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TRES: comparative promoter sequence analysis.

Comparative promoter analysis is a promising strategy for elucidation of common regulatory modules conserved in evolutionarily related sequences or in genes showing common expression profiles. To facilitate such analysis, we have developed a software tool that detects conserved transcription factor binding sites, cis-elements, palindromes and k-tuples simultaneously in a set of sequences, and thus helps to identify putative motifs for designing further experiments.

Animals↗

MethTools--a toolbox to visualize and analyze DNA methylation data.

The Bisulfite Genomic Sequencing technique has found wide acceptance for the generation of DNA-methylation maps with single-base resolution. The method is based on the selective deamination of cytosine to uracil (and subsequent conversion to thymine via PCR), whereas 5-methylcytosine residues remain unchanged. Methylation maps are created by the comparison of bisulfite converted sequences with the untreated genomic sequence. 'MethTools' is a collection of software tools that replaces the time-consuming manual comparison process, generates graphical outputs of methylation patterns and methyl-ation density, estimates the systematic error of the experiment and searches for conserved methylated nucleotide patterns. The programs are written in Perl 5 and C, and the source code can be downloaded. All tools run independently but the programs are interfaced. Thus, a script can perform the entire analysis procedure automatically. In addition, a web-based remote analysis service is offered. Both the source code and the remote analysis are available at http://genome.imb-jena.de/methtools/

Animals↗

Automation comes to the aid of credentialing efforts.

Virtually every hospital and managed care plan performs credentialing for every physician, and it can be a labor-intensive--and redundant--effort. But administrative software tools are being developed and expanded to better gather and keep track of vital information about physicians. Some providers and health plans are also working together to centralize the process by electronically sharing the information.

Chicago↗

Prescription of amiodarone through a computerized template that includes both decision support and executive functions improves the monitoring for toxicities.

The antiarrhythmic drug amiodarone causes severe side effects that warrant active monitoring. In a given patient, monitoring for amiodarone toxicities involves checking past results of five laboratory/imaging tests and reordering four of these tests every 6 to 12 month, a process that is both complex and time-consuming. We hypothesized that a software tool that automated the retrieval and ordering of these tests in a context-sensitive manner would improve the completeness of surveillance for drug toxicities.

Amiodarone↗

Quantitative profiling of differentiation-induced microsomal proteins using isotope-coded affinity tags and mass spectrometry.

An approach to the systematic identification and quantification of the proteins contained in the microsomal fraction of cells is described. It consists of three steps: (1) preparation of microsomal fractions from cells or tissues representing different states; (2) covalent tagging of the proteins with isotope-coded affinity tag (ICAT) reagents followed by proteolysis of the combined labeled protein samples; and (3) isolation, identification, and quantification of the tagged peptides by multidimensional chromatography, automated tandem mass spectrometry, and computational analysis of the obtained data. The method was used to identify and determine the ratios of abundance of each of 491 proteins contained in the microsomal fractions of naïve and in vitro- differentiated human myeloid leukemia (HL-60) cells. The method and the new software tools to support it are well suited to the large-scale, quantitative analysis of membrane proteins and other classes of proteins that have been refractory to standard proteomics technology.

Affinity Labels↗

moiraine: an R package to construct reproducible pipelines for the application and comparison of multi-omics integration methods.

MOTIVATION: In the past decades, many statistical methods for integrating multi-omics data have been developed. They have been implemented into software tools, which differ widely in their programming choices, such as the format required for data input, or the format of the generated integration results. This lack of standards renders cumbersome and time-intensive the application and comparison of different integration tools to the same multi-omics dataset. RESULTS: We have developed the moiraine R package for constructing reproducible multi-omics integration pipelines, which enables users to apply one or more statistical methods for multi-omics integration to their own multi-omics dataset. moiraine facilitates the preprocessing of the omics datasets and automates their formatting for the integration step. It simplifies the interpretation and evaluation of the integration results through the construction of visualizations in which metadata about samples and features can easily be included. Crucially, it enables the comparison of results obtained with different integration tools, allowing users to assess the robustness of their results. AVAILABILITY AND IMPLEMENTATION: The moiraine R package is publicly available at https://github.com/Plant-Food-Research-Open/moiraine; an archival snapshot of the package is available on Zenodo at https://doi.org/10.5281/zenodo.17172718. A detailed tutorial is available at https://plant-food-research-open.github.io/moiraine-manual/.

