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PubMed2005

GenoMiner: a tool for genome-wide search of coding and non-coding conserved sequence tags.

GenoMiner is a software tool that searches for regions of similarity between user-submitted genome or transcript sequences and user-specified whole genome assemblies. The program then identifies conserved sequence tags (CSTs) in these homologous regions and provides a prediction of their coding or non-coding nature. The analysis is carried out through three steps: (1) definition of sequence regions homologous to the query sequence in the selected target genomes by a fast BLAT alignment; (2) identification of CSTs by a more sensitive BLAST-like alignment between the query and the homologous regions in the target genomes and (3) assessment of the coding or non-coding nature of detected CSTs through the computation of a suitable coding potential score. GenoMiner allows the user to search the query sequence against a number of vertebrate genome assemblies in a single run providing a user-friendly graphical output.

Algorithms↗

PubMed1992

A decision table and rule based interpretation system for epileptic discharges.

The representation of the various features of waveforms and their correlations, in EEG recording for the diagnosis of different diseases have been carried out by many researchers due to the impact of knowledge based on expert systems development tools and techniques. The realisation of these system requires a specific hardware and software tool for its implementation, which may be a costly affair. The design and development of low cost effective system for the diagnosis of epileptic patients have been reported in this paper. Two different and linked (at certain stage) approaches (i) decision table; (ii) rule based system have been followed to model the reasoning processes of physician in the diagnosis. In the decision table the features of specific waveforms of EEG are represented in the tabular form. The features are obtained from a 8086 microprocessor based data acquisition system. The rule based system is designed with IF and THEN form of rules using Turbo-Prolog as programming language tool and is implemented on low cost PC-AT. The results obtained are at an intermediate stage of data processing by decision tables and at the final stage being carried out by rule based model. The performance of the system is evaluated by recording of EEG of some epileptic patients. The results obtained are comparable and to a certain extend appreciable in the opinion of the physician.

Decision Support Techniques↗

PubMed2005

[Computer-aided diagnosis and volumetry of pulmonary nodules: current concepts and future perspectives].

For computer-aided detection (CAD) and volumetry of small pulmonary nodules, a number of algorithms have been developed for multislice CT data sets in recent years, with the goal of improving the diagnostic work-up and the follow-up of findings. Recent data show that the detection of small lesions may improve with CAD, suggesting that especially experienced readers may benefit from using CAD systems. This has lead to the recommendation of CAD as a replacement of the second reader in clinical practice. Furthermore, computer-aided volumetry of pulmonary nodules allows a precise determination of nodular growth rates as a prerequisite for a better classification of nodules as benign or malignant. In this article, we review recent developments of CAD and volumetry tools for pulmonary nodules, and address open questions regarding the use of these software tools in clinical routine.

Diagnosis, Computer-Assisted↗

PubMed2005

Interpretation and evaluation of the gamma index and the gamma index angle for the verification of IMRT hybrid plans.

In IMRT, the method for a quantitative comparison of two-dimensional dose distributions is still under development. The gamma evaluation method proposed by Low et al is the most accepted approach and has been adapted by many groups. Based on the concept of Low et al we developed a software tool with an intelligent search algorithm to minimize the calculation time. For the interpretation of deviations a y angle distribution and other tools (dose difference map, profiles, y area histograms, etc) are integrated in the software package. Ten hybrid plans are included in the verification study containing 6 IMRT head and neck cases, 2 IMRT prostate cases and one IMRT paravertebral case as well as a standard uniform intensity conformal 4 field box treatment for comparison. IMRT plans are realized with a segmental MLC delivery technique. The fields of a hybrid plan are applied at once and dose distributions are measured with films in three planes of a verification phantom. All y vector calculations are based on a 3% dose criterion and a 3 mm DTA acceptance criterion. The mean value gamma(mean) (mean value in the y distribution) of the various IMRT plans is 0.45+/-0.10 (1 SD). On average, the percentage of points exceeding the acceptance criteria of gamma < or = 1 (gamma > 1) is 5.8+/-5.4% (1 SD). The mean value of gamma 1% (1% of points have an equal or higher gamma value) is 1.47+/-0.59 (1 SD) for IMRT plans. In 5 out of 27 planes, gamma > 1 is substantially larger than the average. This is also indicated in gamma area histograms. Planes with large areas outside the tolerance criteria were further evaluated using gamma angle distributions. This additional information indicates that the large areas with high gamma values are dominated by the dose difference. It is shown that the deviations are influenced by tongue and groove effects. From the statistical evaluation of gamma values (e.g. gamma area histogram), acceptance criteria for IMRT hybrid plans can be defined. For the interpretation of the gamma maps, distributions of the gamma angle and traditional evaluation methods, such as dose profiles, are still very useful.

