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An ontology for collaborative construction and analysis of cellular pathways.

MOTIVATION: As the scientific curiosity in genome studies shifts toward identification of functions of the genomes in large scale, data produced about cellular processes at molecular level has been accumulating with an accelerating rate. In this regard, it is essential to be able to store, integrate, access and analyze this data effectively with the help of software tools. Clearly this requires a strong ontology that is intuitive, comprehensive and uncomplicated. RESULTS: We define an ontology for an intuitive, comprehensive and uncomplicated representation of cellular events. The ontology presented here enables integration of fragmented or incomplete pathway information via collaboration, and supports manipulation of the stored data. In addition, it facilitates concurrent modifications to the data while maintaining its validity and consistency. Furthermore, novel structures for representation of multiple levels of abstraction for pathways and homologies is provided. Lastly, our ontology supports efficient querying of large amounts of data. We have also developed a software tool named pathway analysis tool for integration and knowledge acquisition (PATIKA) providing an integrated, multi-user environment for visualizing and manipulating network of cellular events. PATIKA implements the basics of our ontology.

Biopolymers↗

Detecting clusters of different geometrical shapes in microarray gene expression data.

MOTIVATION: Clustering has been used as a popular technique for finding groups of genes that show similar expression patterns under multiple experimental conditions. Many clustering methods have been proposed for clustering gene-expression data, including the hierarchical clustering, k-means clustering and self-organizing map (SOM). However, the conventional methods are limited to identify different shapes of clusters because they use a fixed distance norm when calculating the distance between genes. The fixed distance norm imposes a fixed geometrical shape on the clusters regardless of the actual data distribution. Thus, different distance norms are required for handling the different shapes of clusters. RESULTS: We present the Gustafson-Kessel (GK) clustering method for microarray gene-expression data. To detect clusters of different shapes in a dataset, we use an adaptive distance norm that is calculated by a fuzzy covariance matrix (F) of each cluster in which the eigenstructure of F is used as an indicator of the shape of the cluster. Moreover, the GK method is less prone to falling into local minima than the k-means and SOM because it makes decisions through the use of membership degrees of a gene to clusters. The algorithmic procedure is accomplished by the alternating optimization technique, which iteratively improves a sequence of sets of clusters until no further improvement is possible. To test the performance of the GK method, we applied the GK method and well-known conventional methods to three recently published yeast datasets, and compared the performance of each method using the Saccharomyces Genome Database annotations. The clustering results of the GK method are more significantly relevant to the biological annotations than those of the other methods, demonstrating its effectiveness and potential for clustering gene-expression data. AVAILABILITY: The software was developed using Java language, and can be executed on the platforms that JVM (Java Virtual Machine) is running. It is available from the authors upon request. SUPPLEMENTARY INFORMATION: Supplementary data are available at http://dragon.kaist.ac.kr/gk.

Algorithms↗

Radio frequency ablation registration, segmentation, and fusion tool.

The radio frequency ablation segmentation tool (RFAST) is a software application developed using the National Institutes of Health's medical image processing analysis and visualization (MIPAV) API for the specific purpose of assisting physicians in the planning of radio frequency ablation (RFA) procedures. The RFAST application sequentially leads the physician through the steps necessary to register, fuse, segment, visualize, and plan the RFA treatment. Three-dimensional volume visualization of the CT dataset with segmented three dimensional (3-D) surface models enables the physician to interactively position the ablation probe to simulate burns and to semimanually simulate sphere packing in an attempt to optimize probe placement. This paper describes software systems contained in RFAST to address the needs of clinicians in planning, evaluating, and simulating RFA treatments of malignant hepatic tissue.

Algorithms↗

Structural DNA profiles: single sequence queries.

Structural DNA profiles use the structural properties of the constituent octamers either to observe any characteristics of a single sequence that are unusual (a single sequence query) or to visualize a pattern common to a set of sequences (a multiple sequence query). They are an aid in understanding structural reasons for functional DNA activity. Profiles that answer single sequence queries are introduced and Profile Manager (a software application developed to automate profile generation) is presented. Two sequences that are similar by their nucleotide composition but are known to be very different by structure are analyzed, resulting in useful illustrations that agree with the experimental nuclear magnetic resonance structures.

Animals↗

[User friendly analysis of MR investigations of the cerebral perfusion: Windows(R)-based image processing].

