to 16 processors, and efficiency with 64 processors is over 80%. Each evaluation of the objective function requires the solution of nonlinear partial differential equations to describe the impact of spatially distributed pumping and model parameters on model predictions for the spatial and temporal distribution of groundwater contaminants. The second application uses an asynchronous parallel global optimization for groundwater quality model calibration. The time for a single objective function evaluation varies unpredictably, so efficiency is improved with asynchronous parallel calculations to improve load balancing. The third application (done at NCSS) incorporates new global surrogate multi-objective parallel search algorithms into pySOT and applies it to a large watershed calibration problem.

Identifying, Quantifying, Extracting and Enhancing Implicit Parallelism

ERIC Educational Resources Information Center

Agarwal, Mayank

2009-01-01

The shift of the microprocessor industry towards multicore architectures has placed a huge burden on the programmers by requiring explicit parallelization for performance. Implicit Parallelization is an alternative that could ease the burden on programmers by parallelizing applications "under the covers" while maintaining sequential semantics…

Developing Information Power Grid Based Algorithms and Software

NASA Technical Reports Server (NTRS)

Dongarra, Jack

1998-01-01

This exploratory study initiated our effort to understand performance modeling on parallel systems. The basic goal of performance modeling is to understand and predict the performance of a computer program or set of programs on a computer system. Performance modeling has numerous applications, including evaluation of algorithms, optimization of code implementations, parallel library development, comparison of system architectures, parallel system design, and procurement of new systems. Our work lays the basis for the construction of parallel libraries that allow for the reconstruction of application codes on several distinct architectures so as to assure performance portability. Following our strategy, once the requirements of applications are well understood, one can then construct a library in a layered fashion. The top level of this library will consist of architecture-independent geometric, numerical, and symbolic algorithms that are needed by the sample of applications. These routines should be written in a language that is portable across the targeted architectures.

Bilingual parallel programming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foster, I.; Overbeek, R.

1990-01-01

Numerous experiments have demonstrated that computationally intensive algorithms support adequate parallelism to exploit the potential of large parallel machines. Yet successful parallel implementations of serious applications are rare. The limiting factor is clearly programming technology. None of the approaches to parallel programming that have been proposed to date -- whether parallelizing compilers, language extensions, or new concurrent languages -- seem to adequately address the central problems of portability, expressiveness, efficiency, and compatibility with existing software. In this paper, we advocate an alternative approach to parallel programming based on what we call bilingual programming. We present evidence that this approach providesmore » and effective solution to parallel programming problems. The key idea in bilingual programming is to construct the upper levels of applications in a high-level language while coding selected low-level components in low-level languages. This approach permits the advantages of a high-level notation (expressiveness, elegance, conciseness) to be obtained without the cost in performance normally associated with high-level approaches. In addition, it provides a natural framework for reusing existing code.« less

Parallel design patterns for a low-power, software-defined compressed video encoder

NASA Astrophysics Data System (ADS)

Bruns, Michael W.; Hunt, Martin A.; Prasad, Durga; Gunupudi, Nageswara R.; Sonachalam, Sekar

2011-06-01

Video compression algorithms such as H.264 offer much potential for parallel processing that is not always exploited by the technology of a particular implementation. Consumer mobile encoding devices often achieve real-time performance and low power consumption through parallel processing in Application Specific Integrated Circuit (ASIC) technology, but many other applications require a software-defined encoder. High quality compression features needed for some applications such as 10-bit sample depth or 4:2:2 chroma format often go beyond the capability of a typical consumer electronics device. An application may also need to efficiently combine compression with other functions such as noise reduction, image stabilization, real time clocks, GPS data, mission/ESD/user data or software-defined radio in a low power, field upgradable implementation. Low power, software-defined encoders may be implemented using a massively parallel memory-network processor array with 100 or more cores and distributed memory. The large number of processor elements allow the silicon device to operate more efficiently than conventional DSP or CPU technology. A dataflow programming methodology may be used to express all of the encoding processes including motion compensation, transform and quantization, and entropy coding. This is a declarative programming model in which the parallelism of the compression algorithm is expressed as a hierarchical graph of tasks with message communication. Data parallel and task parallel design patterns are supported without the need for explicit global synchronization control. An example is described of an H.264 encoder developed for a commercially available, massively parallel memorynetwork processor device.

Profiling and Improving I/O Performance of a Large-Scale Climate Scientific Application

NASA Technical Reports Server (NTRS)

Liu, Zhuo; Wang, Bin; Wang, Teng; Tian, Yuan; Xu, Cong; Wang, Yandong; Yu, Weikuan; Cruz, Carlos A.; Zhou, Shujia; Clune, Tom;

Implementation of Parallel Dynamic Simulation on Shared-Memory vs. Distributed-Memory Environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Shuangshuang; Chen, Yousu; Wu, Di

2015-12-09

Power system dynamic simulation computes the system response to a sequence of large disturbance, such as sudden changes in generation or load, or a network short circuit followed by protective branch switching operation. It consists of a large set of differential and algebraic equations, which is computational intensive and challenging to solve using single-processor based dynamic simulation solution. High-performance computing (HPC) based parallel computing is a very promising technology to speed up the computation and facilitate the simulation process. This paper presents two different parallel implementations of power grid dynamic simulation using Open Multi-processing (OpenMP) on shared-memory platform, and Messagemore » Passing Interface (MPI) on distributed-memory clusters, respectively. The difference of the parallel simulation algorithms and architectures of the two HPC technologies are illustrated, and their performances for running parallel dynamic simulation are compared and demonstrated.« less

Generalized parallel-perspective stereo mosaics from airborne video.

PubMed

Zhu, Zhigang; Hanson, Allen R; Riseman, Edward M

2004-02-01

In this paper, we present a new method for automatically and efficiently generating stereoscopic mosaics by seamless registration of images collected by a video camera mounted on an airborne platform. Using a parallel-perspective representation, a pair of geometrically registered stereo mosaics can be precisely constructed under quite general motion. A novel parallel ray interpolation for stereo mosaicing (PRISM) approach is proposed to make stereo mosaics seamless in the presence of obvious motion parallax and for rather arbitrary scenes. Parallel-perspective stereo mosaics generated with the PRISM method have better depth resolution than perspective stereo due to the adaptive baseline geometry. Moreover, unlike previous results showing that parallel-perspective stereo has a constant depth error, we conclude that the depth estimation error of stereo mosaics is in fact a linear function of the absolute depths of a scene. Experimental results on long video sequences are given.

