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Bioinformatics.

Computer databases, networks and software tools are essential materials and methods for biomedical research and are involved in almost every aspect of disease gene mapping and positional cloning. Public databases of DNA and protein sequences and genetic and physical map information are increasing rapidly in size and complexity and are also improving in quality, comprehensiveness, interoperability and access. A new generation of software tools for navigating through the biomedical literature has become available. Programs for sequence homology searching and genetic map construction have become more sophisticated, yet easier to use. Global computer networks are bringing state-of-the-art capabilities to all.

Chromosome Mapping↗

Combining fuzzy querying of imprecise data and predictive microbiology using category-based reasoning for prediction of the possible microbial spoilage in foods: application to Listeria monocytogenes.

Various predictive models of microbial behavior have been created and extensive data collection has been done by numerous private or public laboratories. However, significant differences between predicted and observed values in foods have been observed and need to be stressed, understood and explained as much as possible. In this paper, we present a software tool (currently at the level of a prototype) able: (i) to store in a database all relevant information expressed on one hand as qualitative or quantitative data and on the other hand as precise or imprecise data; (ii) to retrieve the more relevant information from the database using queries where criteria may be expressed as fuzzy values in order to enhance the flexibility of the search: (iii) to compute, in addition to the nearest data, an estimation of searched values using statistical models. The architecture of this software tool is structured as a category-based reasoning system. Example queries about Listeria monocytogenes (L. monocytogenes) illustrate the functionalities of this tool.

Computer Simulation↗

Generating multiple alignments on a pangenomic scale.

MOTIVATION: Since novel long read sequencing technologies allow for de novo assembly of many individuals of a species, high-quality assemblies are becoming widely available. For example, the recently published draft human pangenome reference was based on assemblies composed of contigs. There is an urgent need for a software-tool that is able to generate a multiple alignment of genomes of the same species because current multiple sequence alignment programs cannot deal with such a volume of data. RESULTS: We show that the combination of a well-known anchor-based method with the technique of prefix-free parsing yields an approach that is able to generate multiple alignments on a pangenomic scale, provided that large-scale structural variants are rare. Furthermore, experiments with real world data show that our software tool PANgenomic Anchor-based Multiple Alignment significantly outperforms current state-of-the art programs. AVAILABILITY AND IMPLEMENTATION: Source code is available at: https://gitlab.com/qwerzuiop/panama, archived at swh:1:dir:e90c9f664995acca9063245cabdd97549cf39694.

Software↗

Interpretation and reporting of myocardial perfusion SPECT: a summary for technologists.

Interpretation of cardiac perfusion SPECT images, and the subsequent reporting of results to referring physicians, are sometimes taken to be outside the sphere of the nuclear medicine technologist. However, all personnel involved with nuclear medicine procedures contribute to the timeliness and usefulness of the final report. The goal of this article is to review the principles of scan interpretation and reporting, from the standpoint of what technologists need to understand about these processes. In addition, software tools to aid these processes will be discussed, including quantitative image analysis, telemedicine, computer-aided scan interpretation, databases, computer-aided reporting, and Internet-based reporting. Finally, the accuracy of the scan report will be related to the tasks normally performed by technologists, such as the acquisition and processing of images and the entry, transfer, and networking of data. After reading this article, the reader will be able to describe the principles of scan interpretation and reporting, the software tools for telemedicine and computer-aided interpretation, and the role of the technologist in this process.

Allied Health Personnel↗

Correlation between nerve conduction studies and clinical scores in diabetic neuropathy.

Polyneuropathy, a frequent complication of diabetes, can be assessed clinically and electrophysiologically. Neurological examination can be quantified by validated scores, e.g., the neuropathy symptom score (NSS) or the neuropathy disability score (NDS). Such scores exclude electrophysiological aspects of the neuropathy. A software tool was designed to convert electrophysiological data into one single index of polyneuropathy (IPN). This index was calibrated to grade the severity of a polyneuropathy from 0.00 to 1.00. In a series of 38 diabetic patients, we have calculated NSS, NDS, and IPN. We found correlations between these variables, NDS and IPN exhibiting the more significant association. The use of IPN allowed us to demonstrate that nerve conduction values correlated with clinical scores in diabetic polyneuropathy. Such a software tool, by providing a single electrophysiological index, may facilitate clinico-electrophysiological assessment in large descriptive studies or therapeutic trials of diabetic polyneuropathy.

Adolescent↗

New software provides tool for managing contact capitation.

