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Use of 3D chaos game representation to quantify DNA sequence similarity with applications for hierarchical clustering.

A 3D chaos game is shown to be a useful way for encoding DNA sequences. Since matching subsequences in DNA converge in space in 3D chaos game encoding, a DNA sequence's 3D chaos game representation can be used to compare DNA sequences without prior alignment and without truncating or padding any of the sequences. Two proposed methods inspired by shape-similarity comparison techniques show that this form of encoding can perform as well as alignment-based techniques for building phylogenetic trees. The first method uses the volume overlap of intersecting spheres and the second uses shape signatures by summarizing the coordinates, oriented angles, and oriented distances of the 3D chaos game trajectory. The methods are tested using: (1) the first exon of the beta-globin gene for 11 species, (2) mitochondrial DNA from four groups of primates, and (3) a set of synthetic DNA sequences. Simulations show that the proposed methods produce distances that reflect the number of mutation events; additionally, on average, distances resulting from deletion mutations are comparable to those produced by substitution mutations.

Animals↗

Genetic variability of Brazilian Toxoplasma gondii strains detected by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) and simple sequence repeat anchored-PCR (SSR-PCR).

The genetic variability of 19 Toxoplasma gondii strains isolated from humans and animals in Brazil was detected by both random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) and simple sequence repeat anchored-PCR (SSR-PCR) for the first time. Two reference strains, RH (highly virulent) and ME49 (avirulent), were submitted to both assays. Besnoitia sp., Plasmodium falciparum and Babesia bigemina were used as outgroups. RAPD-PCR and SSR-PCR profiles were used for building phenetic trees by unweighted pair group method with arithmetic averages (UPGMA). Phenograms built with TREECONW software showed great similarity in the topology of the trees. Both phenograms presented two major clusters that grouped T. gondii strains according to their murine virulence. The strains AS28, BV and N, which are highly virulent for BALB/c mice, were clustered with the reference strain RH, the highly virulent strain of T. gondii that has been most commonly studied. The group formed by the cystogenic strains showed that the strains which presented a level of virulence more similar to that of ME49 strain (avirulent) also presented a closer genetic relationship. Genetic variation within each lineage was significantly lower (P < 0.05) than that between the lineages. Regarding outgroups, Besnoitia sp. presented the closest relationship to T. gondii while P. falciparum was the most distant. The results presented here demonstrate that intraspecific genetic variability separates Brazilian T. gondii strains into two groups which correlate with murine virulence phenotype.

Animals↗

The effects of an edgeline on speed and lateral position: a meta-analysis.

This paper presents a meta-analysis of studies that have evaluated the effects of an edgeline on speed and lateral position of motorised road users. Together with many other study characteristics, 41 estimates of the effects of an edgeline on speed and 65 on lateral position were extracted from the studies. The results of the evaluation studies show a great variety in effects. Both negative and positive effects on speed and lateral position were found; amongst others, increases in speed up to 10.6 km/h, as well as decreases in speed up to 5.0 km/h, and shifts of the lateral position towards the centre of the road up to 30 cm, as well as shifts towards the edge of the road up to 35 cm. Further analyses resulted in the determination of study characteristics that influence the effects of an edgeline on speed and lateral position. It is concluded that the effects of an edgeline on speed are related to the presence of a centreline. Applying an edgeline to a road without a centreline increases the speed of road users, and replacing a centreline by an edgeline decreases the speed. Results with respect to adding an edgeline to a road with a centreline were unclear. Another conclusion is that shoulder width and road environment contribute to the effects of an edgeline on lateral position. In combination with wide shoulders or buildings and/or trees next to the road, edgelines lead to shifts of the lateral position towards the edge of the road, and in combination with narrow shoulders or open fields, edgelines lead to shifts towards the centre of the road.

Accidents, Traffic↗

Model predictive control of discrete-time hybrid systems with discrete inputs.

This paper proposes and discusses a model predictive control approach to hybrid systems with discrete inputs only. The algorithm, which takes into account a model of a hybrid system, described as a mixed logical dynamical system, is based on a performance-driven reachability analysis. The algorithm abstracts the behavior of the hybrid system by building a "tree of evolution." The nodes of the tree represent the reachable states of a process, and the branches connect two nodes if a transition exists between the corresponding states. A cost-function value is associated with each node, and based on this value the exploration of the tree is driven. As soon as the exploration of the tree is finished, the corresponding input is applied to the system and the procedure is repeated.

Journal Article↗

IMGT/PhyloGene: an on-line tool for comparative analysis of immunoglobulin and T cell receptor genes.

