Estimating the Number of Organisms in Quantal Assays

It has been demonstrated by virologists that, when procedural difficulties can be overcome and host variation can be eliminated, dosage-response data from virus assays conform with the one-particle theory of infection for both plaque counts and tissue cultures. Based on this theory, the number of virus particles from quantal virus assays can be estimated. Here a set of tables is presented from which the number of estimated particles can be obtained directly for several dilution factors and a number of dilution levels. Maximum likelihood estimation of particle counts is also illustrated using a computer program that we have prepared.     

A new test for linkage in the presence of locus heterogeneity.

The detection of linkage in complex traits, although potentially of the greatest value, has proved very difficult. One reason may be the drastic effect that locus heterogeneity has on statistical power. We propose a new test for linkage in the presence of heterogeneity, based upon the sum of individual pedigree maximum lod scores, combined with a bootstrap method for estimating the null-hypothesis distribution. The technique is designed to exploit modern computer capability and to avoid reliance on asymptotic-distribution theory. Numerical comparisons indicate that for small pedigrees this new test can detect linkage with 30%-50% less data than are required by standard methods. A computer program for simulating the distribution and for performing the test of linkage is available from the authors.     

COLONY: a program for parentage and sibship inference from multilocus genotype data

Pedigrees, depicting genealogical relationships between individuals, are important in several research areas. Molecular markers allow inference of pedigrees in wild species where relationship information is impossible to collect by observation. Marker data are analysed statistically using methods based on Mendelian inheritance rules. There are numerous computer programs available to conduct pedigree analysis, but most software is inflexible, both in terms of assumptions and data requirements. Most methods only accommodate monogamous diploid species using codominant markers without genotyping error. In addition, most commonly used methods use pairwise comparisons rather than a full-pedigree likelihood approach, which considers the likelihood of the entire pedigree structure and allows the simultaneous inference of parentage and sibship. Here, we describe colony, a computer program implementing full-pedigree likelihood methods to simultaneously infer sibship and parentage among individuals using multilocus genotype data. colony can be used for both diploid and haplodiploid species; it can use dominant and codominant markers, and can accommodate, and estimate, genotyping error at each locus. In addition, colony can carry out these inferences for both monoecious and dioecious species. The program is available as a Microsoft Windows version, which includes a graphical user interface, and a Macintosh version, which uses an R-based interface.     

PHYLOGENIES FROM RESTRICTION SITES: A MAXIMUM-LIKELIHOOD APPROACH

Restriction sites data can be analyzed by maximum likelihood to obtain estimates of phylogenies. The likelihood methods of Smouse and Li, who were able to compute likelihoods for up to four species under a simplified model of base change, can be extended numerically to deal with any number of species. The computational methods for doing so are outlined. The resulting algorithms are slow but take multiple gains and losses of restriction sites fully into account, unlike parsimony methods. They allow for the failure to observe potential sites that are absent from all species. Analysis of the five-species hominoid data of Ferris and coworkers confirms the pattern found by Smouse and Li with four species—that a chimpanzee-gorilla clade is favored, but not statistically significantly over other tree topologies. A large data set produced by computer simulation has also been analyzed to confirm that the method works properly. The methods used here do not allow for different rates of transitions and transversions. They can be extended to do so, but only at a cost of considerably slower computations. The present method is available in a computer program.     

A description of micro- and mainframe-computer programs to summarize frequency,duration and sequences of behavior

Computer programs were developed to hasten the summarization of behavioral data. Behavioral data may be collected by hand (pencil, paper and watch), strip-chart mechanical event recorder, electronic event recorder or by a computer. These behavioral data, in raw form, enter (electronically or manually) a microcomputer (IBM-PC, 128K) or mainframe computer. The microcomputer version summarizes the number of occurrences (frequency), duration and sequence of each behavior. As a microcomputer memory is limited, a program to summarize larger data sets containing more behavior patterns was developed on our mainframe computer (CDC Cyber 730/760). This sequential analysis program can accumulate up to 10 behavioral sequences (9 orders of transition) of up to 50 behaviors in a data set containing up to 10 000 elements. The computer-summary of each treatment may be combined to determine if treatment differences exist. An example data set is provided.     

Automated classification of MMPI profiles into psychotic, neurotic or personality disorder types.