Algorithms↗

PubMed2006

Multimedia and physiology: a new way to ensure the quality of medical education and medical knowledge.

BACKGROUND: since the eighties and the existence of virtual campuses, the value of computers in distance education has been acknowledged. The development of information and communication technologies is driving at discriminating distance education and on-line education. PURPOSE: the aim of the "Campus Numérique de Physiologie" is not to reproduce an on-line copy of classical textbooks but to put at students' and physicians' disposal the huge possibilities of multimedia resources for an active and easier understanding of complex physiopathological phenomena. METHODS: the on-line course materials were created using both original IBC-made and registered trade-mark software tools. Multiscale modelling and corresponding knowledge bases were implemented by mathematicians, biologists and software engineers from Rennes. The website, which is accessible through a server of the French Virtual Medical University, was developed in the language HTML/PHP connected to a MySQL database. RESULTS: the content managing system is consistent with classical home page facilities and multicriteria browser. Interactive resources are freely available for the site's users. Two- and three-dimensional simulations born out of mathematical qualitative and quantitative models at the molecular, cellular or organic level keep students active with regards to fundamental mechanisms by interactively manipulating the simulation environment. CONCLUSION: authors comment the already available course materials which should stimulate the creation of new documents following a validation by a qualified commission of the "Société de Physiologie". Providing evaluation tests, teachers anticipate that the increasing content of this virtual campus will allow users to gain a complete understanding and an integrative view of many physiopathological mechanisms.

Education, Distance↗

PubMedDate not supplied

New vessel analysis tool for morphometric quantification and visualization of vessels in CT and MR imaging data sets.

Image processing algorithms and a prototypical research software tool have been developed for visualization and quantitative analysis of vessels in data sets from computed tomography and magnetic resonance imaging. The software is based on a sequence of processing steps, which are as follows: (a) vessel segmentation based on a region growing algorithm, (b) interactive "premasking" to optionally exclude interfering structures close to the vessels of interest, (c) distance transform-based skeletonization, (d) multiplanar reformation orthogonal to the vessel path, (e) identification of the lumen boundary on the orthogonal cross-section images, and (f) morphometric measurements. The development of the algorithmic components and the application user interface has been carried out in close cooperation with clinical users to achieve a high degree of usability and flexible support of work flow. The software has been successfully applied to the intracranial arteries, carotid arteries, and abdominal and thoracic aorta, as well as the renal, coronary, and peripheral arteries.

Algorithms↗

PubMed2005

SOP3: a web-based tool for selection of oligonucleotide primers for single nucleotide polymorphism analysis by Pyrosequencing.

SOP3 is a web-based software tool for designing oligonucleotide primers for use in the analysis of single nucleotide polymorphisms (SNPs). Accessible via the Internet, the application is optimized for developing the PCR and sequencing primers that are necessary for Pyrosequencing. The application accepts as input gene name, SNP reference sequence number, or chromosomal nucleotide location. Output can be parsed by gene name, SNP reference number, heterozygosity value, location, chromosome, or function. The location of an individual polymorphism, such as an intron, exon, or 5' or 3' untranslated region is indicated, as are whether nucleotide changes in an exon are associated with a change in an amino acid sequence. SOP3 presents for each entry a set of forward and biotinylated reverse PCR primers as well as a sequencing primer for use during the analysis of SNPs by Pyrosequencing. Theoretical pyrograms for each allele are calculated and presented graphically. The method has been tested in the development of Pyrosequencing assays for determining SNPs and for deletion/insertion polymorphisms in the human genome. Of the SOP3-designed primer sets that were tested, a large majority of the primer sets have successfully produced PCR products and Pyrosequencing data.

