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PubMed2004

Multi-species comparative mapping in silico using the COMPASS strategy.

MOTIVATION: The completion of human and mouse genome sequences provides a valuable resource for decoding other mammalian genomes. The comparative mapping by annotation and sequence similarity (COMPASS) strategy takes advantage of the resource and has been used in several genome-mapping projects. It uses existing comparative genome maps based on conserved regions to predict map locations of a sequence. An automated multiple-species COMPASS tool can facilitate in the genome sequencing effort and comparative genomics study of other mammalian species. RESULTS: The prerequisite of COMPASS is a comparative map table between the reference genome and the predicting genome. We have built and collected comparative maps among five species including human, cattle, pig, mouse and rat. Cattle-human and pig-human comparative maps were built based on the positions of orthologous markers and the conserved synteny groups between human and cattle and human and pig genomes, respectively. Mouse-human and rat-human comparative maps were based on the conserved sequence segments between the two genomes. With a match to human genome sequences, the approximate location of a query sequence can be predicted in cattle, pig, mouse and rat genomes based on the position of the match relatively to the orthologous markers or the conserved segments. AVAILABILITY: The COMPASS-tool and databases are available at http://titan.biotec.uiuc.edu/COMPASS/

Algorithms↗
PubMed2004

Normalization of microarray data using a spatial mixed model analysis which includes splines.

MOTIVATION: Microarray experiments with thousands of genes on a slide and multiple slides used in any experimental set represent a large body of data with many sources of variation. The identification of such sources of variation within microarray experimental sets is critical for correct deciphering of desired gene expression differences. RESULTS: We describe new methods for the normalization using spatial mixed models which include splines and analysis of two-colour spotted microarrays for within slide variation and for a series of slides. The model typically explains 45-85% of the variation on a slide with only approximately 1% of the total degrees of freedom. The results from our methods compare favourably with those from intensity dependent normalization loess methods where we accounted for twice as much uncontrolled and unwanted variation on the slides. We have also developed an index for each EST that combines the various measures of the differential response into a single value that researchers can use to rapidly assess the genes of interest.

Algorithms↗
PubMed2004

Identifying time-lagged gene clusters using gene expression data.

MOTIVATION: Analysis of gene expression data can provide insights into the time-lagged co-regulation of genes/gene clusters. However, existing methods such as the Event Method and the Edge Detection Method are inefficient as they compare only two genes at a time. More importantly, they neglect some important information due to their scoring criterian. In this paper, we propose an efficient algorithm to identify time-lagged co-regulated gene clusters. The algorithm facilitates localized comparison and processes several genes simultaneously to generate detailed and complete time-lagged information for genes/gene clusters. RESULTS: We experimented with the time-series Yeast gene dataset and compared our algorithm with the Event Method. Our results show that our algorithm is not only efficient, but also delivers more reliable and detailed information on time-lagged co-regulation between genes/gene clusters. AVAILABILITY: The software is available upon request. CONTACT: jiliping@comp.nus.edu.sg SUPPLEMENTARY INFORMATION: Supplementary tables and figures for this paper can be found at http://www.comp.nus.edu.sg/~jiliping/p2.htm.

Cluster Analysis↗
PubMed2004

Inference of S-system models of genetic networks using a cooperative coevolutionary algorithm.

MOTIVATION: To resolve the high-dimensionality of the genetic network inference problem in the S-system model, a problem decomposition strategy has been proposed. While this strategy certainly shows promise, it cannot provide a model readily applicable to the computational simulation of the genetic network when the given time-series data contain measurement noise. This is a significant limitation of the problem decomposition, given that our analysis and understanding of the genetic network depend on the computational simulation. RESULTS: We propose a new method for inferring S-system models of large-scale genetic networks. The proposed method is based on the problem decomposition strategy and a cooperative coevolutionary algorithm. As the subproblems divided by the problem decomposition strategy are solved simultaneously using the cooperative coevolutionary algorithm, the proposed method can be used to infer any S-system model ready for computational simulation. To verify the effectiveness of the proposed method, we apply it to two artificial genetic network inference problems. Finally, the proposed method is used to analyze the actual DNA microarray data.

Algorithms↗
PubMed2005

Integration of GO annotations in Correspondence Analysis: facilitating the interpretation of microarray data.

