R/qtl: QTL mapping in experimental crosses

SUMMARY: R/qtl is an extensible, interactive environment for mapping quantitative trait loci (QTLs) in experimental populations derived from inbred lines. It is implemented as an add-on package for the freely-available statistical software, R, and includes functions for estimating genetic maps, identifying genotyping errors, and performing single-QTL and two-dimensional, two-QTL genome scans by multiple methods, with the possible inclusion of covariates. AVAILABILITY: The package is freely available at http://www.biostat.jhsph.edu/~kbroman/qtl.     

OTUbase: an R infrastructure package for operational taxonomic unit data

SUMMARY: OTUbase is an R package designed to facilitate the analysis of operational taxonomic unit (OTU) data and sequence classification (taxonomic) data. Currently there are programs that will cluster sequence data into OTUs and/or classify sequence data into known taxonomies. However, there is a need for software that can take the summarized output of these programs and organize it into easily accessed and manipulated formats. OTUbase provides this structure and organization within R, to allow researchers to easily manipulate the data with the rich library of R packages currently available for additional analysis. AVAILABILITY: OTUbase is an R package available through Bioconductor. It can be found at http://www.bioconductor.org/packages/release/bioc/html/OTUbase.html.     

qpcR: an R package for sigmoidal model selection in quantitative real-time polymerase chain reaction analysis

The qpcR library is an add-on to the free R statistical environment performing sigmoidal model selection in real-time quantitative polymerase chain reaction (PCR) data analysis. Additionally, the package implements the most commonly used algorithms for real-time PCR data analysis and is capable of extensive statistical comparison for the selection and evaluation of the different models based on several measures of goodness of fit. AVAILABILITY: www.dr-spiess.de/qpcR.html. SUPPLEMENTARY INFORMATION: Statistical evaluations of the implemented methods can be found at www.dr-spiess.de under 'Supplemental Data'.     

MetaQuant: a tool for the automatic quantification of GC/MS-based metabolome data

MetaQuant is a Java-based program for the automatic and accurate quantification of GC/MS-based metabolome data. In contrast to other programs MetaQuant is able to quantify hundreds of substances simultaneously with minimal manual intervention. The integration of a self-acting calibration function allows the parallel and fast calibration for several metabolites simultaneously. Finally, MetaQuant is able to import GC/MS data in the common NetCDF format and to export the results of the quantification into Systems Biology Markup Language (SBML), Comma Separated Values (CSV) or Microsoft Excel (XLS) format. AVAILABILITY: MetaQuant is written in Java and is available under an open source license. Precompiled packages for the installation on Windows or Linux operating systems are freely available for download. The source code as well as the installation packages are available at http://bioinformatics.org/metaquant     

Consensus sequences improve PSI-BLAST through mimicking profile-profile alignments

Sequence alignments may be the most fundamental computational resource for molecular biology. The best methods that identify sequence relatedness through profile-profile comparisons are much slower and more complex than sequence-sequence and sequence-profile comparisons such as, respectively, BLAST and PSI-BLAST. Families of related genes and gene products (proteins) can be represented by consensus sequences that list the nucleic/amino acid most frequent at each sequence position in that family. Here, we propose a novel approach for consensus-sequence-based comparisons. This approach improved searches and alignments as a standard add-on to PSI-BLAST without any changes of code. Improvements were particularly significant for more difficult tasks such as the identification of distant structural relations between proteins and their corresponding alignments. Despite the fact that the improvements were higher for more divergent relations, they were consistent even at high accuracy/low error rates for non-trivially related proteins. The improvements were very easy to achieve; no parameter used by PSI-BLAST was altered and no single line of code changed. Furthermore, the consensus sequence add-on required relatively little additional CPU time. We discuss how advanced users of PSI-BLAST can immediately benefit from using consensus sequences on their local computers. We have also made the method available through the Internet (http://www.rostlab.org/services/consensus/).     

