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.     

MIR: a versatile program for the statistical analysis of enzyme kinetic data

We have developed a package program for the estimation of Michaelis-Menten parameters for enzymes that conform to different kinetic mechanisms. Data from different experimental schemes can be fitted with appropriate weighing factors to any of 6 mathematical models, corresponding to 5 kinetic mechanisms: ordered bi-bi, Theorell-Chance, rapid equilibrium random bi-bi, rapid equilibrium ordered bi-bi and ping pong bi-bi. The program also performs a significance test to discriminate between different candidate models. To illustrate the performance of the program, real data from kinetic experiments with glucose 6-phosphate from Leuconostoc mesenteroides have been fitted to different mathematical models, and the results are discussed. The program can be easily implemented for the fitting of kinetic data to any other model.     

FAST (Flexible Analysis by Software Tool) and CHAMP (CHemico-physical AMinoacidic Parameter data bank): a new tool to investigate protein structure

A flexible package designed to study protein structure is described.The package is devoted to the analysis of protein sequencesby drawing structural profiles of specific structure-relatedamino acid parameters. An Aminoacidic Parameters Data Bank (CHAMP)containing 32 different series of physico-chemical parametersof amino acids is available. Sequences can be loaded from anyASCII format data bank or from keyboard. The program possessesa routine which enables easy updating of the protein data bankand CHAMP Data Bank. FAST reads statistical correlations betweentwo plots in order to identify structural similarities. Plotscan be printed, saved or used for correlation, comparison orgraph overlap by using common spreadsheets (e.g. Lotus 123).Plots can be smoothed by a running mean or a running median.The program also has a special feature—a global flexibilityanalysis of proteins. The package runs on IBM or compatiblesand requires DOS 3.0 or later. Received on June 20, 1989; accepted on August 2, 1989     

EDGE: extraction and analysis of differential gene expression

EDGE (Extraction of Differential Gene Expression) is an open source, point-and-click software program for the significance analysis of DNA microarray experiments. EDGE can perform both standard and time course differential expression analysis. The functions are based on newly developed statistical theory and methods. This document introduces the EDGE software package.     

A software package for cDNA microarray data normalization and assessing confidence intervals

DNA microarray data are affected by variations from a number of sources. Before these data can be used to infer biological information, the extent of these variations must be assessed. Here we describe an open source software package, lcDNA, that provides tools for filtering, normalizing, and assessing the statistical significance of cDNA microarray data. The program employs a hierarchical Bayesian model and Markov Chain Monte Carlo simulation to estimate gene-specific confidence intervals for each gene in a cDNA microarray data set. This program is designed to perform these primary analytical operations on data from two-channel spotted, or in situ synthesized, DNA microarrays.     

SCoP: An interactive simulation control program for micro- and minicomputers

A nes software system is described for building simulation programs on micro- and minicomputers. Model equations are written as C subroutines, compiled and linked to the SCoP package to produce a menu-driven, interactive program. The system maintains a database of names, values, and units for all model parameters and variables. Run-time options include several methods for interactive parameter modification and both graphic and tabular outputs, with output values presented as they are calculated. Simulation output values can be compared with experimental data graphically and a companion program SCoPFit is provided for formal optimization of parameter values.     

Modeling individual effects in the Cormack-Jolly-Seber model: a state-space formulation

Summary .   In population and evolutionary biology, there exists considerable interest in individual heterogeneity in parameters of demographic models for open populations. However, flexible and practical solutions to the development of such models have proven to be elusive. In this article, I provide a state-space formulation of open population capture–recapture models with individual effects. The state-space formulation provides a generic and flexible framework for modeling and inference in models with individual effects, and it yields a practical means of estimation in these complex problems via contemporary methods of Markov chain Monte Carlo. A straightforward implementation can be achieved in the software package WinBUGS . I provide an analysis of a simple model with constant parameter detection and survival probability parameters. A second example is based on data from a 7-year study of European dippers, in which a model with year and individual effects is fitted.     

SPOTting Model Parameters Using a Ready-Made Python Package

The choice for specific parameter estimation methods is often more dependent on its availability than its performance. We developed SPOTPY (Statistical Parameter Optimization Tool), an open source python package containing a comprehensive set of methods typically used to calibrate, analyze and optimize parameters for a wide range of ecological models. SPOTPY currently contains eight widely used algorithms, 11 objective functions, and can sample from eight parameter distributions. SPOTPY has a model-independent structure and can be run in parallel from the workstation to large computation clusters using the Message Passing Interface (MPI). We tested SPOTPY in five different case studies to parameterize the Rosenbrock, Griewank and Ackley functions, a one-dimensional physically based soil moisture routine, where we searched for parameters of the van Genuchten-Mualem function and a calibration of a biogeochemistry model with different objective functions. The case studies reveal that the implemented SPOTPY methods can be used for any model with just a minimal amount of code for maximal power of parameter optimization. They further show the benefit of having one package at hand that includes number of well performing parameter search methods, since not every case study can be solved sufficiently with every algorithm or every objective function.     

