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PubMed2005

Collateral missing value imputation: a new robust missing value estimation algorithm for microarray data.

MOTIVATION: Microarray data are used in a range of application areas in biology, although often it contains considerable numbers of missing values. These missing values can significantly affect subsequent statistical analysis and machine learning algorithms so there is a strong motivation to estimate these values as accurately as possible before using these algorithms. While many imputation algorithms have been proposed, more robust techniques need to be developed so that further analysis of biological data can be accurately undertaken. In this paper, an innovative missing value imputation algorithm called collateral missing value estimation (CMVE) is presented which uses multiple covariance-based imputation matrices for the final prediction of missing values. The matrices are computed and optimized using least square regression and linear programming methods. RESULTS: The new CMVE algorithm has been compared with existing estimation techniques including Bayesian principal component analysis imputation (BPCA), least square impute (LSImpute) and K-nearest neighbour (KNN). All these methods were rigorously tested to estimate missing values in three separate non-time series (ovarian cancer based) and one time series (yeast sporulation) dataset. Each method was quantitatively analyzed using the normalized root mean square (NRMS) error measure, covering a wide range of randomly introduced missing value probabilities from 0.01 to 0.2. Experiments were also undertaken on the yeast dataset, which comprised 1.7% actual missing values, to test the hypothesis that CMVE performed better not only for randomly occurring but also for a real distribution of missing values. The results confirmed that CMVE consistently demonstrated superior and robust estimation capability of missing values compared with other methods for both series types of data, for the same order of computational complexity. A concise theoretical framework has also been formulated to validate the improved performance of the CMVE algorithm. AVAILABILITY: The CMVE software is available upon request from the authors.

Algorithms↗
PubMed2006

Functional genomics via multiscale analysis: application to gene expression and ChIP-on-chip data.

UNLABELLED: We present a fast, versatile and adaptive-multiscale algorithm for analyzing a wide-variety of DNA microarray data. Its primary application is in normalization of array data as well as subsequent identification of 'enriched targets', e.g. differentially expressed genes in expression profiling arrays and enriched sites in ChIP-on-chip experimental data. We show how to accommodate the unique characteristics of ChIP-on-chip data, where the set of 'enriched targets' is large, asymmetric and whose proportion to the whole data varies locally. SUPPLEMENTARY INFORMATION: Supplementary figures, related preprint, free software as well as our raw DNA microarray data with PCR validations are available at http://www.math.umn.edu/~lerman/supp/bioinfo06 as well as Bioinformatics online.

Algorithms↗
PubMed2003

Rapid eye movement density is reduced in the normal elderly.

STUDY OBJECTIVES: While there is general agreement on the age changes in non-rapid eye movement sleep, there is conflicting evidence on whether eye movement density (EMD) in rapid eye movement sleep is affected by aging. We therefore performed computer measurement of EMD in young and elderly normal subjects. DESIGN: Sleep electroencephalogram and electrooculogram were recorded in each subject on 4 nonconsecutive baseline nights. Eye movement density in the elderly subjects was compared to that in young adults. SETTING: A sleep research laboratory with 4 separate bedrooms. INTERVENTIONS: Not applicable. PARTICIPANTS: Subjects were 19 young normal adults and 19 elderly normal adults. MEASUREMENTS AND RESULTS: Digitized electrooculograms were analyzed with the extensively validated zero-cross period-amplitude module of PASS PLUS software. The EMD was measured as 0.3 to 2 Hz integrated amplitude per 20-second stage of rapid eye movement sleep. Eye-movement incidence was the number of half waves. Eye-movement amplitude was the sum of peak-trough excursions (curve length) in the average half wave. We also counted visually the number of 2-second epochs with eye movements for 1 baseline night in both groups. The EMD in the elderly subjects was substantially and significantly lower than in the young subjects. Visual scoring of EMD on 1 baseline night confirmed the statistically significant difference between age groups. Period-amplitude analysis revealed that a lower eye-movement incidence rather than reduced amplitude caused the lower EMD in the elderly. The EMD was significantly correlated within subjects across the nonconsecutive baseline nights in both groups; in both, subjects' EMD average across 2 nights provided a correlation greater than .90 with the 4-night mean. CONCLUSIONS: The incidence of eye movements during rapid eye movement sleep is substantially reduced in the elderly. We hypothesize that this reduction is due to degenerative (aging) rather than developmental brain changes. The correlation analysis indicates that EMD is a reasonably stable individual trait in both young and elderly adults. These results encourage normative studies of EMD over a wider age span and continued exploration of the relation of EMD to cognitive function in the elderly.