Evaluation of Tools for Modeling Manufacturing Systems Design with Multiple Levels of Detail

This paper presents an investigation of simulation packages regarding their ability to model business processes related to manufacturing systems. Three simulation packages are investigated: VS7, SIMAN/CINEMA IV, and SIMFACTORY II.5. These packages are evaluated with regard to their capabily of modeling problems related to the manufacturing systems design (MSD) framework, which involves different levels of detail: the conceptual modeling level and the detailed design level. The investigation is based on a case study related to manufacturing systems. The main objective of this investigation is to examine the manufacturing simulation packages and their ability to offer variable detail modeling. Research findings suggest that no simulation environment offers sufficiently flexible facilities for the variable detailed modeling of manufacturing systems design. The paper proposes a method for systems entity classification to increase the levels of detail in an effective manner without duplication of data collection and model building efforts.     

nucleR: a package for non-parametric nucleosome positioning

SUMMARY: nucleR is an R/Bioconductor package for a flexible and fast recognition of nucleosome positioning from next generation sequencing and tiling arrays experiments. The software is integrated with standard high-throughput genomics R packages and allows for in situ visualization as well as to export results to common genome browser formats. AVAILABILITY: Additional information and methodological details can be found at http://mmb.pcb.ub.es/nucleR     

LabArray: real-time imaging and analytical tool for microarrays

SUMMARY: Microarrays have been used to perform high-throughput genetic analyses such as single-nucleotide polymorphisms detection and microbial genome analysis. Some of these analyses require real-time monitoring of the hybridization signals with respect to a varying experimental condition, such as temperature. However, current microarray imaging and analysis packages typically do not possess such real-time capabilities. Therefore, microarray image analyses are often time-consuming and labour-intensive. LabArray was developed to expedite such processes by enabling real-time monitoring of microarray signals. AVAILABILITY: LabArray is available at http://www.eng.nus.edu.sg/civil/Labarray/labarray.htm CONTACT: cveliuwt@nus.edu.sg SUPPLEMENTARY INFORMATION: Screenshots and instructions for use are available at the above website.     

Computational methods for evaluation of cell-based data assessment—Bioconductor

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Highlights► Bioconductor proposes more than 20 R packages for FCM analysis. ► Data infrastructure proposed by flowCore has become the standard for many packages. ► Automated gating is improving but remains an intensive field of research.     

How many genes to start with? A computer simulation about the origin of life

A geneticist's view on the origin of life would focus on individual nucleic acid molecules rather than on their concentrations, on stochastics rather than on differential equations.The package model envisages primordial compartments that contain ensembles of primordial genes. These are replicated independently from each other. During package fission they are distributed to two daughter packages. Packages with a complete ensemble of genes can continue to propagate. However, mutations as well as the stochastic nature of replication and package fission occasionally cause arising packages to miss genes from the ensemble, thus resulting in the death of those packages.A computer simulation, considering the complementarity of RNA as well as abortive termination of replication, yielded results that are similar to those of a preliminary simulation irrespective of these parameters: the results suggest that life could not have started with more than 3 genes, or else the primordial replicase would have to achieve at least a reduction of the replicational error rate by a factor of 13 and a reduction of undue chain termination by a factor of 10 to 25.     

Structure of a Novel O-Linked N-Acetyl-d-glucosamine (O-GlcNAc) Transferase,GtfA, Reveals Insights into the Glycosylation of Pneumococcal Serine-rich Repeat Adhesins

Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a critical role in various biological processes. In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. Here we report the 2.0 Å crystal structure of GtfA, revealing a β-meander add-on domain beyond the catalytic domain. It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. Structural analyses combined with binding assays indicate that this add-on domain contributes to forming an active GtfA-GtfB complex and recognizing the acceptor protein. In addition, the in vitro glycosylation system enables us to map the O-linkages to the serine residues within the first SRR of PsrP. These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides.     