Solutions for the kinetic analysis of 45calcium uptake curves

The classic solutions based on specific activity curves for the kinetic analysis of ⁴⁵Ca movements in three compartment cellular systems cannot be used when the extracellular compartment is one to two orders of magnitude larger than the cellular or tissue compartments. However if the relative radioactivity curve (tracer uptake curve) is analyzed it is possible to calculate all the relevant kinetic parameters. This paper offers the solutions based on relative radioactivity measurements for the calculation of exchange rates, rate constants and compartment sizes of three compartment systems, for series and parallel cases, for closed and open systems.     

StatAlign: an extendable software package for joint Bayesian estimation of alignments and evolutionary trees

MOTIVATION: Bayesian analysis is one of the most popular methods in phylogenetic inference. The most commonly used methods fix a single multiple alignment and consider only substitutions as phylogenetically informative mutations, though alignments and phylogenies should be inferred jointly as insertions and deletions also carry informative signals. Methods addressing these issues have been developed only recently and there has not been so far a user-friendly program with a graphical interface that implements these methods. RESULTS: We have developed an extendable software package in the Java programming language that samples from the joint posterior distribution of phylogenies, alignments and evolutionary parameters by applying the Markov chain Monte Carlo method. The package also offers tools for efficient on-the-fly summarization of the results. It has a graphical interface to configure, start and supervise the analysis, to track the status of the Markov chain and to save the results. The background model for insertions and deletions can be combined with any substitution model. It is easy to add new substitution models to the software package as plugins. The samples from the Markov chain can be summarized in several ways, and new postprocessing plugins may also be installed.     

An integrated family of amino acid sequence analysis programs

During the last years abundant sequence data has become availabledue to the rapid progress in protein and DNA sequencing techniques.The exact three-dimensional structures, however, are availableonly for a fraction of proteins with known sequences. For manypurposes the primary amino acid sequence of a protein can bedirectly used to predict important structural parameters. However,mathematical presentation of the calculated values often makesinterpretation difficult, especially if many proteins must beanalysed and compared. Here we introduce a broad-based, user-definedanalysis of amino acid sequence information. The program packageis based on published algorithms and is designed to access standardprotein data bases, calculate hydropathy, surface probabilityand flexibility values and perform secondary structure predictions.The data output is in an ‘easy-to-read’ graphicformat and several parameters can be superimposed within a singleplot in order to simplify data interpretations. Additionally,this package includes a novel algorithm for the prediction ofpotential antigenic sites. Thus the software package presentedhere offers a powerful means of analysing an amino acid sequencefor the purpose of structure/function studies as well as antigenicsite analyses. These algorithms were written to function incontext with the UWGCG (University of Wisconsin Genetics ComputerGroup) program collection, and are now distributed within thatpackage. Received on March 20, 1987; accepted on September 4, 1987     

GCWIND: a microcomputer program for identifying open reading frames according to codon positional G + C content

GCWIND is a microcomputer (IBM-PC compatible) program for theidentification of protein-coding open reading frames. The programis similar to the FRAME program, but the latter has only beenimplemented for a specialized graphics package. The base compositions(%G+C)for each of the three possible reading phases throughthe DNA sequence are displayed separately, together with thepositions of potential translation initiation and terminationcodons (on the leading and complementary strands), to providean immediate representation of those regions within the sequencethat have coding potential.     

The analysis of dependence in cross-classifications having ordered categories, using log-linear models for frequencies and log-linear models for odds

To analyse the dependence of a qualitative (dichotomous or polytomous) response variable upon one or more qualitative explanatory variables, log-linear models for frequencies are compared with log-linear models for odds, when the categories of the response variable are ordered and the categories of each explanatory variable may be either ordered or unordered. The log-linear models for odds express the odds (or log odds) pertaining to adjacent response categories in terms of appropriate multiplicative (or additive) factors. These models include the 'null log-odds model', the 'uniform log-odds model', the 'parallel log-odds model', and other log-linear models for the odds. With these models, the dependence of the response variable (with ordered categories) can be analyzed in a manner analogous to the usual multiple regression analysis and related analysis of variance and analysis of covariance. Application of log-linear models for the odds sheds light on earlier applications of log-linear models for the frequencies in contingency tables with ordered categories.     

Multi-user system for analysis of data from flow cytometry.