Adult↗
PubMed2002

Predictive factors of self-care capacity in veterans care institution residents.

The aim of this research is to determine which factors affect the self-care capacity of veterans self-pay care institution residents and to build a predictive model of their level of independence. Our study included 404 residents of a veterans care institution. Our data collection involved an integrated, multidisciplinary approach. The tools used by each group were all of high validity and reliability. The resulting data was entered into SPSS statistic software, and then analyzed by related coefficients, Mann- Whitney test, Kruskal-Wallis H test, and stepwise multiple regression. This analysis showed that 12.1% of residents were self-care dependent. Residents medical conditions (stoke, arthritis), physical function (tinnitus, fall), cognitive function (Mini-Mental State Examination score, Geriatric Depression Scale Short-Form score, Acute Confusion Behavior Scale score), and social function (frequency of exercise per week, frequency of visitors), showed correlation with self-care capacity. The predictive model of self-care capacity was built as follows: Self-care predictive value = 93.022 -.274 x GDS score +.196 x MMSE score - 3.222 x Stroke - 1.262 x Arthritis +.225 x Exercise per week. This model explained 10.5% of the total variance. The results of this research can act as a basis for elderly admission to and transfer from veterans care institutions and can be a reference for recommending relevant nursing service. This research also provides important information for those who wish to improve the self-care capacity of care institution residents.

Activities of Daily Living↗
PubMed2000

How to program rate responsive pacemakers.