Unprecedented Therapeutic Potential with a Combination of A2A/NR2B Receptor Antagonists as Observed in the 6-OHDA Lesioned Rat Model of Parkinson's Disease

In Parkinson''s disease, the long-term use of dopamine replacing agents is associated with the development of motor complications; therefore, there is a need for non-dopaminergic drugs. This study evaluated the potential therapeutic impact of six different NR2B and A_2A receptor antagonists given either alone or in combination in unilateral 6-OHDA-lesioned rats without (monotherapy) or with (add-on therapy) the co-administration of L-Dopa: Sch-58261+ Merck 22; Sch-58261+Co-101244; Preladenant + Merck 22; Preladenant + Radiprodil; Tozadenant + Radiprodil; Istradefylline + Co-101244. Animals given monotherapy were assessed on distance traveled and rearing, whereas those given add-on therapy were assessed on contralateral rotations. Three-way mixed ANOVA were conducted to assess the main effect of each drug separately and to determine whether any interaction between two drugs was additive or synergistic. Additional post hoc analyses were conducted to compare the effect of the combination with the effect of the drugs alone. Motor activity improved significantly and was sustained for longer when the drugs were given in combination than when administered separately at the same dose. Similarly, when tested as add-on treatment to L-Dopa, the combinations resulted in higher levels of contralateral rotation in comparison to the single drugs. Of special interest, the activity observed with some combinations could not be described by a simplistic additive effect and involved more subtle synergistic pharmacological interactions. The combined administration of A_2A/NR2B-receptor antagonists improved motor behaviour in 6-OHDA rats. Given the proven translatability of this model such a combination may be expected to be effective in improving motor symptoms in patients.     

SeqSQC: A Bioconductor Package for Evaluating the Sample Quality of Next-generation Sequencing Data

As next-generation sequencing (NGS) technology has become widely used to identify genetic causal variants for various diseases and traits,a number of packages for checking NGS data quality have sprung up in public domains. In addition to the quality of sequencing data,sample quality issues,such as gender mismatch,abnormal inbreeding coefficient,cryptic relatedness,and population outliers,can also have fundamental impact on downstream analysis. However,there is a lack of tools specialized in identifying problematic samples from NGS data,often due to the limitation of sample size and variant counts. We developed SeqSQC,a Bioconductor package,to automate and accelerate sample cleaning in NGS data of any scale. SeqSQC is designed for efficient data storage and access,and equipped with interactive plots for intuitive data visualization to expedite the identification of problematic samples. SeqSQC is available at http://bioconductor. org/packages/SeqSQC.     

Combination HIV Prevention among MSM in South Africa: Results from Agent-based Modeling

HIV prevention trials have demonstrated the effectiveness of a number of behavioral and biomedical interventions. HIV prevention packages are combinations of interventions and offer potential to significantly increase the effectiveness of any single intervention. Estimates of the effectiveness of prevention packages are important for guiding the development of prevention strategies and for characterizing effect sizes before embarking on large scale trials. Unfortunately, most research to date has focused on testing single interventions rather than HIV prevention packages. Here we report the results from agent-based modeling of the effectiveness of HIV prevention packages for men who have sex with men (MSM) in South Africa. We consider packages consisting of four components: antiretroviral therapy for HIV infected persons with CD4 count <350; PrEP for high risk uninfected persons; behavioral interventions to reduce rates of unprotected anal intercourse (UAI); and campaigns to increase HIV testing. We considered 163 HIV prevention packages corresponding to different intensity levels of the four components. We performed 2252 simulation runs of our agent-based model to evaluate those packages. We found that a four component package consisting of a 15% reduction in the rate of UAI, 50% PrEP coverage of high risk uninfected persons, 50% reduction in persons who never test for HIV, and 50% ART coverage over and above persons already receiving ART at baseline, could prevent 33.9% of infections over 5 years (95% confidence interval, 31.5, 36.3). The package components with the largest incremental prevention effects were UAI reduction and PrEP coverage. The impact of increased HIV testing was magnified in the presence of PrEP. We find that HIV prevention packages that include both behavioral and biomedical components can in combination prevent significant numbers of infections with levels of coverage, acceptance and adherence that are potentially achievable among MSM in South Africa.     

