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GoArrays: highly dynamic and efficient microarray probe design.

MOTIVATION: The use of oligonucleotide microarray technology requires a very detailed attention to the design of specific probes spotted on the solid phase. These problems are far from being commonplace since they refer to complex physicochemical constraints. Whereas there are more and more publicly available programs for microarray oligonucleotide design, most of them use the same algorithm or criteria to design oligos, with only little variation. RESULTS: We show that classical approaches used in oligo design software may be inefficient under certain experimental conditions, especially when dealing with complex target mixtures. Indeed, our biological model is a human obligate parasite, the microsporidia Encephalitozoon cuniculi. Targets that are extracted from biological samples are composed of a mixture of pathogen transcripts and host cell transcripts. We propose a new approach to design oligonucleotides which combines good specificity with a potentially high sensitivity. This approach is original in the biological point of view as well as in the algorithmic point of view. We also present an experimental validation of this new strategy by comparing results obtained with standard oligos and with our composite oligos. A specific E.cuniculi microarray will overcome the difficulty to discriminate the parasite mRNAs from the host cell mRNAs demonstrating the power of the microarray approach to elucidate the lifestyle of an intracellular pathogen using mix mRNAs.

Algorithms↗

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↗

Pulmonary nodules: preliminary experience with three-dimensional evaluation.

PURPOSE: To evaluate software designed to calculate pulmonary nodule volume in three dimensions. MATERIALS AND METHODS: Fifty-four solid noncalcified pulmonary nodules measuring 5-18 mm in diameter were studied with computed tomographic (CT) volumetric software. Baseline CT examinations were performed for various indications by using four-detector row multisection CT units, 1.25- or 2.50-mm sections, and a standard reconstruction algorithm. The percentage of successful nodule segmentations, as well as intraobserver variability, interreader agreement, and global repeatability of calculated volumes, was determined on the basis of consecutive measurements performed three times by three different radiologists by using the Bland and Altman method. The software was used to calculate the doubling time of 22 nodules for which a final diagnosis and comparable CT scans were available. RESULTS: Fifty-two (96%) of the 54 nodules were successfully segmented, allowing their volume to be calculated. Repeatability was high: There was no variation in the nine measurements of 35 (67%) of the 52 nodules. The coefficient of variation for the remaining 17 nodules (33%) was 2.26%. Bland and Altman 95% limits of acceptability, calculated on the basis of log-transformed data, yielded a maximum software measurement error of 6.38% of the previous volume measurement. Doubling time ranged from 4 to 188 years for the 13 benign nodules and from 37 to 216 days for the nine malignant nodules. CONCLUSION: Software volumetric analysis yielded repeatable estimates for 96% of the nodules examined. All software-calculated doubling times were in keeping with the benign or malignant nature of the nodules.

Adult↗

BiSearch: primer-design and search tool for PCR on bisulfite-treated genomes.

Bisulfite genomic sequencing is the most widely used technique to analyze the 5-methylation of cytosines, the prevalent covalent DNA modification in mammals. The process is based on the selective transformation of unmethylated cytosines to uridines. Then, the investigated genomic regions are PCR amplified, subcloned and sequenced. During sequencing, the initially unmethylated cytosines are detected as thymines. The efficacy of bisulfite PCR is generally low; mispriming and non-specific amplification often occurs due to the T richness of the target sequences. In order to ameliorate the efficiency of PCR, we developed a new primer-design software called BiSearch, available on the World Wide Web. It has the unique property of analyzing the primer pairs for mispriming sites on the bisulfite-treated genome and determines potential non-specific amplification products with a new search algorithm. The options of primer-design and analysis for mispriming sites can be used sequentially or separately, both on bisulfite-treated and untreated sequences. In silico and in vitro tests of the software suggest that new PCR strategies may increase the efficiency of the amplification.

Algorithms↗

A software for the elaboration of job histories.

This article presents a software designed to help the occupational physician elaborate, print and automatically interrogate the job histories of workers. The need for the surveillance of professional risks throughout careers is the basic assumption on which this software is based and it runs on a PC.

Forms and Records Control↗

[Apple-Macintosh compatible software for documentation, management and evaluation of ultrasound findings in obstetrics].

The advantage of using a computer to automate routine calculations and print out charts of the obstetrical ultrasound examination is obvious. This report describes a software designed to simplify the documentation and analysis of ultrasound data in obstetrics. The system is easy to use, even for persons with little computer knowledge. The programme was written in FoxBase+/Mac (Fox Software, Inc., USA). FoxBase+/Mac takes full advantage of the easy-to-learn, easy-to-use Macintosh interface and is also very fast. Another advantage of this software is that it can be used in teaching. Non-experienced examinators can double-check the correctness of their scanning planes by observing the ultrasound pictures with the markers indicating the right measurement sites and the lists of standard values of biometrical parameters for the corresponding gestational age on the screen. In routine obstetrical ultrasound examinations it takes less than 5 min to enter the foetal biometry data and print out reports. These reports are informative and easy to interpret.

Female↗

[Applications of computer image processing and graph processing technologies in digital modelling of 3-D shapes of teeth, jaw and prosthesis].

