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Factored stochastic trees: a tool for solving complex temporal medical decision models.

The stochastic tree is a continuous-time version of a Markov-cycle tree, useful for constructing and solving medical decision models in which risks of mortality and morbidity may extend over time. Stochastic trees have advantages over Markov-cycle trees in graphic display and computational solution. Like the decision tree or Markov-cycle tree, stochastic tree models of complex medical decision problems can be too large for convenient graphic formulation and display. This paper introduces the notion of factoring a large stochastic tree into simpler components, each of which may be easily displayed. It also shows how the rollback solution procedure for unfactored stochastic trees may be conveniently adapted to solve factored trees. These concepts are illustrated using published examples from the medical literature.

Decision Trees↗

Comparison of microdilution and disc diffusion methods in assessing the in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil against vaginal Candida isolates.

The in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil was evaluated against 99 vaginal Candida strains by the broth microdilution and disc diffusion methods. The microdilution method was performed in accordance with NCCLS-M27A guidelines. An investigational method was used for the disc diffusion test. Fluconazole and tea tree oil minimum inhibitory concentrations (MICs) obtained at 48 h tended to increase 1- to 2-fold or remain the same compared to 24 h readings for most of the isolates tested. C. krusei and C. norvegensis had significantly higher MICs and smaller inhibition zones for fluconazole compared to other species. Tea tree oil MICs were found to be similar, in general, for all Candida spp. tested. The geometric mean MIC of tea tree oil for all isolates was 2.2% (range, 0.25-4%) at 24 h and 3.0% (range, 1-8%) at 48 h. Tea tree oil mean inhibition zone diameter was 24 mm (range, 14-42 mm) at 24 h and 15.8 mm (range, 10-35 mm) at 48 h. In vitro activity of tea tree oil against fluconazole-resistant Candida strains was of particular interest. The isolates had similar tea tree oil MICs and inhibition zone diameters regardless of their fluconazole susceptibility profile. Tea tree oil MIC ranges (inhibition zone diameter ranges) were 2-4% (12-21 mm) and 2% (35 mm) at 48 h for C. krusei and C. norvegensis, respectively. These results suggest that tea tree oil MICs of the fluconazole-resistant isolates are comparable to those of fluconazole-susceptible isolates. This in vitro finding is promising for potential use of topical tea tree oil formulations in the treatment of candidiasis due to fluconazole-resistant strains.

Anti-Infective Agents, Local↗

A survey for nymphs of host-seeking Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae) on tree trunks in deciduous forests.

Trunks of 83 trees in a mixed deciduous forests in Maryland were sampled for the presence of nymphs of the blacklegged tick, Ixodes scapularis Say, and the lone star tick, Amblyomma americanum (L.). Although one or more nymphs of either I. scapularis or A. americanum was found in leaf litter and substrate < or = 1 m from the bases of 47% of the trees sampled, a total of 6 I. scapularis nymphs was found on the trunks of only five trees. No nymphs were found on the trunks of 12 dead trees. No A. americanium nymphs were found on any tree trunks. The trunks were sampled to 2.5 m above the soil, but the nymphs were found < or = 1 m from the ground. More than 50% of I. scapularis nymphs found in the leaf litter < or = 1 m from bases of living trees were north of the trees sampled, whereas few I. scapularis were found west of trees. These findings suggest that the I. scapularis nymphs' presence on tree trunks is of little ecological consequence, unless nymphs were being removed from tree trunks by acquiring hosts at such a rapid rate that nymphal numbers on trunks could not accrue.

Animals↗

Using classification tree and logistic regression methods to diagnose myocardial infarction.

Early and accurate diagnosis of myocardial infarction (MI) in patients who present to the Emergency Room (ER) complaining of chest pain is an important problem in emergency medicine. A number of decision aids have been developed to assist with this problem but have not achieved general use. Machine learning techniques, including classification tree and logistic regression (LR) methods, have the potential to create simple but accurate decision aids. Both a classification tree (FT Tree) and an LR model (FT LR) have been developed to predict the probability that a patient with chest pain is having an MI based solely upon data available at time of presentation to the ER. Training data came from a data set collected in Edinburgh, Scotland. Each model was then tested on a separate Edinburgh data set, as well as on a data set from a different hospital in Sheffield, England. Previously published models, the Goldman classification tree[1] and Kennedy LR equation[2], were evaluated on the same test data sets. On the Edinburgh test set, results showed that the FT Tree, FT LR, and Kennedy LR performed equally well, with ROC curve areas of 94.04%, 94.28%, and 94.30%, respectively, while the Goldman Tree's performance was significantly poorer, with an area of 84.03%. The difference in ROC areas between the first three models and the Goldman model is significant beyond the 0.0001 level. On the Sheffield test set, results showed that the FT Tree, FT LR, and Kennedy LR ROC areas were not significantly different (p > = 0.17), while the FT Tree again outperformed the Goldman Tree (p = 0.006). Unlike previous work[3], this study indicates that classification trees, which have certain advantages over LR models, may perform as well as LR models in the diagnosis of patients with MI.

