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The mouse linkage map. A computer program.

Computer programs have been developed to serve as a method for storing, retrieving, and sorting mouse linkage data. The programs accept and store raw data and reference information for gene linkage; calculate recombination values for each data set and for combined data sets; retrieve, sort, and print-out raw data, references, and recombination values; and generate linkage maps.

Animals↗

TETCORR: a computer program to compute smoothed tetrachoric correlation matrices.

Although many programs exist for computing tetrachoric correlations, these programs typically lack one or more of the following features: (1) efficient processing of a large number of variables and computing of a matrix of coefficients; (2) a matrix-smoothing capability; (3) an accurate, reliable computing algorithm; (4) the ability to handle missing data; and (5) nominal cost. TETCORR, which combines an algorithm developed by Brown (1977) with starting values obtained from Divgi (1979a) for more efficient computation, was created to address these and other user concerns.

Algorithms↗

GOFCOX: a computer program for the goodness-of-fit analysis of the Cox proportional hazards model.

GOFCOX is a user-friendly FORTRAN program for assessing the adequacy of the Cox proportional hazards model. The underlying methodology is based on the comparison of the maximum partial likelihood estimator and a weighted parameter estimator. The latter is the root to an estimation equation that assigns varying weights to the individual contributions to the partial likelihood score function. The weighted and unweighted parameter estimators have the same expectation under the Cox model, but tend to differ when the model is inappropriate. The GOFCOX program computes a rich class of weighted parameter estimators and corresponding goodness-of-fit test statistics. The program runs on both mainframe computers and microcomputers. The running time is minimal even for large data sets. A simple example is provided to illustrate the features of the program.

Computers, Mainframe↗

DISCO--a general computer program for the computation of acid dissociation constants of polyprotic molecules in water and biological fluids, from nuclear magnetic resonance data: application to polyamines.

A new computer program, DISCO, running under Windows, has been developed under the project CSA98P22 falling within the Competitive Support Activities initiative launched within the EU 4th Framework Programme. DISCO allows the calculation of the stepwise acid dissociation constants of polyprotic molecules in water and in complex media (i.e., biofluids, etc.) from nuclear magnetic resonance (NMR) data (chemical shifts) by means of two derivative-free methods: Pit-mapping and Simplex. DISCO performances were tested using simulated-unaffected by experimental error-data sets, for systems having up to seven equilibrium constants and experimental NMR data of spermine, 6-monofluorospermine, and 6,6-difluorospermine, dissolved in D(2)O and in physiological solution (D(2)O/NaCl). Results demonstrated that (i) DISCO enables the determination of pK(A) values with high precision even when small-sized raw data sets are employed, when chemical shifts are measured with low precision (the usual condition in biofluids due to the impossibility to obtain narrow line shape), and when the guess solution, necessary as an initial step of the mathematical iterative process, is fixed within a large interval of variation; (ii) DISCO always converges to the root; (iii) DISCO permits the calculation of pK(A) values which lie within the observed pH range, independent of the narrowness of the pH range.

Algorithms↗

Interactive analysis of phylogeny and character evolution using the computer program MacClade.

Computer programs for phylogenetic analysis have been important tools in systematics and evolutionary biology, but most have been designed primarily for the reconstruction of phylogenetic trees and not the interpretation of patterns of character evolution. Described here is the computer program MacClade, designed for interactive analysis of character evolution and phylogeny. For a given tree and a matrix of character data, MacClade displays its reconstruction of character evolution by shading the branches of the tree to indicate ancestral states. Trees can be manipulated for instance by picking up and moving branches. Assumptions underlying the reconstruction of character evolution can be varied extensively. With these manipulations and MacClade's graphical feedback, one can explore the relationships among phylogenetic trees, character data, assumptions and interpretations of character evolution. MacClade has extensive facilities for editing data, displaying various summaries of character evolution in charts and diagrams, and printing.

Animals↗

General purpose model and a computer program for combined segregation and path analysis (SEGPATH): automatically creating computer programs from symbolic language model specifications.

A general purpose model and a flexible computer program, called SEGPATH, have been developed to assist in the creation and implementation of a variety of genetic epidemiological models. SEGPATH is a computer program which can be used to generate programs to implement linear models for pedigree data, based upon a flexible, model-specification syntax. SEGPATH models can perform segregation analysis, path analysis, or combined segregation and path analysis using any user-specified path model and can be structured to analyze any number of multivariate phenotypes, environmental indices, and/or measured covariate fixed effects (including measured genotypes). Population heterogeneity models, repeated-measures models, longitudinal models, auto-regressive models, developmental models, and gene-by-environment interaction models can all be created under SEGPATH. Pedigree structures can be defined to be arbitrarily complex, and the data analyzed with programs generated by SEGPATH can have any missing value structure, with entire individuals missing, or missing on one or more measurements. Corrections for ascertainment can be done on a vector of phenotypes and/or other measures. Because the model specification syntax is general, SEGPATH can also be used in non-genetic applications where there is a hierarchical structure, such as longitudinal, repeated-measures, time series, or nested models. A variety of applications are demonstrated.

Genetics, Population↗

COMPROC and CHECKNORM: computer programs for comparing accuracies of diagnostic tests using ROC curves in the presence of verification bias.