In this paper, the images of sliced sections or CT sections of the specimen of teeth, jaw and prosthesis were processed by a computer image analysing system, and the plane shape of the 3-D objects of interest on the sections was converted into digital images using a special software module for contour analysing. Then the images were adjusted in scale, modified in coordinates and smoothed in shape, and the data format was transferred for finite-element analysis by a specially designed software. In such ways a method for the digital modelling of the 3-D shape of teeth, jaw and prosthesis was successfully established.

Computer Simulation↗

Alkaline protease production by an isolated Bacillus circulans under solid-state fermentation using agroindustrial waste: process parameters optimization.

Alkaline protease production using isolated Bacillus circulans under solid-state fermentation environment was optimized by using Taguchi orthogonal array (OA) experimental design (DOE) methodology to understand the interaction of a large number of variables spanned by factors and their settings with a small number of experiments in order to economize the process optimization. The software-designed experiments with an OA worksheet of L-27 was selected to optimize fermentation (temperature, particle size, moisture content and pH), nutrition (yeast extract and maltose), and biomaterial-related (inoculum size and incubation time) factors for the best production yields. Analysis of experimental data using Qualitek-4 methodology showed significant variation in enzyme production levels (32,000-73,000 units per gram material) and dependence on the selected factors and their assigned levels. Validation of experimental results on alkaline protease production by this bacterial strain based on DOE methodology revealed 51% enhanced protease production compared to average performance of the fermentation, indicating the importance of this methodology in the evaluation of main and interaction effects of the selected factors individually and in combination for bioprocess optimization.

Agriculture↗

A CAD CAM method for custom below-knee sockets.

The purpose of this investigation was to develop a numerical method for fabricating prosthetic sockets for below-knee amputees. An optical/laser digitiser scans an amputee's stump and collects three dimensional numerical data describing the surface of the limb and describing specific modification site locations. The numerical data from the laser camera representing the stump and modification sites are altered by the prosthetist using a custom computer aided design software system running on a personal computer. Using the altered numerical data a programme is created for a high resolution numerically controlled milling machine and a mould is made. The prosthetist then fabricates a socket. While the system has been tested with below-knee amputees it has been designed for application in most areas of prosthetics and orthotics. Utilising this method 15 patients were fitted. All patients subjectively stated that their "computer designed" socket fitted better than their conventionally made socket. As the research progressed and experience was gained with the system patients were normally fitted with the first socket iteration. The system overcomes five limitations existing with some of the other numerical systems: 1) accurate high resolution surface topography, 2) specific identification of subject modification sites, 3) flexible, user friendly software, 4) high resolution numerically controlled milling, and 5) integrated expansion to other prosthetic and orthotic areas.

Artificial Limbs↗

Computerized protocol for anatomical and functional studies of joints.

This chapter describes a new methodology for the acquisition and computer elaboration of joint anatomy and motion data and the study of their correlation. The method uses a commercial industrial electrogoniometer, custom tools, and software designed and developed by the authors for interactive display of the anatomical structures during joint motion, numerical interpolations of the articular geometries, and kinematic analysis of motion. The original data acquisition protocol and computer elaboration software are described in detail, and a final subheading describes briefly previous studies and future developments.

Biomechanical Phenomena↗

CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design.

We have developed a new primer design strategy for PCR amplification of distantly related gene sequences based on consensus-degenerate hybrid oligonucleotide primers (CODEHOPs). An interactive program has been written to design CODEHOP PCR primers from conserved blocks of amino acids within multiply-aligned protein sequences. Each CODEHOP consists of a pool of related primers containing all possible nucleotide sequences encoding 3-4 highly conserved amino acids within a 3' degenerate core. A longer 5' non-degenerate clamp region contains the most probable nucleotide predicted for each flanking codon. CODEHOPs are used in PCR amplification to isolate distantly related sequences encoding the conserved amino acid sequence. The primer design software and the CODEHOP PCR strategy have been utilized for the identification and characterization of new gene orthologs and paralogs in different plant, animal and bacterial species. In addition, this approach has been successful in identifying new pathogen species. The CODEHOP designer (http://blocks.fhcrc.org/codehop.html) is linked to BlockMaker and the Multiple Alignment Processor within the Blocks Database World Wide Web (http://blocks.fhcrc.org).

Amino Acid Sequence↗

A novel and innovative quantitative kinetic software for virological colorimetric assays.

This study addresses the limited range of quantification with colorimetric assays (ELISA) starting from the analysis of color production in a reference external curve. An automatic ELISA management software, designated Quanti-Kin Detection System (QKDS) is described, which retains the sensitivity of the end-point reading and extends the dynamic range up to five logarithms with mathematical interpretation of color production. The QKDS software is a generic system suitable for different types of ELISA with substrate incubation at room temperature, does not require dedicated instruments, performs accurate quantification (including assay quality control) and has a user friendly interface. Specific applications were developed for three types of analytes: antibodies, viral antigens and nucleic acids. Data are presented on three representative QKDS applications to HIV antibodies, p24 antigen and proviral DNA kits. The precision of quantification is strictly correlated with the precision of the kit; however, for almost all samples with known analyte amount, the error percentage was below 10%, only for two cases in quantification of HIV proviral DNA the error percentage was around 25%. The necessity for a wide quantification range has been demonstrated by measuring clinical samples, which showed a distribution in all possible quantification ranges for all kits.