IMGT/PhyloGene is an on-line software package for comparative analysis of immunoglobulin (IG) and T cell receptor (TR) variable genes of all vertebrate species, newly implemented in IMGT, the international ImMunoGeneTics information system ((R)). IMGT/PhyloGene is strongly associated with the IMGT gene and allele nomenclature and with the IMGT unique numbering for V-REGION, which directly creates standardized alignments from IMGT reference sequences. IMGT/PhyloGene is the first tool to use the IMGT expertized and standardized data for automated comparative analyses, and the first on-line software package for phylogenetic reconstruction to be integrated to a sequence database. Starting from a standardized alignment of selected sequences, IMGT/PhyloGene computes a matrix of evolutionary distances, builds a tree using the Neighbor-Joining (NJ) algorithm, and outputs various graphical tree representations. The resulting IMGT/PhyloGene tree is then used as a support for studying the evolution of particular subregions, such as the CDR-IMGT (Complementarity Determining Regions) or the V-RS (Variable gene Recombination Signals). IMGT/PhyloGene is freely available at http://imgt.cines.fr.

Databases, Nucleic Acid↗

[Decision making in cardiology: methodology].

This article reviews the methods employed in usual clinical thinking for making decisions, the problems and limitations inherent in them and claims that a more frequent utilization of the so called "Evidence Based Medicine" methods is a more valid and efficient alternative for medical decision making. We also describe the theoretical basis and strategies used in the medical decision process; the specific concepts and basic components for building decision trees are also shown. Finally, a real case is presented and approached step by step: the statement of the decision problem, its possible alternatives, the allocation of probabilities to each outcome based on the best available evidence, and the calculations of the expected values (projected usefulness, cost-effectiveness) and sensitivity analysis by means of specific software for making decisions.

Aged↗

Procedure to protect confidentiality of familial data in community genetics and genomic research.

The collection of familial data is an essential step for community genetics programs or genetic research. Ethical issues concerning privacy and confidentiality present a major challenge in such programs. In order to keep familial data confidential, we have developed a family-based numerical coding procedure which allows the use of confidential data and the determination of familial relationships without risk of disclosure. This procedure is composed of two parts: the physical separation of identifying information and individual data; and the use of a code containing all the information required to build family trees. This procedure has been used in Eastern Quebec since 1995, mainly for screening, genetic counseling, research on familial dyslipidemias, public health intervention, and research projects on the genetics of complex traits, such as arterial hypertension and coronary artery disease.

Abstracting and Indexing↗

Supercritical fluid extraction of polycyclic aromatic hydrocarbons from white pine (Pinus strobus) needles and its implications.

A supercritical fluid extraction (SFE) method was developed for the extraction of polycyclic aromatic hydrocarbons (PAHs) from fresh and fallen pine needles. Toluene-modified CO2 was used as the extracting fluid, and the extracted PAHs were analyzed by GC-MS. Using a two-stage extraction procedure, a static extraction at 180 degrees C and a dynamic extraction at 60 degrees C, and an in-cell silica gel plug plus a post-oven silica gel column, the extraction and fractionation of PAHs can be accomplished in one step. Over a seven month period, a significant variation was observed for PAHs in urban samples, while PAHs in mountain samples were at much lower levels (by a factor of approximately 8) and showed little seasonal change. Although dry fallen needles and fresh needles contained similar amounts of PAHs, in the fallen needles the lower molecular weight PAHs were partially lost while the higher molecular weight PAHs were slightly enriched. Pollution in urban areas was found to be highly localized, and buildings and trees are believed to be important factors in the restriction of atmospheric PAHs.

Air Pollution↗

Three quantitative approaches to the diagnosis of abdominal pain in children: practical applications of decision theory.