MOTIVATION: The functional interpretation of microarray datasets still represents a time-consuming and challenging task. Up to now functional categories that are relevant for one or more experimental context(s) have been commonly extracted from a set of regulated genes and presented in long lists. RESULTS: To facilitate interpretation, we integrated Gene Ontology (GO) annotations into Correspondence Analysis to display genes, experimental conditions and gene-annotations in a single plot. The position of the annotations in these plots can be directly used for the functional interpretation of clusters of genes or experimental conditions without the need for comparing long lists of annotations. Correspondence Analysis is not limited in the number of experimental conditions that can be compared simultaneously, allowing an easy identification of characterizing annotations even in complex experimental settings. Due to the rapidly increasing amount of annotation data available, we apply an annotation filter. Hereby the number of displayed annotations can be significantly reduced to a set of descriptive ones, further enhancing the interpretability of the plot. We validated the method on transcription data from Saccharomyces cerevisiae and human pancreatic adenocarcinomas. AVAILABILITY: The M-CHiPS software is accessible for collaborators at http://www.mchips.org

Algorithms↗
PubMed2005

GFINDer: genetic disease and phenotype location statistical analysis and mining of dynamically annotated gene lists.

Phenotype analysis is commonly recognized to be of great importance for gaining insight into genetic interaction underlying inherited diseases. However, few computational contributions have been proposed for this purpose, mainly owing to lack of controlled clinical information easily accessible and structured for computational genome-wise analyses. We developed and made available through GFINDer web server an original approach for the analysis of genetic disorder related genes by exploiting the information on genetic diseases and their clinical phenotypes present in textual form within the Online Mendelian Inheritance in Man (OMIM) database. Because several synonyms for the same name and different names for overlapping concepts are often used in OMIM, we first normalized phenotype location descriptions reducing them to a list of unique controlled terms representing phenotype location categories. Then, we hierarchically structured them and the correspondent genetic diseases according to their topology and granularity of description, respectively. Thus, in GFINDer we could implement specific Genetic Disorders modules for the analysis of these structured data. Such modules allow to automatically annotate user-classified gene lists with updated disease and clinical information, classify them according to the genetic syndrome and the phenotypic location categories, and statistically identify the most relevant categories in each gene class. GFINDer is available for non-profit use at http://www.bioinformatics.polimi.it/GFINDer/.

Data Interpretation, Statistical↗
PubMed2004

Performance of three different unfolding procedures connected to Bonner sphere data.

This paper presents the results obtained in a comparison of three neutron spectrum unfolding procedures based on the SAND, MINCHI and UNFANA computer programs. The calculations were performed with data obtained previously from measurements using the PTB Bonner sphere spectrometer and taken from the literature; the neutron dosimetry was done with the Leake rem-meter. The evaluation of some spectrum hardness quantifiers is also reported. The codes give comparable neutron spectrum results. Relative to ambient dose equivalent derived from the Bonner sphere system, as a function of the unfolding code used, the Leake calculated readings were typically 1.16 to 1.91 and 1.58 to 2.69 times larger for the environment of a transport cask with spent fuel elements (Clab) and inside the containment building of a pressurised water reactor (Ring-G), respectively, depending on the calibration fields.

Algorithms↗
PubMed2005

Analysis of QUADOS problem on TLD-ALBEDO personal dosemeter responses using discrete ordinates and Monte Carlo methods.

In the scope of QUADOS, a Concerted Action of the European Commission, eight calculational problems were prepared in order to evaluate the use of computational codes for dosimetry in radiation protection and medical physics, and to disseminate "good practice" throughout the radiation dosimetry community. This paper focuses on the analysis of the P4 problem on the 'TLD-albedo dosemeter: neutron and/or photon response of a four-element TL-dosemeter mounted on a standard ISO slab phantom'. Altogether 17 solutions were received from the participants, 14 of those transported neutrons and 15 photons. Most participants (16 out of 17) used Monte Carlo methods. These calculations are time-consuming, requiring several days of CPU time to perform the whole set of calculations and achieve good statistical precision. The possibility of using deterministic discrete ordinates codes as an alternative to Monte Carlo was therefore investigated and is presented here. In particular the capacity of the adjoint mode calculations is shown.