A Fortran program has been developed which can objectively classify Minnesota Multiphasic Inventory (MMPI) profiles as being psychotic, neurotic, personality disorder, or indeterminate types. The method used is a set of configural rules, 'Henrichs' rules for males'. The only input data required are K-corrected T scores, which are the end product of standard scoring techniques. To automate these rules it was necessary to rewrite them so that all decisions were the result of arithmetic comparisons or logical tests using only and, or and not. In particular, examination of the Welsh code, which many rules required, had to be stimulated by the use of several sorted arrays. The program has been carefully tested and is in the use in our computer lab.     

Phylogenetic targeting of research effort in evolutionary biology

Many questions in comparative biology require that new data be collected, either to build a comparative database for the first time or to augment existing data. Given resource limitations in collecting data, the question arises as to which species should be studied to increase the size of comparative data sets. By taking hypotheses, existing data relevant to the hypotheses, and a phylogeny, we show that a method of “phylogenetic targeting” can systematically guide data collection while taking into account potentially confounding variables and competing hypotheses. Phylogenetic targeting selects potential candidates for future data collection, using a flexible scoring system based on differences in pairwise comparisons. We used simulations to assess the performance of phylogenetic targeting, as compared with the less systematic approach of randomly selecting species (as might occur when data have been collected without regard to phylogeny and variation in the traits of interest). The simulations revealed that phylogenetic targeting increased the statistical power to detect correlations and that power increased with the number of species in the tree, even when the number of species studied was held constant. We also developed a Web‐based computer program called PhyloTargeting to implement the approach ( http://phylotargeting.fas.harvard.edu ).     

Evaluation and optimization of diagnostic tests using receiver operating characteristic analysis and information theory

We describe a mathematical technique and an associated computer program for comparing, evaluating and optimizing diagnostic tests. The technique combines receiver operating characteristic (ROC) analysis with information theory and cost-benefit analysis to accomplish this. The program is menu driven and highly interactive; it generates 13 possible user-determined ASCII disk files which can be easily converted to graphs. These graphs allow the user to make detailed comparisons among various diagnostic tests for all values of disorder prevalence, and also provide guidelines for cut-off selection in order to optimize tests. These techniques are applied to three published studies of the enzyme screening assay for diagnosis of infection with the HIV virus. We show how graphs produced by this program can be used to compare and optimize these diagnostic tests. The program is written for an IBM-compatible microcomputer running on a DOS operating system.     

A tree reconstruction method that is economical in the number of pairwise comparisons used

A fast method for reconstructing phylogenies from distance data is presented. The method is economical in the number of pairwise comparisons needed. It can be combined with a new phylogenetic alignment procedure to yield an algorithm that gives a complete history of a set of homologous sequences. The method is applicable to very large distance matrices. An auxiliary program was developed that simplifies large phylogenies without ignoring biologically essential features. A set of 213 globins from vertebrates, plants, and Vitreoscilla (a prokaryote) were analyzed using this method.      

Bayesian inference of recent migration rates using multilocus genotypes

A new Bayesian method that uses individual multilocus genotypes to estimate rates of recent immigration (over the last several generations) among populations is presented. The method also estimates the posterior probability distributions of individual immigrant ancestries, population allele frequencies, population inbreeding coefficients, and other parameters of potential interest. The method is implemented in a computer program that relies on Markov chain Monte Carlo techniques to carry out the estimation of posterior probabilities. The program can be used with allozyme, microsatellite, RFLP, SNP, and other kinds of genotype data. We relax several assumptions of early methods for detecting recent immigrants, using genotype data; most significantly, we allow genotype frequencies to deviate from Hardy-Weinberg equilibrium proportions within populations. The program is demonstrated by applying it to two recently published microsatellite data sets for populations of the plant species Centaurea corymbosa and the gray wolf species Canis lupus. A computer simulation study suggests that the program can provide highly accurate estimates of migration rates and individual migrant ancestries, given sufficient genetic differentiation among populations and sufficient numbers of marker loci.     