Algorithms↗

Supporting medical decisions with vector decision trees.

The article presents the extension of a common decision tree concept to a multidimensional - vector - decision tree constructed with the help of evolutionary techniques. In contrary to the common decision tree the vector decision tree can make more than just one suggestion per input sample. It has the functionality of many separate decision trees acting on a same set of training data and answering different questions. Vector decision tree is therefore simple in its form, is easy to use and analyse and can express some relationships between decisions not visible before. To explore and test the possibilities of this concept we developed a software tool--DecRain--for building vector decision trees using the ideas of evolutionary computing. Generated vector decision trees showed good results in comparison to classical decision trees. The concept of vector decision trees can be safely and effectively used in any decision making process.

Algorithms↗

Nymphs of the western black-legged tick (Ixodes pacificus) collected from tree trunks in woodland-grass habitat.

Nymphs of the western black-legged tick, Ixodes pacificus, were found on the trunks of trees during spring and summer in northwestern California. In a woodland-grass habitat, large- and medium-sized (> 130 cm and 80-130 cm in circumference, respectively), moss-covered oak (Quercus spp.) trees supported ticks significantly more often than trees without these characteristics. Additionally, trees with basal leaf-litter and lacking shade (at time of sampling) were significantly associated with the presence of ticks. Mean tick-burdens were > 1 for all oaks (1.06), all trees with basal leaf-litter (1.05), and all trees of large-circumference (1.19); 0.79 ticks per tree were collected over the entire study. Moss reduced the surface temperature of trees by a mean of 1.9 degrees C (range of 1.6-5.0 degrees C) and increased relative humidity by up to 2.5% from the ambient. These microclimatic changes, along with the presence of refugia in bark and western fence lizard (Sceloporus occidentalis) hosts on the lower-most surface of trees, likely accounted for ticks questing on the trunks. Although of undetermined epidemiological significance, the presence of host-seeking I. pacificus nymphs on tree trunks may shed light on the relation of abiotic and biotic factors to the life history of this important vector of disease.

Animals↗

[Selection of tree species composition in Shenyang's urban forest communities].

Tree species selection is the most important basis in urban forest construction, and the key is the selection of tree species composition. Through investigating and analyzing the tree species composition in the parks in Shenyang built-up area, the sequencing of integrate evaluation of various tree species was obtained. By correlation analysis among tree species with the Jaccard quantitative coefficient of correction, the optimal tree species composition and the reference tree composition of Shenyang urban forest were also obtained. The existing status of tree species distribution in Shenyang built-up area was analyzed, the keynote tree species and 8 reference skeleton tree species were recommended, and some advices were presented.

China↗

A rapid heuristic algorithm for finding minimum evolution trees.

The minimum sum of branch lengths (S), or the minimum evolution (ME) principle, has been shown to be a good optimization criterion in phylogenetic inference. Unfortunately, the number of topologies to be analyzed is computationally prohibitive when a large number of taxa are involved. Therefore, simplified, heuristic methods, such as the neighbor-joining (NJ) method, are usually employed instead. The NJ method analyzes only a small number of trees (compared with the size of the entire search space); so, the tree obtained may not be the ME tree (for which the S value is minimum over the entire search space). Different compromises between very restrictive and exhaustive search spaces have been proposed recently. In particular, the "stepwise algorithm" (SA) utilizes what is known in computer science as the "beam search," whereas the NJ method employs a "greedy search." SA is virtually guaranteed to find the ME trees while being much faster than exhaustive search algorithms. In this study we propose an even faster method for finding the ME tree. The new algorithm adjusts its search exhaustiveness (from greedy to complete) according to the statistical reliability of the tree node being reconstructed. It is also virtually guaranteed to find the ME tree. The performances and computational efficiencies of ME, SA, NJ, and our new method were compared in extensive simulation studies. The new algorithm was found to perform practically as well as the SA (and, therefore, ME) methods and slightly better than the NJ method. For searching for the globally optimal ME tree, the new algorithm is significantly faster than existing ones, thus making it relatively practical for obtaining all trees with an S value equal to or smaller than that of the NJ tree, even when a large number of taxa is involved.