PURPOSE: Quick and user-friendly analysis of perfusion and diffusion weighted MRI by means of interactive computer software. METHOD: A Windows(R)-based software was developed for analysis of perfusion (PWI) and diffusion (DWI) MR imaging. The computer program was developed in the programming language C++ using optimized algorithms, so that a high computing speed on Win95/98/NT systems is achieved. The established SVD algorithms of Østergaard et al. for quantitative perfusion analysis were implemented. RESULTS: Perfusion parameter maps of the cerebral blood flow (rCBF), the mean transit time (MTT) and the cerebral blood volume (rCBV) in consideration of the arterial input function (AIF) can be calculated and visualized using color tables. Additionally, the calculation of "time-to-peak" maps (TTP) and of maps of the percentage change in signal intensity (PC) is possible. The analysis of n = 10 normal persons shows perfusion values that agree with those found in the literature. DISCUSSION: With the computer program developed here color-coded perfusion parameter maps can be calculated easily. Because of the high computing speed it is possible to get information about tissue perfusion on the basis of the large MR data sets even in acute investigations.

Algorithms↗

Verification of single-peptide protein identifications by the application of complementary database search algorithms.

Data produced from the MudPIT analysis of yeast (S. cerevisiae) and rice (O. sativa) were used to develop a technique to validate single-peptide protein identifications using complementary database search algorithms. This results in a considerable reduction of overall false-positive rates for protein identifications; the overall false discovery rates in yeast are reduced from near 25% to less than 1%, and the false discovery rate of yeast single-peptide protein identifications becomes negligible. This technique can be employed by laboratories utilizing a SEQUEST-based proteomic analysis platform, incorporating the XTandem algorithm as a complementary tool for verification of single-peptide protein identifications. We have achieved this using open-source software, including several data-manipulation software tools developed in our laboratory, which are freely available to download.

Algorithms↗

An experimental network of general practitioners for purposes of epidemiological surveillance in Italy.

A Computer Network of General Practitioners (GPs) has been established, connecting 150 general practitioners representing a statistically selected national sample, homogeneously distributed all over Italy. The purpose of the network is to increase the epidemiological surveillance on the health status of the Italian community, to collect useful data on the routine activity of the GPs, to promote computer use among them, and to organize some "ad hoc" investigations on specific subjects (case-control studies). To this purpose, a specific software was developed, both to meet the requirements of epidemiological research and to manage general practitioners' clinical files. A working prototype of a health card using micro-computer technology will also be experimented with a subset of the GPs.

Computer Communication Networks↗

Three-dimensional computer reconstruction of prostate cancer from radical prostatectomy specimens: evaluation of the model by core biopsy simulation.

OBJECTIVES: A technique was developed for three-dimensional (3D) modeling of prostate cancer and transrectal biopsies. To test the model, the cancer yield of a simulated 10-biopsy protocol was compared with a simulated sextant protocol and with preoperative biopsies regarding cancer detection and correlation with tumor volume. METHODS: Transrectal ultrasound-guided core biopsies were taken from 81 men according to a standardized 10-biopsy protocol that included sextant biopsies. The patients underwent radical prostatectomy and specimens were step-sectioned and whole-mounted. Cancer and the prostate capsule were outlined on the slides and the regions transferred to a computer software program developed by our group. A 3D volume of each prostate was reconstructed from the sections. Virtual core biopsy needles imitating the positions of the real biopsies were inserted into the prostate and the cancer yield was calculated. Only the standardized positions were considered in this study (ie, additional biopsies from hypoechoic foci were not accounted for). RESULTS: Of the cancers detected with 10 standardized virtual biopsies, 24% would have remained undetected with sextant biopsies. The cancer yield of 10 virtual biopsies correlated with the preoperative biopsies (r = 0.64) and with the tumor volume (r = 0.56). A multiple regression analysis showed that the cancer yield of a simulation of 10 biopsies correlated better with tumor volume than did a simulation of sextant biopsies (P = 0.02). CONCLUSIONS: We conclude that computer-assisted 3D reconstruction of prostate cancer can be used as a model for evaluation and optimization of biopsy protocols.

Adult↗

Quantitative analysis of immunofluorescence and lipofuscin distribution in human cortical areas by dual-channel confocal laser scanning microscopy.

