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1.
Background
Complex PCR applications for large genome-scale projects require fast, reliable and often highly sophisticated primer design software applications. Presently, such applications use pipelining methods to utilise many third party applications and this involves file parsing, interfacing and data conversion, which is slow and prone to error. A fully integrated suite of software tools for primer design would considerably improve the development time, the processing speed, and the reliability of bespoke primer design software applications.Results
The PD5 software library is an open-source collection of classes and utilities, providing a complete collection of software building blocks for primer design and analysis. It is written in object-oriented C++ with an emphasis on classes suitable for efficient and rapid development of bespoke primer design programs. The modular design of the software library simplifies the development of specific applications and also integration with existing third party software where necessary. We demonstrate several applications created using this software library that have already proved to be effective, but we view the project as a dynamic environment for building primer design software and it is open for future development by the bioinformatics community. Therefore, the PD5 software library is published under the terms of the GNU General Public License, which guarantee access to source-code and allow redistribution and modification.Conclusions
The PD5 software library is downloadable from Google Code and the accompanying Wiki includes instructions and examples: http://code.google.com/p/primer-design 相似文献2.
Isaak Y Tecle Jeremy D Edwards Naama Menda Chiedozie Egesi Ismail Y Rabbi Peter Kulakow Robert Kawuki Jean-Luc Jannink Lukas A Mueller 《BMC bioinformatics》2014,15(1)
Background
Genomic selection (GS) promises to improve accuracy in estimating breeding values and genetic gain for quantitative traits compared to traditional breeding methods. Its reliance on high-throughput genome-wide markers and statistical complexity, however, is a serious challenge in data management, analysis, and sharing. A bioinformatics infrastructure for data storage and access, and user-friendly web-based tool for analysis and sharing output is needed to make GS more practical for breeders.Results
We have developed a web-based tool, called solGS, for predicting genomic estimated breeding values (GEBVs) of individuals, using a Ridge-Regression Best Linear Unbiased Predictor (RR-BLUP) model. It has an intuitive web-interface for selecting a training population for modeling and estimating genomic estimated breeding values of selection candidates. It estimates phenotypic correlation and heritability of traits and selection indices of individuals. Raw data is stored in a generic database schema, Chado Natural Diversity, co-developed by multiple database groups. Analysis output is graphically visualized and can be interactively explored online or downloaded in text format. An instance of its implementation can be accessed at the NEXTGEN Cassava breeding database, http://cassavabase.org/solgs.Conclusions
solGS enables breeders to store raw data and estimate GEBVs of individuals online, in an intuitive and interactive workflow. It can be adapted to any breeding program.Electronic supplementary material
The online version of this article (doi:10.1186/s12859-014-0398-7) contains supplementary material, which is available to authorized users. 相似文献3.
Background
Predicting type-1 Human Immunodeficiency Virus (HIV-1) protease cleavage site in protein molecules and determining its specificity is an important task which has attracted considerable attention in the research community. Achievements in this area are expected to result in effective drug design (especially for HIV-1 protease inhibitors) against this life-threatening virus. However, some drawbacks (like the shortage of the available training data and the high dimensionality of the feature space) turn this task into a difficult classification problem. Thus, various machine learning techniques, and specifically several classification methods have been proposed in order to increase the accuracy of the classification model. In addition, for several classification problems, which are characterized by having few samples and many features, selecting the most relevant features is a major factor for increasing classification accuracy.Results
We propose for HIV-1 data a consistency-based feature selection approach in conjunction with recursive feature elimination of support vector machines (SVMs). We used various classifiers for evaluating the results obtained from the feature selection process. We further demonstrated the effectiveness of our proposed method by comparing it with a state-of-the-art feature selection method applied on HIV-1 data, and we evaluated the reported results based on attributes which have been selected from different combinations.Conclusion
Applying feature selection on training data before realizing the classification task seems to be a reasonable data-mining process when working with types of data similar to HIV-1. On HIV-1 data, some feature selection or extraction operations in conjunction with different classifiers have been tested and noteworthy outcomes have been reported. These facts motivate for the work presented in this paper.Software availability
The software is available at http://ozyer.etu.edu.tr/c-fs-svm.rar.The software can be downloaded at esnag.etu.edu.tr/software/hiv_cleavage_site_prediction.rar; you will find a readme file which explains how to set the software in order to work. 相似文献4.