Because oxygen uptake (VO2) increases linearly with heart rate during exercise, the oxygen pulse reserve (OPR) method (VO2 reserve divided by heart rate reserve) may provide a valid guide for rate responsive parameter tailoring. Using custom-made software (Pacing Rate Profile Software [PRPS]) it is possible to predict the exercise pacing rate profile with significant accuracy, according to the patient's functional class when ergospirometry apparatus is not available for a cardiopulmonary stress test (CPX). PRPS for Windows is based on the OPR method and some known workload/metabolic cost of exercise relationships during effort. The present study had two aims; first, to evaluate the reliability of PRPS in accurately predicting pacing rate profiles; and second, the suitability of activity and metabolic rate responsive sensors in supplying pacing rates sufficiently near to those predicted using CPX or PRPS. To test the reliability of PRPS we studied 244 patients, NYHA Class I-II, under two different stress test protocols. In one, the bicycle protocol (25 W, 2-minute steps), we tested 137 normal patients (94 men and 43 women, mean age 67 +/- 15 years). Sixty-eight of these were simultaneously CPX tested. PRPS predicted pacing rates were matched against the patients' sinus rhythms or their theoretical CPX measured VO2 heart rates (OPR method). Linear regression analysis was highly significant (r = 0.93 and r = 0.97, respectively). The other, the treadmill protocol, consisted of three different protocols. (1) Speed Incremental Treadmill Stress Test (SITST): 57 patients underwent CPX (33 men and 24 women, mean age 67 +/- 15 years, NYHA Class I-II). All had been pacemaker implanted for SSS and/or advanced atrioventricular block (AVB). PRPS pacing rates were matched against CPX VO2 OPR calculated heart rates (r = 0.93), (linear regression analysis). (2) CAEP: 30 patients underwent CPX (26 men and 4 women, mean age 61 +/- 11 years, NYHA Class I-II). Thirteen of them had been pacemaker implanted for SSS and/or advanced AVB. In all 30 patients the PRPS rates were matched against CPX VO2 calculated rates (r = 0.90). In the 17 normal nonimplanted patients, the PRPS rates were also matched against sinus rhythms, (r = 0.80). (3) Weber: 20 patients underwent CPX (16 men and 4 women, mean age 68 +/- 8 years, NYHA Class I-II). As above, in six normal nonimplanted patients, statistical analysis between PRPS rates and sinus rhythms was performed (r = 0.89). The comparison between PRPS theoretical pacing rates and VO2 predicted rates in all 20 patients was also statistically significant (r = 0.93). Finally, to test the reliability of PRPS also in NYHA Class III-IV patients, we tested 22 implanted patients (15 men and 7 women, mean age 70 +/- 9 years) and compared PRPS predicted rates against VO2 CPX measured rates (r = 0.92). To determine if the wide variety of RR pacers were able to supply pacing rates near to those predicted, whether by means of CPX or PRPS, we studied a total of 89 patients: 49 of these (26 men and 23 women, mean age 66 +/- 12 years) had been implanted with activity sensors; 12 patients (11 men and one woman, mean age 70 +/- 7 years) had been implanted with metabolic sensors, and finally 28 patients (19 men and 9 women, mean age 70 +/- 12 years) had been implanted with dual sensors (activity + QT or minute ventilation). Linear regression analysis showed r = 0.93 for activity sensors, r = 0.94 for metabolic sensors, and r = 0.92 for dual sensor. In conclusion, when rate responsive pacing causes symptoms or functional impairment, physicians must provide a personalized rate response tailoring derived from precise, simple physiological testing. OPR is an easy physiological method for tailoring rate response settings, suitable for activity and metabolic sensors. When ergospirometry apparatus is not available, PRPS can successfully replace CPX testing for tailoring.

Aged↗
PubMed2000

Atrial overdriving is beneficial in patients with atrial arrhythmias: first results of the PROVE Study.

The AF Prevention by Overdriving (PROVE) trial is an ongoing prospective study of the effectiveness of atrial overdrive pacing combined with an Automatic Rest Rate function in the prevention of atrial arrhythmias. All patients who have received a Talent DR 213 pacemaker are eligible for enrollment into the study. After a 1-month monitoring period, the patients are divided into two groups. Group I includes patients with > or = 2 appropriate mode-switch (MS) episodes, or 1 MS episode of > or = 10 minutes, and/or > 300 atrial runs of > 5 beats/month. Group II includes all other patients. The number and duration of atrial arrhythmias are measured the pacemaker's Automatic Interpretation and Data Analysis software (AIDA). Patients' quality-of-life is measured by a validated functional status questionnaire. After having been grouped, the patients are randomly assigned, in a crossover design, to standard DDDR or overdrive pacing + Rest Rate, each programmed for a 3-month period. Preliminary results in 78 patients show a 34% reduction in the mean number of MS, and a mean 48% shortening of the overall duration of the episodes by overdrive pacing + Rest Rate, achieved by a mean 84% prevalence of atrial pacing. Overdrive pacing + Rest Rate was well tolerated and associated with a slight improvement in quality-of-life.

Aged↗
PubMed1992

Comparison of poly- and monoclonal antibodies for determination of B-cell clonal excess in an routine clinical laboratory.

Flow cytometry (FCM) has gained wide use in the determination of clonality in B-cell lymphoproliferative diseases and many methodological variations exist. We have compared the suitability of a) dual fluorochrome (FITC/PE)-labelled monoclonal antibodies, b) single fluorochrome (FITC)-labelled monoclonal antibodies and c) F(ab')2 fragments of FITC-labelled polyclonal antibodies for flow cytometric determination of clonality using commercially available software and a short sample preparation protocol. The FCM method was validated by analysis of immunoglobulin heavy chain and light chain gene rearrangements. We recommend the use of FITC-labelled monoclonals to obtain three parameters, the kappa/lambda ratio, D and D/S(n) values (Kolmogorov-Smirnov statistics) instead of the commonly used kappa/lambda ratio and D values only. This allows the use of a rapid sample preparation protocol to blood and bone marrow aspirates without sacrificing sensitivity or specificity obtained by the usual FCM method.