Algorithms↗

The RecA protein as a model molecule for molecular systematic studies of bacteria: comparison of trees of RecAs and 16S rRNAs from the same species.

The evolution of the RecA protein was analyzed using molecular phylogenetic techniques. Phylogenetic trees of all currently available complete RecA proteins were inferred using multiple maximum parsimony and distance matrix methods. Comparison and analysis of the trees reveal that the inferred relationships among these proteins are highly robust. The RecA trees show consistent subdivisions corresponding to many of the major bacterial groups found in trees of other molecules including the alpha, beta, gamma, delta, epsilon proteobacteria, cyanobacteria, high-GC gram-positives, and the Deinococcus-Thermus group. However, there are interesting differences between the RecA trees and these other trees. For example, in all the RecA trees the proteins from gram-positive species are not monophyletic. In addition, the RecAs of the cyanobacteria consistently group with those of the high-GC gram-positives. To evaluate possible causes and implications of these and other differences phylogenetic trees were generated for small-subunit rRNA sequences from the same (or closely related) species as represented in the RecA analysis. The trees of the two molecules using these equivalent species-sets are highly congruent and have similar resolving power for close, medium, and deep branches in the history of bacteria. The implications of the particular similarities and differences between the trees are discussed. Some of the features that make RecA useful for molecular systematics and for studies of protein evolution are also discussed.

Amino Acid Sequence↗

Analysis of tree rings using inductively coupled plasma mass spectrometry to record fluctuations in a metal pollution episode.

Analysis of Acer pseudoplatanus L. (sycamore) tree rings using ICP-MS was used to assess the impact of metal deposition on trees growing in the vicinity of a metal refinery at Prescot, north-west England compared to a reference site at Croxteth 6 km distant receiving minimal deposition. No difference in tree growth between sites was recorded. Large reductions in Cu and Cd deposition since the late 1970s was accompanied by a steep decline in Cd concentrations in the outer rings in trees close to the refinery. A similar reduction in Cu concentrations was less apparent due to a tendency for Cu to increase in the outer rings. Zinc and Ni were higher in xylem at Prescot compared to Croxteth. There was no trend in Zn concentrations at either site although Ni concentrations increased in trees close to the refinery after 1982. Manganese concentrations in xylem were much higher at Prescot; Mn levels declined until the late 1970s and then increased slightly in later years interspersed by large concentration peaks within individual years during the 1980s. There was little change in Mn concentrations in trees at Croxteth during this period. Calcium, Mg and Sr concentrations remained steady or declined slightly in rings formed since 1965 in trees at Croxteth. Concentrations of Ca, Mg and Sr were higher in rings formed prior to the mid 1970s in trees at Prescot, but declined steadily after this period, although peaks in concentrations of each element were recorded in individual years during the 1980s. Phosphorous concentrations in rings increased towards the cambium at Croxteth, although P levels decreased in rings formed after 1982 at Prescot. No difference in K concentrations between sites was recorded. Lead concentrations in xylem at both sites declined steadily in rings formed after 1970, although concentrations were higher at the reference site. Analysis of individual sycamore tree rings appears to record short-term changes in pollution episodes, with little lateral movement of elements occurring. It is suggested that changes in element concentrations in trees close to the refinery are a result of reduced metal deposition combined with increased soil acidity due to reduced buffering capacity of metal ions in rainfall.

Journal Article↗

Using classification trees to assess low birth weight outcomes.

OBJECTIVE: Low birth weight (LBW) is a major public health problem. Compared to normal weight infants, LBW is positively associated with infant mortality and negatively associated with normative childhood cognitive and physical development. In the past two decades, research has identified important risk factors of LBW. In this study, we used classification trees to study the interactive nature of these factors. In particular we: (1) identify subgroups of women who are at a high risk of a LBW outcome in seven geographical regions of Florida, and (2) study the predictive performance of classification trees by comparing the tree-based results to those obtained using logistic regression. METHODS: The data, 181,690 singleton births, were derived from Florida birth certificates recorded in 1998. Classification trees and logistic regression models were built based on seven geographical regions. The outcome variable consisted of two classes, namely LBW (< 2500 g) and normal birth weight (> or = 2500 g) cases, while a large number of known risk factors was examined. Tree and logistic regression models were compared using Receiving Operating Curves, and sensitivity and specificity analyses. RESULTS: The use of classification trees has revealed a number of high-risk subgroups. For instance, White, Hispanic or Other non-white mothers who were healthy and smoked with a weight gain less than 20 lbs had a higher risk of a LBW birth compared to those with the same characteristics but with a weight gain of more than 20 lbs. Factors such as parity and marital status were important predictors for pregnancy outcomes among nonsmoker White, Hispanic or Other non-white mothers. Furthermore, we found that Black mothers were directly classified as a high-risk subgroup in the regions of Panhandle, Northeast, North Central, while in the Southern regions a series of other characteristics further defined the high-risk subgroup of Black mothers. Overall, the differences in predictive performance between tree models and logistic regression were minimal. CONCLUSION: The present study demonstrated that classification trees can be used to identify high-risk subgroups of mothers who are at risk of LBW outcomes. Although these exploratory tree analyses revealed a number of distinctive variable interactions for each geographical area, the variable selection was similar across all seven regions. This study also demonstrated that classification trees did not outperform logistic regression models or vice versa; both approaches provided useful analyses of the data.