The main drawback to contact capitation has been its administrative complexity. Now, a San Francisco managed care firm has released an Internet-based system that offers a simple process for determining contact values and payment amounts.

California↗

Use of three-dimensional computer graphic animation to illustrate cleft lip and palate surgery.

OBJECTIVE: Three-dimensional (3D) computer animation is not commonly used to illustrate surgical techniques. This article describes the surgery-specific processes that were required to produce animations to teach cleft lip and palate surgery. MATERIALS AND METHODS: Three-dimensional models were created using CT scans of two Chinese children with unrepaired clefts (one unilateral and one bilateral). We programmed several custom software tools, including an incision tool, a forceps tool, and a fat tool. RESULTS: Three-dimensional animation was found to be particularly useful for illustrating surgical concepts. Positioning the virtual "camera" made it possible to view the anatomy from angles that are impossible to obtain with a real camera. Transparency allows the underlying anatomy to be seen during surgical repair while maintaining a view of the overlaying tissue relationships. Finally, the representation of motion allows modeling of anatomical mechanics that cannot be done with static illustrations. The animations presented in this article can be viewed on-line at http://www.smiletrain.org/programs/virtual_surgery2.htm. CONCLUSIONS: Sophisticated surgical procedures are clarified with the use of 3D animation software and customized software tools. The next step in the development of this technology is the creation of interactive simulators that recreate the experience of surgery in a safe, digital environment.

Child↗

[A comparison of the monitor and alternator findings of digital thoracic images with the aid of a computer-supported procedure].

PURPOSE: To compare softcopy and hardcopy reading of chest radiographs a software tool was designed for creating lesions with clearly defined size, location and contrast. METHOD: An ROC study was performed using a set of chest radiographs with 300 simulated small nodules and linear details displayed on film and on a 1 K monitor. Six observers participated in the study. ROC curves were generated on the basis of 7200 decisions. RESULTS: There was no significant difference in observer performance overall (AUC = Area under curve). Monitor: 0.84 +/- 0.08 vs. AUC, Film: 0.84 +/- 0.08). Slight, but not statistical significant differences were found in the detection of low-contrast lung nodules and of linear lung details. CONCLUSION: Soft-copy reading using a high quality 1 K CRT display provides the same accuracy for the detection of subtle computer-simulated lesions as hardcopy reading. A software tool could be used for assigning optimal characteristics of CRT- and hardcopy displays using clearly defined lesions as a gold standard.

Computer Simulation↗

MetaCyc: a multiorganism database of metabolic pathways and enzymes.

The MetaCyc database (see URL http://MetaCyc.org) is a collection of metabolic pathways and enzymes from a wide variety of organisms, primarily microorganisms and plants. The goal of MetaCyc is to contain a representative sample of each experimentally elucidated pathway, and thereby to catalog the universe of metabolism. MetaCyc also describes reactions, chemical compounds and genes. Many of the pathways and enzymes in MetaCyc contain extensive information, including comments and literature citations. SRI's Pathway Tools software supports querying, visualization and curation of MetaCyc. With its wide breadth and depth of metabolic information, MetaCyc is a valuable resource for a variety of applications. MetaCyc is the reference database of pathways and enzymes that is used in conjunction with SRI's metabolic pathway prediction program to create Pathway/Genome Databases that can be augmented with curation from the scientific literature and published on the world wide web. MetaCyc also serves as a readily accessible comprehensive resource on microbial and plant pathways for genome analysis, basic research, education, metabolic engineering and systems biology. In the past 2 years the data content and the Pathway Tools software used to query, visualize and edit MetaCyc have been expanded significantly. These enhancements are described in this paper.

Biochemical Phenomena↗

Software for automated analysis of DNA fingerprinting gels.

Here we describe software tools for the automated detection of DNA restriction fragments resolved on agarose fingerprinting gels. We present a mathematical model for the location and shape of the restriction fragments as a function of fragment size, with model parameters determined empirically from "marker" lanes containing molecular size standards. Automated identification of restriction fragments involves several steps, including: image preprocessing, to put the data in a form consistent with a linear model; marker lane analysis, for determination of the model parameters; and data lane analysis, a procedure for detecting restriction fragment multiplets while simultaneously determining the amplitude curve that describes restriction fragment amplitude as a function of mobility. In validation experiments conducted on fingerprinted and sequenced Bacterial Artificial Chromosome (BAC) clones, sensitivity and specificity of restriction fragment identification exceeded 96% on restriction fragments ranging in size from 600 base pairs (bp) to 30,000 bp. The integrated suite of software tools, written in MATLAB and collectively called BandLeader, is in use at the BC Cancer Agency Genome Sciences Centre (GSC) and the Washington University Genome Sequencing Center, and has been provided to the Wellcome Trust Sanger Institute and the Whitehead Institute. Employed in a production mode at the GSC, BandLeader has been used to perform automated restriction fragment identification for more than 850,000 BAC clones for mouse, rat, bovine, and poplar fingerprint mapping projects.