A method for quantitative analysis of confocal laser scanning microscopy (CLSM) images of immunofluorescence and lipofuscin in human brain cortical areas is described. Indirect immunofluorescence was used to show the distribution and density of a synaptic vesicle protein--synaptophysin (p38). Dual channel CLSM was used for imaging immunofluorescence and autofluorescence of lipofuscin granules. Special software was developed for quantitative analysis of the CLSM images. The method has been tested in studies of frontal, temporal, motor, visual, and entorhinal cortices in normal and pathological human brains (Rett syndrome and autism). Using this technique the intensity and amount of p38 immunoreactivity was quantified after subtraction of lipofuscin fluorescence. In normal cortex no statistically significant differences were found for p38 antigen between layers II, III and V. The highest concentration of p38 immunoreactivity was found in the frontal cortex. In Rett syndrome and autistic patients, the p38 immunofluorescence in the investigated cortex areas appeared reduced compared with normal. The software is also suitable for quantitative analysis of double-labelled immunofluorescent specimens in animals without lipofuscin.

Adolescent↗

Conceptual development of an information systems framework for improving continuity in epidemiological research.

Lack of continuity is a problem for survey-based epidemiological research. Poor access to experience and inadequate retention of information means new projects seldom build on successful predecessors to the maximum possible extent. We have designed a data management framework which addresses this problem using a well-known information systems approach. Our ideas provide a means of storing data in a manner which reflects the original research concepts. This makes collected data accessible and understandable without reference to the questionnaire, and allows new questionnaires to be designed quickly and easily. Our framework provides a means for recording developmental, conceptual and other supporting information and documentation which is traditionally poorly conserved. We illustrate the components of the framework using a major Australian epidemiological project as a case study. Once the necessary software is developed, our framework will improve organisational memory within individual research units and has the potential to become a valuable support tool for survey-based research.

Australia↗

In vivo study of the kinematics in axial rotation of the lumbar spine after total intervertebral disc replacement: long-term results: a 10-14 years follow up evaluation.

INTRODUCTION: We did not find any in vivo study of spinal segment kinematics after disc replacement, especially over the long term. In vitro studies did show that it restores almost normal kinematics except for axial rotation. The goal of this study is to develop a new technique in order to analyse axial rotation of a spinal segment, in vivo, after total disc replacement. MATERIALS AND METHODS: A comparative retrospective study of motion in axial rotation at L4L5 level was carried out on 17 patients with artificial discs versus six healthy volunteers. Five patients carried one prostheses at L4L5 level and 12 carried two prosthesis at L4L5 and L5S1 levels. The follow up ranged from 10.8 to 14.3 years (average 12.4+/-1, median 12.6). Dynamic radiographs in axial rotation were made using a special protocol. A new technique associating a stereographic method and image processing software was developed in order to evaluate the range of motion in axial rotation as well as the mechanical coupling. RESULTS: The standard deviation of angular measurements was 1.8 degrees . Eleven (65%) patients had a normal mobility in torsion, identical to those of the volunteers and of the literature, whereas six (35%) had an abnormal increased mobility. If only one disc was replaced, mobility in torsion was identical to that of the volunteers, in the case of two replaced discs, 50% (6/12) of the patients had an abnormal increased mobility. In the sub-group of normal mobility, the coupling was identical to that of the volunteers. In the sub-group of increased mobility, the coupling was different with a strong flexion (10 degrees ), increased by about 7 degrees (P<0.001). CONCLUSION: The implementation of only one discal prosthesis SB Charité seems to restore kinematics close to that of the healthy volunteers and comparable to the literature. The implementation of two adjacent prostheses does not restore normal kinematics in 50% of the cases. It is probable that the existence of active stabilizing elements explains the difference with the in vitro studies carried out beforehand.

Adult↗

Demonstration of a software package for the reconstruction of the dynamically changing structure of the human heart from cone beam x-ray projections.

The Dynamic Spatial Reconstructor (DSR) is a device constructed at the Biodynamics Research Unit of the Mayo Clinic for (among other things) the visualization of the beating heart inside the intact thorax. The device consists of 28 rotating X-ray sources arranged on a circular arc at 6 degrees intervals (total span 162 degrees) and a matching set of 28 imaging systems. The whole thorax of the patient is projected onto the two-dimensional screen of the imaging systems by cone beams of X rays from the sources. All of the X-ray sources are switched on and off within a total period of 10 milliseconds. The Medical Image Processing Group at the State University of New York at Buffalo has developed a software package for the design and evaluation of algorithms to be used by the DSR. In this paper we illustrate the operation of the package and a particular algorithm for the reconstruction of the dynamically changing structure of the heart from data collected by the DSR.

Computers↗

Grateful Med Version 2.0: an overview for searchers.

Grateful Med is a software interface developed by the National Library of Medicine (NLM) for searching several of NLM's databases: MEDLINE, its backfiles to 1966, and CATLINE. It is designed to facilitate access to medical information by health professionals and other end users with limited or no searching experience. This article describes the basic approach and specific searching features of Version 2.0 of the system.