Thermal stability of G-rich anti-parallel DNA triplexes upon insertion of LNA and α-L-LNA.

PubMed

Kosbar, Tamer R; Sofan, Mamdouh A; Abou-Zeid, Laila; Pedersen, Erik B

2015-05-14

G-rich anti-parallel DNA triplexes were modified with LNA or α-L-LNA in their Watson-Crick and TFO strands. The triplexes were formed by targeting a pyrimidine strand to a putative hairpin formed by Hoogsteen base pairing in order to use the UV melting method to evaluate the stability of the triplexes. Their thermal stability was reduced when the TFO strand was modified with LNA or α-L-LNA. The same trend was observed when the TFO strand and the purine Watson-Crick strand both were modified with LNA. When all triad components were modified with α-L-LNA and LNA in the middle of the triplex, the thermal melting was increased. When the pyrimidine sequence was modified with a single insertion of LNA or α-L-LNA the ΔTm increased. Moreover, increasing the number of α-L-LNA in the pyrimidine target sequence to six insertions, leads to a high increase in the thermal stability. The conformational S-type structure of α-L-LNA in anti-parallel triplexes is preferable for triplex stability.

Mapping 3D genome architecture through in situ DNase Hi-C.

PubMed

Ramani, Vijay; Cusanovich, Darren A; Hause, Ronald J; Ma, Wenxiu; Qiu, Ruolan; Deng, Xinxian; Blau, C Anthony; Disteche, Christine M; Noble, William S; Shendure, Jay; Duan, Zhijun

2016-11-01

With the advent of massively parallel sequencing, considerable work has gone into adapting chromosome conformation capture (3C) techniques to study chromosomal architecture at a genome-wide scale. We recently demonstrated that the inactive murine X chromosome adopts a bipartite structure using a novel 3C protocol, termed in situ DNase Hi-C. Like traditional Hi-C protocols, in situ DNase Hi-C requires that chromatin be chemically cross-linked, digested, end-repaired, and proximity-ligated with a biotinylated bridge adaptor. The resulting ligation products are optionally sheared, affinity-purified via streptavidin bead immobilization, and subjected to traditional next-generation library preparation for Illumina paired-end sequencing. Importantly, in situ DNase Hi-C obviates the dependence on a restriction enzyme to digest chromatin, instead relying on the endonuclease DNase I. Libraries generated by in situ DNase Hi-C have a higher effective resolution than traditional Hi-C libraries, which makes them valuable in cases in which high sequencing depth is allowed for, or when hybrid capture technologies are expected to be used. The protocol described here, which involves ∼4 d of bench work, is optimized for the study of mammalian cells, but it can be broadly applicable to any cell or tissue of interest, given experimental parameter optimization.

Massively parallel digital high resolution melt for rapid and absolutely quantitative sequence profiling

NASA Astrophysics Data System (ADS)

Velez, Daniel Ortiz; Mack, Hannah; Jupe, Julietta; Hawker, Sinead; Kulkarni, Ninad; Hedayatnia, Behnam; Zhang, Yang; Lawrence, Shelley; Fraley, Stephanie I.

2017-02-01

In clinical diagnostics and pathogen detection, profiling of complex samples for low-level genotypes represents a significant challenge. Advances in speed, sensitivity, and extent of multiplexing of molecular pathogen detection assays are needed to improve patient care. We report the development of an integrated platform enabling the identification of bacterial pathogen DNA sequences in complex samples in less than four hours. The system incorporates a microfluidic chip and instrumentation to accomplish universal PCR amplification, High Resolution Melting (HRM), and machine learning within 20,000 picoliter scale reactions, simultaneously. Clinically relevant concentrations of bacterial DNA molecules are separated by digitization across 20,000 reactions and amplified with universal primers targeting the bacterial 16S gene. Amplification is followed by HRM sequence fingerprinting in all reactions, simultaneously. The resulting bacteria-specific melt curves are identified by Support Vector Machine learning, and individual pathogen loads are quantified. The platform reduces reaction volumes by 99.995% and achieves a greater than 200-fold increase in dynamic range of detection compared to traditional PCR HRM approaches. Type I and II error rates are reduced by 99% and 100% respectively, compared to intercalating dye-based digital PCR (dPCR) methods. This technology could impact a number of quantitative profiling applications, especially infectious disease diagnostics.

A high-speed linear algebra library with automatic parallelism

NASA Technical Reports Server (NTRS)

Boucher, Michael L.

1994-01-01

Parallel or distributed processing is key to getting highest performance workstations. However, designing and implementing efficient parallel algorithms is difficult and error-prone. It is even more difficult to write code that is both portable to and efficient on many different computers. Finally, it is harder still to satisfy the above requirements and include the reliability and ease of use required of commercial software intended for use in a production environment. As a result, the application of parallel processing technology to commercial software has been extremely small even though there are numerous computationally demanding programs that would significantly benefit from application of parallel processing. This paper describes DSSLIB, which is a library of subroutines that perform many of the time-consuming computations in engineering and scientific software. DSSLIB combines the high efficiency and speed of parallel computation with a serial programming model that eliminates many undesirable side-effects of typical parallel code. The result is a simple way to incorporate the power of parallel processing into commercial software without compromising maintainability, reliability, or ease of use. This gives significant advantages over less powerful non-parallel entries in the market.

Tempest: Accelerated MS/MS database search software for heterogeneous computing platforms

PubMed Central

Adamo, Mark E.; Gerber, Scott A.

2017-01-01

MS/MS database search algorithms derive a set of candidate peptide sequences from in-silico digest of a protein sequence database, and compute theoretical fragmentation patterns to match these candidates against observed MS/MS spectra. The original Tempest publication described these operations mapped to a CPU-GPU model, in which the CPU generates peptide candidates that are asynchronously sent to a discrete GPU to be scored against experimental spectra in parallel (Milloy et al., 2012). The current version of Tempest expands this model, incorporating OpenCL to offer seamless parallelization across multicore CPUs, GPUs, integrated graphics chips, and general-purpose coprocessors. Three protocols describe how to configure and run a Tempest search, including discussion of how to leverage Tempest's unique feature set to produce optimal results. PMID:27603022

Mitochondrial gene rearrangements confirm the parallel evolution of the crab-like form.