BioJava: an open-source framework for bioinformatics

SUMMARY: BioJava is a mature open-source project that provides a framework for processing of biological data. BioJava contains powerful analysis and statistical routines, tools for parsing common file formats and packages for manipulating sequences and 3D structures. It enables rapid bioinformatics application development in the Java programming language. AVAILABILITY: BioJava is an open-source project distributed under the Lesser GPL (LGPL). BioJava can be downloaded from the BioJava website (http://www.biojava.org). BioJava requires Java 1.5 or higher. All queries should be directed to the BioJava mailing lists. Details are available at http://biojava.org/wiki/BioJava:MailingLists.     

Sperm package morphology in scorpions and its relation to phylogeny

Sperm packages are widespread in the order Scorpiones, but absent in the family Buthidae. The morphology of sperm packages is diverse and apparently has phylogenetic information. The objectives of this work were to show diversity of sperm packages and to provide a quantitative basis for using sperm packages’ morphology as a taxonomic character. For this, we conducted a morphological analysis and comparison of the different sperm packages of species of the family Bothriuridae. The seminal content from males of species of Bothriuridae was studied. Specimens from Iuridae, Buthidae, Euscorpiidae, Liochelidae, Scorpionidae, Vaejovidae, Chaerilidae, and Chactidae were used for comparison. Digital images of sperm packages were measured and statistically analysed based on the following variables: total length, head width, head–body angle, total area, and head length. Pairs of variables were also contrasted, and all the variables were correlated with the current phylogenetic hypothesis for Bothriuridae. High morphological diversity and variability in measures was observed. In general, measurements were similar within each genus, but differed amongst genera. Cane‐like sperm packages are very common in species of the family Bothriuridae. Species from Bothriurus show a wide range of sperm package shapes, some of them shared with Timogenes and Vachonia species, supporting the idea of nonmonophyly of the genus. Many species showed sperm package dimorphism inside a single male. Some of the analysed features fit well with the phylogenetic hypothesis in Bothriuridae, and the general package shape shows high correlation with scorpion phylogeny in other families. Bent and round packages are the most common amongst the different families. Sperm packages are not developed in Chaerilidae, as in Buthidae. This is the first morphological and comparative analysis of sperm packages in scorpions, and reveals much greater diversity in this trait than previously known. Our results reinforce the idea that the study of morphology of sperm packages would contribute characters for scorpion phylogeny at different levels. © 2011 The Linnean Society of London, Zoological Journal of the Linnean Society, 2011, 161 , 463–483.     

Memes: A motif analysis environment in R using tools from the MEME Suite

Identification of biopolymer motifs represents a key step in the analysis of biological sequences. The MEME Suite is a widely used toolkit for comprehensive analysis of biopolymer motifs; however, these tools are poorly integrated within popular analysis frameworks like the R/Bioconductor project, creating barriers to their use. Here we present memes, an R package that provides a seamless R interface to a selection of popular MEME Suite tools. memes provides a novel “data aware” interface to these tools, enabling rapid and complex discriminative motif analysis workflows. In addition to interfacing with popular MEME Suite tools, memes leverages existing R/Bioconductor data structures to store the multidimensional data returned by MEME Suite tools for rapid data access and manipulation. Finally, memes provides data visualization capabilities to facilitate communication of results. memes is available as a Bioconductor package at https://bioconductor.org/packages/memes, and the source code can be found at github.com/snystrom/memes.     

GenomeDiagram: a python package for the visualization of large-scale genomic data

SUMMARY: We present GenomeDiagram, a flexible, open-source Python module for the visualization of large-scale genomic, comparative genomic and other data with reference to a single chromosome or other biological sequence. GenomeDiagram may be used to generate publication-quality vector graphics, rastered images and in-line streamed graphics for webpages. The package integrates with datatypes from the BioPython project, and is available for Windows, Linux and Mac OS X systems. AVAILABILITY: GenomeDiagram is freely available as source code (under GNU Public License) at http://bioinf.scri.ac.uk/lp/programs.html, and requires Python 2.3 or higher, and recent versions of the ReportLab and BioPython packages. SUPPLEMENTARY INFORMATION: A user manual, example code and images are available at http://bioinf.scri.ac.uk/lp/programs.html.