To assess relative accuracies of two diagnostic tests, we often compare the areas under the receiver operating characteristic (ROC) curves of these two tests in a paired design. Standard methods for analyzing data from a paired design require that every patient tested has the known disease status. In practice, however, some of the patients with test results may not have verified disease status. Any analysis using only verified cases may result in verification bias. COMPROC is an easy to use program for comparing the effectiveness of two diagnostic tests based on the area under the ROC curve in the presence of verification bias. COMPROC compensates for verification bias by implementing the maximum likelihood (ML) estimation of the areas and covariance matrix of two ROC curves under the missing at random (MAR) assumption as described by Zhou (Biometrics 54 (1998) 349-366). This method assumes normality of the difference of the two ROC curve area estimators. We also describe a program CHECKNORM that does a bootstrap analysis to test this normality assumption (B. Efron, R.J. Tibshirani, An Introduction to the Bootstrap, Chapman and Hall, London, 1993). COMPROC allows for the inclusion of observed covariates that may influence the decision to verify the disease status of a patient. The program computes the estimates of the area under the ROC curve for the two diagnostic tests along with the variance of each area, the covariance between the two areas, a two-sided p-value, and a confidence interval for the difference of the areas. The programs COMPROC and CHECKNORM require the scripting language Perl and the statistical software SAS and can be run on both UNIX machines as well as PCs. The use of COMPROC and CHECKNORM is illustrated in a clinical study designed to compare relative accuracies of MRI and CT in detecting pancreatic cancer.

Area Under Curve↗

Can community health workers screen under 5 yr children with computer program.

EKALAVYA computer program aims at high risk screening of under 5 children in Primary Health Centers by Community Health Workers (CHWs) simulating existing programs like CSSM, ICDS etc. This integrates many common symptoms like fever, respiratory, diarrhea, convulsions etc. along with health promotional aspects like growth, immunization etc. at Community Health Workers skills level. EKALAVYA program was user friendly for CHWs who were trained in 2-3 weeks. CHWs with computer guidance were compared with clinical evaluation of Research Team in 96 pediatric OPD cases in a teaching institution. Overall concordance was 91.66%. Symptom wise and severity wise analysis also showed good concordance. The study also indicated training and programme errors which could be easily corrected. EKALAVYA Program is now ready for field trial in PHCs for the guidance of CHWs in decision making.

Child Health Services↗

Dosimetric protocols in radiotherapy: a computer program.

A computer program to evaluate the dose to water in a specified point for low, medium and high energy photon and electron radiotherapeutic beams using different ionization chambers, phantom materials and new dosimetric standard protocols has been developed. The absorbed dose to air cavity calibration factors of the ionization chambers at the radiation quality, the updated physical quantities and dosimetric parameters are part of the data base, which is extendable to individual users' needs. Moreover, the management software permits comparison of different dosimetric protocols and reduction of errors on the dose delivered to patients.

Humans↗

Subsite mapping of the binding region of alpha-amylases with a computer program.

A computer program has been evaluated for subsite map calculations of depolymerases. The program runs in windows and uses the experimentally determined bond cleavage frequencies (BCFs) for determination of the number of subsites, the position of the catalytic site and for calculation of subsite binding energies. The apparent free energy values were optimized by minimization of the differences of the measured and calculated BCF data. The program called suma (SUbsite Mapping of alpha-Amylases) is freely available for research and educational purposes via the Internet (E-mail: gyemant@tigris.klte.hu). The advantages of this program are demonstrated through alpha-amylases of different origin, e.g. porcine pancreatic alpha-amylase (PPA) studied in our laboratory, in addition to barley and rice alpha-amylases published in the literature. Results confirm the popular 'five subsite model' for PPA with three glycone and two aglycone binding sites. Calculations for barley alpha-amylase justify the '6 + 2 + (1) model' prediction. The binding area of barley alpha-amylase is composed of six glycone, two aglycone binding sites followed by a barrier subsite at the reducing end of the binding site. Calculations for rice alpha-amylase represent an entirely new map with a '(1) + 2 + 5 model', where '(1)' is a barrier subsite at the nonreducing end of the binding site and there are two glycone and five aglycone binding sites. The rice model may be reminiscent of the action of the bacterial maltogenic amylase, that is, suggesting an exo-mechanism for this enzyme.

Algorithms↗

Reduction of an eight-state mechanism of cotransport to a six-state model using a new computer program.

A computer program was developed to allow easy derivation of steady-state velocity and binding equations for multireactant mechanisms including or without rapid equilibrium segments. Its usefulness is illustrated by deriving the rate equation of the most general sequential iso ordered ter ter mechanism of cotransport in which two Na+ ions bind first to the carrier and mirror symmetry is assumed. It is demonstrated that this mechanism cannot be easily reduced to a previously proposed six-state model of Na+-D-glucose cotransport, which also includes a number of implicit assumptions. In fact, the latter model may only be valid over a restricted range of Na+ concentrations or when assuming very strong positive cooperativity for Na+ binding to the glucose symporter within a rapid equilibrium segment. We thus propose an equivalent eight-state model in which the concept of positive cooperativity is best explained within the framework of a polymeric structure of the transport protein involving a minimum number of two transport-competent and identical subunits. This model also includes an obligatory slow isomerization step between the Na+ and glucose-binding sequences, the nature of which might reflect the presence of functionally asymmetrical subunits.

Biological Transport↗

Analysing isoenzyme band patterns using similarity coefficients: a personal computer program.

A computer program in Fortran 77 was developed to analyse the isoenzyme patterns of trypanosomes isolated from African sleeping sickness patients, to allow biochemical relationships between populations of trypanosomes from different hosts and geographic areas to be elucidated. However, the generality of the design allows it to be used with presence/absence data from a variety of sources, including DNA fingerprints. The program reads in isoenzyme band patterns from an ASCII file and calculates a matrix of similarity coefficients. Four different similarity measures are offered, suitable for presence/absence data from a range of organisms and experimental procedures. The matrix of similarity values produced is suitable for analysis by ordination methods including principal coordinates analysis, and the production of dendrograms and icicle plots using SPSS/PC+.

Animals↗