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Incorporation of a set enumeration trees-based classifier into a hybrid computer-assisted diagnosis scheme for mass detection.

RATIONALE AND OBJECTIVES: The authors evaluated whether a hybrid classifier of two independent computer-aided diagnosis (CAD) schemes, the set enumeration (SE) trees approach and an artificial neural network (ANN), could improve the detection of masses on digitized mammograms. The potential benefits resulting from the interpretability of the SE trees model was also explored. MATERIALS AND METHODS: Two hundred thirty verified mass regions and 230 negative but suspicious regions were randomly selected from 618 digitized mammograms. Each region was represented by a 24-parameter feature vector. These features were used as input data for the SE trees and ANN-based schemes. After the positive and negative regions were randomly segmented into five exclusive partitions, a fivefold cross-validation method was applied to evaluate and compare the performance of the SE trees, ANN, and hybrid system in the identification of masses. RESULTS: The performance of the SE trees approach was comparable to that of the ANN. The average area under the receiver operating characteristic (ROC) curves for all five partitions was 0.88 (standard deviation, 0.04). Owing to the relatively low correlation between the region-based results of the SE trees and ANN methods, the hybrid classifier yielded a significantly improved performance, with an area under the ROC curve of 0.94 (standard deviation, 0.02; P < .05). CONCLUSION: The hybrid CAD scheme significantly improved performance. The amenability of the SE trees models to interpretation may aid in the assessment of the importance of specific features.

Artificial Intelligence↗

Late diagnosis of tree nut and sesame allergy in patients previously sensitized but tolerant to peanut.

BACKGROUND: Recent studies have indicated that tolerance to peanut can occur in patients with a history of peanut allergy. Tree nut and sesame allergies have been reported to occur at increased incidence in patients with peanut allergy. Although the coexistence may be simply due to a predisposition to food allergy in these individuals, cross-reactivity has been demonstrated between peanut and tree nuts and between peanut and sesame seed. OBJECTIVE: To describe 3 patients previously sensitized but tolerant to peanut who were subsequently diagnosed as having either tree nut or sesame allergy. METHODS: All the patients had a clinical history of peanut sensitivity and underwent follow-up peanut skin testing to commercial extracts using a bifurcated needle followed by a graded peanut challenge. One patient had a previous positive radioallergosorbent test reaction to sesame and underwent a graded sesame challenge. RESULTS: All the patients had negative peanut challenge results. Two patients subsequently had exposure to tree nuts at home and had systemic reactions and positive skin test reactions to the incriminated tree nut. One patient had a positive challenge reaction to sesame. CONCLUSION: Demonstration of tolerance to peanut may falsely reassure patients and physicians that patients no longer need to avoid tree nuts or sesame. Tree nut and sesame allergies can exist or develop in patients despite the development of tolerance to peanut.

Adolescent↗

Utilization of the relative complexity measure to construct a phylogenetic tree for fungi.

The relative complexity measure (RCM) is a new approach to evaluate relatedness of DNA sequences which eliminates the requirement to align sequences prior to analysis, a step required with standard reference methods. The value of the RCM approach to generate distance matrices for use in phylogenetic analysis of organisms has not been determined. This study compared RCM with the algorithmic and tree searching reference methods for phylogenetic analysis using fungal sequences. Sequences of the cytochrome b gene and the 18S rDNA gene were obtained from the GenBank database to determine feasibility of this method for phylogenetic relatedness. The RCM approach was also used to construct a phylogenetic tree using internal transcribed spacer (ITS) sequences from 23 medically relevant fungal species. The robustness of the RCM and reference approaches was determined by comparing the topology of seven medically relevant fungi within the phylogenetic trees generated after progressive removal of 10, 20, 30, 40 and 50% of the nucleotide bases from either the 5' or 3' end of the three genomic target sequences. The results demonstrated that the RCM method was equivalent to the reference methods for construction of phylogenetic trees from cytochrome b and 18S rDNA gene sequences. The phylogenetic tree constructed using the ITS sequence generated no contradictory topology. The RCM generated trees retained the appropriate topology after removal of up to 50% of the cytochrome b sequence, 40% of the ITS sequence, and 30% of the 18S gene target sequence. Comparatively, the reference methods failed to maintain topology after only a 10% sequence deletion for each genomic target. The results showed the RCM to be a reliable and robust computational approach for use in the construction of fungal phylogenetic trees without the requirement for prior sequence alignment.