Jason A. Greenbaum Erika Assarsson Jo L. Chung Steven Head Alessandro Sette Bjoern Peters 《PloS one》2010,5(4)
Background
Genomic tiling arrays have been described in the scientific literature since 2003, yet there is a shortage of user-friendly applications available for their analysis.Methodology/Principal Findings
Tiling Array Analyzer (TiArA) is a software program that provides a user-friendly graphical interface for the background subtraction, normalization, and summarization of data acquired through the Affymetrix tiling array platform. The background signal is empirically measured using a group of nonspecific probes with varying levels of GC content and normalization is performed to enforce a common dynamic range.Conclusions/Significance
TiArA is implemented as a standalone program for Linux systems and is available as a cross-platform virtual machine that will run under most modern operating systems using virtualization software such as Sun VirtualBox or VMware. The software is available as a Debian package or a virtual appliance at http://purl.org/NET/tiara. 相似文献5.
6.
Background
High-throughput RNA interference (RNAi) screening has become a widely used approach to elucidating gene functions. However, analysis and annotation of large data sets generated from these screens has been a challenge for researchers without a programming background. Over the years, numerous data analysis methods were produced for plate quality control and hit selection and implemented by a few open-access software packages. Recently, strictly standardized mean difference (SSMD) has become a widely used method for RNAi screening analysis mainly due to its better control of false negative and false positive rates and its ability to quantify RNAi effects with a statistical basis. We have developed GUItars to enable researchers without a programming background to use SSMD as both a plate quality and a hit selection metric to analyze large data sets.Results
The software is accompanied by an intuitive graphical user interface for easy and rapid analysis workflow. SSMD analysis methods have been provided to the users along with traditionally-used z-score, normalized percent activity, and t-test methods for hit selection. GUItars is capable of analyzing large-scale data sets from screens with or without replicates. The software is designed to automatically generate and save numerous graphical outputs known to be among the most informative high-throughput data visualization tools capturing plate-wise and screen-wise performances. Graphical outputs are also written in HTML format for easy access, and a comprehensive summary of screening results is written into tab-delimited output files.Conclusion
With GUItars, we demonstrated robust SSMD-based analysis workflow on a 3840-gene small interfering RNA (siRNA) library and identified 200 siRNAs that increased and 150 siRNAs that decreased the assay activities with moderate to stronger effects. GUItars enables rapid analysis and illustration of data from large- or small-scale RNAi screens using SSMD and other traditional analysis methods. The software is freely available at http://sourceforge.net/projects/guitars/. 相似文献7.
Background
Real-time quantitative PCR (qPCR) is still the gold-standard technique for gene-expression quantification. Recent technological advances of this method allow for the high-throughput gene-expression analysis, without the limitations of sample space and reagent used. However, non-commercial and user-friendly software for the management and analysis of these data is not available.Results
The recently developed commercial microarrays allow for the drawing of standard curves of multiple assays using the same n-fold diluted samples. Data Analysis Gene (DAG) Expression software has been developed to perform high-throughput gene-expression data analysis using standard curves for relative quantification and one or multiple reference genes for sample normalization. We discuss the application of DAG Expression in the analysis of data from an experiment performed with Fluidigm technology, in which 48 genes and 115 samples were measured. Furthermore, the quality of our analysis was tested and compared with other available methods.Conclusions
DAG Expression is a freely available software that permits the automated analysis and visualization of high-throughput qPCR. A detailed manual and a demo-experiment are provided within the DAG Expression software at http://www.dagexpression.com/dage.zip. 相似文献8.
?zgün Babur Ugur Dogrusoz Merve ?ak?r Bülent Arman Aksoy Nikolaus Schultz Chris Sander Emek Demir 《BMC genomics》2014,15(1)
Background
Dynamic visual exploration of detailed pathway information can help researchers digest and interpret complex mechanisms and genomic datasets.Results
ChiBE is a free, open-source software tool for visualizing, querying, and analyzing human biological pathways in BioPAX format. The recently released version 2 can search for neighborhoods, paths between molecules, and common regulators/targets of molecules, on large integrated cellular networks in the Pathway Commons database as well as in local BioPAX models. Resulting networks can be automatically laid out for visualization using a graphically rich, process-centric notation. Profiling data from the cBioPortal for Cancer Genomics and expression data from the Gene Expression Omnibus can be overlaid on these networks.Conclusions
ChiBE’s new capabilities are organized around a genomics-oriented workflow and offer a unique comprehensive pathway analysis solution for genomics researchers. The software is freely available at http://code.google.com/p/chibe. 相似文献9.