Seriation of Anthropological Data: A Computer Program for Matrix-Ordering

A new digital computer program has been developed for the seriation of anthropological data. The program facilitates and refines procedures in the application of certain matrix-ordering approaches, such as the Brainerd-Robinson technique. The new program has special advantages for obtaining the best ordering of a case that is inherent in the data, together with special provisions for experimentation. Some of the innovations consist of working with the whole matrix pattern from start to finish, more exhaustive row-column comparisons, provision for specifying different ordering criteria, consistent utilization of a chosen criterion for matrix evaluation as well as for row-column placement, and a means of lessening the effect of input-order bias. The program is designed to produce a close approximation of an ideal model in order to place data collections as accurately as possible on a continuum of similarity for purposes such as chronological ordering and the expression of intercultural relationships.     

Barcoding Neotropical birds: assessing the impact of nonmonophyly in a highly diverse group

In this study, we verified the power of DNA barcodes to discriminate Neotropical birds using Bayesian tree reconstructions of a total of 7404 COI sequences from 1521 species, including 55 Brazilian species with no previous barcode data. We found that 10.4% of species were nonmonophyletic, most likely due to inaccurate taxonomy, incomplete lineage sorting or hybridization. At least 0.5% of the sequences (2.5% of the sampled species) retrieved from GenBank were associated with database errors (poor‐quality sequences, NuMTs, misidentification or unnoticed hybridization). Paraphyletic species (5.8% of the total) can be related to rapid speciation events leading to nonreciprocal monophyly between recently diverged sister species, or to absence of synapomorphies in the small COI region analysed. We also performed two series of genetic distance calculations under the K2P model for intraspecific and interspecific comparisons: the first included all COI sequences, and the second included only monophyletic taxa observed in the Bayesian trees. As expected, the mean and median pairwise distances were smaller for intraspecific than for interspecific comparisons. However, there was no precise ‘barcode gap’, which was shown to be larger in the monophyletic taxon data set than for the data from all species, as expected. Our results indicated that although database errors may explain some of the difficulties in the species discrimination of Neotropical birds, distance‐based barcode assignment may also be compromised because of the high diversity of bird species and more complex speciation events in the Neotropics.     

Evaluation of the rates of biological processes from tracer kinetic data. IV. Digital simulation of nucleic acid metabolism in bacteria

A flexible computer program was set up to simulate the kinetics of the amounts of radioactivity and the amounts of substance in various classes of nucleic acids for a generalized biological system. This program works by transferring numbers from registers to other registers corresponding to the amounts of isotope label or the amount of substance moving from one pool or compartment to another for each successive time interval. It is practical to choose the time interval small enough so that the same results are accurately obtained with this type of computation as with the analytical solution for the most realistic and complicated case previously formulated. Much more complicated situations now can be treated with this recursion program and questions of relevance to current molecular biology can be answered. The questions treated in this paper are directed to enteric microorganisms and are as follows. (1) What are the conditions under which a short pulse reflects net synthesis and what are the conditions where it reflects total synthesis? (2) What are the conditions that measurement of intermediate pool specific activity can yield information about the turnover and concentration of unstable macromolecules in the system? (3) How prolonged can a pulse be and still label the species of RNA substantially in proportion to their rates of synthesis? (4) What are the amounts and rates of synthesis and degradation of ribosomal precursors best fitting data in the literature?     

MCS/SEL/BAS program--an overlapping clustering method with examples from mating type interactions of ciliated protozoa

The MCS/SEL/BAS program provides a method for group recognition,based on a criterion of homegeneity within the groups. The basicaim of this clustering method is not to ‘force’data into a number of separate groups, as it allows the possibilitythat a given element in the data set can be assigned to morethan one group. Moreover, a parsimonious path through the groupsis sought by selecting groups on the basis of two suitably chosen,peak-ordered criteria. This selection continues until a coveringof the data set is obtained (i. e., until each element in thedata set is assigned to at least one group). Then relationshipsoccurring among the set of selected groups are investigatedby means of two coefficients, called overlapping and cohesioncoefficient, respectively. The utility of this program has beendemonstrated here in elaborating large sets of data derivedfrom mating type interactions of ciliates, but it can be usedalso for analyzing data derived from a wide spectrum of compatibilityphenomena exhibited by other living organisms. Algorithms ofthis program are written in BASIC and formulated in a conversationalmode for processing on a Macintosh. A computer program (MCS/SEL/BAS)is available from G.Mancini upon request. Received on September 18, 1990; accepted on January 21, 1991     

