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An information-based sequence distance and its application to whole mitochondrial genome phylogeny.

MOTIVATION: Traditional sequence distances require an alignment and therefore are not directly applicable to the problem of whole genome phylogeny where events such as rearrangements make full length alignments impossible. We present a sequence distance that works on unaligned sequences using the information theoretical concept of Kolmogorov complexity and a program to estimate this distance. RESULTS: We establish the mathematical foundations of our distance and illustrate its use by constructing a phylogeny of the Eutherian orders using complete unaligned mitochondrial genomes. This phylogeny is consistent with the commonly accepted one for the Eutherians. A second, larger mammalian dataset is also analyzed, yielding a phylogeny generally consistent with the commonly accepted one for the mammals. AVAILABILITY: The program to estimate our sequence distance, is available at http://www.cs.cityu.edu.hk/~cssamk/gencomp/GenCompress1.htm. The distance matrices used to generate our phylogenies are available at http://www.math.uwaterloo.ca/~mli/distance.html.

Animals↗

Sternomental distance as the sole predictor of difficult laryngoscopy in obstetric anaesthesia.

Sternomental distance and view at laryngoscopy were documented in 523 parturients undergoing elective or emergency Caesarean section under general anaesthesia. Eighteen (3.5%) had a grade III or IV laryngoscopic view (Cormack and Lehane's classification) and were classified as potentially difficult tracheal intubations. There was a significant difference between sternomental distance in those patients with a grade III or IV laryngoscopic view compared with those with a grade I or II (13.17 (SD 1.54) cm vs 14.3 (1.49) cm; P = 0.0013). A sternomental distance of 13.5 cm or less with the head fully extended on the neck and the mouth closed provided, using discriminant analysis, the best cut-off point for predicting subsequent difficult laryngoscopy. A sternomental distance of 13.5 cm or less had a sensitivity, specificity, positive and negative predictive values of 66.7%, 71.1%, 7.6% and 98.4%, respectively. While there was no association between sternomental distance and age, weight, height or body mass index (BMI), there was a significant association between grade of laryngoscopy (III and IV) and older (P = 0.049) and heavier (P = 0.0495) mothers. The results suggest that while sternomental distance on its own may not be an adequate sole predictor of subsequent difficult laryngoscopy the measurement should be incorporated into a series of quick and simple preoperative tests.

Adolescent↗

Coincident recombination during mitosis in saccharomyces: distance-dependent and -independent components.

In mitosis, coincident recombination events between widely separated markers occur more frequently than expected for two independent acts. Several different mechanisms have been proposed to account for this phenomenon. It has been argued that coincident recombination could be due to either an extensive region of heteroduplex DNA or some other distance-dependent mechanism. Alternately, it has been suggested that at least some is due to subpopulations of cells which undergo recombination at very high frequencies. The purpose of these experiments is to evaluate the possible contribution of distance-dependent and distance-independent components. By comparing the coincident recombination frequencies for markers on the same homolog as well as pairs of unlinked sites, we show that there is a strong distance-dependent component for at least 8.8-35-kbp, depending on the type of recombination event (conversion or intrachromosomal exchange). For larger distances separating sites, a distance-independent mechanism(s) results in higher than expected frequencies.

Cloning, Molecular↗

Genome rearrangement distances and gene order phylogeny in gamma-Proteobacteria.

Genome rearrangements have been studied in 30 gamma-proteobacterial complete genomes by comparing the order of a reduced set of genes on the chromosome. This set included those genes fulfilling several characteristics, the main ones being that an ortholog was present in every genome and that none of them had been acquired by horizontal gene transfer. Genome rearrangement distances were estimated based on either the number of breakpoints or the minimal number of inversions separating two genomes. Breakpoint and inversion distances were highly correlated, indicating that inversions were the main type of rearrangement event in gamma-Proteobacteria. In general, the progressive increase in sequence-based distances between genome pairs was associated with the increase in their rearrangement-based distances but with several groups of distances not following this pattern. Compared with free-living enteric bacteria, the lineages of Pasteurellaceae were evolving, on average, to relatively higher rates of between 2.02 and 1.64, while the endosymbiotic bacterial lineages of Buchnera aphidicola and Wigglesworthia glossinidia were evolving at moderately higher rates of 1.38 and 1.35, respectively. Because we know that the rearrangement rate in the Bu. aphidicola lineage was close to zero during the last 100-150 Myr of evolution, we deduced that a much higher rate took place in the first period of lineage evolution after the divergence of the Escherichia coli lineage. On the other hand, the lineage of the endosymbiont Blochmannia floridanus did present an almost identical rate to free-living enteric bacteria, indicating that the increase in the genome rearrangement rate is not a general change associated with bacterial endosymbiosis. Phylogenetic reconstruction based on rearrangement distances showed a different topology from the one inferred by sequence information. This topology broke the proposed monophyly of the three endosymbiotic lineages and placed Bl. floridanus as a closer relative to E. coli than Yersinia pestis. These results indicate that the phylogeny of these insect endosymbionts is still an open question that will require the development of specific phylogenetic methods to confirm whether the sisterhood of the three endosymbiotic lineages is real or a consequence of a long-branch attraction phenomenon.