Lei Li Hin-chung Wong Wenyan Nong Man Kit Cheung Patrick Tik Wan Law Kai Man Kam Hoi Shan Kwan 《BMC genomics》2014,15(1)
Background
Vibrio parahaemolyticus is a Gram-negative halophilic bacterium. Infections with the bacterium could become systemic and can be life-threatening to immunocompromised individuals. Genome sequences of a few clinical isolates of V. parahaemolyticus are currently available, but the genome dynamics across the species and virulence potential of environmental strains on a genome-scale have not been described before.Results
Here we present genome sequences of four V. parahaemolyticus clinical strains from stool samples of patients and five environmental strains in Hong Kong. Phylogenomics analysis based on single nucleotide polymorphisms revealed a clear distinction between the clinical and environmental isolates. A new gene cluster belonging to the biofilm associated proteins of V. parahaemolyticus was found in clincial strains. In addition, a novel small genomic island frequently found among clinical isolates was reported. A few environmental strains were found harboring virulence genes and prophage elements, indicating their virulence potential. A unique biphenyl degradation pathway was also reported. A database for V. parahaemolyticus (http://kwanlab.bio.cuhk.edu.hk/vp) was constructed here as a platform to access and analyze genome sequences and annotations of the bacterium.Conclusions
We have performed a comparative genomics analysis of clinical and environmental strains of V. parahaemolyticus. Our analyses could facilitate understanding of the phylogenetic diversity and niche adaptation of this bacterium.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-1135) contains supplementary material, which is available to authorized users. 相似文献10.
Background
Large clinical genomics studies using next generation DNA sequencing require the ability to select and track samples from a large population of patients through many experimental steps. With the number of clinical genome sequencing studies increasing, it is critical to maintain adequate laboratory information management systems to manage the thousands of patient samples that are subject to this type of genetic analysis.Results
To meet the needs of clinical population studies using genome sequencing, we developed a web-based laboratory information management system (LIMS) with a flexible configuration that is adaptable to continuously evolving experimental protocols of next generation DNA sequencing technologies. Our system is referred to as MendeLIMS, is easily implemented with open source tools and is also highly configurable and extensible. MendeLIMS has been invaluable in the management of our clinical genome sequencing studies.Conclusions
We maintain a publicly available demonstration version of the application for evaluation purposes at http://mendelims.stanford.edu. MendeLIMS is programmed in Ruby on Rails (RoR) and accesses data stored in SQL-compliant relational databases. Software is freely available for non-commercial use at http://dna-discovery.stanford.edu/software/mendelims/.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-290) contains supplementary material, which is available to authorized users. 相似文献11.
Nickolai Titov Blake F. Dear Luke Johnston Carolyn Lorian Judy Zou Bethany Wootton Jay Spence Peter M. McEvoy Ronald M. Rapee 《PloS one》2013,8(7)
Background
Depression and anxiety are common, disabling and chronic. Self-guided internet-delivered treatments are popular, but few people complete them. New strategies are required to realise their potential.Aims
To evaluate the effect of automated emails on the effectiveness, safety, and acceptability of a new automated transdiagnostic self-guided internet-delivered treatment, the Wellbeing Course, for people with depression and anxiety.Method
A randomised controlled trial was conducted through the website: www.ecentreclinic.org. Two hundred and fifty seven people with elevated symptoms were randomly allocated to the 8 week course either with or without automated emails, or to a waitlist control group. Primary outcome measures were the Patient Health Questionnaire 9-Item (PHQ-9) and the Generalized Anxiety Disorder 7-Item (GAD-7).Results
Participants in the treatment groups had lower PHQ-9 and GAD-7 scores at post-treatment than controls. Automated emails increased rates of course completion (58% vs. 35%), and improved outcomes in a subsample with elevated symptoms.Conclusions
The new self-guided course was beneficial, and automated emails facilitated outcomes. Further attention to strategies that facilitate adherence, learning, and safety will help realise the potential of self-guided interventions.Trial Registration
Australian and New Zealand Clinical Trials Registry ACTRN12610001058066 相似文献12.
Kathleen M. Griffiths Andrew J. Mackinnon Dimity A. Crisp Helen Christensen Kylie Bennett Louise Farrer 《PloS one》2012,7(12)
Background
Internet support groups (ISGs) are popular, particularly among people with depression, but there is little high quality evidence concerning their effectiveness.Aim
The study aimed to evaluate the efficacy of an ISG for reducing depressive symptoms among community members when used alone and in combination with an automated Internet-based psychotherapy training program.Method
Volunteers with elevated psychological distress were identified using a community-based screening postal survey. Participants were randomised to one of four 12-week conditions: depression Internet Support Group (ISG), automated depression Internet Training Program (ITP), combination of the two (ITP+ISG), or a control website with delayed access to e-couch at 6 months. Assessments were conducted at baseline, post-intervention, 6 and 12 months.Results
There was no change in depressive symptoms relative to control after 3 months of exposure to the ISG. However, both the ISG alone and the combined ISG+ITP group showed significantly greater reduction in depressive symptoms at 6 and 12 months follow-up than the control group. The ITP program was effective relative to control at post-intervention but not at 6 months.Conclusions
ISGs for depression are promising and warrant further empirical investigation.Trial Registration
Controlled-Trials.com ISRCTN65657330 相似文献13.
