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Learning multiple evolutionary pathways from cross-sectional data.

We introduce a mixture model of trees to describe evolutionary processes that are characterized by the ordered accumulation of permanent genetic changes. The basic building block of the model is a directed weighted tree that generates a probability distribution on the set of all patterns of genetic events. We present an EM-like algorithm for learning a mixture model of K trees and show how to determine K with a maximum likelihood approach. As a case study, we consider the accumulation of mutations in the HIV-1 reverse transcriptase that are associated with drug resistance. The fitted model is statistically validated as a density estimator, and the stability of the model topology is analyzed. We obtain a generative probabilistic model for the development of drug resistance in HIV that agrees with biological knowledge. Further applications and extensions of the model are discussed.

Algorithms↗

Scaling of program fitness spaces.

We investigate the distribution of fitness of programs concentrating on those represented as parse trees and, particularly, how such distributions scale with respect to changes in the size of the programs. By using a combination of enumeration and Monte Carlo sampling on a large number of problems from three very different areas, we suggest that, in general, once some minimum size threshold has been exceeded, the distribution of performance is approximately independent of program length. We proof this for both linear programs and simple side effect free parse trees. We give the density of solutions to the parity problems in program trees which are composed of XOR building blocks. Limited experiments with programs including side effects and iteration suggest a similar result may also hold for this wider class of programs.

Algorithms↗

GPT.EXE: a powerful tool for the visualization and analysis of general processing tree models.

This paper introduces GPT.EXE, a computer program for designing and implementing general processing tree (GPT) models. First, designing and building GPT models using this program is discussed. The second major emphasis is a description of various statistical procedures that can be carried out with GPT.EXE. There is also a brief section on the on-line documentation of this program. Throughout the text, pictures of windows from the program are displayed to help explain the procedures being described by the text.

Cognition↗

The shady side of solar protection.

OBJECTIVE: To determine the value of shade in protecting humans from solar ultraviolet (UV) radiation. DESIGN AND SETTING: Measurement with photometers of protection factors for ultraviolet B radiation (UVB) and for total solar radiation for different types of trees and other structures during the summer months (1995-1997) in south-east Queensland. (The protection ratio is the ratio of the intensity of UVB or total solar radiation in direct sunlight to that in shade.) RESULTS: For summer sun at midday, the mean (SD) UV protection ratio for the shade of trees (n = 65) was 4.21 (1.36) on a horizontal surface and 1.33 (0.30) on a vertical surface. In contrast, the mean (SD) protection ratio for total solar energy (primarily infrared) was much higher (12.1 [1.4]). Trees common in recreational areas in Australia (eucalypts: UV protection ratio, 3.52 [0.79]; Norfolk Island pines: UV protection ratio, 3.72 [0.98]) offered reduced protection compared with trees with more dense foliage (UV protection ratio, 5.48 [1.44]). Over a whole day, measurement of shade by trees and other structures showed that the UV protection ratio was lower in the morning and afternoon. Shade from awnings, buildings and hats gave similar results to those for trees. Both at midday and over a whole day satisfactory protection (UV protection ratio > 15) was obtained only in shade which eliminated exposure to the sky as well as to direct sunlight; for example, in thickly wooded areas and under low, widely overhanging structures. CONCLUSIONS: Most forms of shade, while useful, offer people insufficient protection from solar UV. A fair-skinned person sheltering under a tree could suffer sunburn after less than one hour. There is a need for appropriate design of structural shade, use of other solar protection measures in conjunction with shade, and research on behavioural responses to shade.

Facility Design and Construction↗

Accelerating protein classification using suffix trees.

Position-specific scoring matrices have been used extensively to recognize highly conserved protein regions. We present a method for accelerating these searches using a suffix tree data structure computed from the sequences to be searched. Building on earlier work that allows evaluation of a scoring matrix to be stopped early, the suffix tree-based method excludes many protein segments from consideration at once by pruning entire subtrees. Although suffix trees are usually expensive in space, the fact that scoring matrix evaluation requires an in-order traversal allows nodes to be stored more compactly without loss of speed, and our implementation requires only 17 bytes of primary memory per input symbol. Searches are accelerated by up to a factor of ten.

Animals↗

Building supertrees: an empirical assessment using the grass family (Poaceae).