Algorithms↗

Trichloroethylene uptake by apple and peach trees and transfer to fruit.

A greenhouse study was conducted to quantify 14C-trichloroethylene (TCE) uptake and transfer into the edible fruit of apple and peach trees. Trees were subsurface irrigated with solutions of 14C [TCE] that bracketed groundwater concentrations (5 and 500 microg/L) found in residential areas surrounding Hill Air Force Base, UT, where trace amounts of TCE had been found in several fruits during a preliminary field survey. Nondosed control trees were grown within the canopy of the dosed trees and in a separate greenhouse. Tissue samples were analyzed for 14C and TCE using combustion/liquid scintillation counting (LSC) and headspace/gas chromatography/mass spectrometry (HS/GC/MS). Tissue was also extracted and analyzed by GC/MS for dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), and trichloroethanol (TCEt), three specific TCE metabolites that have been previously identified in laboratory and field studies. No 14C was detected in the nonexposed control trees. Exposed trees contained levels of 14C that were proportional to the exposure concentration. 14C concentrations were greatest in leaves followed by branches and fruits. At the end of the study, TCE was detected only in roots implying that the 14C in the leaves, branches, and fruit was associated with unidentified nonvolatile TCE transformation products and/or is nonextractable. However, TCAA and DCAA were positively identified only in leaves collected during the first year from an apple tree exposed to the high dose treatment. Additional data for other chemicals and fruittrees are needed to better understand the potential transfer of organic compounds to edible fruit.

Carbon Isotopes↗

Identification of aflatoxin M1-N7-guanine in liver and urine of tree shrews and rats following administration of aflatoxin B1.

Epidemiological studies have shown that exposure to aflatoxin B(1) (AFB(1)) and concurrent infection with hepatitis B lead to a multiplicative risk of developing liver cancer. This chemical-viral interaction can be recapitulated in the tree shrew (Tupia belangeri chinensis). As an initial characterization of this model, the metabolism of AFB(1) in tree shrews has been examined and compared to a sensitive bioassay species, the rat. Utilizing LC/MS/MS, an unreported product, aflatoxin M(1)-N(7)-guanine (AFM(1)-N(7)-guanine), was detected in urine and hepatic DNA samples 24 h after administration of 400 microg/kg AFB(1). In hepatic DNA isolated from tree shrews, AFM(1)-N(7)-guanine was the predominant adduct, 0.74 +/- 0.14 pmol/mg DNA, as compared to 0.37 +/- 0.07 pmol/mg DNA of AFB(1)-N(7)-guanine. Conversely, in rat liver, 6.56 +/- 2.41 pmol/mg DNA of AFB(1)-N(7)-guanine and 0.42 +/- 0.13 pmol/mg DNA of AFM(1)-N(7)-guanine were detected. Rats excreted 1.00 +/- 0.21 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.29 +/- 0.10 pmol AFM(1)-N(7)-guanine/mg creatinine as compared to 0.60 +/- 0.12 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.69 +/- 0.16 pmol AFM(1)-N(7)-guanine/mg creatinine excreted by the tree shrew. Furthermore, tree shrew urine contained 40 times more of the hydroxylated metabolite, AFM(1), than was excreted by rats. In vitro experiments confirmed this difference in oxidative metabolism. Hepatic microsomes isolated from tree shrews failed to produce aflatoxin Q(1) or aflatoxin P(1) but formed a significantly greater amount of AFM(1) than rat microsomes. Bioassays indicated that the tree shrew was considerably more resistant than the rat to AFB(1) hepatocarcinogenesis, which may reflect the significant differences in metabolic profiles of the two species.

Administration, Oral↗

Tree-ring analysis for the assessment of anthropogenic changes and trends.