Hanneke de Waal Cornelis J. Stam Marieke M. Lansbergen Rico L. Wieggers Patrick J. G. H. Kamphuis Philip Scheltens Fernando Maestú Elisabeth C. W. van Straaten 《PloS one》2014,9(1)
Background
Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials.Objective
To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD.Design
A 24-week randomised, controlled, double-blind, parallel-group, multi-country study.Participants
179 drug-naïve mild AD patients who participated in the Souvenir II study.Intervention
Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks.Outcome
In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance.Results
The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance.Conclusions
The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions.Trial registration
Dutch Trial Register NTR1975. 相似文献14.
Objective
To evaluate the effectiveness of a school-based intervention involving the families and teachers that aimed to promote healthy eating habits in adolescents; the ultimate aim of the intervention was to reduce the increase in body mass index (BMI) of the students.Design
Paired cluster randomized school-based trial conducted with a sample of fifth graders.Setting
Twenty classes were randomly assigned into either an intervention group or a control group.Participants
From a total of 574 eligible students, 559 students participated in the study (intervention: 10 classes with 277 participants; control: 10 classes with 282 participants). The mean age of students was 11 years.Intervention
Students attended 9 nutritional education sessions during the 2010 academic year. Parents/guardians and teachers received information on the same subjects.Main Outcome Measurement
Changes in BMI and percentage of body fat.Results
Intention-to-treat analysis showed that changes in BMI were not significantly different between the 2 groups (β = 0.003; p = 0.75). There was a major reduction in the consumption of sugar-sweetened beverages and cookies in the intervention group; students in this group also consumed more fruits.Conclusion
Encouraging the adoption of healthy eating habits promoted important changes in the adolescent diet, but this did not lead to a reduction in BMI gain. Strategies based exclusively on the quality of diet may not reduce weight gain among adolescents.Trial Registration
Clinicaltrials.gov NCT01046474. 相似文献15.
Derek J. Hoare Nicolas Van Labeke Abby McCormack Magdalena Sereda Sandra Smith Hala Al Taher Victoria L. Kowalkowski Mike Sharples Deborah A. Hall 《PloS one》2014,9(9)
Background
Previous studies of frequency discrimination training (FDT) for tinnitus used repetitive task-based training programmes relying on extrinsic factors to motivate participation. Studies reported limited improvement in tinnitus symptoms.Purpose
To evaluate FDT exploiting intrinsic motivations by integrating training with computer-gameplay.Methods
Sixty participants were randomly assigned to train on either a conventional task-based training, or one of two interactive game-based training platforms over six weeks. Outcomes included assessment of motivation, tinnitus handicap, and performance on tests of attention.Results
Participants reported greater intrinsic motivation to train on the interactive game-based platforms, yet compliance of all three groups was similar (∼70%) and changes in self-reported tinnitus severity were not significant. There was no difference between groups in terms of change in tinnitus severity or performance on measures of attention.Conclusion
FDT can be integrated within an intrinsically motivating game. Whilst this may improve participant experience, in this instance it did not translate to additional compliance or therapeutic benefit.Trial Registration
ClinicalTrials.gov NCT02095262 相似文献16.
