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GeneFisher--software support for the detection of postulated genes.

When a family of genes from closely related organisms is known, there is a certain change to extract the corresponding gene from the genome of another related organism. This can be done by polymerase chain reaction, provided that a pair of suitable primers can be designed. In contrast to primer design for a single, known target sequence, systematic primer design for an unknown target given a group of homologues can by no means be done manually. GeneFisher is a software tool which automates this task, and takes special care to make the impact of the manifold design parameters transparent to the user.

Algorithms↗

[Experiences with a Token Ring Network in blood bank administration of the Hannover medical university].

The Token Ring Network is a Local Area Network of IBM. It is a very helpful tool for modulating working processes by personal computers. The Token Ring is a network of the third generation and constructed like a star net. The blood bank of the Medical University of Hannover (MHH) is using the Token Ring for the administration of blood storage and donors. Medical data of foreign laboratories are transmitted into the blood bank computer. During the last year, we had no difficulties working with this software tool in response time and data security and it seemed to us a very cheap opportunity for data integration and data collection on decentralized systems.

Blood Banks↗

A framework and tools for authoring, editing, documenting, sharing, searching, navigating, and executing computer-based clinical guidelines.

With the spread of managed care and integrated delivery networks, an increased emphasis has been placed on the cost-effectiveness of clinical practices. The need has been recognized to use guidelines to support education, and to integrate them into clinical practice. A specification for guideline representation that would facilitate computer-based clinical guideline sharing has been developed by the InterMed Collaboratory. Called GLIF (GuideLine Interchange Format), this specification and its proposed extensions have been the basis for our implementation of a framework and suite of integrated software tools for guideline authoring and editing, packaging in XML, Internet distribution, navigation, eligibility determination, and automatic execution.

Eligibility Determination↗

Monitoring clinical performance: the role of software architecture.

Methods of assessing and monitoring the performance of clinicians have received a lot of publicity in recent years. We review the main methodologies concentrating on the distinction between monitoring individual performance and monitoring aggregated performance. We also highlight the importance and difficulties associated with incorporating and assessing risk factors into the process. We discuss how software architecture can be developed to implement these methodologies. We illustrate this development by a case study involving the creation of a software tool to produce funnel plots to analyse surgeon performance. We discuss how such tools are currently evaluated and propose that in future assessments of usability would benefit from an experimental study.

Computer Systems↗

Algorithmic approaches for computing elementary modes in large biochemical reaction networks.

The concept of elementary (flux) modes provides a rigorous description of pathways in metabolic networks and proved to be valuable in a number of applications. However, the computation of elementary modes is a hard computational task that gave rise to several variants of algorithms during the last years. This work brings substantial progresses to this issue. The authors start with a brief review of results obtained from previous work regarding (a) a unified framework for elementary-mode computation, (b) network compression and redundancy removal and (c) the binary approach by which elementary modes are determined as binary patterns reducing the memory demand drastically without loss of speed. Then the authors will address herein further issues. First, a new way to perform the elementarity tests required during the computation of elementary modes which empirically improves significantly the computation time in large networks is proposed. Second, a method to compute only those elementary modes where certain reactions are involved is derived. Relying on this method, a promising approach for computing EMs in a completely distributed manner by decomposing the full problem in arbitrarity many sub-tasks is presented. The new methods have been implemented in the freely available software tools FluxAnalyzer and Metatool and benchmark tests in realistic networks emphasise the potential of our proposed algorithms.

Algorithms↗

A new semiempirical mathematical model for prediction of internal filtration in hollow fiber hemodialyzers.

The potential of convective solute transport for blood purification has been widely explored. New techniques (such as hemodiafiltration), based on a combination of diffusion and convection techniques, have been developed. Owing to the internal filtration/backfiltration (IF/BF) phenomenon, high-flux dialysis also relies on a convective component, which, however, is hard to quantify and thus optimize. In this work, we developed a mathematical model designed to supply the clinician with a quantification of the IF/BF fluxes taking place during high-flux dialysis. IF fluxes are predicted based on the machine settings and blood hematocrit/protein concentration. The hydraulic characteristics of commercial dialyzers were derived from bloodless bench tests. Moreover, an in vitro blood test was conducted on a 1.8 m(2) polysulfone dialyzer using an established scintigraphic analysis, for verification of model prediction accuracy. Results of simulations show that the IF/BF rate is sensitive to the blood flow rate and (to a lesser extent) to the dialysate flow rate. Increasing net ultrafiltration rates resulted in parallel increases of direct filtration and simultaneous decreases of BF. IF/BF is rather influenced by blood composition, due to the complex dependence of oncotic pressure and blood viscosity upon hematocrit and plasma protein concentration. Simulation results showed an excellent agreement with the experimental results obtained with scintigraphy, with only a 3% prediction error. With respect to some previous works, this model is simpler in its theoretical approach. It allows implementation into a user-friendly software tool and might be used to predict the convective component in high-flux dialysis and possibly to optimize it.