Computer Simulation↗
PubMed2005

A theoretical, practical, predictive model of faculty and department research productivity.

PURPOSE: Although numerous characteristics impact faculty research productivity, and although researchers have suggested comprehensive theoretical models to explain the relationship between these characteristics and levels of faculty research productivity, few studies have assessed these models. This study tests the ability of the Bland et al. (2002) model-based on individual, institutional, and leadership variables influencing faculty research productivity-to explain individual and group (department) research productivity within the context of a large medical school. METHOD: This study used data from a University of Minnesota Medical School-Twin Cities vitality survey conducted in 2000 that had a response rate of 76% (n = 465 faculty). A statistical software package was used to conduct t tests, logistic regressions, and multiple regressions on these data. RESULTS: The validity of faculty, department, and leadership characteristics identified in the Bland et al. (2002) model were confirmed as necessary for high levels of research productivity. Faculty productivity was influenced more by individual and institutional characteristics; group productivity was more affected by institutional and leadership characteristics. CONCLUSION: The characteristics and groupings (individual, institutional, and leadership) in the Bland et al. (2002) model predict faculty research productivity. Research productivity is influenced by the interaction of the three broad groupings, and it is the dynamic interplay of individual and institutional characteristics, supplemented with effective leadership, that determines the productivity of individuals and departments.

Adult↗
PubMed2005

Investigating the use of sampling for maximising the efficiency of student-generated faculty teaching evaluations.

PURPOSE: Surveys of medical students are widely used to evaluate course content and faculty teaching within the medical school. Gathering information that accurately reflects student perceptions requires that students buy into the evaluation process and be willing to provide thoughtful responses to the teaching evaluation. To maintain student commitment, it is important that medical students are not overburdened with poorly planned evaluations. Sampling might decrease the number of evaluations required of students and might also reduce the proportion of non-responses and other forms of inattentive response biases. METHODS: A sampling technique employed within a large medical lecture is described and evaluated. A generalisability study of the teacher evaluations is conducted. RESULTS: A high response rate and high levels of reliability were obtained by sampling a small proportion of the total class. The largest source of error was related to rater and utilising sufficient numbers of student-raters is critical to achieving reliable results. CONCLUSION: Sampling can reduce evaluation demands placed on students, and preserve reliability and increase the validity of mean evaluation scores. With computer presentation, efficient sampling techniques become practical and should be part of software packages used to present teacher evaluations.

Attitude of Health Personnel↗
PubMed2006

Accuracy of dental digitizers.

UNLABELLED: The need for proper validation and verification methodology for CAD/CAM systems is imminent. CAD/CAM systems consisting of an optical impression system, design software and a fabrication machine have to perform to a certain level, whereby manufacturers need to prove the effectiveness of the system as a whole. However, especially when dental surface digitization devices are used as open, stand-alone applications in dental outsourcing, a reliable standard test for comparison is necessary. PURPOSE: This study evaluates a proposed test method to be used to quantify "digitizing quality" with respect to accuracy and reproducibility of two dental surface digitization devices. Comparability of the characteristics should be ensured. METHOD: Two laser light section scanners: DentaScope II and D200 were evaluated by means of the 'Sphere Test', that involves repeated measurements of a precision ball (radius: 6mm) according to a pre-defined protocol. The surface information was received as unmatched, overlapping point clouds and statistically processed with a newly developed software package. The standard deviation of all points as well as a measure for undercutting the equator were determined. RESULTS: The standard deviation for the radius for D and S were 7.7 (+/-0.8) and 13.9 (+/-1.0) microm respectively. The equator undercut elevations were -2.0 degrees and -0.25 degrees for scanner D and S respectively. CONCLUSION: Scanner D had a significantly higher accuracy than S (p<0.05), corresponding with the smaller pixel distance of the sensor. Both devices show adequate accuracy and reproducibility and have an adequate ability to detect the equator. The test is also suitable for calibration purposes.

Computer-Aided Design↗
PubMed2003

Brachytherapy dosimetry of 125I and 103Pd sources using an updated cross section library for the MCNP Monte Carlo transport code.