PubMed Central

Morrison, C L; Harvey, A W; Lavery, S; Tieu, K; Huang, Y; Cunningham, C W

2002-01-01

The repeated appearance of strikingly similar crab-like forms in independent decapod crustacean lineages represents a remarkable case of parallel evolution. Uncertainty surrounding the phylogenetic relationships among crab-like lineages has hampered evolutionary studies. As is often the case, aligned DNA sequences by themselves were unable to fully resolve these relationships. Four nested mitochondrial gene rearrangements--including one of the few reported movements of an arthropod protein-coding gene--are congruent with the DNA phylogeny and help to resolve a crucial node. A phylogenetic analysis of DNA sequences, and gene rearrangements, supported five independent origins of the crab-like form, and suggests that the evolution of the crab-like form may be irreversible. This result supports the utility of mitochondrial gene rearrangements in phylogenetic reconstruction. PMID:11886621

FPGA-based architecture for motion recovering in real-time

NASA Astrophysics Data System (ADS)

Arias-Estrada, Miguel; Maya-Rueda, Selene E.; Torres-Huitzil, Cesar

2002-03-01

A key problem in the computer vision field is the measurement of object motion in a scene. The main goal is to compute an approximation of the 3D motion from the analysis of an image sequence. Once computed, this information can be used as a basis to reach higher level goals in different applications. Motion estimation algorithms pose a significant computational load for the sequential processors limiting its use in practical applications. In this work we propose a hardware architecture for motion estimation in real time based on FPGA technology. The technique used for motion estimation is Optical Flow due to its accuracy, and the density of velocity estimation, however other techniques are being explored. The architecture is composed of parallel modules working in a pipeline scheme to reach high throughput rates near gigaflops. The modules are organized in a regular structure to provide a high degree of flexibility to cover different applications. Some results will be presented and the real-time performance will be discussed and analyzed. The architecture is prototyped in an FPGA board with a Virtex device interfaced to a digital imager.

Dynamic load balancing of applications

DOEpatents

Wheat, S.R.

1997-05-13

An application-level method for dynamically maintaining global load balance on a parallel computer, particularly on massively parallel MIMD computers is disclosed. Global load balancing is achieved by overlapping neighborhoods of processors, where each neighborhood performs local load balancing. The method supports a large class of finite element and finite difference based applications and provides an automatic element management system to which applications are easily integrated. 13 figs.

Role of APOE Isoforms in the Pathogenesis of TBI Induced Alzheimer’s Disease

DTIC Science & Technology

2015-10-01

global deletion, APOE targeted replacement, complex breeding, CCI model optimization, mRNA library generation, high throughput massive parallel ...ATP binding cassette transporter A1 (ABCA1) is a lipid transporter that controls the generation of HDL in plasma and ApoE-containing lipoproteins in... parallel sequencing, mRNA-seq, behavioral testing, mem- ory impairement, recovery. 3 Overall Project Summary During the reported period, we have been able

Renal magnetic resonance angiography at 3.0 Tesla using a 32-element phased-array coil system and parallel imaging in 2 directions.

PubMed

Fenchel, Michael; Nael, Kambiz; Deshpande, Vibhas S; Finn, J Paul; Kramer, Ulrich; Miller, Stephan; Ruehm, Stefan; Laub, Gerhard

2006-09-01

The aim of the present study was to assess the feasibility of renal magnetic resonance angiography at 3.0 T using a phased-array coil system with 32-coil elements. Specifically, high parallel imaging factors were used for an increased spatial resolution and anatomic coverage of the whole abdomen. Signal-to-noise values and the g-factor distribution of the 32 element coil were examined in phantom studies for the magnetic resonance angiography (MRA) sequence. Eleven volunteers (6 men, median age of 30.0 years) were examined on a 3.0-T MR scanner (Magnetom Trio, Siemens Medical Solutions, Malvern, PA) using a 32-element phased-array coil (prototype from In vivo Corp.). Contrast-enhanced 3D-MRA (TR 2.95 milliseconds, TE 1.12 milliseconds, flip angle 25-30 degrees , bandwidth 650 Hz/pixel) was acquired with integrated generalized autocalibrating partially parallel acquisition (GRAPPA), in both phase- and slice-encoding direction. Images were assessed by 2 independent observers with regard to image quality, noise and presence of artifacts. Signal-to-noise levels of 22.2 +/- 22.0 and 57.9 +/- 49.0 were measured with (GRAPPAx6) and without parallel-imaging, respectively. The mean g-factor of the 32-element coil for GRAPPA with an acceleration of 3 and 2 in the phase-encoding and slice-encoding direction, respectively, was 1.61. High image quality was found in 9 of 11 volunteers (2.6 +/- 0.8) with good overall interobserver agreement (k = 0.87). Relatively low image quality with higher noise levels were encountered in 2 volunteers. MRA at 3.0 T using a 32-element phased-array coil is feasible in healthy volunteers. High diagnostic image quality and extended anatomic coverage could be achieved with application of high parallel imaging factors.

SAAS-CNV: A Joint Segmentation Approach on Aggregated and Allele Specific Signals for the Identification of Somatic Copy Number Alterations with Next-Generation Sequencing Data.

PubMed

Zhang, Zhongyang; Hao, Ke

2015-11-01

Cancer genomes exhibit profound somatic copy number alterations (SCNAs). Studying tumor SCNAs using massively parallel sequencing provides unprecedented resolution and meanwhile gives rise to new challenges in data analysis, complicated by tumor aneuploidy and heterogeneity as well as normal cell contamination. While the majority of read depth based methods utilize total sequencing depth alone for SCNA inference, the allele specific signals are undervalued. We proposed a joint segmentation and inference approach using both signals to meet some of the challenges. Our method consists of four major steps: 1) extracting read depth supporting reference and alternative alleles at each SNP/Indel locus and comparing the total read depth and alternative allele proportion between tumor and matched normal sample; 2) performing joint segmentation on the two signal dimensions; 3) correcting the copy number baseline from which the SCNA state is determined; 4) calling SCNA state for each segment based on both signal dimensions. The method is applicable to whole exome/genome sequencing (WES/WGS) as well as SNP array data in a tumor-control study. We applied the method to a dataset containing no SCNAs to test the specificity, created by pairing sequencing replicates of a single HapMap sample as normal/tumor pairs, as well as a large-scale WGS dataset consisting of 88 liver tumors along with adjacent normal tissues. Compared with representative methods, our method demonstrated improved accuracy, scalability to large cancer studies, capability in handling both sequencing and SNP array data, and the potential to improve the estimation of tumor ploidy and purity.