BACKGROUND/PURPOSE: The authors compared 3 quantitative methods for assisting clinicians in the differential diagnosis of abdominal pain in children, where the most common important endpoint is whether the patient has appendicitis. Pretest probability in different age and sex groups were determined to perform Bayesian analysis, binary logistic regression was used to determine which variables were statistically significantly likely to contribute to a diagnosis, and recursive partitioning was used to build decision trees with quantitative endpoints. METHODS: The records of all children (1,208) seen at a large urban emergency department (ED) with a chief complaint of abdominal pain were immediately reviewed retrospectively (24 to 72 hours after the encounter). Attempts were made to contact all the patients' families to determine an accurate final diagnosis. A total of 1,008 (83%) families were contacted. Data were analyzed by calculation of the posttest probability, recursive partitioning, and binary logistic regression. RESULTS: In all groups the most common diagnosis was abdominal pain (ICD-9 Code 789). After this, however, the order of the most common final diagnoses for abdominal pain varied significantly. The entire group had a pretest probability of appendicitis of 0.06. This varied with age and sex from 0.02 in boys 2 to 5 years old to 0.16 in boys older than 12 years. In boys age 5 to 12, recursive partitioning and binary logistic regression agreed on guarding and anorexia as important variables. Guarding and tenderness were important in girls age 5 to 12. In boys age greater than 12, both agreed on guarding and anorexia. Using sensitivities and specificities from the literature, computed tomography improved the posttest probability for the group from.06 to.33; ultrasound improved it from.06 to.48; and barium enema improved it from.06 to.58. CONCLUSIONS: Knowing the pretest probabilities in a specific population allows the physician to evaluate the likely diagnoses first. Other quantitative methods can help judge how much importance a certain criterion should have in the decision making and how much a particular test is likely to influence the probability of a correct diagnosis. It now should be possible to make these sophisticated quantitative methods readily available to clinicians via the computer.

Abdominal Pain↗

[Chemical accident in Schönbeck--an assessment of the risk to health and environment].

Travelling from Belgium to the BUNA works in Schkopau, ten of eighteen tank wagons filled with vinyl chloride (VC) derailed on the Magdeburg-Halle railway line just outside Schönebeck station. One wagon exploded and four others went up in flames. Buildings and trees in gardens located in the immediate vicinity of the track caught fire and burned. Four owners of garden plots suffered burns. A total of 28 people received inpatient treatment in a nearby hospital, another 268 people were treated as outpatients. The typical symptoms of fume poisoning such as headache, nausea, irritations of respiratory tract and eyes were the primarily diagnosed problems. The vegetation was damaged by flue gases and developing HCl causing fire and caustic burns. Fire brigades and special task forces succeeded to control the looming danger of health and environmental hazards by cooling the burning wagons and pumping the liquid gases from the tank wagons. Vinyl chloride which was released over several days was measured in residential areas to be 0.06-8 ml/m3 air. Vinyl chloride is a gas which is heavier than air. When exposed to light it will be degraded within a few days. A technical guide concentration of 3 ml/m3 air has been adopted for its cancerogenic potential. Dioxin values measured in soils and plants were in the natural range of 20 ng I-TE/kg DS. These values increased to 8300 ng at the very seat of the fire only. With the water used for fire fighting vinyl chloride penetrated into the groundwater revealing values of up to 73 mg/litre. A total of 292 urine samples taken from patients and members of the rescue forces, residents and a control group were tested for their contents of the VC metabolite thiodiacetic acid. However, this number does not allow to draw any conclusions with regard to a potential increase in the risk of cancer. With 0.27, 0.43 and 0.37 mg/litre of urine, the mean values are in the normal range for unexposed people. Only three cases showing values of up to 3.1 mg/litre indicated that a real exposure had taken place. The environmental and health authorities have evaluated the results of the measurements at site. They had set up a consultancy service and were integrated in civil forums. When the project "Extension of the vinyl chloride plant" for PVC production at Buna Sow Leuna Olefinverbund GmbH will be completed, deliveries of vinyl chloride by rail and road will be unnecessary in future. However, the problem of transporting dangerous goods and a complex training of task forces will continue to be of topical importance.

Accidents, Traffic↗

Ancient origin for Hawaiian Drosophilinae inferred from protein comparisons.

Immunological comparisons of a larval hemolymph protein enabled us to build a tree relating major groups of drosophiline flies in Hawaii to one another and to continental flies. The tree agrees in topology with that based on internal anatomy. Relative rate tests suggest that evolution of hemolymph proteins has been about as fast in Hawaii as on continents. Since the absolute rate of evolution of hemolymph proteins in continental flies is known, one can erect an approximate time scale for Hawaiian fly evolution. According to this scale, the Hawaiian fly fauna stems from a colonist that landed on the archipelago about 42 million years ago-i.e., before any of the present islands harboring drosophilines formed. This date fits with the geological history of the archipelago, which has witnessed the sequential rise and erosion of many islands during the past 70 million years. We discuss the bearing of the molecular time scale on views about rates of organismal evolution in the Hawaiian flies.

Animals↗

In vivo selection of functional ribosomes with variations in the rRNA-binding site of Escherichia coli ribosomal protein S8: evolutionary implications.

