A practical, bioinformatic workflow system for large data sets generated by next-generation sequencing

Transcriptomics (at the level of single cells, tissues and/or whole organisms) underpins many fields of biomedical science, from understanding the basic cellular function in model organisms, to the elucidation of the biological events that govern the development and progression of human diseases, and the exploration of the mechanisms of survival, drug-resistance and virulence of pathogens. Next-generation sequencing (NGS) technologies are contributing to a massive expansion of transcriptomics in all fields and are reducing the cost, time and performance barriers presented by conventional approaches. However, bioinformatic tools for the analysis of the sequence data sets produced by these technologies can be daunting to researchers with limited or no expertise in bioinformatics. Here, we constructed a semi-automated, bioinformatic workflow system, and critically evaluated it for the analysis and annotation of large-scale sequence data sets generated by NGS. We demonstrated its utility for the exploration of differences in the transcriptomes among various stages and both sexes of an economically important parasitic worm (Oesophagostomum dentatum) as well as the prediction and prioritization of essential molecules (including GTPases, protein kinases and phosphatases) as novel drug target candidates. This workflow system provides a practical tool for the assembly, annotation and analysis of NGS data sets, also to researchers with a limited bioinformatic expertise. The custom-written Perl, Python and Unix shell computer scripts used can be readily modified or adapted to suit many different applications. This system is now utilized routinely for the analysis of data sets from pathogens of major socio-economic importance and can, in principle, be applied to transcriptomics data sets from any organism

A practical, bioinformatic workflow system for large data sets generated by next-generation sequencing

Transcriptomics (at the level of single cells, tissues and/or whole organisms) underpins many fields of biomedical science, from understanding the basic cellular function in model organisms, to the elucidation of the biological events that govern the development and progression of human diseases, and the exploration of the mechanisms of survival, drug-resistance and virulence of pathogens. Next-generation sequencing (NGS) technologies are contributing to a massive expansion of transcriptomics in all fields and are reducing the cost, time and performance barriers presented by conventional approaches. However, bioinformatic tools for the analysis of the sequence data sets produced by these technologies can be daunting to researchers with limited or no expertise in bioinformatics. Here, we constructed a semi-automated, bioinformatic workflow system, and critically evaluated it for the analysis and annotation of large-scale sequence data sets generated by NGS. We demonstrated its utility for the exploration of differences in the transcriptomes among various stages and both sexes of an economically important parasitic worm (Oesophagostomum dentatum) as well as the prediction and prioritization of essential molecules (including GTPases, protein kinases and phosphatases) as novel drug target candidates. This workflow system provides a practical tool for the assembly, annotation and analysis of NGS data sets, also to researchers with a limited bioinformatic expertise. The custom-written Perl, Python and Unix shell computer scripts used can be readily modified or adapted to suit many different applications. This system is now utilized routinely for the analysis of data sets from pathogens of major socio-economic importance and can, in principle, be applied to transcriptomics data sets from any organism

A robust high-sensitivity algorithm for automated detection of proteins in two-dimensional electrophoresis gels

The automated interpretation of two-dimensional gel electrophoresis images used in protein separation and analysis presents a formidable problem in the detection and characterization of ill-defined spatial objects. We describe in this paper a hierarchical algorithm that provides a robust, high-sensitivity solution to this problem, which can be easily adapted to a variety of experimental situations. The software implementation of this algorithm functions as part of a complete package designed for general protein gel analysis applications

VETA x ray data acquisition and control system

We describe the X-ray Data Acquisition and Control System (XDACS) used together with the X-ray Detection System (XDS) to characterize the X-ray image during testing of the AXAF P1/H1 mirror pair at the MSFC X-ray Calibration Facility. A variety of X-ray data were acquired, analyzed and archived during the testing including: mirror alignment, encircled energy, effective area, point spread function, system housekeeping and proportional counter window uniformity data. The system architecture is presented with emphasis placed on key features that include a layered UNIX tool approach, dedicated subsystem controllers, real-time X-window displays, flexibility in combining tools, network connectivity and system extensibility. The VETA test data archive is also described