SAAS-CNV: A Joint Segmentation Approach on Aggregated and Allele Specific Signals for the Identification of Somatic Copy Number Alterations with Next-Generation Sequencing Data

PubMed Central

Zhang, Zhongyang; Hao, Ke

2015-01-01

Cancer genomes exhibit profound somatic copy number alterations (SCNAs). Studying tumor SCNAs using massively parallel sequencing provides unprecedented resolution and meanwhile gives rise to new challenges in data analysis, complicated by tumor aneuploidy and heterogeneity as well as normal cell contamination. While the majority of read depth based methods utilize total sequencing depth alone for SCNA inference, the allele specific signals are undervalued. We proposed a joint segmentation and inference approach using both signals to meet some of the challenges. Our method consists of four major steps: 1) extracting read depth supporting reference and alternative alleles at each SNP/Indel locus and comparing the total read depth and alternative allele proportion between tumor and matched normal sample; 2) performing joint segmentation on the two signal dimensions; 3) correcting the copy number baseline from which the SCNA state is determined; 4) calling SCNA state for each segment based on both signal dimensions. The method is applicable to whole exome/genome sequencing (WES/WGS) as well as SNP array data in a tumor-control study. We applied the method to a dataset containing no SCNAs to test the specificity, created by pairing sequencing replicates of a single HapMap sample as normal/tumor pairs, as well as a large-scale WGS dataset consisting of 88 liver tumors along with adjacent normal tissues. Compared with representative methods, our method demonstrated improved accuracy, scalability to large cancer studies, capability in handling both sequencing and SNP array data, and the potential to improve the estimation of tumor ploidy and purity. PMID:26583378

Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer Patients.

PubMed

König, Katharina; Peifer, Martin; Fassunke, Jana; Ihle, Michaela A; Künstlinger, Helen; Heydt, Carina; Stamm, Katrin; Ueckeroth, Frank; Vollbrecht, Claudia; Bos, Marc; Gardizi, Masyar; Scheffler, Matthias; Nogova, Lucia; Leenders, Frauke; Albus, Kerstin; Meder, Lydia; Becker, Kerstin; Florin, Alexandra; Rommerscheidt-Fuss, Ursula; Altmüller, Janine; Kloth, Michael; Nürnberg, Peter; Henkel, Thomas; Bikár, Sven-Ernö; Sos, Martin L; Geese, William J; Strauss, Lewis; Ko, Yon-Dschun; Gerigk, Ulrich; Odenthal, Margarete; Zander, Thomas; Wolf, Jürgen; Merkelbach-Bruse, Sabine; Buettner, Reinhard; Heukamp, Lukas C

2015-07-01

The Network Genomic Medicine Lung Cancer was set up to rapidly translate scientific advances into early clinical trials of targeted therapies in lung cancer performing molecular analyses of more than 3500 patients annually. Because sequential analysis of the relevant driver mutations on fixated samples is challenging in terms of workload, tissue availability, and cost, we established multiplex parallel sequencing in routine diagnostics. The aim was to analyze all therapeutically relevant mutations in lung cancer samples in a high-throughput fashion while significantly reducing turnaround time and amount of input DNA compared with conventional dideoxy sequencing of single polymerase chain reaction amplicons. In this study, we demonstrate the feasibility of a 102 amplicon multiplex polymerase chain reaction followed by sequencing on an Illumina sequencer on formalin-fixed paraffin-embedded tissue in routine diagnostics. Analysis of a validation cohort of 180 samples showed this approach to require significantly less input material and to be more reliable, robust, and cost-effective than conventional dideoxy sequencing. Subsequently, 2657 lung cancer patients were analyzed. We observed that comprehensive biomarker testing provided novel information in addition to histological diagnosis and clinical staging. In 2657 consecutively analyzed lung cancer samples, we identified driver mutations at the expected prevalence. Furthermore we found potentially targetable DDR2 mutations at a frequency of 3% in both adenocarcinomas and squamous cell carcinomas. Overall, our data demonstrate the utility of systematic sequencing analysis in a clinical routine setting and highlight the dramatic impact of such an approach on the availability of therapeutic strategies for the targeted treatment of individual cancer patients.

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba’s Fruit Eating Bat, Carollia perspicillata

PubMed Central

Kordes, Sebastian; Kössl, Manfred

2017-01-01

Abstract For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units’ responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams. PMID:29242823

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba's Fruit Eating Bat, Carollia perspicillata.

PubMed

Beetz, M Jerome; Kordes, Sebastian; García-Rosales, Francisco; Kössl, Manfred; Hechavarría, Julio C

2017-01-01

For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units' responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams.

Statistical method to compare massive parallel sequencing pipelines.

PubMed

Elsensohn, M H; Leblay, N; Dimassi, S; Campan-Fournier, A; Labalme, A; Roucher-Boulez, F; Sanlaville, D; Lesca, G; Bardel, C; Roy, P

2017-03-01

Today, sequencing is frequently carried out by Massive Parallel Sequencing (MPS) that cuts drastically sequencing time and expenses. Nevertheless, Sanger sequencing remains the main validation method to confirm the presence of variants. The analysis of MPS data involves the development of several bioinformatic tools, academic or commercial. We present here a statistical method to compare MPS pipelines and test it in a comparison between an academic (BWA-GATK) and a commercial pipeline (TMAP-NextGENe®), with and without reference to a gold standard (here, Sanger sequencing), on a panel of 41 genes in 43 epileptic patients. This method used the number of variants to fit log-linear models for pairwise agreements between pipelines. To assess the heterogeneity of the margins and the odds ratios of agreement, four log-linear models were used: a full model, a homogeneous-margin model, a model with single odds ratio for all patients, and a model with single intercept. Then a log-linear mixed model was fitted considering the biological variability as a random effect. Among the 390,339 base-pairs sequenced, TMAP-NextGENe® and BWA-GATK found, on average, 2253.49 and 1857.14 variants (single nucleotide variants and indels), respectively. Against the gold standard, the pipelines had similar sensitivities (63.47% vs. 63.42%) and close but significantly different specificities (99.57% vs. 99.65%; p < 0.001). Same-trend results were obtained when only single nucleotide variants were considered (99.98% specificity and 76.81% sensitivity for both pipelines). The method allows thus pipeline comparison and selection. It is generalizable to all types of MPS data and all pipelines.

Contrast-enhanced T1-weighted fluid-attenuated inversion-recovery BLADE magnetic resonance imaging of the brain: an alternative to spin-echo technique for detection of brain lesions in the unsedated pediatric patient?