Adolescent↗

Using genetic algorithms for the construction of phylogenetic trees: application to G-protein coupled receptor sequences.

Many different phylogenetic clustering techniques are used currently. One approach is to first determine the topology with a common clustering method and then calculate the branch lengths of the tree. If the resulting tree is not optimal exchanging tree branches can make some local changes in the tree topology. The whole process can be iterated until a satisfactory result has been obtained. The efficiency of this method fully depends on the initially generated tree. Although local changes are made, the optimal tree will never be found if the initial tree is poorly chosen. In this article, genetic algorithms are applied such that the optimal tree can be found even with a bad initial tree topology. This tree generating method is tested by comparing its results with the results of the FITCH program in the PHYLIP software package. Two simulated data sets and a real data set are used.

Algorithms↗

Automatic 3D vascular tree construction in CT angiography.

This study presents an automatic method for 3D reconstruction of vascular trees using computed-tomography angiographic (CTA) images. The program starts with the CTA slices, performs a sequential procedure of 3D image formation, preprocessing, segmentation, thinning, skeleton pruning and tree construction. It ends with vascular trees along with quantitative data about the trees such as values of diameter, length and bifurcation angles. All the involved algorithms are presented with the emphasis given to the skeleton pruning and tree construction algorithms. The skeletons obtained using a 3D thinning algorithm may contain cycles, spurs, isolated sticks, and non-unit-width parts, which hinder tree construction. As a solution to this problem, a skeleton pruning and tree construction algorithm is proposed. At each stage of the automatic procedure, 3D rendering is provided for visual inspection of the computed results. In the final output, the constructed vascular trees are visualized by rendering the 3D trees and the 3D binary image together in a transparent display mode. The program is carried out in a fully automatic fashion, with a few default settings. Occasionally, user intervention is needed at the 3D segmentation stage to impose an appropriate threshold when the automatic 3D segmentation is obviously sub-optimal for vessel delineation. Experimental demonstrations on both coronary artery phantom and a cast of coronary artery tree of a swine animal model are provided.

Angiography↗

A tree island approach to inferring phylogeny in the ant subfamily Formicinae, with especial reference to the evolution of weaving.

The ant subfamily Formicinae is a large assemblage (2458 species (J. Nat. Hist. 29 (1995) 1037), including species that weave leaf nests together with larval silk and in which the metapleural gland-the ancestrally defining ant character-has been secondarily lost. We used sequences from two mitochondrial genes (cytochrome b and cytochrome oxidase 2) from 18 formicine and 4 outgroup taxa to derive a robust phylogeny, employing a search for tree islands using 10000 randomly constructed trees as starting points and deriving a maximum likelihood consensus tree from the ML tree and those not significantly different from it. Non-parametric bootstrapping showed that the ML consensus tree fit the data significantly better than three scenarios based on morphology, with that of Bolton (Identification Guide to the Ant Genera of the World, Harvard University Press, Cambridge, MA) being the best among these alternative trees. Trait mapping showed that weaving had arisen at least four times and possibly been lost once. A maximum likelihood analysis showed that loss of the metapleural gland is significantly associated with the weaver life-pattern. The graph of the frequencies with which trees were discovered versus their likelihood indicates that trees with high likelihoods have much larger basins of attraction than those with lower likelihoods. While this result indicates that single searches are more likely to find high- than low-likelihood tree islands, it also indicates that searching only for the single best tree may lose important information.

Animals↗

Universal trees based on large combined protein sequence data sets.