SICLE: A high-throughput tool for extracting evolutionary relationships from phylogenetic trees

We present the phylogeny analysis software SICLE (Sister Clade Extractor), an easy-to-use, high- throughput tool to describe the nearest neighbors to a node of interest in a phylogenetic tree as well as the support value for the relationship. The application is a command line utility that can be embedded into a phylogenetic analysis pipeline or can be used as a subroutine within another C++ program. As a test case, we applied this new tool to the published phylome of Salinibacter ruber, a species of halophilic Bacteriodetes, identifying 13 unique sister relationships to S. ruber across the 4589 gene phylogenies. S. ruber grouped with bacteria, most often other Bacteriodetes, in the majority of phylogenies, but 91 phylogenies showed a branch-supported sister association between S. ruber and Archaea, an evolutionarily intriguing relationship indicative of horizontal gene transfer. This test case demonstrates how SICLE makes it possible to summarize the phylogenetic information produced by automated phylogenetic pipelines to rapidly identify and quantify the possible evolutionary relationships that merit further investigation. SICLE is available for free for noncommercial use at http://eebweb.arizona.edu/sicle/.Comment: 8 pages, 4 figures in journal submission forma

SIRENA: A CAD environment for behavioural modelling and simulation of VLSI cellular neural network chips

This paper presents SIRENA, a CAD environment for the simulation and modelling of mixed-signal VLSI parallel processing chips based on cellular neural networks. SIRENA includes capabilities for: (a) the description of nominal and non-ideal operation of CNN analogue circuitry at the behavioural level; (b) performing realistic simulations of the transient evolution of physical CNNs including deviations due to second-order effects of the hardware; and, (c) evaluating sensitivity figures, and realize noise and Monte Carlo simulations in the time domain. These capabilities portray SIRENA as better suited for CNN chip development than algorithmic simulation packages (such as OpenSimulator, Sesame) or conventional neural networks simulators (RCS, GENESIS, SFINX), which are not oriented to the evaluation of hardware non-idealities. As compared to conventional electrical simulators (such as HSPICE or ELDO-FAS), SIRENA provides easier modelling of the hardware parasitics, a significant reduction in computation time, and similar accuracy levels. Consequently, iteration during the design procedure becomes possible, supporting decision making regarding design strategies and dimensioning. SIRENA has been developed using object-oriented programming techniques in C, and currently runs under the UNIX operating system and X-Windows framework. It employs a dedicated high-level hardware description language: DECEL, fitted to the description of non-idealities arising in CNN hardware. This language has been developed aiming generality, in the sense of making no restrictions on the network models that can be implemented. SIRENA is highly modular and composed of independent tools. This simplifies future expansions and improvements.Comisión Interministerial de Ciencia y Tecnología TIC96-1392-C02-0

A Programming Environment Evaluation Methodology for Object-Oriented Systems

The object-oriented design strategy as both a problem decomposition and system development paradigm has made impressive inroads into the various areas of the computing sciences. Substantial development productivity improvements have been demonstrated in areas ranging from artificial intelligence to user interface design. However, there has been very little progress in the formal characterization of these productivity improvements and in the identification of the underlying cognitive mechanisms. The development and validation of models and metrics of this sort require large amounts of systematically-gathered structural and productivity data. There has, however, been a notable lack of systematically-gathered information on these development environments. A large part of this problem is attributable to the lack of a systematic programming environment evaluation methodology that is appropriate to the evaluation of object-oriented systems

Info Navigator: A visualization tool for document searching and browsing

In this paper we investigate the retrieval performance of monophonic and polyphonic queries made on a polyphonic music database. We extend the n-gram approach for full-music indexing of monophonic music data to polyphonic music using both rhythm and pitch information. We define an experimental framework for a comparative and fault-tolerance study of various n-gramming strategies and encoding levels. For monophonic queries, we focus in particular on query-by-humming systems, and for polyphonic queries on query-by-example. Error models addressed in several studies are surveyed for the fault-tolerance study. Our experiments show that different n-gramming strategies and encoding precision differ widely in their effectiveness. We present the results of our study on a collection of 6366 polyphonic MIDI-encoded music pieces