PubMed

Alibek, Sedat; Adamietz, Boris; Cavallaro, Alexander; Stemmer, Alto; Anders, Katharina; Kramer, Manuel; Bautz, Werner; Staatz, Gundula

2008-08-01

We compared contrast-enhanced T1-weighted magnetic resonance (MR) imaging of the brain using different types of data acquisition techniques: periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER, BLADE) imaging versus standard k-space sampling (conventional spin-echo pulse sequence) in the unsedated pediatric patient with focus on artifact reduction, overall image quality, and lesion detectability. Forty-eight pediatric patients (aged 3 months to 18 years) were scanned with a clinical 1.5-T whole body MR scanner. Cross-sectional contrast-enhanced T1-weighted spin-echo sequence was compared to a T1-weighted dark-fluid fluid-attenuated inversion-recovery (FLAIR) BLADE sequence for qualitative and quantitative criteria (image artifacts, image quality, lesion detectability) by two experienced radiologists. Imaging protocols were matched for imaging parameters. Reader agreement was assessed using the exact Bowker test. BLADE images showed significantly less pulsation and motion artifacts than the standard T1-weighted spin-echo sequence scan. BLADE images showed statistically significant lower signal-to-noise ratio but higher contrast-to-noise ratios with superior gray-white matter contrast. All lesions were demonstrated on FLAIR BLADE imaging, and one false-positive lesion was visible in spin-echo sequence images. BLADE MR imaging at 1.5 T is applicable for central nervous system imaging of the unsedated pediatric patient, reduces motion and pulsation artifacts, and minimizes the need for sedation or general anesthesia without loss of relevant diagnostic information.

Investigation of modulation parameters in multiplexing gas chromatography.

PubMed

Trapp, Oliver

2010-10-22

Combination of information technology and separation sciences opens a new avenue to achieve high sample throughputs and therefore is of great interest to bypass bottlenecks in catalyst screening of parallelized reactors or using multitier well plates in reaction optimization. Multiplexing gas chromatography utilizes pseudo-random injection sequences derived from Hadamard matrices to perform rapid sample injections which gives a convoluted chromatogram containing the information of a single sample or of several samples with similar analyte composition. The conventional chromatogram is obtained by application of the Hadamard transform using the known injection sequence or in case of several samples an averaged transformed chromatogram is obtained which can be used in a Gauss-Jordan deconvolution procedure to obtain all single chromatograms of the individual samples. The performance of such a system depends on the modulation precision and on the parameters, e.g. the sequence length and modulation interval. Here we demonstrate the effects of the sequence length and modulation interval on the deconvoluted chromatogram, peak shapes and peak integration for sequences between 9-bit (511 elements) and 13-bit (8191 elements) and modulation intervals Δt between 5 s and 500 ms using a mixture of five components. It could be demonstrated that even for high-speed modulation at time intervals of 500 ms the chromatographic information is very well preserved and that the separation efficiency can be improved by very narrow sample injections. Furthermore this study shows that the relative peak areas in multiplexed chromatograms do not deviate from conventionally recorded chromatograms. Copyright © 2010 Elsevier B.V. All rights reserved.

AC losses in horizontally parallel HTS tapes for possible wireless power transfer applications

NASA Astrophysics Data System (ADS)

Shen, Boyang; Geng, Jianzhao; Zhang, Xiuchang; Fu, Lin; Li, Chao; Zhang, Heng; Dong, Qihuan; Ma, Jun; Gawith, James; Coombs, T. A.

2017-12-01

This paper presents the concept of using horizontally parallel HTS tapes with AC loss study, and the investigation on possible wireless power transfer (WPT) applications. An example of three parallel HTS tapes was proposed, whose AC loss study was carried out both from experiment using electrical method; and simulation using 2D H-formulation on the FEM platform of COMSOL Multiphysics. The electromagnetic induction around the three parallel tapes was monitored using COMSOL simulation. The electromagnetic induction and AC losses generated by a conventional three turn coil was simulated as well, and then compared to the case of three parallel tapes with the same AC transport current. The analysis demonstrates that HTS parallel tapes could be potentially used into wireless power transfer systems, which could have lower total AC losses than conventional HTS coils.

Clinical Validation of Copy Number Variant Detection from Targeted Next-Generation Sequencing Panels.

PubMed

Kerkhof, Jennifer; Schenkel, Laila C; Reilly, Jack; McRobbie, Sheri; Aref-Eshghi, Erfan; Stuart, Alan; Rupar, C Anthony; Adams, Paul; Hegele, Robert A; Lin, Hanxin; Rodenhiser, David; Knoll, Joan; Ainsworth, Peter J; Sadikovic, Bekim

2017-11-01

Next-generation sequencing (NGS) technology has rapidly replaced Sanger sequencing in the assessment of sequence variations in clinical genetics laboratories. One major limitation of current NGS approaches is the ability to detect copy number variations (CNVs) approximately >50 bp. Because these represent a major mutational burden in many genetic disorders, parallel CNV assessment using alternate supplemental methods, along with the NGS analysis, is normally required, resulting in increased labor, costs, and turnaround times. The objective of this study was to clinically validate a novel CNV detection algorithm using targeted clinical NGS gene panel data. We have applied this approach in a retrospective cohort of 391 samples and a prospective cohort of 2375 samples and found a 100% sensitivity (95% CI, 89%-100%) for 37 unique events and a high degree of specificity to detect CNVs across nine distinct targeted NGS gene panels. This NGS CNV pipeline enables stand-alone first-tier assessment for CNV and sequence variants in a clinical laboratory setting, dispensing with the need for parallel CNV analysis using classic techniques, such as microarray, long-range PCR, or multiplex ligation-dependent probe amplification. This NGS CNV pipeline can also be applied to the assessment of complex genomic regions, including pseudogenic DNA sequences, such as the PMS2CL gene, and to mitochondrial genome heteroplasmy detection. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Molecular Cytogenetics Guides Massively Parallel Sequencing of a Radiation-Induced Chromosome Translocation in Human Cells.