Investigation of Pine (Pinus sylvestris L.) annual radial increment (width of annual tree rings) was carried out in the surroundings of one of the largest pollution sources in Lithuania - Jonava Nitrogen Fertilizers Plant. The main objective of investigation was to analyse different sides of anthropogenic transformations of tree-ring series in the polluted environment: changes in tree growth intensity: variance changes in tree-ring series: changes in the relations with natural external factors. Three different periods of tree reaction to the environmental pollution were singled out - fertilization period, depression period and recovery period since annual emissions were essentially reduced. The variance of tree-ring series has increased several times in the polluted environment. Reaction of trees to the impact of climatic factors (temperature, precipitation) has changed significantly in the polluted environment and their sensitivity has also increased.

Air Pollutants↗

Using phylogeographic analyses of gene trees to test species status and processes.

A gene tree is an evolutionary reconstruction of the genealogical history of the genetic variation found in a sample of homologous genes or DNA regions that have experienced little or no recombination. Gene trees have the potential of straddling the interface between intra- and interspecific evolution. It is precisely at this interface that the process of speciation occurs, and gene trees can therefore be used as a powerful tool to probe this interface. One application is to infer species status. The cohesion species is defined as an evolutionary lineage or set of lineages with genetic exchangeability and/or ecological interchangeability. This species concept can be phrased in terms of null hypotheses that can be tested rigorously and objectively by using gene trees. First, an overlay of geography upon the gene tree is used to test the null hypothesis that the sample is from a single evolutionary lineage. This phase of testing can indicate that the sampled organisms are indeed from a single lineage and therefore a single cohesion species. In other cases, this null hypothesis is not rejected due to a lack of power or inadequate sampling. Alternatively, this null hypothesis can be rejected because two or more lineages are in the sample. The test can identify lineages even when hybridization and lineage sorting occur. Only when this null hypothesis is rejected is there the potential for more than one cohesion species. Although all cohesion species are evolutionary lineages, not all evolutionary lineages are cohesion species. Therefore, if the first null hypothesis is rejected, a second null hypothesis is tested that all lineages are genetically exchangeable and/or ecologically interchangeable. This second test is accomplished by direct contrasts of previously identified lineages or by overlaying reproductive and/or ecological data upon the gene tree and testing for significant transitions that are concordant with the previously identified lineages. Only when this second null hypothesis is rejected is a lineage elevated to the status of cohesion species. By using gene trees in this manner, species can be identified with objective, a priori criteria with an inference procedure that automatically yields much insight into the process of speciation. When one or more of the null hypotheses cannot be rejected, this procedure also provides specific guidance for future work that will be needed to judge species status.

Animals↗

A classification tree for predicting recurrent falling in community-dwelling older persons.

OBJECTIVES: To develop a classification tree for predicting the risk of recurrent falling in community-dwelling older persons using tree-structured survival analysis (TSSA). DESIGN: A prospective cohort study. SETTING: A community in the Netherlands. PARTICIPANTS: One thousand three hundred sixty-five community-dwelling older persons (>/=65) from the Longitudinal Aging Study Amsterdam (LASA). MEASUREMENTS: In 1995, physical, cognitive, emotional, and social aspects of functioning were assessed. Subsequently, a prospective fall follow-up, specifically on recurrent falls (two falls within 6 months) was conducted for 3 years. RESULTS: The classification tree included 11 end groups differing in risk of recurrent falling based on a minimum of two and a maximum of six predictors. The first split in the tree involved two or more falls versus fewer than two falls in the year preceding the interview. Respondents with two or more falls in the year preceding the interview (n=193) and with at least two functional limitations (n=98) had a 75% risk of becoming a recurrent faller, whereas respondents with fewer than two functional limitations were further divided into a group with regular dizziness (n=11, risk of 68%) and a group with no regular dizziness (n=84, risk of 30%). In respondents with fewer than two falls in the year preceding the interview (n=1,172), the risk of becoming a recurrent faller varied between 9% and 70%. Predictors in this branch of the tree were low performance, low handgrip strength, alcohol use, pain, high level of education, and high level of physical activity. CONCLUSION: This classification tree included 11 end groups differing in the risk of recurrent falling based on specific combinations of a maximum of six easily measurable predictors. The classification tree can identify subjects who are eligible for preventive measures in public health strategies.