Permanent implantation of low energy (20-40 keV) photon emitting radioactive seeds to treat prostate cancer is an important treatment option for patients. In order to produce accurate implant brachytherapy treatment plans, the dosimetry of a single source must be well characterized. Monte Carlo based transport calculations can be used for source characterization, but must have up to date cross section libraries to produce accurate dosimetry results. This work benchmarks the MCNP code and its photon cross section library for low energy photon brachytherapy applications. In particular, we calculate the emitted photon spectrum, air kerma, depth dose in water, and radial dose function for both 125I and 103Pd based seeds and compare to other published results. Our results show that MCNP's cross section library differs from recent data primarily in the photoelectric cross section for low energies and low atomic number materials. In water, differences as large as 10% in the photoelectric cross section and 6% in the total cross section occur at 125I and 103Pd photon energies. This leads to differences in the dose rate constant of 3% and 5%, and differences as large as 18% and 20% in the radial dose function for the 125I and 103Pd based seeds, respectively. Using a partially updated photon library, calculations of the dose rate constant and radial dose function agree with other published results. Further, the use of the updated photon library allows us to verify air kerma and depth dose in water calculations performed using MCNP's perturbation feature to simulate updated cross sections. We conclude that in order to most effectively use MCNP for low energy photon brachytherapy applications, we must update its cross section library. Following this update, the MCNP code system will be a very effective tool for low energy photon brachytherapy dosimetry applications.

Brachytherapy↗
PubMed2003

Diagnosis of Ovarian Cancer Using Decision Tree Classification of Mass Spectral Data.

Recent reports from our laboratory and others support the SELDI ProteinChip technology as a potential clinical diagnostic tool when combined with $n$ -dimensional analyses algorithms. The objective of this study was to determine if the commercially available classification algorithm biomarker patterns software (BPS), which is based on a classification and regression tree (CART), would be effective in discriminating ovarian cancer from benign diseases and healthy controls. Serum protein mass spectrum profiles from 139 patients with either ovarian cancer, benign pelvic diseases, or healthy women were analyzed using the BPS software. A decision tree, using five protein peaks resulted in an accuracy of 81.5% in the cross-validation analysis and 80%in a blinded set of samples in differentiating the ovarian cancer from the control groups. The potential, advantages, and drawbacks of the BPS system as a bioinformatic tool for the analysis of the SELDI high-dimensional proteomic data are discussed.

Journal Article↗
PubMedDate not supplied

Novel noninvasive sensitive determination of tear volume changes in normal cats.

We describe a novel, high-resolution and noninvasive method for measuring tear volume changes in cats. The method entails photographing at the lid margin the tear meniscus area defined by instillation of 0.1% fluorescein solution into the cul-de-sac. The inferior tear meniscus area was obtained from the digitized images with computer-assisted software. The tear meniscus area increased in proportion to the saline volume applied into the conjunctival sac, which validates the technique. Furthermore, this technique detected with high sensitivity previously described increases in tear fluid secretion induced by the P2Y(2) agonist. We demonstrate in cats that changes in conjunctival sac tear volume can be evaluated by measurement of its inferior tear meniscus area.

Animals↗
PubMed2003

An integrated gene annotation and transcriptional profiling approach towards the full gene content of the Drosophila genome.

BACKGROUND: While the genome sequences for a variety of organisms are now available, the precise number of the genes encoded is still a matter of debate. For the human genome several stringent annotation approaches have resulted in the same number of potential genes, but a careful comparison revealed only limited overlap. This indicates that only the combination of different computational prediction methods and experimental evaluation of such in silico data will provide more complete genome annotations. In order to get a more complete gene content of the Drosophila melanogaster genome, we based our new D. melanogaster whole-transcriptome microarray, the Heidelberg FlyArray, on the combination of the Berkeley Drosophila Genome Project (BDGP) annotation and a novel ab initio gene prediction of lower stringency using the Fgenesh software. RESULTS: Here we provide evidence for the transcription of approximately 2,600 additional genes predicted by Fgenesh. Validation of the developmental profiling data by RT-PCR and in situ hybridization indicates a lower limit of 2,000 novel annotations, thus substantially raising the number of genes that make a fly. CONCLUSIONS: The successful design and application of this novel Drosophila microarray on the basis of our integrated in silico/wet biology approach confirms our expectation that in silico approaches alone will always tend to be incomplete. The identification of at least 2,000 novel genes highlights the importance of gathering experimental evidence to discover all genes within a genome. Moreover, as such an approach is independent of homology criteria, it will allow the discovery of novel genes unrelated to known protein families or those that have not been strictly conserved between species.