PubMed

Cornforth, Michael N; Anur, Pavana; Wang, Nicholas; Robinson, Erin; Ray, F Andrew; Bedford, Joel S; Loucas, Bradford D; Williams, Eli S; Peto, Myron; Spellman, Paul; Kollipara, Rahul; Kittler, Ralf; Gray, Joe W; Bailey, Susan M

2018-05-11

Chromosome rearrangements are large-scale structural variants that are recognized drivers of oncogenic events in cancers of all types. Cytogenetics allows for their rapid, genome-wide detection, but does not provide gene-level resolution. Massively parallel sequencing (MPS) promises DNA sequence-level characterization of the specific breakpoints involved, but is strongly influenced by bioinformatics filters that affect detection efficiency. We sought to characterize the breakpoint junctions of chromosomal translocations and inversions in the clonal derivatives of human cells exposed to ionizing radiation. Here, we describe the first successful use of DNA paired-end analysis to locate and sequence across the breakpoint junctions of a radiation-induced reciprocal translocation. The analyses employed, with varying degrees of success, several well-known bioinformatics algorithms, a task made difficult by the involvement of repetitive DNA sequences. As for underlying mechanisms, the results of Sanger sequencing suggested that the translocation in question was likely formed via microhomology-mediated non-homologous end joining (mmNHEJ). To our knowledge, this represents the first use of MPS to characterize the breakpoint junctions of a radiation-induced chromosomal translocation in human cells. Curiously, these same approaches were unsuccessful when applied to the analysis of inversions previously identified by directional genomic hybridization (dGH). We conclude that molecular cytogenetics continues to provide critical guidance for structural variant discovery, validation and in "tuning" analysis filters to enable robust breakpoint identification at the base pair level.

A high performance parallel algorithm for 1-D FFT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, R.C.; Gustavson, F.G.; Zubair, M.

1994-12-31

In this paper the authors propose a parallel high performance FFT algorithm based on a multi-dimensional formulation. They use this to solve a commonly encountered FFT based kernel on a distributed memory parallel machine, the IBM scalable parallel system, SP1. The kernel requires a forward FFT computation of an input sequence, multiplication of the transformed data by a coefficient array, and finally an inverse FFT computation of the resultant data. They show that the multi-dimensional formulation helps in reducing the communication costs and also improves the single node performance by effectively utilizing the memory system of the node. They implementedmore » this kernel on the IBM SP1 and observed a performance of 1.25 GFLOPS on a 64-node machine.« less

Manyscale Computing for Sensor Processing in Support of Space Situational Awareness

NASA Astrophysics Data System (ADS)

Schmalz, M.; Chapman, W.; Hayden, E.; Sahni, S.; Ranka, S.

2014-09-01

Increasing image and signal data burden associated with sensor data processing in support of space situational awareness implies continuing computational throughput growth beyond the petascale regime. In addition to growing applications data burden and diversity, the breadth, diversity and scalability of high performance computing architectures and their various organizations challenge the development of a single, unifying, practicable model of parallel computation. Therefore, models for scalable parallel processing have exploited architectural and structural idiosyncrasies, yielding potential misapplications when legacy programs are ported among such architectures. In response to this challenge, we have developed a concise, efficient computational paradigm and software called Manyscale Computing to facilitate efficient mapping of annotated application codes to heterogeneous parallel architectures. Our theory, algorithms, software, and experimental results support partitioning and scheduling of application codes for envisioned parallel architectures, in terms of work atoms that are mapped (for example) to threads or thread blocks on computational hardware. Because of the rigor, completeness, conciseness, and layered design of our manyscale approach, application-to-architecture mapping is feasible and scalable for architectures at petascales, exascales, and above. Further, our methodology is simple, relying primarily on a small set of primitive mapping operations and support routines that are readily implemented on modern parallel processors such as graphics processing units (GPUs) and hybrid multi-processors (HMPs). In this paper, we overview the opportunities and challenges of manyscale computing for image and signal processing in support of space situational awareness applications. We discuss applications in terms of a layered hardware architecture (laboratory > supercomputer > rack > processor > component hierarchy). Demonstration applications include performance analysis and results in terms of execution time as well as storage, power, and energy consumption for bus-connected and/or networked architectures. The feasibility of the manyscale paradigm is demonstrated by addressing four principal challenges: (1) architectural/structural diversity, parallelism, and locality, (2) masking of I/O and memory latencies, (3) scalability of design as well as implementation, and (4) efficient representation/expression of parallel applications. Examples will demonstrate how manyscale computing helps solve these challenges efficiently on real-world computing systems.

High-speed 3D surface measurement with a fringe projection based optical sensor

NASA Astrophysics Data System (ADS)

Bräuer-Burchardt, Christian; Heist, Stefan; Kühmstedt, Peter; Notni, Gunther

2014-05-01

A new optical sensor based on fringe projection technique for the accurate and fast measurement of the surface of objects mainly for industrial inspection tasks is introduced. High-speed fringe projection and image recording with 180 Hz allows 3D rates up to 60 Hz. The high measurement velocity was achieved by consequent fringe code reduction and parallel data processing. Reduction of the image sequence length was obtained by omission of the Gray-code sequence by using the geometric restrictions of the measurement objects. The sensor realizes three different measurement fields between 20 x 20 mm2 and 40 x 40 mm2 with lateral spatial solutions between 10 μm and 20 μm with the same working distance. Measurement object height extension is between +/- 0.5 mm and +/- 2 mm. Height resolution between 1 μm and 5 μm can be achieved depending on the properties of the measurement objects. The sensor may be used e.g. for quality inspection of conductor boards or plugs in real-time industrial applications.

Massively Parallel Sequencing of Forensic STRs Using the Ion Chef™ and the Ion S5™ XL Systems.

PubMed

Wang, Le; Chen, Man; Wu, Bo; Liu, Yi-Cheng; Zhang, Guang-Feng; Jiang, Li; Xu, Xiu-Lan; Zhao, Xing-Chun; Ji, An-Quan; Ye, Jian

2018-03-01

Next-generation sequencing (NGS) has been used to genotype forensic short tandem repeat (STR) markers for individual identification and kinship analysis. STR data from several NGS platforms have been published, but forensic application trials using the Ion S5™ XL system have not been reported. In this work, we report sensitivity, reproducibility, mixture, simulated degradation, and casework sample data on the Ion Chef™ and S5™ XL systems using an early access 25-plex panel. Sensitivity experiments showed that over 97% of the alleles were detectable with down to 62 pg input of genomic DNA. In mixture studies, alleles from minor contributors were correctly assigned at 1:9 and 9:1 ratios. NGS successfully gave 12 full genotype results from 13 challenging casework samples, compared with five full results using the CE platform. In conclusion, the Ion Chef™ and the Ion S5™ XL systems provided an alternative and promising approach for forensic STR genotyping. © 2018 American Academy of Forensic Sciences.