Algorithms↗

PubMed1991

Mapping sequenced E.coli genes by computer: software, strategies and examples.

Methods are presented for organizing and integrating DNA sequence data, restriction maps, and genetic maps for the same organism but from a variety of sources (databases, publications, personal communications). Proper software tools are essential for successful organization of such diverse data into an ordered, cohesive body of information, and a suite of novel software to support this endeavor is described. Though these tools automate much of the task, a variety of strategies is needed to cope with recalcitrant cases. We describe such strategies and illustrate their application with numerous examples. These strategies have allowed us to order, analyze, and display over one megabase of E. coli DNA sequence information. The integration task often exposes inconsistencies in the available data, perhaps caused by strain polymorphisms or human oversight, necessitating the application of sound biological judgment. The examples illustrate both the level of expertise required of the database curator and the knowledge gained as apparent inconsistencies are resolved. The software and mapping methods are applicable to the study of any genome for which a high resolution restriction map is available. They were developed to support a weakly coordinated sequencing effort involving many laboratories, but would also be useful for highly orchestrated sequencing projects.

Base Sequence↗

PubMed2005

AUTOGSCAN: powerful tools for automated genome-wide linkage and linkage disequilibrium analysis.

Genome-wide linkage analysis using multiple traits and statistical software packages is a tedious process which requires a significant amount of manual file manipulation. Different linkage analysis programs require different input file formats, making the task of analyzing data with multiple methods even more time-consuming. We have developed a software tool, AUTOGSCAN, that automates file formatting, the running of statistical analyses, and the summarizing of resulting statistics for whole genome scans with a push of a button, using several independent, and often idiosyncratic, statistical software packages such as MERLIN, SOLAR and GENEHUNTER. We also describe a program, ANALYZE, designed to run qualitative linkage analysis with several different statistical strategies and programs to efficiently screen for linkage and linkage disequilibrium for a given discrete trait. The ANALYZE program can also be used by AUTOGSCAN in a genome-wide sense.

Genetic Linkage↗

PubMed2004

Filtering of ineffective siRNAs and improved siRNA design tool.

MOTIVATION: Short interfering RNAs (siRNAs) can be used to suppress gene expression and possess many potential applications in therapy, but how to design an effective siRNA is still not clear. Based on the MPI (Max-Planck-Institute) basic principles, a number of siRNA design tools have been developed recently. The set of candidates reported by these tools is usually large and often contains ineffective siRNAs. In view of this, we initiate the study of filtering ineffective siRNAs. RESULTS: The contribution of this paper is 2-fold. First, we propose a fair scheme to compare existing design tools based on real data in the literature. Second, we attempt to improve the MPI principles and existing tools by an algorithm that can filter ineffective siRNAs. The algorithm is based on some new observations on the secondary structure, which we have verified by AI techniques (decision trees and support vector machines). We have tested our algorithm together with the MPI principles and the existing tools. The results show that our filtering algorithm is effective. AVAILABILITY: The siRNA design software tool can be found in the website http://www.cs.hku.hk/~sirna/ CONTACT: smyiu@cs.hku.hk

Algorithms↗

PubMed2004

Automated and accurate deposition of structures solved by X-ray diffraction to the Protein Data Bank.

The RCSB Protein Data Bank (PDB) has a number of options for deposition of structural data and has developed software tools to facilitate the process. In addition to ADIT and the PDB Validation Suite, a new software application, pdb_extract, has been designed to promote automatic data deposition of structures solved by X-ray diffraction. The pdb_extract software can extract information about data reduction, phasing, molecular replacement, density modification and refinement from the output files produced by many X-ray crystallographic applications. The options, procedures and tools for accurate and automated PDB data deposition are described here.

Automation↗

PubMed2002

A SAS macro for the analysis of cell survival curves.