Antibodies↗
PubMed1997

Application of photoshop-based image analysis to quantification of hormone receptor expression in breast cancer.

The benefit of quantifying estrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer is well established. However, in routine breast cancer diagnosis, receptor expression is often quantified in arbitrary scores with high inter- and intraobserver variability. In this study we tested the validity of an image analysis system employing inexpensive, commercially available computer software on a personal computer. In a series of 28 invasive ductal breast cancers, immunohistochemical determinations of ER and PR were performed, along with biochemical analyses on fresh tumor homogenates, by the dextran-coated charcoal technique (DCC) and by enzyme immunoassay (EIA). From each immunohistochemical slide, three representative tumor fields (x20 objective) were captured and digitized with a Macintosh personal computer. Using the tools of Photoshop software, optical density plots of tumor cell nuclei were generated and, after background subtraction, were used as an index of immunostaining intensity. This immunostaining index showed a strong semilogarithmic correlation with biochemical receptor assessments of ER (DCC, r = 0.70, p < 0.001; EIA, r = 0.76, p < 0.001) and even better of PR (DCC, r = 0.86; p < 0.01; EIA, r = 0.80, p < 0.001). A strong linear correlation of ER and PR quantification was also seen between DCC and EIA techniques (ER, r = 0.62, p < 0.001; PR, r = 0.92, p < 0.001). This study demonstrates that a simple, inexpensive, commercially available software program can be accurately applied to the quantification of immunohistochemical hormone receptor studies.

Breast Neoplasms↗
PubMed2005

Indirect comparisons of competing interventions.

OBJECTIVES: To survey the frequency of use of indirect comparisons in systematic reviews and evaluate the methods used in their analysis and interpretation. Also to identify alternative statistical approaches for the analysis of indirect comparisons, to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within reviews. DATA SOURCES: Electronic databases. REVIEW METHODS: The Database of Abstracts of Reviews of Effects (DARE) was searched for systematic reviews involving meta-analysis of randomised controlled trials (RCTs) that reported both direct and indirect comparisons, or indirect comparisons alone. A systematic review of MEDLINE and other databases was carried out to identify published methods for analysing indirect comparisons. Study designs were created using data from the International Stroke Trial. Random samples of patients receiving aspirin, heparin or placebo in 16 centres were used to create meta-analyses, with half of the trials comparing aspirin and placebo and half heparin and placebo. Methods for indirect comparisons were used to estimate the contrast between aspirin and heparin. The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results. Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken. RESULTS: Of the reviews identified through DARE, 31/327 (9.5%) included indirect comparisons. A further five reviews including indirect comparisons were identified through electronic searching. Few reviews carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest. Few methodological papers were identified. Some valid approaches for aggregate data that could be applied using standard software were found: the adjusted indirect comparison, meta-regression and, for binary data only, multiple logistic regression (fixed effect models only). Simulation studies showed that the naive method is liable to bias and also produces over-precise answers. Several methods provide correct answers if strong but unverifiable assumptions are fulfilled. Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly randomised comparisons. Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies, but the direction of such discrepancy is unpredictable. CONCLUSIONS: Direct evidence from good-quality RCTs should be used wherever possible. Without this evidence, it may be necessary to look for indirect comparisons from RCTs. However, the results may be susceptible to bias. When making indirect comparisons within a systematic review, an adjusted indirect comparison method should ideally be used employing the random effects model. If both direct and indirect comparisons are possible within a review, it is recommended that these be done separately before considering whether to pool data. There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect. Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons. Research into how evidence from indirect comparisons compares to that from non-randomised studies may also be warranted. Investigations using individual patient data from a meta-analysis of several RCTs using different protocols and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful.