Helen Anne Snooks Ben Carter Jeremy Dale Theresa Foster Ioan Humphreys Philippa Anne Logan Ronan Anthony Lyons Suzanne Margaret Mason Ceri James Phillips Antonio Sanchez Mushtaq Wani Alan Watkins Bridget Elizabeth Wells Richard Whitfield Ian Trevor Russell 《PloS one》2014,9(9)
Objective
To evaluate effectiveness, safety and cost-effectiveness of Computerised Clinical Decision Support (CCDS) for paramedics attending older people who fall.Design
Cluster trial randomised by paramedic; modelling.Setting
13 ambulance stations in two UK emergency ambulance services.Participants
42 of 409 eligible paramedics, who attended 779 older patients for a reported fall.Interventions
Intervention paramedics received CCDS on Tablet computers to guide patient care. Control paramedics provided care as usual. One service had already installed electronic data capture.Main Outcome Measures
Effectiveness: patients referred to falls service, patient reported quality of life and satisfaction, processes of care.Safety
Further emergency contacts or death within one month.Cost-Effectiveness
Costs and quality of life. We used findings from published Community Falls Prevention Trial to model cost-effectiveness.Results
17 intervention paramedics used CCDS for 54 (12.4%) of 436 participants. They referred 42 (9.6%) to falls services, compared with 17 (5.0%) of 343 participants seen by 19 control paramedics [Odds ratio (OR) 2.04, 95% CI 1.12 to 3.72]. No adverse events were related to the intervention. Non-significant differences between groups included: subsequent emergency contacts (34.6% versus 29.1%; OR 1.27, 95% CI 0.93 to 1.72); quality of life (mean SF12 differences: MCS −0.74, 95% CI −2.83 to +1.28; PCS −0.13, 95% CI −1.65 to +1.39) and non-conveyance (42.0% versus 36.7%; OR 1.13, 95% CI 0.84 to 1.52). However ambulance job cycle time was 8.9 minutes longer for intervention patients (95% CI 2.3 to 15.3). Average net cost of implementing CCDS was £208 per patient with existing electronic data capture, and £308 without. Modelling estimated cost per quality-adjusted life-year at £15,000 with existing electronic data capture; and £22,200 without.Conclusions
Intervention paramedics referred twice as many participants to falls services with no difference in safety. CCDS is potentially cost-effective, especially with existing electronic data capture.Trial Registration
ISRCTN Register ISRCTN10538608 相似文献17.
Vishal Saxena Shweta Ramdas Courtney Rothrock Ochoa David Wallace Pradeep Bhide Isaac Kohane 《PloS one》2012,7(12)
Background
Numerous linkage studies have been performed in pedigrees of Autism Spectrum Disorders, and these studies point to diverse loci and etiologies of autism in different pedigrees. The underlying pattern may be identified by an integrative approach, especially since ASD is a complex disorder manifested through many loci.Method
Autism spectrum disorder (ASD) was studied through two different and independent genome-scale measurement modalities. We analyzed the results of copy number variation in autism and triangulated these with linkage studies.Results
Consistently across both genome-scale measurements, the same two molecular themes emerged: immune/chemokine pathways and developmental pathways.Conclusion
Linkage studies in aggregate do indeed share a thematic consistency, one which structural analyses recapitulate with high significance. These results also show for the first time that genomic profiling of pathways using a recombination distance metric can capture pathways that are consistent with those obtained from copy number variations (CNV). 相似文献18.
19.
Christine Danel Mathieu Kabran André Inwoley Anani Badje Jean Louis Herrmann Raoul Moh Jér?me Lecarrou Delphine Gabillard Jean Baptiste Ntakpe Nina Deschamps Eric Ouattara Christian Perronne Serge Eholie Xavier Anglaret 《PloS one》2014,9(10)
Objective
To assess the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) test for active tuberculosis (TB) in HIV adults, and its variation over time in patients on antiretroviral therapy (ART) and/or isoniazide preventive therapy (IPT).Methods
Transversal study and cohort nested in the Temprano ANRS 12136 randomized controlled trial assessing benefits of initiating ART earlier than currently recommended by World Health Organization, with or without a 6-month IPT. Performance of QFT-GIT for detecting active TB at baseline in the first 50% participants, and 12-month incidence of conversion/reversion in the first 25% participants were assessed. QFT-GIT threshold for positivity was 0.35 IU/ml.Results
Among the 975 first participants (median baseline CD4 count 383/mm3, positive QFT-GIT test 35%), 2.7% had active TB at baseline. QFT-GIT sensitivity, specificity, positive and negative predictive value for active TB were 88.0%, 66.6%, 6.5% and 99.5%. For the 444 patients with a second test at 12 months, rates for conversion and reversion were 9.3% and 14%. Reversion was more frequent in patients without ART and younger patients. IPT and early ART were not associated with reversion/conversion.Conclusion
A negative QFT-GIT could rule out active TB in HIV-infected adults not severely immunosuppressed, thus avoiding repeated TB testing and accelerating diagnosis and care for other diseases.Trial Registration
ClinicalTrials.gov NCT00495651. 相似文献20.
Stefano Balducci Silvano Zanuso Patrizia Cardelli Laura Salvi Alessandra Bazuro Luca Pugliese Carla Maccora Carla Iacobini Francesco G. Conti Antonio Nicolucci Giuseppe Pugliese for the Italian Diabetes Exercise Study Investigators 《PloS one》2012,7(11)