Universal trees of life based on small-subunit (SSU) ribosomal RNA (rRNA) support the separate mono/holophyly of the domains Archaea (archaebacteria), Bacteria (eubacteria) and Eucarya (eukaryotes) and the placement of extreme thermophiles at the base of the Bacteria. The concept of universal tree reconstruction recently has been upset by protein trees that show intermixing of species from different domains. Such tree topologies have been attributed to either extensive horizontal gene transfer or degradation of phylogenetic signals because of saturation for amino acid substitutions. Here we use large combined alignments of 23 orthologous proteins conserved across 45 species from all domains to construct highly robust universal trees. Although individual protein trees are variable in their support of domain integrity, trees based on combined protein data sets strongly support separate monophyletic domains. Within the Bacteria, we placed spirochaetes as the earliest derived bacterial group. However, elimination from the combined protein alignment of nine protein data sets, which were likely candidates for horizontal gene transfer, resulted in trees showing thermophiles as the earliest evolved bacterial lineage. Thus, combined protein universal trees are highly congruent with SSU rRNA trees in their strong support for the separate monophyly of domains as well as the early evolution of thermophilic Bacteria.

Amino Acid Sequence↗

The tree squirrel HP-25 gene is a pseudogene.

The gene for the hibernation-specific protein HP-25 is expressed in the liver in hibernating species of the squirrel family (chipmunk and ground squirrel), but not in a nonhibernating species (tree squirrel). To investigate why the HP-25 gene is not expressed in the tree squirrel, we isolated the tree squirrel HP-25 gene and compared its gene structure and promoter activity with that of the chipmunk. The tree squirrel HP-25 gene is composed of three exons, and the gene structures are conserved between the tree squirrel and chipmunk. However, the tree squirrel HP-25 gene has an insertional mutation of 13 nucleotides in exon 2 that disrupts the ORF. In the chipmunk HP-25 gene, the 80-bp 5' flanking sequence is sufficient for the liver-specific promoter activity, and HNF-4, which binds to the sequence from nucleotides -67 to -51, is involved in its transcriptional regulation. In contrast, the corresponding tree squirrel 5' flanking sequence had almost no promoter activity in HepG2 cells, and HNF-4 did not bind to the corresponding region of the tree squirrel HP-25 gene. Furthermore, a tree squirrel-type G to A mutation at -57 in the chipmunk HP-25 gene promoter context abolished its binding to and transactivation by HNF-4. Thus, the point mutation in the HNF-4-binding site is likely to be involved in the lack of HP-25 gene expression in the tree squirrel.

Amino Acid Sequence↗

The shape of supertrees to come: tree shape related properties of fourteen supertree methods.

Using a simple example and simulations, we explore the impact of input tree shape upon a broad range of supertree methods. We find that input tree shape can affect how conflict is resolved by several supertree methods and that input tree shape effects may be substantial. Standard and irreversible matrix representation with parsimony (MRP), MinFlip, duplication-only Gene Tree Parsimony (GTP), and an implementation of the average consensus method have a tendency to resolve conflict in favor of relationships in unbalanced trees. Purvis MRP and the average dendrogram method appear to have an opposite tendency. Biases with respect to tree shape are correlated with objective functions that are based upon unusual asymmetric tree-to-tree distance or fit measures. Split, quartet, and triplet fit, most similar supertree, and MinCut methods (provided the latter are interpreted as Adams consensus-like supertrees) are not revealed to have any bias with respect to tree shape by our example, but whether this holds more generally is an open problem. Future development and evaluation of supertree methods should consider explicitly the undesirable biases and other properties that we highlight. In the meantime, use of a single, arbitrarily chosen supertree method is discouraged. Use of multiple methods and/or weighting schemes may allow practical assessment of the extent to which inferences from real data depend upon methodological biases with respect to input tree shape or size.

Classification↗

Ligand-receptor pairing via tree comparison.

This paper introduces a novel class of tree comparison problems strongly motivated by an important and cost intensive step in drug discovery pipeline viz., mapping cell bound receptors to the ligands they bind to and vice versa. Tree comparison studies motivated by problems such as virus-host tree comparison, gene-species tree comparison and consensus tree problem have been reported. None of these studies are applicable in our context because in all these problems, there is a well-defined mapping of the nodes the trees are built on across the set of trees being compared. A new class of tree comparison problems arises in cases where finding the correspondence among the nodes of the trees being compared is itself the problem. The problem arises while trying to find the interclass correspondence between the members of a pair of coevolving classes, e.g., cell bound receptors and their ligands. Given the evolution of the two classes, the combinatorial problem is to find a mapping among the leaves of the two trees that optimizes a given cost function. In this work we formulate various combinatorial optimization problems motivated by the aforementioned biological problem for the first time. We present hardness results, give an efficient algorithm for a restriction of the problem and demonstrate its applicability.

Algorithms↗