Bias↗
PubMed2004

High-throughput gene sequencing assay development for hereditary nonpolyposis colon cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary colon cancer syndrome and is responsible for as many as 10% of all colorectal cancers. Hereditary nonpolyposis colorectal cancer is autosomally dominant with a prevalence of 1 in 200-2000 and exhibits incomplete penetrance. Affected individuals have an approximately 70% lifetime risk of colon cancer with a mean age of onset of 44 years and an approximately 40% lifetime risk of endometrial cancer. At least 5 mismatch repair genes (MLH1, MSH2, MSH6, PMS1, PMS2) have been implicated in HNPCC; however, no predominant mutations were found in these genes. Mutation detection by direct sequencing has proven to be the most sensitive method. We have developed high-throughput full-length sequencing assays of the MLH1, MSH2, and MSH6 genes. These 3 genes account for approximately 90% of all germline mutations found in HNPCC. In our assays, 19 exons of MLH1, 16 exons of MSH2, 10 exons of MSH6, and the adjacent splice sites were amplified using polymerase chain reaction and loaded onto a capillary sequencing machine. Results were analyzed using sequence analysis software and stored in a relational database. Our assay method was validated using 15 affected patients and normal controls. It is anticipated that our high-throughput assay technique will provide accurate diagnoses for patients at risk for HNPCC and thereby facilitate early curative intervention.

Base Pair Mismatch↗
PubMed2001

Virtual reality as clinical tool: immersion and three-dimensionality in the relationship between patient and therapist.

VR represents the maximum level of evolution in interaction between man and computer systems. In Clinical Psychology, the virtual cyberspace offers a series of powerful and valid applications for diagnosis and therapy. The qualities that make VR software reliable and particularly useful in the practice of assessment and rehabilitation of certain psychopathological dysfunctions emerge with extreme clarity from the specialist literature. VR constitutes a three-dimensional interface that puts the interacting subject in a condition of active exchange with a world re-created via the computer. The possibility of not limiting the paradigm of interaction in a unidirectional sense represents the strong point of the new technology: man is not simply an external observer of pictures or one who passively experiences the reality created by the computer, but on the contrary may actively modify the three-dimensional world in which he is acting, in a condition of complete sensorial immersion. The nature of this exchange means that the subject feels actually present in this new context. The feeling of "actual presence" is perhaps the peculiar characteristic of this tool and is made possible both by the realistic reproduction of the cybernetic environments and by the involvement of all the sensorimotor channels during interaction. In this paper we focus on the characteristics of the new configuration in the relationship between patient and therapist.

Arousal↗
PubMed2004

Identifying controlled substance patterns of utilization requiring evaluation using administrative claims data.

OBJECTIVES: To develop a systems approach to identify, for further evaluation, patients with potential controlled substance misuse or mismanagement using software queries applied to administrative health claims data. STUDY DESIGN: Retrospective validation of the system using insurance claims. PATIENTS AND METHODS: Data from administrative health claims databases representing nearly 7 million individuals younger than 65 years were used by multidisciplinary expert panels to develop and validate controlled substance patterns of utilization requiring evaluation (CS-PURE) criteria. RESULTS: Thirty-four CS-PURE queries were developed in SAS and applied to administrative claims records to identify patients with potential controlled substance misuse or mismanagement. From these, we identified 10 CS-PURE with the highest expert agreement that intervention was warranted. Expert panel agree, ment that CS-PURE correctly identified cases ranged from 48% to 100%, with at least 50% agreement in 9 of 10 CS-PURE. The prevalence rates for CS-PURE ranged from 0.001% to 0.252%. This translates to identifying between 5 and 1116 patients for individual CS-PURE in a 500 000-member health plan. CONCLUSIONS: We developed and empirically validated a group of queries using CS-PURE to identify patients with potential controlled substance misuse or mismanagement that would warrant further evaluation by the treating physician, a quality assurance function, or the medical director. Claims-based CS-PURE identification is generalizable to most health insurers with access to medical and pharmaceutical claims records. Although CS-PURE are not direct measures of misuse, they can direct attention to potential problems to determine if intervention is needed.