This paper describes a SAS macro for the statistical analyses of cell survival data obtained after radiation treatment using the methods of R.E. Tarone et al. (Mutation Research 111 (1983) 79-96). These analyses are usually required on a routine basis by all biomedical research laboratories involved in cell survival assays generating dose-response curves aimed at characterizing radiosensitive mutant cell strains or individuals whose body cells exhibit enhanced sensitivity to radiation and other genotoxic agents. Statistical methods of linear regression are applied to data from repeated experiments with a cell line/strain and weighted estimates of a common slope and its variance are obtained. The methods are currently implemented in two APL programs. These programs are not easily accessible to most biomedical statisticians and researchers because APL is not a common software tool for statistical analysis. Implementation of these methods in SAS, a widely used commercial software for statistical analysis, is expected to help resolve this issue. We illustrate the application of the macro using an example data set obtained in our laboratory, and hope that other investigators may find it useful in analyzing their data.

Cell Survival↗

PubMed2003

Multidisciplinary modelling of biomedical systems.

This paper describes general principles and example results of a new software tool being developed for physiologically-based modelling of biomedical systems within a multidisciplinary framework. The aim is to overcome some limitations of currently available software designed either for general purpose or for highly specialised modelling applications. In fact, general purpose tools usually impose explicit coding of mathematical model equations or non-intuitive system representations, whereas specialised software use domain-specific notations that allow efficient and convenient model building only for special classes of systems. The aim of the present study is to pursue intuitive representation of various, possibly interacting, types of biological systems described as interconnected physical components, such as mass and energy storage elements, active and passive transport or biochemical transformations. The presented software generates automatically the mathematical model equations that can be coded in different formats. This allows interoperability with other existing software, e.g. for numerical simulation, symbolic analysis or text processing. A multi-domain structural language has been defined for an intuitive, hierarchical and self-explanatory specification of physiological models. The proposed strategies may become useful for dissemination and integration of multidisciplinary modelling knowledge.

Computational Biology↗

PubMed2006

Statistical measures of the structure of genomic sequences: entropy, complexity, and position information.

Identifying regions of DNA with extreme statistical characteristics is an important aspect of the structural analysis of complete genomes. Linguistic methods, mainly based on estimating word frequency, can be used for this as they allow for the delineation of regions of low complexity. Low complexity may be due to biased nucleotide composition, by tandem- or dispersed repeats, by palindrome-hairpin structures, as well as by a combination of all these features. We developed software tools in which various numerical measures of text complexity are implemented, including combinatorial and linguistic ones. We also added Hurst exponent estimate to the software to measure dependencies in DNA sequences. By applying these tools to various functional genomic regions, we demonstrate that the complexity of introns and regulatory regions is lower than that of coding regions, whilst Hurst exponent is larger. Further analysis of promoter sequences revealed that the lower complexity of these regions is associated with long-range correlations caused by transcription factor binding sites.

Algorithms↗

PubMed2005

Intra-operative visualisation of 3D temperature maps and 3D navigation during tissue cryoablation.

Thermotherapeutic tools are increasingly used for tissue ablation, although the intra-operative monitoring is not adequate for such procedures. This is a main challenge for more extensive use of any ablative technique. The present work focuses on treatment of hepatic tumours by cryo therapy. For any thermotherapeutic tool there are specific thermal conditions that have to be met to ensure treatment adequacy. A software tool was made to calculate and visualise 3D temperature distributions during hepatic cryoablation combined with a 3D intra-operative navigation system. This system aids the user in placing the cryoprobe using an optical tracking system and 3D visualisation of the probe placement in relation to the target anatomy and the planned trajectory. 3D temperature distributions are calculated and visualized intra-operatively. The system is integrated with an interventional Magnetic Resonance 0.5T scanner. The system was tested in an animal experiment, exemplifying the usefulness of the navigation system and its ability to give intuitive feedback to the user on thermodynamic conditions induced in the target region. The system constitutes a novel tool for enhanced intra-operative control during cryoablative procedures, and motivates for studies using this tool to investigate predictors applied as indicators of treatment adequacy and patient outcome.