Animals↗
PubMed2004

ELXR: a resource for rapid exon-directed sequence analysis.

ELXR (Exon Locator and Extractor for Resequencing) streamlines the process of determining exon/intron boundaries and designing PCR and sequencing primers for high-throughput resequencing of exons. We have pre-computed ELXR primer sets for all exons identified from the human, mouse, and rat mRNA reference sequence (RefSeq) public databases curated by the National Center for Biotechnology Information. The resulting exon-flanking PCR primer pairs have been compiled into a system called ELXRdb, which may be searched by keyword, gene name or RefSeq accession number.

Algorithms↗
PubMed1996

Orientation of the lumbar facet joints: association with degenerative disc disease.

The orientation of the lumbar facet joints was studied with magnetic resonance imaging in 140 subjects to determine if there is an association between facet tropism and intervertebral disc disease or between the orientation of the facet joints and degenerative spondylolisthesis. The 140 subjects were divided into four groups: sixty-seven asymptomatic volunteers, forty-six of whom did not have a herniated disc on magnetic resonance scans (Group I) and twenty-one who did (Group II); forty-six symptomatic patients who had a herniated disc confirmed operatively (Group III); and twenty-seven patients who had degenerative spondylolisthesis at the interspace between the fourth and fifth lumbar vertebrae (Group IV). Axial scans were made at each lumbar level and digitized, and the facet joint angle was measured by two independent observers with use of image analysis software in a personal computer. The technique of measurement of the facet angles on magnetic resonance scans was validated with a subset of subjects who also had computed tomography scans made. Similar values were obtained with the two methods (r = 0.92; p = 0.00001). For the forty-six asymptomatic volunteers who did not have a herniated disc on the magnetic resonance scans (Group I), the median facet tropism was 5 to 6 degrees and was more than 10 degrees in 24 per cent (eleven) of the subjects. There was no association between increased facet tropism and disc degeneration. At the level of the fourth and fifth lumbar vertebrae, the median facet tropism was 10.3 degrees in the symptomatic patients who had a herniated disc at the same level and 5.4 degrees in the asymptomatic volunteers (Group I) (p = 0.05). The mean orientation of the lumbar facet angles relative to the coronal plane was more sagittal at all levels in the patients who had degenerative spondylolisthesis. The greatest difference was at the level of the fourth and fifth lumbar vertebrae (p = 0.000001). The mean facet angle was 41 degrees (95 per cent confidence interval, 37.6 to 44.6 degrees) in the asymptomatic volunteers and 60 degrees (95 per cent confidence interval, 52.7 to 67.1 degrees) in the patients who had degenerative spondylolisthesis. Furthermore, both the left and the right facet joints were more sagittally oriented in the patients who had degenerative spondylolisthesis. An individual in who both facet-joint angles at the level of the fourth and fifth lumbar vertebrae were more than 45 degrees relative to the coronal plane was twenty-five times more likely to have degenerative spondylolisthesis (95 per cent confidence interval, seven to ninety-eight times). The increase in facet angles at levels other than that of the spondylolisthesis suggests that increased facet angles represent variations in anatomy rather than a secondary result of spondylolisthesis.

Adult↗
PubMed1986

Using computerized testing in the psychiatric hospital.

This article addresses the uses of the computer in psychological testing and particularly in reference to its use in psychiatric hospitals. Psychologists have received the training necessary to administer and interpret psychological tests. Psychological tests have been used for assessing the patient's level of intellectual functioning, for a better understanding of personality dynamics, for the recognition of organic factors affecting patients' behavior, and for making differential diagnoses. At present there have been numerous attempts to computerize the administration, scoring, and interpretation of standardized psychological tests, but the reliability and validity of these programs is still in question. There exists a tremendous variation in the quality of the software products available. Other issues are who takes responsibility for the statements made in the computerized report, and who administers the tests and under what conditions.

Hospital Bed Capacity, 100 to 299↗