Computer Simulation↗

[CT-based software-supported prediction of the postoperative lung function after partial resection of the lung].

PURPOSE: The predicted postoperative forced exspiratory volume in one second (FEV (1)) is an important functional factor for predicting the operability of patients with bronchial carcinoma. A software tool that uses a preoperative chest MSCT and pulmonary function test (PFT) for largely automated prediction of the FEV (1) was evaluated. MATERIALS AND METHODS: Fifteen patients with surgically treated lung cancer were examined with a preoperative chest MSCT (1.25 mm slice thickness, 0.8 mm reconstruction increment) and PFT before and after surgery. CT scans were analyzed by the prototype software MeVisPulmo (MeVis gGmbH, Bremen) that predicted the postoperative FEV (1) as a percentage of the preoperative values measured by PFT. The automated segmentation and volumetry of lung lobes were performed either without or with minimal user interaction. Patients underwent lobectomy in twelve cases (6 upper lobes, 1 middle lobe, 5 lower lobes) and pneumectomy in three cases. The predicted FEV (1) values were compared to the observed postoperative values as a standard of reference. The additional functional parameters "total lung capacity" (TLC) and "forced vital capacity" (FVC) were compared to the FEV (1) results. RESULTS: Automated calculation of predicted postoperative lung function was successful in all cases. Due to an implausible PFT, two of the 15 patients were excluded from the collective. A mean postoperative FEV (1) value of 75 % (SD +/- 12 %) of the preoperative FEV (1) was calculated and 74 % (SD +/- 12 %) was actually measured. The deviations of the predicted value from the measured postoperative FEV (1) ranged between - 289 ml (-12 % of the measured postoperative FEV (1)) and + 294 ml (+ 15 % of the postoperative FEV (1)). The mean deviation (absolute value) was 137 +/- 77 ml/s. This corresponds to 7 +/- 3 % of the measured postoperative FEV (1). Bland-Altman-Statistics showed the 95 % "limits of agreement" for the predicted FEV (1) values to be between - 341 ml and + 301 ml, corresponding to - 17.5 % and + 15.8 of the measured postoperative FEV (1) value. Analysis of the TLC and FVC yielded similar results. CONCLUSION: In the present pilot study the software-assisted prediction of the postoperative FEV (1) using a preoperative MSCT and pulmonary function test corresponded satisfactorily with the observed postoperative values. The introduced approach may make it possible to obtain additional information for the prediction of functional operability prior to performing lung cancer surgery.

Adenocarcinoma↗

XML schemas for common bioinformatic data types and their application in workflow systems.

BACKGROUND: Today, there is a growing need in bioinformatics to combine available software tools into chains, thus building complex applications from existing single-task tools. To create such workflows, the tools involved have to be able to work with each other's data--therefore, a common set of well-defined data formats is needed. Unfortunately, current bioinformatic tools use a great variety of heterogeneous formats. RESULTS: Acknowledging the need for common formats, the Helmholtz Open BioInformatics Technology network (HOBIT) identified several basic data types used in bioinformatics and developed appropriate format descriptions, formally defined by XML schemas, and incorporated them in a Java library (BioDOM). These schemas currently cover sequence, sequence alignment, RNA secondary structure and RNA secondary structure alignment formats in a form that is independent of any specific program, thus enabling seamless interoperation of different tools. All XML formats are available at http://bioschemas.sourceforge.net, the BioDOM library can be obtained at http://biodom.sourceforge.net. CONCLUSION: The HOBIT XML schemas and the BioDOM library simplify adding XML support to newly created and existing bioinformatic tools, enabling these tools to interoperate seamlessly in workflow scenarios.

Algorithms↗

Using regular expressions to abstract blood pressure and treatment intensification information from the text of physician notes.