Biological Evolution↗

Assessment of protein distance measures and tree-building methods for phylogenetic tree reconstruction.

Distance-based methods are popular for reconstructing evolutionary trees of protein sequences, mainly because of their speed and generality. A number of variants of the classical neighbor-joining (NJ) algorithm have been proposed, as well as a number of methods to estimate protein distances. We here present a large-scale assessment of performance in reconstructing the correct tree topology for the most popular algorithms. The programs BIONJ, FastME, Weighbor, and standard NJ were run using 12 distance estimators, producing 48 tree-building/distance estimation method combinations. These were evaluated on a test set based on real trees taken from 100 Pfam families. Each tree was used to generate multiple sequence alignments with the ROSE program using three evolutionary models. The accuracy of each method was analyzed as a function of both sequence divergence and location in the tree. We found that BIONJ produced the overall best results, although the average accuracy differed little between the tree-building methods (normally less than 1%). A noticeable trend was that FastME performed poorer than the rest on long branches. Weighbor was several orders of magnitude slower than the other programs. Larger differences were observed when using different distance estimators. Protein-adapted Jukes-Cantor and Kimura distance correction produced clearly poorer results than the other methods, even worse than uncorrected distances. We also assessed the recently developed Scoredist measure, which performed equally well as more complex methods.

Base Sequence↗

PIDD: database for Protein Inter-atomic Distance Distributions.

Protein Inter-atomic Distance Distributions (PIDD) is a dedicated database and structural bio-informatics system for distance based protein modeling. The database is developed to host and analyze the statistical data for protein inter-atomic distances based on their distributions in databases of known protein structures such as in the Protein Data Bank (PDB). PIDD is capable of generating, caching, and displaying the statistical distributions of the distances of various types and ranges. The collected information can be used to extract geometric restraints or mean-force potentials for protein structure determination including nuclear magnetic resonance structure determination and comparative model refinement. PIDD is supported with a friendly designed web interface so that users can easily specify the distance types and ranges, and retrieve, visualize or download the distributions of the distances as they desire. PIDD is freely accessible at http://www.math.iastate.edu/pidd.

Databases, Protein↗

cgDist: Nucleotide-level distance calculation from cgMLST allelic profiles.

Bacterial genomic surveillance requires balancing computational efficiency with genetic resolution for effective cluster investigation. cgMLST distance calculations treat all allelic differences as equivalent units, obscuring nucleotide-level variation. Furthermore, single nucleotide polymorphism-based pipelines provide finer resolution at substantially higher computational cost, which limits their routine deployment in surveillance laboratories. We present cgDist, an algorithm that calculates nucleotide-level distances directly from cgMLST allelic profiles, providing finer resolution than allele-count distances by leveraging within-allele nucleotide variation. The cache architecture stores alignment statistics, enabling distance calculation modes without computation and supporting both dataset-specific and schema-complete cache generation. This design enables incremental surveillance analysis, with performance benefits as laboratories accumulate alignment data. cgDist functions as a precision 'zoom lens' for the investigation of clusters identified through initial cgMLST screening. Rather than restructuring population relationships, this targeted approach concentrates enhanced resolution where it is most informative. The algorithm ensures that cgDist distances are greater than or equal to corresponding cgMLST distances, preserving epidemiological interpretability while adding genetic discrimination. By increasing resolution within identified clusters, cgDist may also support outbreak investigation, a potential application that remains to be evaluated on outbreak-derived data.

Algorithms↗

Ca2+-induced distance change between points on actin and troponin in skeletal muscle thin filaments estimated by fluorescence energy transfer spectroscopy.

Fluorescence resonance energy transfer spectroscopy has been used to study the spatial relationships between probes attached to actin and troponin in the reconstituted skeletal muscle thin filament in the presence and absence of Ca2+ ions. Gln-41 and the nucleotide-binding site of actin were selectively labeled with the acceptor probe: fluorescein cadaverine and 2'(or 3')-O-(2,4,6-trinitrophenyl)adenosine 5'-diphosphate (TNP-ADP), respectively. Troponin was selectively labeled at positions 9 or 133 of troponin-I and 98 of troponin-C with a donor probe; 5-(2-iodoacetylaminoethyl)aminonaphthalene 1-sulfonic acid (IAEDANS). The distances between probes attached to position 133 of TnI and Gln-41 or the nucleotide site of actin were determined to be 51.6+/-1.2 and 42.7+/-0.9 A respectively in the presence of Ca2+, and these distances decreased by 11.5 and 9.3 A respectively in the absence of Ca2+ ions. The distances between the probes attached to position 9 of TnI and Gln-41 or the nucleotide site of actin were determined to be 59.1+/-2.0 or 49.3+/-1.5 A respectively in the presence of Ca2+, and the distances decreased by 5.3 or 3.7 A in the absence of Ca2+. The distances between probes attached to position 98 of TnC and Gln-41 or the nucleotide site of actin were determined to be 55.1+/-1.7 and 57+/-5 A in the presence of Ca2+ and the distances increased slightly by approximately 1 A in the absence of Ca2+. The results suggest that the C-terminal domain of troponin I moves to the outer domain of actin during inhibition, while the C-terminal domain of TnC does not move much.