Functional Analysis With a Barcoder Yeast Gene Overexpression System

PubMed Central

Douglas, Alison C.; Smith, Andrew M.; Sharifpoor, Sara; Yan, Zhun; Durbic, Tanja; Heisler, Lawrence E.; Lee, Anna Y.; Ryan, Owen; Göttert, Hendrikje; Surendra, Anu; van Dyk, Dewald; Giaever, Guri; Boone, Charles; Nislow, Corey; Andrews, Brenda J.

2012-01-01

Systematic analysis of gene overexpression phenotypes provides an insight into gene function, enzyme targets, and biological pathways. Here, we describe a novel functional genomics platform that enables a highly parallel and systematic assessment of overexpression phenotypes in pooled cultures. First, we constructed a genome-level collection of ~5100 yeast barcoder strains, each of which carries a unique barcode, enabling pooled fitness assays with a barcode microarray or sequencing readout. Second, we constructed a yeast open reading frame (ORF) galactose-induced overexpression array by generating a genome-wide set of yeast transformants, each of which carries an individual plasmid-born and sequence-verified ORF derived from the Saccharomyces cerevisiae full-length EXpression-ready (FLEX) collection. We combined these collections genetically using synthetic genetic array methodology, generating ~5100 strains, each of which is barcoded and overexpresses a specific ORF, a set we termed “barFLEX.” Additional synthetic genetic array allows the barFLEX collection to be moved into different genetic backgrounds. As a proof-of-principle, we describe the properties of the barFLEX overexpression collection and its application in synthetic dosage lethality studies under different environmental conditions. PMID:23050238

Accurate multiplex polony sequencing of an evolved bacterial genome.

PubMed

Shendure, Jay; Porreca, Gregory J; Reppas, Nikos B; Lin, Xiaoxia; McCutcheon, John P; Rosenbaum, Abraham M; Wang, Michael D; Zhang, Kun; Mitra, Robi D; Church, George M

2005-09-09

We describe a DNA sequencing technology in which a commonly available, inexpensive epifluorescence microscope is converted to rapid nonelectrophoretic DNA sequencing automation. We apply this technology to resequence an evolved strain of Escherichia coli at less than one error per million consensus bases. A cell-free, mate-paired library provided single DNA molecules that were amplified in parallel to 1-micrometer beads by emulsion polymerase chain reaction. Millions of beads were immobilized in a polyacrylamide gel and subjected to automated cycles of sequencing by ligation and four-color imaging. Cost per base was roughly one-ninth as much as that of conventional sequencing. Our protocols were implemented with off-the-shelf instrumentation and reagents.

Detection of novel mutations that cause autosomal dominant retinitis pigmentosa in candidate genes by long-range PCR amplification and next-generation sequencing

PubMed Central

Dias, Miguel de Sousa; Hernan, Imma; Pascual, Beatriz; Borràs, Emma; Mañé, Begoña; Gamundi, Maria José

2013-01-01

Purpose To devise an effective method for detecting mutations in 12 genes (CA4, CRX, IMPDH1, NR2E3, RP9, PRPF3, PRPF8, PRPF31, PRPH2, RHO, RP1, and TOPORS) commonly associated with autosomal dominant retinitis pigmentosa (adRP) that account for more than 95% of known mutations. Methods We used long-range PCR (LR-PCR) amplification and next-generation sequencing (NGS) performed in a GS Junior 454 benchtop sequencing platform. Twenty LR-PCR fragments, between 3,000 and 10,000 bp, containing all coding exons and flanking regions of the 12 genes, were obtained from DNA samples of patients with adRP. Sequencing libraries were prepared with an enzymatic (Fragmentase technology) method. Results Complete coverage of the coding and flanking sequences of the 12 genes assayed was obtained with NGS, with an average sequence depth of 380× (ranging from 128× to 1,077×). Five previous known mutations in the adRP genes were detected with a sequence variation percentage between 35% and 65%. We also performed a parallel sequence analysis of four samples, three of them new patients with index adRP, in which two novel mutations were detected in RHO (p.Asn73del) and PRPF31 (p.Ile109del). Conclusions The results demonstrate that genomic LR-PCR amplification together with NGS is an effective method for analyzing individual patient samples for mutations in a monogenic heterogeneous disease such as adRP. This approach proved effective for the parallel analysis of adRP and has been introduced as routine. Additionally, this approach could be extended to other heterogeneous genetic diseases. PMID:23559859

Methodes iteratives paralleles: Applications en neutronique et en mecanique des fluides

NASA Astrophysics Data System (ADS)

Qaddouri, Abdessamad

Dans cette these, le calcul parallele est applique successivement a la neutronique et a la mecanique des fluides. Dans chacune de ces deux applications, des methodes iteratives sont utilisees pour resoudre le systeme d'equations algebriques resultant de la discretisation des equations du probleme physique. Dans le probleme de neutronique, le calcul des matrices des probabilites de collision (PC) ainsi qu'un schema iteratif multigroupe utilisant une methode inverse de puissance sont parallelises. Dans le probleme de mecanique des fluides, un code d'elements finis utilisant un algorithme iteratif du type GMRES preconditionne est parallelise. Cette these est presentee sous forme de six articles suivis d'une conclusion. Les cinq premiers articles traitent des applications en neutronique, articles qui representent l'evolution de notre travail dans ce domaine. Cette evolution passe par un calcul parallele des matrices des PC et un algorithme multigroupe parallele teste sur un probleme unidimensionnel (article 1), puis par deux algorithmes paralleles l'un mutiregion l'autre multigroupe, testes sur des problemes bidimensionnels (articles 2--3). Ces deux premieres etapes sont suivies par l'application de deux techniques d'acceleration, le rebalancement neutronique et la minimisation du residu aux deux algorithmes paralleles (article 4). Finalement, on a mis en oeuvre l'algorithme multigroupe et le calcul parallele des matrices des PC sur un code de production DRAGON ou les tests sont plus realistes et peuvent etre tridimensionnels (article 5). Le sixieme article (article 6), consacre a l'application a la mecanique des fluides, traite la parallelisation d'un code d'elements finis FES ou le partitionneur de graphe METIS et la librairie PSPARSLIB sont utilises.

Predicting helix orientation for coiled-coil dimers

PubMed Central

Apgar, James R.; Gutwin, Karl N.; Keating, Amy E.