A new program is described for the analysis of DNA histograms from flow cytometry. The fundamental model representing the cell population is similar to one described previously. It assumes the population is grouped into compartments, each consisting of cells having approximately the same DNA content. After staining the cells with an appropriate fluorochrome, the fluorescence distribution of cells within each compartment is assumed to be Gaussian. In the present algorithm, the parameters of the model can either be computed directly by the program from the data, or can be specified as input by the user. When synchronous cell populations lacking distinct G1 and G2/M phases are analyzed, the parameter values must first be obtained using an appropriate control. Percentages of cells in the various compartments are computed using a gradient search method described by Bevington.     

A calculator program for clinical application of the Bayesian method of predicting plasma drug levels

A pharmacokinetic program that allows individualization of drug dosage regimens through the Bayesian method is described. The program, which is designed for the Hewlett-Packard HP-41 CV calculator, is based upon the one-compartment open model with either instantaneous or zero-order absorption. Individualized estimation of the patient's kinetic parameters (clearance and volume of distribution) is performed by analyzing the plasma levels measured in the patient as well as considering the population data of the drug. After estimating the individual kinetic parameters by the Bayesian method, the program predicts the dosage regimen that will elicit the desired peak and trough plasma levels at steady state. For comparison purposes, the least-squares estimates for clearance and volume of distribution are calculated, and dosage prediction can also be made on the basis of the least-squares estimates. The least-squares estimates can be used to calculate population pharmacokinetic parameters according to the Standard Two-Stage method. Several examples of clinical use of the program are presented. The examples refer to patients with classic hemophilia who were treated with Factor VIII concentrates. In these patients, the Bayesian kinetic parameters of Factor VIII have been estimated through the calculator program. The Bayesian parameter estimates generated by the HP-41 have been compared with those determined by a Bayesian program (ADVISE) designed for microcomputers.     

MLEP: an R package for exploring the maximum likelihood estimates of penetrance parameters

ABSTRACT: BACKGROUND: Linkage analysis is a useful tool for detecting genetic variants that regulate a trait of interest, especially genes associated with a given disease. Although penetrance parameters play an important role in determining gene location, they are assigned arbitrary values according to the researcher's intuition or as estimated by the maximum likelihood principle. Several methods exist by which to evaluate the maximum likelihood estimates of penetrance, although not all of these are supported by software packages and some are biased by marker genotype information, even when disease development is due solely to the genotype of a single allele. FINDINGS: Programs for exploring the maximum likelihood estimates of penetrance parameters were developed using the R statistical programming language supplemented by external C functions. The software returns a vector of polynomial coefficients of penetrance parameters, representing the likelihood of pedigree data. From the likelihood polynomial supplied by the proposed method, the likelihood value and its gradient can be precisely computed. To reduce the effect of the supplied dataset on the likelihood function, feasible parameter constraints can be introduced into maximum likelihood estimates, thus enabling flexible exploration of the penetrance estimates. An auxiliary program generates a perspective plot allowing visual validation of the model's convergence. The functions are collectively available as the MLEP R package. CONCLUSIONS: Linkage analysis using penetrance parameters estimated by the MLEP package enables feasible localization of a disease locus. This is shown through a simulation study and by demonstrating how the package is used to explore maximum likelihood estimates. Although the input dataset tends to bias the likelihood estimates, the method yields accurate results superior to the analysis using intuitive penetrance values for disease with low allele frequencies. MLEP is part of the Comprehensive R Archive Network and is freely available at http://cran.r-project.org/web/packages/MLEP/index.html.     

ClustScan: an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures

The program package ‘ClustScan’ (Cluster Scanner) is designed for rapid, semi-automatic, annotation of DNA sequences encoding modular biosynthetic enzymes including polyketide synthases (PKS), non-ribosomal peptide synthetases (NRPS) and hybrid (PKS/NRPS) enzymes. The program displays the predicted chemical structures of products as well as allowing export of the structures in a standard format for analyses with other programs. Recent advances in understanding of enzyme function are incorporated to make knowledge-based predictions about the stereochemistry of products. The program structure allows easy incorporation of additional knowledge about domain specificities and function. The results of analyses are presented to the user in a graphical interface, which also allows easy editing of the predictions to incorporate user experience. The versatility of this program package has been demonstrated by annotating biochemical pathways in microbial, invertebrate animal and metagenomic datasets. The speed and convenience of the package allows the annotation of all PKS and NRPS clusters in a complete Actinobacteria genome in 2–3 man hours. The open architecture of ClustScan allows easy integration with other programs, facilitating further analyses of results, which is useful for a broad range of researchers in the chemical and biological sciences.