Animals↗

Cone beam computed tomography in craniofacial imaging.

Cone beam computed tomography (CT) has the potential to reduce the size and cost of CT scanners. Because this emerging technology produces images with isotropic submillimeter spatial resolution, it is ideally suited for dedicated dentomaxillofacial CT scanning. When combined with application-specific software tools, cone beam computed tomography can provide dentomaxillofacial practitioners with a complete solution for performing specific diagnostic and surgical tasks, such as dental implant planning. In this paper, we provide a brief overview of cone beam scanning technology and compare it with the fan beam scanning used in conventional CT scanners. We introduce 'DentoCAT', a relatively small, low-cost cone beam CT scanner dedicated for dentomaxillofacial imaging developed at Xoran Technologies. We present images generated by the DentoCAT scanner and provide an assessment of its performance in terms of spatial resolution and effective radiation dose. Finally, we illustrate the clinical utility of the scanner by presenting the results we have obtained to date using the DentoCAT scanner in conjunction with an implant planning software tool.

Dental Implants↗

Dynamic computed tomography: a novel technique to study lung aeration and atelectasis formation during experimental CPR.

OBJECTIVE: To develop an image based technique to study the effect of different ventilatory strategies on lung ventilation and alveolar recruitment during cardiopulmonary resuscitation (CPR). DESIGN: (1) Technical development of the following components: (a) construction of an external chest compression device, which does not interfere with CT imaging, and (b) development of a software tool to detect lung parenchyma automatically and to calculate radiological density parameters. (2) Feasibility studies: three strategies of CPR ventilation were performed and imaged in one animal each (pigs, 25 kg): volume-constant ventilation (VCV), no ventilation, or continuous airway pressure (CPAP). One minute after induction of circulatory arrest inside the CT scanner, external chest compressions started at a rate of 100 cpm, and one of the ventilation modes was initiated. After 1 min, intravenous epinephrine was added as a bolus (40 microg/kg), followed by a continuous infusion (13 microg/kg per min). Six minutes later, dynamic CT acquisitions (temporal resolution: 100 ms) commenced. Simultaneously, arterial blood gases, acid base status and haemodynamics were sampled. RESULTS: Using a modified chest compression device, dynamic CT acquisitions are feasible during closed-chest CPR. In three pilot experiments with different ventilation strategies, the dedicated software tool allowed to quantify ventilated, atelectatic and over-distended fractions of total lung area. VCV showed a large amount of atelectasis, which was recruited during every respiratory cycle. No ventilation led to atelectasis to govern over 50% of the total lung area. CPAP caused less atelectasis as VCV, and no cyclic recruitment and de-recruitment phenomena were observed. CONCLUSIONS: We demonstrate a novel experimental set up, which allows quantification of different lung compartments during ongoing CPR and may become useful in comparing the direct pulmonary effects of different ventilatory strategies in the settings of Basic and Advanced Cardiac Life Support.

Animals↗

Exploiting EST databases for the development and characterization of gene-derived SSR-markers in barley (Hordeum vulgare L.).

A software tool was developed for the identification of simple sequence repeats (SSRs) in a barley ( Hordeum vulgare L.) EST (expressed sequence tag) database comprising 24,595 sequences. In total, 1,856 SSR-containing sequences were identified. Trimeric SSR repeat motifs appeared to be the most abundant type. A subset of 311 primer pairs flanking SSR loci have been used for screening polymorphisms among six barley cultivars, being parents of three mapping populations. As a result, 76 EST-derived SSR-markers were integrated into a barley genetic consensus map. A correlation between polymorphism and the number of repeats was observed for SSRs built of dimeric up to tetrameric units. 3'-ESTs yielded a higher portion of polymorphic SSRs (64%) than 5'-ESTs did. The estimated PIC (polymorphic information content) value was 0.45 +/- 0.03. Approximately 80% of the SSR-markers amplified DNA fragments in Hordeum bulbosum, followed by rye, wheat (both about 60%) and rice (40%). A subset of 38 EST-derived SSR-markers comprising 114 alleles were used to investigate genetic diversity among 54 barley cultivars. In accordance with a previous, RFLP-based, study, spring and winter cultivars, as well as two- and six-rowed barleys, formed separate clades upon PCoA analysis. The results show that: (1) with the software tool developed, EST databases can be efficiently exploited for the development of cDNA-SSRs, (2) EST-derived SSRs are significantly less polymorphic than those derived from genomic regions, (3) a considerable portion of the developed SSRs can be transferred to related species, and (4) compared to RFLP-markers, cDNA-SSRs yield similar patterns of genetic diversity.