MEDLARS↗

Cardiac PET imaging in mice with simultaneous cardiac and respiratory gating.

Gating firmware and software were developed for the microPET II small animal scanner. The measured cardiac and respiratory signals were collected and converted to TTL gating signals by a Biopac MP150 data acquisition system and sent to microPET II through two BNC connectors on the front panel. During acquisition, the coincidence monitor takes the average of the last eight gate input cycles and inserts this into the list mode data stream on the falling edge of the gating pulse. This value is then used to determine the current time interval of the next gate cycle when the list mode data are sorted into sinograms. The gating firmware and software were validated by an experiment using a rotating point source. Mouse heart (18F-FDG) and bone (18F(-)) imaging was performed with simultaneous cardiac and respiratory gating. It was clearly demonstrated that the contractile function of the mouse heart can be studied by cardiac-gated imaging with microPET II. The left ventricular volumes at different times of the cardiac cycle were measured and the ejection fraction was calculated. In the bone scan, no detectable movement caused by heart contraction was observed. Respiratory motion was more subtle with virtually no motion for more than 75% of the respiratory cycle. The motion of the mouse heart and bones in the thorax caused by respiration was less than 1 mm. It appears with the current resolution of PET, and the small fraction of the respiratory cycle in which motion occurs, that respiratory gating is probably not necessary for most mouse cardiac studies.

Animals↗

PACER: a software tool for PACS decision makers.

This paper describes the development of the software package PACER as it evolved from a cost model to a software package for PACS decision making. PACER was developed as part of the TEASS topic from the EurIPACS project. EurIPACS is an EU subsidized project covering a wide area of PACS related research. The TEASS topic concerns the evaluation of prototype PACSystems in three European hospitals. PACER allows the user to evaluate costs of various PACS implementation scenarios and compare them to the costs of the current film based situation. Its cost calculation is based on a straight forward description of costs of a film based radiology department and of PACS. The PACER cost analysis can consider stepwise introduction of PACS and a corresponding stepwise disappearance of the film environment. This analysis includes effects of price developments. PACER calculates costs and expenses for a number of years in succession. The calculated results can be analysed using graphs, tables and sensitivity analysis tools. Preliminary tests in three hospitals indicate that PACER can indeed be a useful tool in the decision process concerning PACS.

Costs and Cost Analysis↗

The medical software quality deployment method.

UNLABELLED: The objective of this study was to develop a Quality Function Deployment (QFD) model for design of information systems in health-care environments. Consecutive blocked-subject case studies were conducted, based on action research methods. RESULTS: Starting with a QFD model for software development, a model for information system design, the Medical Software Quality Deployment (MSQD) model, was developed. The MSQD model was divided into the pre-study phase, in which the customer categories and their power to influence the design are determined; the data collection phase, in which the voice of customers (VoC) is identified by observations and interviews and quantified by Critical. Incident questionnaires; the need specification phase, where the VoC is specified into ranked customer needs; and the design phase where the customer needs are transformed stepwise to technical requirements and design attributes. QFD showed to be useful for integrating the values of different customer categories in software development for health-care settings. In the later design phases, other quality methods should be used for software implementation and testing.

Consumer Behavior↗

SCATPLOT: a computer program for determination of binding parameters of non-linear non-cooperative ligand-substrate interactions.

The importance of computer-assisted analysis of a non-linear binding phenomenon through Scatchard equation has been widely acknowledged. While several user-friendly softwares [LIGAND, SCTFIT, ALLFIT] are available for determining the binding parameters of nonlinear Scatchard phenomenon, there is no easily available software covering the class of phenomena described by the McGhee and von Hippel formalism [J. Mol. Biol. 86, 469-489 (1974)]. We report here user-friendly software, SCATPLOT, developed in Turbo BASIC, for the numerical estimation of binding parameters of a non-cooperative ligand-substrate interaction doing best fit to the experimental data on the basis of McGhee and von Hippel equation for a nonlinear Scatchard plot. A new parameter has also been incorporated to guide the process of least square analysis and subsequent determination of binding parameters.

Algorithms↗

Comparative study of intensive care unit (ICU) performance.

It is possible to evaluate ICU performance using severity-of-illness systems, but are these systems objective enough to draw comparison between different units? A software was developed to allow data collection and calculation of the score APACHE II [1] and administrative hospital indicators. To provide homogeneity, all data were collected following the same protocol and verified by one author.

APACHE↗