Large and comprehensive phylogenetic trees are desirable for studying macroevolutionary processes and for classification purposes. Such trees can be obtained in two different ways. Either the widest possible range of taxa can be sampled and used in a phylogenetic analysis to produce a "big tree," or preexisting topologies can be used to create a supertree. Although large multigene analyses are often favored, combinable data are not always available, and supertrees offer a suitable solution. The most commonly used method of supertree reconstruction, matrix representation with parsimony (MRP), is presented here. We used a combined data set for the Poaceae to (1) assess the differences between an approach that uses combined data and one that uses different MRP modifications based on the character partitions and (2) investigate the advantages and disadvantages of these modifications. Baum and Ragan and Purvis modifications gave similar results. Incorporating bootstrap support associated with pre-existing topologies improved Baum and Ragan modification and its similarity with a combined analysis. Finally, we used the supertree reconstruction approach on 55 published phylogenies to build one of most comprehensive phylogenetic trees published for the grass family including 403 taxa and discuss its strengths and weaknesses in relation to other published hypotheses.

Data Interpretation, Statistical↗

Ant-gardens of tropical Asian rainforests.

Ant-garden (AG) associations are systems of epiphytic plants and arboricolous (i.e., tree-living) ants, in which the ants build fragile carton nests containing organic material. They collect and incorporate seeds or fruits of epiphytes that then germinate and grow on the nest [sensu Corbara et al. (1999) 38:73-89]. The plant roots stabilize the nest carton. AGs have been well-known in the neotropics for more than 100 years. In contrast, reports on similar associations in the paleotropics are scarce so far. After discovering a first common AG system on giant bamboo [Kaufmann et al. (2001) 48:125-133], we started a large-scale survey for AGs in Peninsular Malaysia, Borneo, Java, and southern Thailand. A great variety of AG systems (altogether including 18 ant species and 51 plant species) was discovered and is described in the present paper. The high number of species participating in AG associations was reflected by a great variability in the specific appearances of the nest gardens. Frequently, further groups of organisms (e.g., hemipteran trophobionts, fungi) were also involved. Preference patterns of particular ant and epiphyte species for each other and for particular phorophytes (carrier trees) were detected. We integrate domatia-producing, so-called ant-house epiphytes in our study and compare their phases of establishment, as well as other characteristics, to "classical" AGs, coming to the conclusion that they should be regarded only as a special type of AG epiphyte and not as a separate ecological category.

Animals↗

The construction of a 'topic tree': a way of familiarizing a teaching staff to problem-oriented learning in a master's programme in public health.

At the planning stage of a community-oriented and problem-based learning master's programme in public health it is indispensable to build a network of teachers, experts in specific fields, willing to guide the students in acquiring new competencies and ready to facilitate the experimental learning process. We discuss in this paper the construction and the utilisation of the 'topic tree'. In addition we show how the teaching staff get acquainted with that educational methodology by experimenting with it themselves (prior to the students). About 10 experts, each one a specialist in a given field, have conceptualized their approach in building a topic tree (concept tree); such a tree makes it possible to schematize the topics to be understood in order to solve a given problem and the relationship existing between actions to be undertaken. The experiment, meant to initiate the teaching staff in experimental learning procedures, was appreciated by all the experts, who considered it a creative and stimulating method. It also permitted the construction of a bibliography including key documents concerning each identified priority health problem. We discuss the utility and the relevance of our approach in the perspective of initiating teachers in experiential learning based on problem-solving.

Algorithms↗

Fast computation of supertrees for compatible phylogenies with nested taxa.

Typically, supertree methods combine a collection of source trees in which just the leaves are labeled by taxa. In such methods the resulting supertree is also leaf labeled. An underlying assumption in these methods is that across all trees in the collection, no two of the taxa are nested; for example, "buttercups" and "plants" are nested taxa. Motivated by Page, the first supertree algorithm for allowing the source trees to collectively have nested taxa is called AncestralBuild. Here, in addition to taxa labeling the leaves, the source trees may have taxa labeling some of their interior nodes. Taxa-labeling interior nodes are at a higher taxonomic level than that of their descendants (for example, genera versus species). Analogous to the supertree method Build for deciding the compatibility of a collection of source trees in which just the leaves are labeled, AncestralBuild is a polynomial-time algorithm for deciding the compatibility of a collection of source trees in which some of the interior nodes are also labeled by taxa. Although a more general method, in this paper we show that the original description of AncestralBuild can be modified so that the running time is as fast as the current fastest running time for Build. Fast computation for deciding compatibility is essential if one is to make use of phylogenetic databases that contain thousands of trees on tens of thousands of taxa. This is particularly so as AncestralBuild is incorporated as a basic tool inside more general supertree methods (that is, methods that always output a tree regardless of the compatibility of the source trees). We apply the method to propose a comprehensive phylogeny of the strepsirrhines, a major group of the primates.

Algorithms↗

Discovery of predictive models in an injury surveillance database: an application of data mining in clinical research.