Animals↗

Perception and visualization of human posture information for computer-aided ergonomic analysis.

This article reports three experiments that examined the effects of photographic method, computerized visualization scheme, and posture complexity on posture perception and specification for computer-aided ergonomic analysis. The subjects were presented with photographs of working postures, and were required to manipulate human forms generated by an ergonomics software program to match the postures in the photographs. The first experiment showed a clear advantage of using a three-dimensional (3-D) human form graphic with two photographs when complex, asymmetric postures were analysed. However, the use of a 3-D human graphic display and two photographs jeopardized the subjects' posture specification performance when simple, symmetric postures were analysed. The results of the second and the third experiment demonstrated the importance of achieving congruency between photographic and computer display perspectives in improving posture specification performance. Implications for ergonomic job analysis and ergonomics software design are discussed.

Adult↗

Three-dimensional imaging on a CT or MR scanner.

Three-dimensional (3D) imaging on a CT or magnetic resonance scanner by the use of software that runs on the scanner's computer is one of a number of approaches to 3D imaging that have become available in recent years. It is shown that this particular approach can be made very inexpensive, provided that it is used in an appropriate manner in the clinical environment. The proposed methodology for the clinical use of 3D imaging on the scanner is illustrated by a discussion of the use of 3D98 (software designed for the GE CT/T 9800 scanner) for the 3D imaging of craniofacial surgical cases.

Head↗

Audit in restorative dentistry.

Auditing activity requires patient data to be collected and analysed to allow comparisons to be made and conclusions drawn. Within the General Dental Services the Dental Practice Board regularly collects practitioner specific clinical data and distributes this to allow dentists to compare their own clinical activity with local and national means. In hospital dentistry, a software package has been developed to enable orthodontic audit to be performed in hospital practice. The package is now being piloted in several centres. A similar software package is required for auditing restorative dentistry activity in units where consultant services are provided. Hospital patient administration systems provide demographic data and appointment systems predominantly with little opportunity for patient specific clinical analysis. Carefully designed software will allow appropriate clinical data and analysis. To ensure compliance and accurate recording both by clinical and support staff it is essential that any software system should be easy to use.

Dental Service, Hospital↗

Mprobe 2.0: computer-aided probe design for oligonucleotide microarray.

UNLABELLED: DNA chips have proven to be effective tools in detecting gene expression levels. Compared with DNA chips using complementary DNA as probes, oligonucleotide microarrays using oligonucleotides as probes have attracted great attention because of their well known advantages. The design of gene-specific probes for each target is essential to the development of oligonucleotide microarrays. We have previously reported the development of a probe design software termed Mprobe 1.0. Here, we present a new version of this software, termed Mprobe 2.0. Several new features are included in Mprobe 2.0. Firstly, a paradox-based sequence database management system has been developed and integrated into the software, which consequently allows interoperability with sequences in GenBank, EMBL, and FASTA formats. Secondly, in contrast to setting a fixed threshold for the secondary structure of probes in Mprobe 1.0 and other related software, Mprobe 2.0 employs a different method. After parameters such as GC type, probe melting temperature and GC contents have been evaluated, candidate probes are sorted by the free energy from high to low value, followed by specificity analysis. Thirdly, Mprobe 2.0 provides users with substantial parameter options in the visual mode. Mprobe 2.0 possesses an easier interface for users to manage sequences annotated in different formats and design the optimal probes for oligonucleotide microarrays and other applications. AVAILABILITY: The program is free for non-commercial users and can be downloaded from the web page http://www.biosun.org.cn/mprobe/ CONTACT: Wuju Li (wujuli@yahoo.com or liwj@nic.bmi.ac.cn).

Algorithms↗

[High-performance dynamic ECG review & analysis system].

This paper describes the design of a high-performance dynamic ECG Review & Analysis system used for not only clinical diagnosis but also medical research. A new ECG pattern classifier with Variable Area Template is applied to improve the quantity of ECG analysis results, while the optimized software design ensures the other performances. The results show that this system has higher performance than the old ones and is valuable for medical research.

Computer Systems↗

Computers in the cognitive rehabilitation of brain-injured persons.

Currently there is a rapid expansion of work among rehabilitation professionals in applying computer-assisted instructional technology to remediate cognitive deficits resulting from brain injury. The present article presents a framework for relating the various theoretical, empirical, and clinical challenges raised by the coalescence of two such recently emerging disciplines as computer-assisted instruction and cognitive rehabilitation. These challenges are presented from the perspectives of diverse disciplines, including cognitive science, rehabilitation professions, and computer science. A set of guiding principles are derived for evaluating the potential efficacy of currently existing programs and for directing future developmental work in software design, evaluation research, and service delivery.

Animals↗