Adolescent↗
PubMed1993

Digital subtraction radiography.

Subtraction radiography offers greater visualization of radiographic changes between a pair of radiographs by subtracting out the unchanging background distractions. Originally, subtraction was achieved by using positive and negative prints in angiography. The advent of digital imaging devices has led to validation of quantitative measurements from digital subtraction images. As well, computer software manipulations have allowed for more flexibility in the clinical application of subtraction imaging. The clinical application of digital subtraction radiography is discussed along with clinical cases.

Humans↗
PubMed1996

The cell sectioning model. Nuclear/cytoplasmic ratio studied by computer simulation.

OBJECTIVE: Stereologic analysis can be supported using methods of modeling and simulation. To illustrate the use of a mathematical cell sectioning model (CSM) in predicting two-dimensional (2-D) measurement characteristics of sectioned cells by means of computer-assisted simulation, the present study was performed. STUDY DESIGN: Computer software based on the CSM was developed to simulate 2-D nuclear/cytoplasmic (N/C) ratio distributions and to test the sensitivity of the parameter to several factors. Simulations were performed with the following feature set for cells of simulated populations: (1) size, shape (approximated by an ellipsoid of rotation) and orientation of the cell, and (2) size, shape and intracellular position of the nucleus. RESULTS: The computer tests showed that the value of the 2-D N/C ratio depends upon many factors; the real three-dimensional N/C ratio is only one. Statistical characteristics of a 2-D N/C ratio sample were found to be sensitive to changes in (1) the nuclear position inside the cell, (2) cell shape, and (3) orientation of the asymmetric cell with respect to a cutting plane. CONCLUSION: CSM tests demonstrated the model validity of and potentials for using it as an algorithm for morphometry software. Taking into account the sensitivity of the 2-D N/C ratio parameter to various factors, great care must be used in interpreting its observations.

Animals↗
PubMed2003

Dissolution and assaying of multicomponent tablets by chemometric methods using computer-aided spectrophotometer.

Dissolution of three component tablets containing paracetamol (APAP), propyphenazone (PP), and caffeine (CAF) was carried out by USP paddle method. Three chemometric methods; inverse least square (ILS), principal component regression (PCR) and partial least squares (PLS) were applied to simultaneous assay of APAP, PP and CAF in tablets. The PCR, PLS and ILS methods were applied to simultaneous dissolution APAP, PP and CAF in tablets using a double beam UV-Vis spectrophotometer without any chemical separation and any graphical treatment of the overlapping spectra of three drugs. Twenty two mixture solutions in different concentrations were prepared in simulated gastric juice (SGJ, USP) for the chemometric calibrations as training set. The absorbance data matrix was obtained by measuring the absorbance at 14 wavelength points (from 222.5 to 292.5 nm) with the intervals of 5 nm (Deltalambda=5 nm) in the spectral region between 200 and 310 nm. Training set and absorbance data were used for the calibrations of chemometric methods. The developed calibrations were tested for the previously prepared solutions of mixture of three drugs for the validation of the assay method. The chemometric calculations were performed by using the 'MAPLE VRSQUO; software. The results of three chemometric methods were statistically compared with each other. These chemometric calibrations were successfully applied to the content uniformity and dissolution of the multicomponent tablets without any separation procedure. The synthetic mixtures of three drugs were used for the validity of the calibrations. Means recoveries (percent) and relative standard deviation of PLS, PCR and ILS methods were found to be 100.1+/-0.6, 101.4+/-1.6 and 100.1+/-0.6 for APAP; 100.9+/-3.2, 102.0+/-3.3 and 100.9+/-3.2 for PP; 99.9+/-3.5, 101.6+/-3.3 and 99.9+/-3.2 for CAF, respectively. Dissolution profiles of three component tablets were performed. More than 95% of drugs were dissolved within 15 min. All of the three-chemometric methods in this study can be satisfactorily used for the quantitative analysis and for dissolutions test of multicomponent dosage form.