The highly conserved nature of rRNA sequences throughout evolution allows these molecules to be used to build philogenic trees of different species. It is unknown whether the stability of specific interactions and structural features of rRNA reflects an optimal adaptation to a functional task or an evolutionary trap. In the work reported here, we have applied an in vivo selection strategy to demonstrate that unnatural sequences do work as a functional replacement of the highly conserved binding site of ribosomal protein S8. However, growth competition experiments performed between Escherichia coli isolates containing natural and unnatural S8-binding sites showed that the fate of each isolate depended on the growth condition. In exponentially growing cells, one unnatural variant was found to be equivalent to wild type in competition experiments performed in rich media. In culture conditions leading to slow growth, however, cells containing the wild-type sequence were the ultimate winner of the competition, emphasizing that the wild-type sequence is, in fact, the most fit solution for the S8-binding site.

Base Sequence↗

Scaling up accurate phylogenetic reconstruction from gene-order data.

MOTIVATION: Phylogenetic reconstruction from gene-order data has attracted increasing attention from both biologists and computer scientists over the last few years. Methods used in reconstruction include distance-based methods (such as neighbor-joining), parsimony methods using sequence-based encodings, Bayesian approaches, and direct optimization. The latter, pioneered by Sankoff and extended by us with the software suite GRAPPA, is the most accurate approach, but cannot handle more than about 15 genomes of limited size (e.g. organelles). RESULTS: We report here on our successful efforts to scale up direct optimization through a two-step approach: the first step decomposes the dataset into smaller pieces and runs the direct optimization (GRAPPA) on the smaller pieces, while the second step builds a tree from the results obtained on the smaller pieces. We used the sophisticated disk-covering method (DCM) pioneered by Warnow and her group, suitably modified to take into account the computational limitations of GRAPPA. We find that DCM-GRAPPA scales gracefully to at least 1000 genomes of a few hundred genes each and retains surprisingly high accuracy throughout the range: in our experiments, the topological error rate rarely exceeded a few percent. Thus, reconstruction based on gene-order data can now be accomplished with high accuracy on datasets of significant size.

Algorithms↗

Neighbor-joining revealed.

It is nearly 20 years since the landmark paper (Saitou and Nei 1987) in Molecular Biology and Evolution introducing Neighbor-Joining (NJ). The method has become the most widely used method for building phylogenetic trees from distances, and the original paper has been cited about 13,000 times (Science Citation Index). Yet the question "what does the NJ method seek to do?" has until recently proved somewhat elusive, leading to some imprecise claims and misunderstanding. However, a rigorous answer to this question has recently been provided by further mathematical investigation, and the purpose of this note is to highlight these results and their significance for interpreting NJ. The origins of this story lie in a paper by Pauplin (2000) though its continuation has unfolded in more mathematically inclined literature. Our aim here is to make these findings more widely accessible.

Algorithms↗

Review of morbidity and mortality associated with falls from heights among patients presenting to a major trauma centre.

OBJECTIVE: To compare differences in demographics and injuries of patients presenting after falls from heights at home and at work. METHOD: A retrospective case series review of patients treated by the Royal Adelaide Hospital (RAH) Trauma Service following a fall from a ladder, scaffold, building, or tree between July 2000 and December 2003. RESULTS: Two hundred and eighty-two patients fulfilled study criteria. The 162 (57.4%, 95% confidence interval [CI] 48.9-60.5) injured at home were significantly (P < 0.001) older (mean age 53.9 years, 95% CI 51.3-56.7) than those injured at work (mean age 41.2 years, 95% CI 38.6-43.8). Injury severity score (ISS) was similar in the two groups. Those injured at home were more likely to be admitted to hospital and have significantly longer hospital stays (P = 0.003). Thirteen deaths were recorded, eight (61.5%) from home, all over 49 years old. Ladders were implicated in seven (53.8%, 95% CI 26.7-80.9) of the deaths. A 67% (95% CI 55.4-79.0) increase in the number of presentations following falls at home over the study period was significantly greater than the 12.2% (95% CI 10.7-13.7) increase in total trauma presentations during this time (P = 0.0007). CONCLUSIONS: Injuries resulting from falls at home are increasing. This group tends to be elderly and at risk of significant injury and prolonged hospital stays. Causes are multifactorial and might be related to increased popularity of home renovations. Ladders are implicated in many of these accidents. As emergency physicians we should target this population to educate them in safe ladder use.

Abdominal Injuries↗

Geometrical gradients in the distribution of temperature and absorbed ultraviolet radiation in ocular tissues.