This case study examined the utility of regular expressions to identify clinical data relevant to the epidemiology of treatment of hypertension. We designed a software tool that employed regular expressions to identify and extract instances of documented blood pressure values and anti-hypertensive treatment intensification from the text of physician notes. We determined sensitivity, specificity and precision of identification of blood pressure values and anti-hypertensive treatment intensification using a gold standard of manual abstraction of 600 notes by two independent reviewers. The software processed 370 Mb of text per hour, and identified elevated blood pressure documented in free text physician notes with sensitivity and specificity of 98%, and precision of 93.2%. Anti-hypertensive treatment intensification was identified with sensitivity 83.8%, specificity of 95.0%, and precision of 85.9%. Regular expressions can be an effective method for focused information extraction tasks related to high-priority disease areas such as hypertension.

Blood Pressure↗

A local alignment tool for very long DNA sequences.

This paper presents a practical program, called sim2, for building local alignments of two sequences, each of which may be hundreds of kilobases long. sim2 first constructs n best non-intersecting chains of 'fragments', such as all occurrences of identical 5-tuples in each of two DNA sequences, for any specified n > or = 1. Each chain is then refined by delivering an optimal alignment in a region delimited by the chain. sim2 requires only space proportional to the size of the input sequences and the output alignments, and the same source code runs on Unix machines, on Macintoshes, on PCs, and on DEC Alpha PCs. We also describe an application of sim2 for aligning long DNA sequences from Escherichia coli. sim2 facilitates contig-building by providing a complete view of the related sequences, so differences can be analyzed and inconsistencies resolved. Examples are shown using the alignment display and editing functions from the software tool ChromoScope.

Amino Acid Sequence↗

Integration of physiology and fluid dynamics.

The purpose of strategies for the integration of fluid dynamics and physiology is the development of more reliable simulation tools to accelerate the process of scale-up. The rigorous mathematical modeling of the richly interactive relationship between the dynamic response of biosystems and the physical environment changing in time and space must rest on the link between coupled momentum, energy and mass balances and structured modeling of the biophase. With the exponential increase in massive computer capabilities hard- and software tools became available for simulation strategies based on such holistic integration approaches. The review discusses fundamental aspects of application of computational fluid dynamics (CFD) to three-dimensional two-phase turbulence flow in stirred tank bioreactors. Examples of coupling momentum and material balance equations with simple unstructured kinetic models for the behavior of the biophase are used to illustrate the application of these strategies to the selection of suitable impeller configurations. The examples reviewed in this paper include distribution of carbon and energy source in fed batch cultures as well as dissolved oxygen fields during aerobic fermentations. A more precise forecasting of the impact of the multitude of interactions must, however, rest upon a rigorous understanding of the response of the cell factory to the complex dynamic stimulation due to space- and time-dependent concentration fields. The paper also introduces some ideas for fast and very fast experimental observations of intracellular pool concentrations based on stimulus response methods. These observations finally lead to a more complex integration approach based on the coupling of CFD and structured metabolic models.

Bioreactors↗

Selection of oligonucleotide probes for protein coding sequences.

MOTIVATION: Large arrays of oligonucleotide probes have become popular tools for analyzing RNA expression. However to date most oligo collections contain poorly validated sequences or are biased toward untranslated regions (UTRs). Here we present a strategy for picking oligos for microarrays that focus on a design universe consisting exclusively of protein coding regions. We describe the constraints in oligo design that are imposed by this strategy, as well as a software tool that allows the strategy to be applied broadly. RESULT: In this work we sequentially apply a variety of simple filters to candidate sequences for oligo probes. The primary filter is a rejection of probes that contain contiguous identity with any other sequence in the sample universe that exceeds a pre-established threshold length. We find that rejection of oligos that contain 15 bases of perfect match with other sequences in the design universe is a feasible strategy for oligo selection for probe arrays designed to interrogate mammalian RNA populations. Filters to remove sequences with low complexity and predicted poor probe accessibility narrow the candidate probe space only slightly. Rejection based on global sequence alignment is performed as a secondary, rather than primary, test, leading to an algorithm that is computationally efficient. Splice isoforms pose unique challenges and we find that isoform prevalence will for the most part have to be determined by analysis of the patterns of hybridization of partially redundant oligonucleotides. AVAILABILITY: The oligo design program OligoPicker and its source code are freely available at our website.

Algorithms↗

Rapid prototyping of database systems in human genetics data collection.