Accidental Falls↗

Matchings and phylogenetic trees.

This paper presents a natural coordinate system for phylogenetic trees using a correspondence with the set of perfect matchings in the complete graph. This correspondence produces a distance between phylogenetic trees, and a way of enumerating all trees in a minimal step order. It is useful in randomized algorithms because it enables moves on the space of trees that make random optimization strategies "mix" quickly. It also promises a generalization to intermediary trees when data are not decisive as to their choice of tree, and a new way of constructing Bayesian priors on tree space.

Animals↗

Missing the forest for the trees: phylogenetic compression and its implications for inferring complex evolutionary histories.

Phylogenetic tree reconstruction is difficult in the presence of lateral gene transfer and other processes generating conflicting signals. We develop a new approach to this problem using ideas borrowed from algorithmic information theory. It selects the hypothesis that simultaneously minimizes the descriptive complexity of the tree(s) plus the data when encoded using those tree(s). In practice this is the hypothesis that can compress the data the most. We show not only that phylogenetic compression is an efficient method for encoding most phylogenetic data sets and is more efficient than compression schemes designed for single sequences, but also that it provides a clear information theoretic rule for determining when a collection of conflicting trees is a better explanation of the data than a single tree. By casting the parsimony problem in this more general framework, we also conclude that the so-called total-evidence tree--the tree constructed from all the data simultaneously--is not always the most economical explanation of the data.

Algorithms↗

Can weighting improve bushy trees? Models of cytochrome b evolution and the molecular systematics of pipits and wagtails (Aves: Motacillidae).

Among-site rate variation (alpha) and transition bias (kappa) have been shown, most often as independent parameters, to be important dynamics in DNA evolution. Accounting for these dynamics should result in better estimates of phylogenetic relationships. To test this idea, we simultaneously estimated overall (averaged over all codon positions) and codon-specific values of alpha and kappa, using maximum likelihood analyses of cytochrome b data from all genera of pipits and wagtails (Aves: Motacillidae), and six outgroup species, using initial trees generated with default values. Estimates of alpha and kappa were robust to initial tree topology and suggested substantial among-site rate variation even within codon classes; alpha was lowest (large among-site rate variation) at second-codon and highest (low among-site rate variation) at third-codon positions. When overall values were applied, there were shifts in tree topology and dramatic and statistically significant improvements in log-likelihood scores of trees compared with the scores from application of default values. Applying codon-specific values resulted in yet another highly significant increase in likelihood. However, although incorporating substitution dynamics into maximum likelihood, maximum parsimony, and neighbor-joining analyses resulted in increases in congruence among trees, there were only minor improvements in phylogenetic signal, and none of the successive approximations tree topologies were statistically distinguishable from one another by the data. We suggest that the bushlike nature of many higher-level phylogenies in birds makes estimating the dynamics of DNA evolution less sensitive to tree topology but also less susceptible to improvement via weighting.

Animals↗

Gene proximity analysis across whole genomes via PQ trees.

Permutations on strings representing gene clusters on genomes have been studied earlier by Uno and Yagiura (2000), Heber and Stoye (2001), Bergeron et al. (2002), Eres et al. (2003), and Schmidt and Stoye (2004) and the idea of a maximal permutation pattern was introduced by Eres et al. (2003). In this paper, we present a new tool for representation and detection of gene clusters in multiple genomes, using PQ trees (Booth and Leuker, 1976): this describes the inner structure and the relations between clusters succinctly, aids in filtering meaningful from apparently meaningless clusters, and also gives a natural and meaningful way of visualizing complex clusters. We identify a minimal consensus PQ tree and prove that it is equivalent to a maximal pi pattern (Eres et al., 2003) and each subgraph of the PQ tree corresponds to a nonmaximal permutation pattern. We present a general scheme to handle multiplicity in permutations and also give a linear time algorithm to construct the minimal consensus PQ tree. Further, we demonstrate the results on whole genome datasets. In our analysis of the whole genomes of human and rat, we found about 1.5 million common gene clusters but only about 500 minimal consensus PQ trees, with E. Coli K-12 and B. Subtilis genomes, we found only about 450 minimal consensus PQ trees out of about 15,000 gene clusters, and when comparing eight different Chloroplast genomes, we found only 77 minimal consensus PQ trees out of about 6,700 gene clusters. Further, we show specific instances of functionally related genes in two of the cases.