Numerical Analysis, Computer-Assisted↗
PubMedDate not supplied

Protocols for clinical care.

This paper describes the work of the DILEMMA project to provide protocol-based decision support in a variety of clinical domains. We give an outline of the generic protocol model that DILEMMA has produced, and the protocol task manager (PTM) software developed to assist protocol use in routine clinical practice. We summarise the validation of the model carried out to date, and take a quick look at the place of protocols in the wider context of clinical decision support.

Clinical Protocols↗
PubMed2006

Evaluation of sequence alignments and oligonucleotide probes with respect to three-dimensional structure of ribosomal RNA using ARB software package.

BACKGROUND: Availability of high-resolution RNA crystal structures for the 30S and 50S ribosomal subunits and the subsequent validation of comparative secondary structure models have prompted the biologists to use three-dimensional structure of ribosomal RNA (rRNA) for evaluating sequence alignments of rRNA genes. Furthermore, the secondary and tertiary structural features of rRNA are highly useful and successfully employed in designing rRNA targeted oligonucleotide probes intended for in situ hybridization experiments. RNA3D, a program to combine sequence alignment information with three-dimensional structure of rRNA was developed. Integration into ARB software package, which is used extensively by the scientific community for phylogenetic analysis and molecular probe designing, has substantially extended the functionality of ARB software suite with 3D environment. RESULTS: Three-dimensional structure of rRNA is visualized in OpenGL 3D environment with the abilities to change the display and overlay information onto the molecule, dynamically. Phylogenetic information derived from the multiple sequence alignments can be overlaid onto the molecule structure in a real time. Superimposition of both statistical and non-statistical sequence associated information onto the rRNA 3D structure can be done using customizable color scheme, which is also applied to a textual sequence alignment for reference. Oligonucleotide probes designed by ARB probe design tools can be mapped onto the 3D structure along with the probe accessibility models for evaluation with respect to secondary and tertiary structural conformations of rRNA. CONCLUSION: Visualization of three-dimensional structure of rRNA in an intuitive display provides the biologists with the greater possibilities to carry out structure based phylogenetic analysis. Coupled with secondary structure models of rRNA, RNA3D program aids in validating the sequence alignments of rRNA genes and evaluating probe target sites. Superimposition of the information derived from the multiple sequence alignment onto the molecule dynamically allows the researchers to observe any sequence inherited characteristics (phylogenetic information) in real-time environment. The extended ARB software package is made freely available for the scientific community via http://www.arb-home.de.

Algorithms↗
PubMed2000

Pk-fit: a pharmacokinetic/pharmacodynamic and statistical data analysis software.

This paper presents a new software, Pk-fit, to fit nonlinear models to kinetic and dynamic data. Directly connected to the spreadsheet, a statistical software component manager is available. In the data manager, Pk-fit includes the noncompartmental analysis module, the compartmental analysis module, the nonlinear kinetic process module, the drug absorption module, the pharmacodynamic data modeling module, the simultaneous fitting module, and the user-defined library module. In this paper, we present a detailed comparison of the kinetic analysis using Pk-fit and common software packages, PCNONLIN, MODFIT, MKMODEL, NONMEM, and SIPHAR, based on the textbook published by Gabrielsson in 1992, "Compilation of Analyzed Data Sets for Pharmacokinetic Software Evaluation." The comparison of Pk-fit with the reference softwares revealed that the parameters and their dispersion found with Pk-fit are consistent with the ones estimated with the other programs. In conclusion, Pk-fit constituted a valid tool for pharmacokinetic/pharmacodynamic data analysis.

Data Interpretation, Statistical↗