The geographical variations in the incidence of age-related ocular changes such as presbyopia and cataracts and diseases such as pterygium and droplet keratopathies have led to theories pointing to sunlight, ultraviolet radiation (UVR) exposure and ambient temperature as potential etiological factors. Some epidemiological evidence also points to an association of age-related macular degeneration to sunlight exposure. The actual distribution of sunlight exposure and the determination of temperature variations of different tissues within the anterior segment of the eye are difficult to assess. Of greatest importance are the geometrical factors that influence selective UVR exposures to different segments of the lens, cornea and retina. Studies show that the temperature of the lens and cornea varies by several degrees depending upon climate, and that the incidence of nuclear cataract incidence is greater in areas of higher ambient temperature (i.e., in the tropics). Likewise, sunlight exposure to local areas of the cornea, lens and retina varies greatly in different environments. However, epidemiological studies of the influence of environmental UVR in the development of cataract, pterygium, droplet keratopathies and age-related macular degeneration have produced surprisingly inconsistent findings. The lack of consistent results is seen to be due largely to either incomplete or erroneous estimates of outdoor UV exposure dose. Geometrical factors dominate the determination of UVR exposure of the eye. The degree of lid opening limits ocular exposure to rays entering at angles near the horizon. Clouds redistribute overhead UVR to the horizon sky. Mountains, trees and building shield the eye from direct sky exposure. Most ground surfaces reflect little UVR. The result is that highest UVR exposure occurs during light overcast where the horizon is visible and ground surface reflection is high. By contrast, exposure in a high mountain valley (lower ambient temperature) with green foliage results in a much lower ocular dose. Other findings of these studies show that retinal exposure to light and UVR in daylight occurs largely in the superior retina.

Animals↗

A statistical score for assessing the quality of multiple sequence alignments.

BACKGROUND: Multiple sequence alignment is the foundation of many important applications in bioinformatics that aim at detecting functionally important regions, predicting protein structures, building phylogenetic trees etc. Although the automatic construction of a multiple sequence alignment for a set of remotely related sequences cause a very challenging and error-prone task, many downstream analyses still rely heavily on the accuracy of the alignments. RESULTS: To address the need for an objective evaluation framework, we introduce a statistical score that assesses the quality of a given multiple sequence alignment. The quality assessment is based on counting the number of significantly conserved positions in the alignment using importance sampling method in conjunction with statistical profile analysis framework. We first evaluate a novel objective function used in the alignment quality score for measuring the positional conservation. The results for the Src homology 2 (SH2) domain, Ras-like proteins, peptidase M13, subtilase and beta-lactamase families demonstrate that the score can distinguish sequence patterns with different degrees of conservation. Secondly, we evaluate the quality of the alignments produced by several widely used multiple sequence alignment programs using a novel alignment quality score and a commonly used sum of pairs method. According to these results, the Mafft strategy L-INS-i outperforms the other methods, although the difference between the Probcons, TCoffee and Muscle is mostly insignificant. The novel alignment quality score provides similar results than the sum of pairs method. CONCLUSION: The results indicate that the proposed statistical score is useful in assessing the quality of multiple sequence alignments.

Algorithms↗

Fold classification based on secondary structure--how much is gained by including loop topology?

BACKGROUND: It has been proposed that secondary structure information can be used to classify (to some extend) protein folds. Since this method utilizes very limited information about the protein structure, it is not surprising that it has a higher error rate than the approaches that use full 3D fold description. On the other hand, the comparing of 3D protein structures is computing intensive. This raises the question to what extend the error rate can be decreased with each new source of information, especially if the new information can still be used with simple alignment algorithms. We consider the question whether the information about closed loops can improve the accuracy of this approach. While the answer appears to be obvious, we had to overcome two challenges. First, how to code and to compare topological information in such a way that local alignment of strings will properly identify similar structures. Second, how to properly measure the effect of new information in a large data sample. We investigate alternative ways of computing and presenting this information. RESULTS: We used the set of beta proteins with at most 30% pairwise identity to test the approach; local alignment scores were used to build a tree of clusters which was evaluated using a new log-odd cluster scoring function. In particular, we derive a closed formula for the probability of obtaining a given score by chance. Parameters of local alignment function were optimized using a genetic algorithm. Of 81 folds that had more than one representative in our data set, log-odds scores registered significantly better clustering in 27 cases and significantly worse in 6 cases, and small differences in the remaining cases. Various notions of the significant change or average change were considered and tried, and the results were all pointing in the same direction. CONCLUSION: We found that, on average, properly presented information about the loop topology improves noticeably the accuracy of the method but the benefits vary between fold families as measured by log-odds cluster score.

Algorithms↗