Algorithms↗

Stature of sub-arctic birch in relation to growth rate, lifespan and tree form.

BACKGROUND AND AIMS: Sub-arctic mountain birch Betula pubescens var. pumila communities in the North Atlantic region are of variable stature, ranging from prostrate scrubs to forests with trees up to 12 m high. Four hypotheses were tested, relating growth and population characteristics of sub-arctic birch woodland and scrub to tree stature; i.e. the variable stature of birch woods is due to differences in (1) the mean growth rate; (2) the age-related patterns of growth rate; (3) the life expectancy of stems; or (4) the tree form. METHODS: A stratified random sample of 300 birch trees was drawn from the total population of indigenous birch woodlands and scrub in Iceland, yielding 286 valid sample genets. The population was divided into three sub-populations with dominant trees 0-2, 2-4 and 4-12 m tall, referred to as birch scrub, birch scrub-woodland and birch forest, respectively. KEY RESULTS: Trees in the scrub population were of more contorted growth form than birch in the scrub-woodland and forest populations. Mean growth rates, mean age and median life expectancies increased significantly with sub-population of greater tree stature. At the population level, annual increment and longevity of birch stems was apparently interrelated as the stems in vigorously growing birch sub-populations had a longer life expectancy than those of slower growth. However, no difference was observed between sub-populations in age-related patterns of extension growth rate. CONCLUSIONS: The results were consistent with hypotheses (1), (3) and (4), but hypothesis (2) was rejected. Hence, mountain birch of more vigorous growth attains a greater stature than birch of lesser increment due to faster extension growth rate and a longer lifespan. In addition, the more contorted stem form of scrub populations contributes to their low stature.

Betula↗

T-REX: reconstructing and visualizing phylogenetic trees and reticulation networks.

UNLABELLED: T-REX (tree and reticulogram reconstruction) is an application to reconstruct phylogenetic trees and reticulation networks from distance matrices. The application includes a number of tree fitting methods like NJ, UNJ or ADDTREE which have been very popular in phylogenetic analysis. At the same time, the software comprises several new methods of phylogenetic analysis such as: tree reconstruction using weights, tree inference from incomplete distance matrices or modeling a reticulation network for a collection of objects or species. T-REX also allows the user to visualize obtained tree or network structures using Hierarchical, Radial or Axial types of tree drawing and manipulate them interactively. AVAILABILITY: T-REX is a freeware package available online at: http://www.fas.umontreal.ca/biol/casgrain/en/labo/t-rex

Algorithms↗

A simple algorithm to infer gene duplication and speciation events on a gene tree.

MOTIVATION: When analyzing protein sequences using sequence similarity searches, orthologous sequences (that diverged by speciation) are more reliable predictors of a new protein's function than paralogous sequences (that diverged by gene duplication), because duplication enables functional diversification. The utility of phylogenetic information in high-throughput genome annotation ('phylogenomics') is widely recognized, but existing approaches are either manual or indirect (e.g. not based on phylogenetic trees). Our goal is to automate phylogenomics using explicit phylogenetic inference. A necessary component is an algorithm to infer speciation and duplication events in a given gene tree. RESULTS: We give an algorithm to infer speciation and duplication events on a gene tree by comparison to a trusted species tree. This algorithm has a worst-case running time of O(n(2)) which is inferior to two previous algorithms that are approximately O(n) for a gene tree of sequences. However, our algorithm is extremely simple, and its asymptotic worst case behavior is only realized on pathological data sets. We show empirically, using 1750 gene trees constructed from the Pfam protein family database, that it appears to be a practical (and often superior) algorithm for analyzing real gene trees. AVAILABILITY: http://www.genetics.wustl.edu/eddy/forester.