A simulation program examining the use of ratios as raw variables in analyses of variance

An interactive, BASIC-PLUS, simulation program is described for performing a large number of multivariate analyses in accord with, or in violation of, known underlying models. Using a PDP 11/40 computer, random numbers are generated and converted into bivariate normal observations X and Y. These data are then analyzed according to three models. The three analyses are: (1) a standard analysis of variance ignoring the concomitant variable; (2) an analysis of covariance; (3) an analysis of variance on the ratio Y/X. The program can be used to examine the effect of performing multivariate analyses on data transformed into ratios. The utility of the program is the simplicity with which one can alter the underlying models and/or the mathematical relationships between X and Y. Output provides comparisons between models by accumulating rejections and other statistics on critical F-values for each model.     

Web servlet-assisted, dial-in flow cytometry data analysis

BACKGROUND: The obvious benefits of centralized data storage notwithstanding, the size of modern flow cytometry data files discourages their transmission over commonly used telephone modem connections. The proposed solution is to install at the central location a web servlet that can extract compact data arrays, of a form dependent on the requested display type, from the stored files and transmit them to a remote client computer program for display. METHODS: A client program and a web servlet, both written in the Java programming language, were designed to communicate over standard network connections. The client program creates familiar numerical and graphical display types and allows the creation of gates from combinations of user-defined regions. Data compression techniques further reduce transmission times for data arrays that are already much smaller than the data file itself. RESULTS: For typical data files, network transmission times were reduced more than 700-fold for extraction of one-dimensional (1-D) histograms, between 18 and 120-fold for 2-D histograms, and 6-fold for color-coded dot plots. Numerous display formats are possible without further access to the data file. CONCLUSIONS: This scheme enables telephone modem access to centrally stored data without restricting flexibility of display format or preventing comparisons with locally stored files.     

Origins of the Ceboidea viewed from an immunological perspective

Ceboid origins were reviewed from the standpoint of immunodiffusion systematics. Computer processing of spur size data from several thousand trefoil Ouchterlony plate comparisons using rabbit antisera to proteins of various primate, tree shrew and elephant shrew species depicted antigenic distances among the various species. A least squares procedure (executed by a new computer program AJUST) corrected for nonreciprocity in the raw antigenic distance matrix. Another computer program (UWPGM) then produced a cladogram from the normalized antigenic distance matrix. Within the cladogram, tree shrews are closer to undisputed primates than to non-primates. The undisputed primates appear as a monophyletic assemblage, consisting of two major lineages: the Strepsirhini, including lorisoid and lemuroid branches, and the Haplorhini. Haplorhini divides into a tarsioid branch and Anthropoidea. The latter consists of two sister groups, Catarrhini (Hominoidea and Cercopithecoidea) and Platyrrhini (Ceboidea). Thus, this cladogram supports those hypotheses of ceboid origins which depict the phyletic line ancestral to the extant Anthropoidea as first separating from strepsirhine and tarsioid lineages before splitting apart into Platyrrhini and Catarrhini. Present evidence does not reveal if the most recent common ancestor of platyrrhines and catarrhines was morphologically still a prosimian or if it existed late enough in the Tertiary to have reached the simian grade.     

中国角叉菜属(Chondrus)的分类研究：形态观察和rbcL序列分析

采用rbcL序列分析结合传统形态观察的方法 ,对我国福建省平潭县和漳浦县、山东省青岛市及辽宁省大连市采集的角叉菜属样品进行了研究。新鲜或硅胶干燥样品被用于总DNA提取并用于PCR反应 ,PCR扩增产物回收后直接用于测序反应 ,序列数据经ClustalX1 .8软件排序后 ,采用MEGA2 .1软件根据Kimura’s双因子法计算遗传距离 ,并应用邻接法 (neighbor - joint ing)和最大简约法 (MaximumParsimony)构建系统树 ,Bootstrap法 (5 0 0次重复 )评估分支可信度。研究表明 :确认中国存在Chondrusocellatus、Chondrusnipponicus和Chondrusarmatus三种角叉菜 ;原报道产于我国东南沿海的角叉菜Chondrusocellatus应为Grateloupiaimbricata ;原报道产于大连小平岛的角叉菜Chondrusyendoi应为Mazzaellajaponica。