This work examines some of the problems encountered in developing small and large database application systems involving human genetics data collection efforts that include data on individuals as well as family pedigree data. Rapid prototyping of a database application requires software tools to produce the application with little or no programming. Features of MEGADATS-4 that provide for rapid prototyping and for producing stand-alone applications are examined.

Data Collection↗

CT-based software for 3-D localization and reconstruction in stepping source brachytherapy.

This paper describes innovative software for catheter localization and three-dimensional (3-D) reconstruction in stepping source brachytherapy applications. Patient information is a set of computed tomography (CT) slices scanned during the implantation of brachytherapy catheters. Catheter geometry and patient anatomy are exported for use with dose calculation software modules. The errors produced by the system are also encouragingly low. Time saving was achieved, in terms of other traditional reconstruction techniques. Various automated procedures, 3-D graphics and a user-friendly GUI, have contributed to providing a powerful, comprehensive software tool, directly useable in the clinical practice.

Brachytherapy↗

An implementation of the trigram phrase matching method for text similarity problems.

The representation of texts by term vectors with element values calculated by a TFIDF method yields to significant results in text similarity problems, such as finding related documents in bibliographic or full-text databases and identifying MeSH concepts from medical texts by lexical approach and also harmonizing journal citation in ISI/SciELO references and normalizing author's affiliation in MEDLINE. Our work considered "trigrams" as the terms (elements) of a term vector representing a text, according to the Trigram Phrase Matching published by the NLM's Indexing Initiative and its logarithmic Term Frequency-Inverse Document Frequency method for term weighting. Trigrams are overlapping 3-char strings from a text, extracted by a couple of rules, and a trigram matching method may improve the probability of identifying synonym phrases or similar texts. The matching process was implemented as a simple algorithm, and requires a certain amount of computer resources. An efficiency-focused C-programming was adopted. In addition, some heuristic rules improved the efficiency of the method and made it feasible a regular "find your scientific production in SciELO collection" information service. We describe an implementation of the Trigram Matching method, the software tool we developed and a set of experimental parameters for the above results.

Abstracting and Indexing↗

SynBrowse: a synteny browser for comparative sequence analysis.

MOTIVATION: The recent efforts of various sequence projects to sequence deeply into various phylogenies provide great resources for comparative sequence analysis. A generic and portable tool is essential for scientists to visualize and analyze sequence comparisons. RESULTS: We have developed SynBrowse, a synteny browser for visualizing and analyzing genome alignments both within and between species. It is intended to help scientists study macrosynteny, microsynteny and homologous genes between sequences. It can also aid with the identification of uncharacterized genes, putative regulatory elements and novel structural features of a species. SynBrowse is a GBrowse (the Generic Genome Browser) family software tool that runs on top of the open source BioPerl modules. It consists of two components: a web-based front end and a set of relational database back ends. Each database stores pre-computed alignments from a focus sequence to reference sequences in addition to the genome annotations of the focus sequence. The user interface lets end users select a key comparative alignment type and search for syntenic blocks between two sequences and zoom in to view the relationships among the corresponding genome annotations in detail. SynBrowse is portable with simple installation, flexible configuration, convenient data input and easy integration with other components of a model organism system. AVAILABILITY: The software is available at http://www.gmod.org CONTACT: vbrendel@iastate.edu

Algorithms↗

Old and new models for office automation.

The emerging generation of office automation systems combines new and existing software and procedures. While managers may be able to select from a broad array of software tools, they may also be required to use certain others. This article discusses organization design as the context for office automation; mature computer-based systems as one application of organization design variables; and emerging office automation systems as another application of those variables. The article concludes that Management Information System models developed for mature systems may be helpful where the use of software application is required for the individual worker; diffusion of innovation models recently developed for computing systems may be helpful where the type of software is optional for the individual worker.

Automation↗

[Computer-assisted speech recognition in diagnostic pathology. Development of the DragonDictate-30 K system for documentation].

The speech recognition system DragonDictate-30 K is the first commercially available product for personal computers (PC) that includes a thesaurus of 30,000 words which can replace the computer keyboard completely for report writing. The system is speaker-adaptative, i.e., it can learn the phonetic pattern of the pathologist's voice. We have developed a thesaurus with special terms from the field of diagnostic pathology to shorten the time-consuming training phase. DragonDictate is compatible with all text-oriented DOS computer software tools. The recommended minimal hardware configuration is a personal computer with a 80,486 processor with 16 MB on board and a 200 MB hard disk.

Computer Peripherals↗