Software↗

Characterization and interpretation of electrical signals from random networks of cultured neurons.

The main purpose of this paper is to describe several software tools specifically adapted to characterize the electrophysiological behavior of a population of neurons coupled to a planar array of microtransducers by analyzing the recorded signals. Both graphic and signal processing tools are considered. They include: image analysis of the neuronal network topology, peak detection procedure, multi-graphics visualization, spike classification, cross-correlation, interspike and interbursting interval analysis. These tools are utilized to characterize changes induced in the electrophysiological behavior of populations of cultured neurons by modifications to the medium-culture.

Animals↗

CARMAweb: comprehensive R- and bioconductor-based web service for microarray data analysis.

CARMAweb (Comprehensive R-based Microarray Analysis web service) is a web application designed for the analysis of microarray data. CARMAweb performs data preprocessing (background correction, quality control and normalization), detection of differentially expressed genes, cluster analysis, dimension reduction and visualization, classification, and Gene Ontology-term analysis. This web application accepts raw data from a variety of imaging software tools for the most widely used microarray platforms: Affymetrix GeneChips, spotted two-color microarrays and Applied Biosystems (ABI) microarrays. R and packages from the Bioconductor project are used as an analytical engine in combination with the R function Sweave, which allows automatic generation of analysis reports. These report files contain all R commands used to perform the analysis and guarantee therefore a maximum transparency and reproducibility for each analysis. The web application is implemented in Java based on the latest J2EE (Java 2 Enterprise Edition) software technology. CARMAweb is freely available at https://carmaweb.genome.tugraz.at.

Cluster Analysis↗

G4SNVHunter: An R/Bioconductor Package for Evaluating SNV-Induced Disruption of G-Quadruplex Structures Leveraging the G4Hunter Algorithm.

G-quadruplexes (G4s) are nucleic acid secondary structures with important regulatory functions. Single-nucleotide variants (SNVs), one of the most common forms of genetic variation, can potentially impact the formation of G4 structures if they occur within G4 regions. However, there is currently a lack of software tools specifically designed to assess such effects. Here, we present an R/Bioconductor package named G4SNVHunter, which enables rapid detection of variants that may disrupt G4 structures. This tool, based on the core principles of the G4Hunter algorithm, can provide precise quantitative assessment of the propensity for G4 formation within genomic sequences. Specialized experimental methods can then be designed based on the results provided by G4SNVHunter to further verify the specific functions of the affected G4 structures, facilitating deeper insights into the biological impacts of genetic variants from the perspective of G4 structures. To showcase the functionality of the G4SNVHunter package, we analyzed the Neandertal and Denisovan archaic introgressed variants detected by the Sprime software, and identified approximately 5,800 variants located within G4 regions, among which around 230 may impair G4 structure formation propensity. The source code for the G4SNVHunter package has been publicly released under the MIT license at https://github.com/rongxinzh/G4SNVHunter and https://bioconductor.org/packages/devel/bioc/html/G4SNVHunter.html.

G-Quadruplexes↗

Computer software for process hazards analysis.

Computerized software tools are assuming major significance in conducting HAZOPs. This is because they have the potential to offer better online presentations and performance to HAZOP teams, as well as better documentation and downstream tracking. The chances of something being "missed" are greatly reduced. We know, only too well, that HAZOP sessions can be like the industrial equivalent of a trip to the dentist. Sessions can (and usually do) become arduous and painstaking. To make the process easier for all those involved, we need all the help computerized software can provide. In this paper I have outlined the challenges addressed in the production of Windows software for performing HAZOP and other forms of PHA. The object is to produce more "intelligent", more user-friendly software for performing HAZOP where technical interaction between team members is of key significance. HAZOP techniques, having already proven themselves, are extending into the field of computer control and human error. This makes further demands on HAZOP software and emphasizes its importance.