Animals↗

PubMed2004

Assessment of right ventricular function by 16-detector-row CT: comparison with magnetic resonance imaging.

The purpose of this study was to determine right ventricular (RV) function from 16-detector-row CT by using two different software tools in comparison with MRI. Nineteen patients underwent cardiac CT. (1) With semiautomated contour detection software end-diastolic and end-systolic RV volumes were determined from short-axis CT reformations (MPR) created at every 10% of the RR-interval. (2) End-systolic and end-diastolic axial images were transformed to 3D to determine the volumes by using a threshold-supported reconstruction algorithm. Steady-state free-precession cine-MRI of the heart was done in short-axis orientation. RV function could not be analyzed in one patient because of sternal wire artifacts in MRI. Mean end-diastolic (155.4+/-54.6 ml) and end-systolic (79.1+/-37.0 ml) RV volumes determined with MPR correlated well with MRI [151.9+/-53.7 ml (r=0.98) and 75.0+/-36.0 ml (r=0.96), respectively (P<0.001)]. RV stroke volume (76.2+/-20.2 ml for MPR-CT, 76.9+/-20.7 ml for MRI, r=0.93) showed a good correlation and RV ejection fraction (50.8+/-8.4% for MPR-CT, 51.9+/-7.4% for MRI, r=0.74) only a moderate one. Threshold supported 3D reconstructions revealed insufficient correlations with MRI (r=0.31-0.59). MPR-based semiautomated analysis of cardiac 16 detector-row CT allows for RV functional analysis. The results correlate well with MRI findings. Threshold value-supported 3D reconstructions did not show satisfying results because of inhomogeneities of RV contrast enhancement.

Aged↗

PubMed2003

The evaluation of brain activity in response to taste stimuli--a pilot study and method for central taste activation as assessed by event-related fMRI.

BACKGROUND: Brain pathways contribute to the regulation of appetite behaviors, and advancements in brain imaging offer new opportunities in determining whether disturbances of these pathways play a role in pathological feeding behaviors in humans. We developed a standardized method for the assessment of brain activation in response to taste stimuli. METHODS: Five healthy control women were positioned in a 1.5 T GE magnet resonance (MR) scanner for functional MR imaging (fMRI). They received 1.0 cm3 samples of 1 M glucose solution or artificial saliva (25 mM KCl, 2 mM NaHCO3). Fluid challenges were delivered by a programmable syringe pump (J-Kem Scientific, St. Louis, MO). E-Prime software (Psychology Software Tools Inc., Pittsburgh, PA) coordinated taste stimulation with MR scanning. Data were analyzed using NeuroImaging software (NIS). RESULTS: Healthy women showed increased orbitofrontal cortex activation when glucose was compared to artificial saliva. In addition, mesial and lateral temporal cortical regions contrasted glucose from artificial saliva. CONCLUSIONS: This study demonstrates a design for the systematic study of brain activation after taste stimulation using fMRI and computer controlled stimulus delivery. The results are consistent with previous studies, showing activation in higher order brain centers that are involved in emotional coding of taste experience.

Adult↗

PubMed2003

Improved statistical methods for hit selection in high-throughput screening.

High-throughput screening (HTS) plays a central role in modern drug discovery, allowing the rapid screening of large compound collections against a variety of putative drug targets. HTS is an industrial-scale process, relying on sophisticated automation, control, and state-of-the art detection technologies to organize, test, and measure hundreds of thousands to millions of compounds in nano- to microliter volumes. Despite this high technology, hit selection for HTS is still typically done using simple data analysis and basic statistical methods. The authors discuss in this article some shortcomings of these methods and present alternatives based on modern methods of statistical data analysis. Most important, they describe and show numerous real examples from the biologist-friendly Stat Server HTS application (SHS), a custom-developed software tool built on the commercially available S-PLUS and StatServer statistical analysis and server software. This system remotely processes HTS data using powerful and sophisticated statistical methodology but insulates users from the technical details by outputting results in a variety of readily interpretable graphs and tables.

Algorithms↗