Algorithms↗

TREECON: a software package for the construction and drawing of evolutionary trees.

A package of programs (run by a management program called TREECON) was developed for the construction and drawing of evolutionary trees. The program MATRIX calculates dissimilarity values and can perform boostrap analysis on nucleic acid sequences. TREE implements different evolutionary tree constructing methods based on distance matrices. Because some of these methods produce unrooted evolutionary trees, a program ROOT places a root on the tree. Finally, the program DRAW draws the evolutionary tree, changes its size or topology, and produces drawings suitable for publication. Whereas, MATRIX is suited only for nucleic acids, the modules TREE, ROOT and DRAW are applicable to any kind of dissimilarity matrix. The programs run on IBM-compatible microcomputers using the DOS operating system.

Algorithms↗

LAML-Pro: joint maximum likelihood inference of cell genotypes and cell lineage trees.

MOTIVATION: Recent dynamic lineage tracing technologies use genome editing to induce heritable mutations, or edits, that accumulate across successive cell divisions. These edits are measured using single-cell sequencing or imaging, providing data to reconstruct cell lineages at single-cell resolution. Current computational approaches to infer cell lineage trees, or phylogenies, from these data perform two separate steps: (i) Identify each cell's edits (genotype) from the raw sequencing or imaging data; (ii) Infer a cell lineage tree from the cell genotypes. However, genotyping cells is an inexact process and genotype errors can yield an inaccurate lineage tree. For example, using fluorescence based-imaging to measure edits results in a high fraction (&#x2248;25%-50%) of uncertain or erroneous genotypes. RESULTS: We introduce Lineage Analysis via Maximum Likelihood with PRobabilistic Observations (LAML-Pro), an algorithm that jointly infers cell genotypes and a cell lineage tree. LAML-Pro is based on the Probabilistic Mixed-type Missing Observation (PMMO) model, which we derive to describe both the genome editing and genotype observation processes. LAML-Pro constructs lineage trees from thousands of cells in under an hour by leveraging the sparsity of transitions under the PMMO model. On simulated data, we demonstrate that LAML-Pro corrects genotype errors and infers substantially more accurate trees than existing methods which are vulnerable to genotype errors. Applied to data from two recent imaging-based lineage tracing systems, LAML-Pro reduces genotype errors by 5-fold and produces more spatially coherent lineage trees compared to existing methods. AVAILABILITY AND IMPLEMENTATION: LAML-Pro is implemented in C++ and is available as both a command-line interface and as a Python library at: github.com/raphael-group/LAML-Pro.

Cell Lineage↗

Impact of Phyllocnistis citrella (Lepidoptera: Gracillariidae) on leaf area development and yield of mature citrus trees in the Mediterranean area.

Seasonal population trends and damage to citrus trees by the leafminer Phyllocnistis citrella Stainton were studied in the Valencia area of eastern Spain from 1996 to 1999. The area-wide seasonal flushing pattern of citrus trees and leafminer population trends were determined in 10 mature citrus orchards. In the 10 orchards, the annual percentage of new shoots that developed in the spring ranged from 51 to 96% for individual orchards (mean of 80%). Phyllocnistis citrella populations damaged new leaves from July to November. During this period, approximately 45% of the new leaf area was lost due to leafminer mining. In addition, at three mature citrus orchards, two 'Navelina' sweet oranges from 1996 to 1999 and one 'Clementine' mandarin (variety 'Clemenules') in 1998 and 1999, the leaf area damage, spring flushing pattern, and crop yield were determined in trees sprayed one to three times a year with abamectin (Epimeck, 0.02%) to control P. citrella and compared with nonsprayed control trees. In these three orchards, damaged leaf area in summer-fall flushes was on average 52% in nonsprayed and 8% in sprayed trees. No significant differences were found between sprayed and nonsprayed trees in the spring flushing and flowering pattern, number of fruits or fruit diameter. In Mediterranean areas, P. citrella damaged only 5-15% of the annual new leaf area of mature trees and yield was usually not affected by the pest.

Animals↗