Artificial Intelligence↗

A design framework to model retinas.

Neuro-engineering is providing biomedical engineers with technology to interface the nervous system, which is useful to create prosthetic devices to palliate sensorial or motor disabilities. Motivated by the success of cochlear implants for deaf patients, we are now facing the challenge of creating a prosthetic visual system for the blind. An artificial retina whose response to stimuli can be matched to biological ones is required. To make easier the task of modeling, tuning and testing these retinal models, we have created a software tool that allows flexible and parametric definition and testing of retina-like models. The program can be fed with a variety of video or image sources, and the results can be easily compared to biological recordings of retinal ganglionar activity in response to the same stimuli. This tool can be useful, not only for this prosthetic purpose, but for any other research involving bio-inspired image processing with a neuromorphic output.

Artificial Organs↗

Multislice CT colonography: current status and limitations.

CT colonography (CTC) is a promising method for colorectal screening providing a full structural evaluation of the entire colon and gaining in popularity due to a superior safety profile, a low rate of complications, and high patient acceptance. Multislice CT (MSCT) has further improved the diagnostic potential of CTC by generating high-resolution CT images of the abdomen and pelvis in shorter acquisition times than was previously possible. Over the past year, multiple studies have been published on every aspect of CTC including techniques, image display, image reconstruction, and clinical trial results assessing the feasibility of CTC as a screening tool. Yet despite increasing clinical use, the appropriate role of CTC in colorectal cancer screening remains undefined and barriers to widespread adoption remain. In particular, though the test is generally regarded as easy to perform, accurate interpretation requires a steep learning curve. While several large studies have found high sensitivity and specificity, the accuracy of CTC in a screening population has yet to be verified and almost no health insurance plans reimburse for its use in colorectal screening. Ongoing research in computer-aided detection and new software tools, however, have the potential to increase accuracy and ease of interpretation significantly, accelerating its acceptance as a colorectal screening tool.

Colon↗

[A software program for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) with oxygen-sensitive (3)He-MRI].

PURPOSE: To develop a software tool for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) as well as its time course during apnea. MATERIAL AND METHODS: T (1)-relaxation times of hyperpolarized (3)He are reduced by paramagnetic oxygen rendering (3)He-MRI sensitive to oxygen and thus allowing the assessment of the local oxygen partial pressure in the pulmonary airspaces. Oxygen-related relaxation and loss of polarization by RF-excitation can be discriminated by acquiring two image series with varying interscan delay and/or flip angles. Software was developed to calculate the p(A)O(2) and the decay rate in user-defined regions of interest (ROIs) automatically. Moreover, parameter maps can be calculated. In addition to the analysis of 2-dimensional data sets, the software allows the evaluation of 3-dimensional measurements for the first time. Artifacts due to lung motion were reduced by implementing a motion correction algorithm. RESULTS: The software was successfully applied to data sets from healthy volunteers and from patients with various lung diseases. The parameter maps demonstrated a more homogeneous distribution of p(A)O(2) for the volunteers than for the patients. A regional increase in p(A)O(2) was found in a few patients. CONCLUSION: The described software allows the absolute quantification of p(A)O(2) as well as its variation over time. In the future, therefore, the software may gain importance for detecting mismatches between ventilation and perfusion, e. g., in patients with pulmonary embolism or chronic obstructive lung diseases.

Adult↗

Informatics solutions for high-throughput proteomics.

The success of mass-spectrometry-based proteomics as a method for analyzing proteins in biological samples is accompanied by challenges owning to demands for increased throughput. These challenges arise from the vast volume of data generated by proteomics experiments combined with the heterogeneity in data formats, processing methods, software tools and databases that are involved in the translation of spectral data into relevant and actionable information for scientists. Informatics aims to provide answers to these challenges by transferring existing solutions from information management to proteomics and/or by generating novel computational methods for automation of proteomics data processing.