A new, evolutionary computation-based approach to discovering prediction models in surveillance data was developed and evaluated. This approach was operationalized in EpiCS, a type of learning classifier system specially adapted to model clinical data. In applying EpiCS to a large, prospective injury surveillance database, EpiCS was found to create accurate predictive models quickly that were highly robust, being able to classify > 99% of cases early during training. After training, EpiCS classified novel data more accurately (p < 0.001) than either logistic regression or decision tree induction (C4.5), two traditional methods for discovering or building predictive models.

Artificial Intelligence↗

Effect of imidacloprid tree treatments on the occurrence of Formosan subterranean termites, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), in independent monitors.

Periodic sampling of 87 independent monitors, initially active with the Formosan subterranean termite, Coptotermes formosanus Shiraki, was conducted. Monitors, located in eight sectors adjacent to seven buildings, were various distances (1-46 m) from 57 trees treated with 0.1% imidacloprid foam. Termites collected from six of the eight sectors showed latent mortality attributed to imidacloprid intoxication at all monitor-tree distances. Approximately 6 mo after treatment, termite populations had recovered in these sectors. Another sector showed termite population suppression for approximately 15 mo, followed by recovery. Imidacloprid tree treatments did not control C. formosanus populations in independent monitors adjacent to the treatments.

Animals↗

Application of formal methods to biological regulatory networks: extending Thomas' asynchronous logical approach with temporal logic.

Based on the discrete definition of biological regulatory networks developed by René Thomas, we provide a computer science formal approach to treat temporal properties of biological regulatory networks, expressed in computational tree logic. It is then possible to build all the models satisfying a set of given temporal properties. Our approach is illustrated with the mucus production in Pseudomonas aeruginosa. This application of formal methods from computer science to biological regulatory networks should open the way to many other fruitful applications.

Computational Biology↗

Color constancy in natural scenes explained by global image statistics.

To what extent do observers' judgments of surface color with natural scenes depend on global image statistics? To address this question, a psychophysical experiment was performed in which images of natural scenes under two successive daylights were presented on a computer-controlled high-resolution color monitor. Observers reported whether there was a change in reflectance of a test surface in the scene. The scenes were obtained with a hyperspectral imaging system and included variously trees, shrubs, grasses, ferns, flowers, rocks, and buildings. Discrimination performance, quantified on a scale of 0 to 1 with a color-constancy index, varied from 0.69 to 0.97 over 21 scenes and two illuminant changes, from a correlated color temperature of 25,000 K to 6700 K and from 4000 K to 6700 K. The best account of these effects was provided by receptor-based rather than colorimetric properties of the images. Thus, in a linear regression, 43% of the variance in constancy index was explained by the log of the mean relative deviation in spatial cone-excitation ratios evaluated globally across the two images of a scene. A further 20% was explained by including the mean chroma of the first image and its difference from that of the second image and a further 7% by the mean difference in hue. Together, all four global color properties accounted for 70% of the variance and provided a good fit to the effects of scene and of illuminant change on color constancy, and, additionally, of changing test-surface position. By contrast, a spatial-frequency analysis of the images showed that the gradient of the luminance amplitude spectrum accounted for only 5% of the variance.

Color↗

Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes.

OBJECTIVE: To determine the extent of genetic variation among internationally collected HIV-1 isolates, to analyse phylogenetic relationships and the geographic distribution of different variants. DESIGN: Phylogenetic comparison of 70 HIV-1 isolates collected in 15 countries on four continents. METHODS: To sequence the complete gag genome of HIV-1 isolates, build multiple sequence alignments and construct phylogenetic trees using distance matrix methods and maximum parsimony algorithms. RESULTS: Phylogenetic tree analysis identified seven distinct genotypes. The seven genotypes were evident by both distance matrix methods and maximum parsimony analysis, and were strongly supported by bootstrap resampling of the data. The intra-genotypic gag distances averaged 7%, whereas the inter-genotypic distances averaged 14%. The geographic distribution of variants was complex. Some genotypes have apparently migrated to several continents and many areas harbor a mixture of genotypes. Related variants may cluster in certain areas, particularly isolates from a single city collected over a short time. CONCLUSIONS: The genetic variation among HIV-1 isolates is more extensive than previously appreciated. At least seven distinct HIV-1 genotypes can be identified. Diversification, migration and establishment of local, temporal 'blooms' of particular variants may all occur concomitantly.

Africa↗

Intrathoracic airway trees: segmentation and airway morphology analysis from low-dose CT scans.