2008-01-01

The alpha-helical coiled coil is a structurally simple protein oligomerization or interaction motif consisting of two or more alpha helices twisted into a supercoiled bundle. Coiled coils can differ in their stoichiometry, helix orientation and axial alignment. Because of the near degeneracy of many of these variants, coiled coils pose a challenge to fold recognition methods for structure prediction. Whereas distinctions between some protein folds can be discriminated on the basis of hydrophobic/polar patterning or secondary structure propensities, the sequence differences that encode important details of coiled-coil structure can be subtle. This is emblematic of a larger problem in the field of protein structure and interaction prediction: that of establishing specificity between closely similar structures. We tested the behavior of different computational models on the problem of recognizing the correct orientation - parallel vs. antiparallel - of pairs of alpha helices that can form a dimeric coiled coil. For each of 131 examples of known structure, we constructed a large number of both parallel and antiparallel structural models and used these to asses the ability of five energy functions to recognize the correct fold. We also developed and tested three sequenced-based approaches that make use of varying degrees of implicit structural information. The best structural methods performed similarly to the best sequence methods, correctly categorizing ∼81% of dimers. Steric compatibility with the fold was important for some coiled coils we investigated. For many examples, the correct orientation was determined by smaller energy differences between parallel and antiparallel structures distributed over many residues and energy components. Prediction methods that used structure but incorporated varying approximations and assumptions showed quite different behaviors when used to investigate energetic contributions to orientation preference. Sequence based methods were sensitive to the choice of residue-pair interactions scored. PMID:18506779

Application of integration algorithms in a parallel processing environment for the simulation of jet engines

NASA Technical Reports Server (NTRS)

Krosel, S. M.; Milner, E. J.

1982-01-01

The application of Predictor corrector integration algorithms developed for the digital parallel processing environment are investigated. The algorithms are implemented and evaluated through the use of a software simulator which provides an approximate representation of the parallel processing hardware. Test cases which focus on the use of the algorithms are presented and a specific application using a linear model of a turbofan engine is considered. Results are presented showing the effects of integration step size and the number of processors on simulation accuracy. Real time performance, interprocessor communication, and algorithm startup are also discussed.

Parallelization of Finite Element Analysis Codes Using Heterogeneous Distributed Computing

NASA Technical Reports Server (NTRS)

Ozguner, Fusun

1996-01-01

Performance gains in computer design are quickly consumed as users seek to analyze larger problems to a higher degree of accuracy. Innovative computational methods, such as parallel and distributed computing, seek to multiply the power of existing hardware technology to satisfy the computational demands of large applications. In the early stages of this project, experiments were performed using two large, coarse-grained applications, CSTEM and METCAN. These applications were parallelized on an Intel iPSC/860 hypercube. It was found that the overall speedup was very low, due to large, inherently sequential code segments present in the applications. The overall execution time T(sub par), of the application is dependent on these sequential segments. If these segments make up a significant fraction of the overall code, the application will have a poor speedup measure.

Graphics applications utilizing parallel processing

NASA Technical Reports Server (NTRS)

Rice, John R.

1990-01-01

The results are presented of research conducted to develop a parallel graphic application algorithm to depict the numerical solution of the 1-D wave equation, the vibrating string. The research was conducted on a Flexible Flex/32 multiprocessor and a Sequent Balance 21000 multiprocessor. The wave equation is implemented using the finite difference method. The synchronization issues that arose from the parallel implementation and the strategies used to alleviate the effects of the synchronization overhead are discussed.

[Series: Medical Applications of the PHITS Code (2): Acceleration by Parallel Computing].

PubMed

Furuta, Takuya; Sato, Tatsuhiko

2015-01-01

Time-consuming Monte Carlo dose calculation becomes feasible owing to the development of computer technology. However, the recent development is due to emergence of the multi-core high performance computers. Therefore, parallel computing becomes a key to achieve good performance of software programs. A Monte Carlo simulation code PHITS contains two parallel computing functions, the distributed-memory parallelization using protocols of message passing interface (MPI) and the shared-memory parallelization using open multi-processing (OpenMP) directives. Users can choose the two functions according to their needs. This paper gives the explanation of the two functions with their advantages and disadvantages. Some test applications are also provided to show their performance using a typical multi-core high performance workstation.

SCORPIO: A Scalable Two-Phase Parallel I/O Library With Application To A Large Scale Subsurface Simulator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sreepathi, Sarat; Sripathi, Vamsi; Mills, Richard T

2013-01-01

Inefficient parallel I/O is known to be a major bottleneck among scientific applications employed on supercomputers as the number of processor cores grows into the thousands. Our prior experience indicated that parallel I/O libraries such as HDF5 that rely on MPI-IO do not scale well beyond 10K processor cores, especially on parallel file systems (like Lustre) with single point of resource contention. Our previous optimization efforts for a massively parallel multi-phase and multi-component subsurface simulator (PFLOTRAN) led to a two-phase I/O approach at the application level where a set of designated processes participate in the I/O process by splitting themore » I/O operation into a communication phase and a disk I/O phase. The designated I/O processes are created by splitting the MPI global communicator into multiple sub-communicators. The root process in each sub-communicator is responsible for performing the I/O operations for the entire group and then distributing the data to rest of the group. This approach resulted in over 25X speedup in HDF I/O read performance and 3X speedup in write performance for PFLOTRAN at over 100K processor cores on the ORNL Jaguar supercomputer. This research describes the design and development of a general purpose parallel I/O library, SCORPIO (SCalable block-ORiented Parallel I/O) that incorporates our optimized two-phase I/O approach. The library provides a simplified higher level abstraction to the user, sitting atop existing parallel I/O libraries (such as HDF5) and implements optimized I/O access patterns that can scale on larger number of processors. Performance results with standard benchmark problems and PFLOTRAN indicate that our library is able to maintain the same speedups as before with the added flexibility of being applicable to a wider range of I/O intensive applications.« less

Long sequence correlation coprocessor

NASA Astrophysics Data System (ADS)

Gage, Douglas W.

1994-09-01

A long sequence correlation coprocessor (LSCC) accelerates the bitwise correlation of arbitrarily long digital sequences by calculating in parallel the correlation score for 16, for example, adjacent bit alignments between two binary sequences. The LSCC integrated circuit is incorporated into a computer system with memory storage buffers and a separate general purpose computer processor which serves as its controller. Each of the LSCC's set of sequential counters simultaneously tallies a separate correlation coefficient. During each LSCC clock cycle, computer enable logic associated with each counter compares one bit of a first sequence with one bit of a second sequence to increment the counter if the bits are the same. A shift register assures that the same bit of the first sequence is simultaneously compared to different bits of the second sequence to simultaneously calculate the correlation coefficient by the different counters to represent different alignments of the two sequences.