DNA, Plant↗

Research software for radiotherapy gel dosimetry.

Gel dosimetry using magnetic resonance imaging is a technique which allows measurement of three-dimensional absorbed dose distributions in radiation therapy. This paper presents details of a software tool written specifically to provide facilities to perform image processing required in research and development of gel dosimetry. Collections of magnetic resonance images can be converted into either longitudinal or transverse nuclear magnetic resonance relaxation images. The conversions are accomplished by means of a pixel-by-pixel non-linear least squares fitting algorithm. Adjustments can be made to the number of parameters used in the fitting algorithm. Fundamental image manipulation tools such as window width/level display adjustment, zooming, profile and region of interest tools are provided. The software has been developed using MATLAB (The MathWorks Inc., Natick, MA) running on Windows 95. User interaction is via a windows graphical user interface (GUI). Data such as statistics from regions of interest can be exported to other windows applications for further processing. Flexibility is incorporated in the GUI design by taking advantage of the developmental aspects of the MATLAB environment. Although originally designed for gel dosimetry, the software can be used in any application of MRI which requires production and manipulation of relaxation time images.

Gels↗

GenomeComp: a visualization tool for microbial genome comparison.

We have developed a software tool, GenomeComp, for summarizing, parsing and visualizing the genome sequences comparison results derived from voluminous BLAST textual output. With GenomeComp, the variation between genomes can be easily highlighted, such as repeat regions, insertions, deletions and rearrangements of genomic segments. This software provides a new visualizing tool for microbe comparative genomics.

Computational Biology↗

Sequence assembly with CAFTOOLS.

Large-scale genomic sequencing requires a software infrastructure to support and integrate applications that are not directly compatible. We describe a suite of software tools built around the Common Assembly Format (CAF), a comprehensive representation of a sequence assembly as a text file. These tools form the backbone of sequencing informatics at the Sanger Centre and the Genome Sequencing Center. The CAF format is intentionally flexible, and our Perl and C libraries, which parse and manipulate it, provide powerful tools for creating new applications as well as wrappers to incorporate other software. The tools are available free by anonymous FTP from ftp://ftp.sanger.ac.uk/pub/badger/.

Algorithms↗

A clinical tool for nursing.

The background of this software tool stretches back nearly 20 years to original systems techniques developed within an area of computer science called artificial intelligence. Research reflects efforts to capture the reasoning processes of healthcare experts.

Clinical Protocols↗

vcfsim: flexible simulation of all-sites VCFs with missing data.

BACKGROUND |: VCFs are the most widely used data format for encoding genetic variation. By design, standard VCFs do not include data from sites where all individuals are homozygous for the reference allele ("invariant sites") and thus do not differentiate these from sites where data are completely missing. However, missing data are a key feature of biological datasets across all domains of genomics, and many recent studies have shown that missing data can introduce a variety of statistical biases in the estimation of key population genetic parameters. A solution to this limitation is to include invariant sites in a standard VCF, creating an "all-sites VCF", exposing missing and invariant sites explicitly. One hurdle to the wider adoption of all-sites VCFs is a reliable parameterized simulation framework for generating biologically realistic all-sites VCFs. RESULTS |: Here, we introduce an open-source command line tool, vcfsim, that interfaces with the popular coalescent simulation platform msprime and provides convenience functions for simulating all-sites VCFs with variable levels of ploidy and missing data. We show that the post-processed VCFs generated using vcfsim align precisely with population genetic expectations (i.e. are statistically identical to raw msprime output), accurately introduce missing data, and permit the simulation of data with varying ploidy levels, including the simulation of intraindividual ploidy variation (e.g. heterogametic sex chromosomes) and population structures. CONCLUSIONS |: Our results vcfsim is a useful and easy-to-use tool for the benchmarking of new software tools, performing population genetic inference, training of machine learning models, and the exploration of the effects of missing data in genomics data sets.

Benchmarking↗