The segmentation of the human airway tree from volumetric computed tomography (CT) images builds an important step for many clinical applications and for physiological studies. Previously proposed algorithms suffer from one or several problems: leaking into the surrounding lung parenchyma, the need for the user to manually adjust parameters, excessive runtime. Low-dose CT scans are increasingly utilized in lung screening studies, but segmenting them with traditional airway segmentation algorithms often yields less than satisfying results. In this paper, a new airway segmentation method based on fuzzy connectivity is presented. Small adaptive regions of interest are used that follow the airway branches as they are segmented. This has several advantages. It makes it possible to detect leaks early and avoid them, the segmentation algorithm can automatically adapt to changing image parameters, and the computing time is kept within moderate values. The new method is robust in the sense that it works on various types of scans (low-dose and regular dose, normal subjects and diseased subjects) without the need for the user to manually adjust any parameters. Comparison with a commonly used region-grow segmentation algorithm shows that the newly proposed method retrieves a significantly higher count of airway branches. A method that conducts accurate cross-sectional airway measurements on airways is presented as an additional processing step. Measurements are conducted in the original gray-level volume. Validation on a phantom shows that subvoxel accuracy is achieved for all airway sizes and airway orientations.

Algorithms↗

Mitochondrial cytochrome b gene analysis of Aspergillus fumigatus and related species.

Nucleotide sequences of 426 bp from the mitochondrial (mt) cytochrome b genes of six anamorph species and two species of Neosartorya teleomophs of Aspergillus section Fumigati were determined. These sequences were used to build nucleotide- and amino acid-based trees for phylogenetic analysis. Thirteen strains of A. fumigatus including 10 clinical isolates of A. fumigatus, 1 type culture of A. fumigatus var. fumigatus, 1 type culture of A. fumigatus var. ellipticus, and 1 strain of A. fumigatus var. albus, had the same nucleotide sequences. One strain of A. fumisynnematus, two strains labeled A. neoellipticus, two strains of A. viridinutans, and one strain of A. duricaulis had distinct nucleotide and amino acid sequences. Two strains of A. brevipes were divided into two types. One produced a 1,500-bp fragment that included an intron. The nucleotide sequences of its two exons were similar to those of the A. fumigatus, and the derived amino acid sequence was the same as that for A. fumigatus. The other produced a 426-bp fragment and had the same nucleotide and amino acid sequences as A. unilateralis. Neosartorya fischeri var. fischeri and N. stramenia had nucleotide sequences that differed from that of A. fumigatus. These species possessed their own characteristic nucleotide sequences that differed from each other. In comparisons of homologous sequences from four other pathogenic species of Aspergillus, regions specific to section Fumigati were found. The mt cytochrome b gene analysis was valuable for the identification, classification, and phylogenetic analysis of isolates of section Fumigati.

Amino Acid Sequence↗

CAGER: classification analysis of gene expression regulation using multiple information sources.

BACKGROUND: Many classification approaches have been applied to analyzing transcriptional regulation of gene expressions. These methods build models that can explain a gene's expression level from the regulatory elements (features) on its promoter sequence. Different types of features, such as experimentally verified binding motifs, motifs discovered by computer programs, or transcription factor binding data measured with Chromatin Immunoprecipitation (ChIP) assays, have been used towards this goal. Each type of features has been shown successful in modeling gene transcriptional regulation under certain conditions. However, no comparison has been made to evaluate the relative merit of these features. Furthermore, most publicly available classification tools were not designed specifically for modeling transcriptional regulation, and do not allow the user to combine different types of features. RESULTS: In this study, we use a specific classification method, decision trees, to model transcriptional regulation in yeast with features based on predefined motifs, automatically identified motifs, ChlP-chip data, or their combinations. We compare the accuracies and stability of these models, and analyze their capabilities in identifying functionally related genes. Furthermore, we design and implement a user-friendly web server called CAGER (Classification Analysis of Gene Expression Regulation) that integrates several software components for automated analysis of transcriptional regulation using decision trees. Finally, we use CAGER to study the transcriptional regulation of Arabidopsis genes in response to abscisic acid, and report some interesting new results. CONCLUSION: Models built with ChlP-chip data suffer from low accuracies when the condition under which gene expressions are measured is significantly different from the condition under which the ChIP experiment is conducted. Models built with automatically identified motifs can sometimes discover new features, but their modeling accuracies may have been over-estimated in previous studies. Furthermore, models built with automatically identified motifs are not stable with respect to noises. A combination of ChlP-chip data and predefined motifs can substantially improve modeling accuracies, and is effective in identifying true regulons. The CAGER web server, which is freely available at http://cic.cs.wustl.edu/CAGER/, allows the user to select combinations of different feature types for building decision trees, and interact with the models graphically. We believe that it will be a useful tool to facilitate the discovery of gene transcriptional regulatory networks.

Algorithms↗