Databases, Protein↗

A database system for integrated clinical trial management, control, statistical analysis and ICH-compliant reporting.

Clinical trial management and quality assurance is a complex activity that, when manually executed, is prone to errors and delays, and organizations involved in the conduct of clinical drug trials must rely on database systems to ensure adequate data integrity and timely reporting. We report the design and implementation of an integrated computer system for the management and control of multiple phase II to IV clinical drug trials, and for automated generation of monitoring and statistical analysis reports that are fully compliant with international guidelines. This Windows-based system incorporates a number of third-party software tools and applications, and its major components are COATI (Control, Assessment and Tracking of Therapeutic Investigations), a client-server database application; DART (Data Analysis and Reporting Tool) for automated data abstraction and reporting; and PANDA (Data Analysis Package) for automated statistical analysis. The system is in production for two years and was used in 15 clinical trials in a diversity of medical conditions and study designs.

Clinical Trials as Topic↗

Application of a human error framework to conduct train accident/incident investigations.

Accident/incident investigations are an important qualitative approach to understanding and managing transportation safety. To better understand potential safety implications of recently introduced remote control locomotive (RCL) operations in railroad yard switching, researchers investigated six railroad accidents/incidents. To conduct the investigations, researchers first modified the human factors analysis and classification system (HFACS) to optimize its applicability to the railroad industry (HFACS-RR) and then developed accident/incident data collection and analysis tools based on HFACS-RR. A total of 36 probable contributing factors were identified among the six accidents/incidents investigated. Each accident/incident was associated with multiple contributing factors, and, for each accident/incident, active failures and latent conditions were identified. The application of HFACS-RR and a theoretically driven approach to investigating accidents/incidents involving human error ensured that all levels of the system were considered during data collection and analysis phases of the investigation and that investigations were systematic and thorough. Future work is underway to develop a handheld software tool that incorporates these data collection and analysis tools.

Accidents↗

PROF_ PAT 1.3: updated database of patterns used to detect local similarities.

MOTIVATION: When analysing novel protein sequences, it is now essential to extend search strategies to include a range of 'secondary' databases. Pattern databases have become vital tools for identifying distant relationships in sequences, and hence for predicting protein function and structure. The main drawback of such methods is the relatively small representation of proteins in trial samples at the time of their construction. Therefore, a negative result of an amino acid sequence comparison with such a databank forces a researcher to search for similarities in the original protein banks. We developed a database of patterns constructed for groups of related proteins with maximum representation of amino acid sequences of SWISS-PROT in the groups. RESULTS: Software tools and a new method have been designed to construct patterns of protein families. By using such method, a new version of databank of protein family patterns, PROF_ PAT 1.3, is produced. This bank is based on SWISS-PROT (r1.38) and TrEMBL (r1.11), and contains patterns of more than 13 000 groups of related proteins in a format similar to that of the PROSITE. Motifs of patterns, which had the minimum level of probability to be found in random sequences, were selected. Flexible fast search program accompanies the bank. The researcher can specify a similarity matrix (the type PAM, BLOSUM and other). Variable levels of similarity can be set (permitting search strategies ranging from exact matches to increasing levels of 'fuzziness'). AVAILABILITY: The Internet address for comparing sequences with the bank is: http://wwwmgs.bionet.nsc.ru/mgs/programs/prof_pat/. The local version of the bank and search programs (approximately 50 Mb) is available via ftp: ftp://ftp.bionet.nsc. ru/pub/biology/vector/prof_pat/, and ftp://ftp.ebi.ac. uk/pub/databases/prof_pat/. Another appropriate way for its external use is to mail amino acid sequences to bachin@vector.nsc.ru for comparison with PROF_ PAT 1.3.

Databases, Factual↗

Healthcare users and computerised resources.

This paper concerns users' views on computerised resources. The focus concerns a software tool that could be used to allow safety conscious user manipulation of the combination of these computerised resources. It is of concern to the authors that computerised resources used in healthcare should reflect users' working practices rather than working practices being changed to reflect computerised resources.

Attitude to Computers↗