Actin Cytoskeleton↗

Estimation of evolutionary distance for reconstructing molecular phylogenetic trees.

The most commonly used measure of evolutionary distance in molecular phylogenetics is the number of nucleotide substitutions per site. However, this number is not necessarily most efficient for reconstructing a phylogenetic tree. In order to evaluate the accuracy of evolutionary distance, D(t), for obtaining the correct tree topology, an accuracy index, A(t), was proposed. This index is defined as D'(t)/square root of[D(t)], where D'(t) is the first derivative of D(t) with respect to evolutionary time and V[D(t)] is the sampling variance of evolutionary distance. Using A(t), namely, finding the condition under which A(t) gives the maximum value, we can obtain an evolutionary distance which is efficient for obtaining the correct topology. Under the assumption that the transversional changes do not occur as frequently as the transitional changes, we obtained the evolutionary distances which are expected to give the correct topology more often than are the other distances.

Computer Simulation↗

A novel measure of genetic distance for highly polymorphic tandem repeat loci.

Genetic distance measures are indicators of relatedness among populations or species and are useful for reconstructing the historic and phylogenetic relationships among such groups. Classical measures of genetic distance were developed to analyze biochemical and serological polymorphisms, systems which generally show limited variability. However, these traditional measures of genetic distance are inadequate for the analysis of certain classes of variable number tandem repeat (VNTR) loci, which have a larger number of alleles and higher levels of heterozygosity than traditional genetic markers. At the higher levels of heterozygosity observed at these loci, the standard measures of genetic distance are nonlinear and do not account for the mutational mechanisms of hypervariable loci. We have developed a measure of genetic distance, DSW, which is appropriate for the analysis of highly polymorphic DNA loci. Using computer simulations of diverging populations, we show that DSW conforms to linearity and that the variance is similar in magnitude to traditional measures of genetic distance. Comparisons of phylogenetic trees derived from the simulated divergence of human racial groups demonstrate that the branch lengths of trees prepared using DSW are more similar to the model tree than those generated using other measures. Finally, we demonstrate the applicability of DSW to evolutionary analysis by reconstructing the relationships among eight human populations using 14 microsatellite and STR loci. The phylogenetic trees generated using DSW are different from trees constructed with traditional measures and better reflect the well-documented ancient divergence of African and non-African populations.

Animals↗

Protein distance constraints predicted by neural networks and probability density functions.

We predict interatomic Calpha distances by two independent data driven methods. The first method uses statistically derived probability distributions of the pairwise distance between two amino acids, whilst the latter method consists of a neural network prediction approach equipped with windows taking the context of the two residues into account. These two methods are used to predict whether distances in independent test sets were above or below given thresholds. We investigate which distance thresholds produce the most information-rich constraints and, in turn, the optimal performance of the two methods. The predictions are based on a data set derived using a new threshold which defines when sequence similarity implies structural similarity. We show that distances in proteins are predicted more accurately by neural networks than by probability density functions. We show that the accuracy of the predictions can be further increased by using sequence profiles. A threading method based on the predicted distances is presented. A homepage with software, predictions and data related to this paper is available at http://www.cbs.dtu.dk/services/CPHmodels/.

Amino Acids↗

Determination of three-dimensional structures of proteins by simulated annealing with interproton distance restraints. Application to crambin, potato carboxypeptidase inhibitor and barley serine proteinase inhibitor 2.

An automated method, based on the principle of simulated annealing, is presented for determining the three-dimensional structures of proteins on the basis of short (less than 5 A) interproton distance data derived from nuclear Overhauser enhancement (NOE) measurements. The method makes use of Newton's equations of motion to increase temporarily the temperature of the system in order to search for the global minimum region of a target function comprising purely geometric restraints. These consist of interproton distances supplemented by bond lengths, bond angles, planes and soft van der Waals repulsion terms. The latter replace the dihedral, van der Waals, electrostatic and hydrogen-bonding potentials of the empirical energy function used in molecular dynamics simulations. The method presented involves the implementation of a number of innovations over our previous restrained molecular dynamics approach [Clore, G.M., Brünger, A.T., Karplus, M. and Gronenborn, A.M. (1986) J. Mol. Biol., 191, 523-551]. These include the development of a new effective potential for the interproton distance restraints whose functional form is dependent on the magnitude of the difference between calculated and target values, and the design and implementation of robust and fully automatic protocol. The method is tested on three systems: the model system crambin (46 residues) using X-ray structure derived interproton distance restraints, and potato carboxypeptidase inhibitor (CPI; 39 residues) and barley serine proteinase inhibitor 2 (BSPI-2; 64 residues) using experimentally derived interproton distance restraints. Calculations were carried out starting from the extended strands which had atomic r.m.s. differences of 57, 38 and 33 A with respect to the crystal structures of BSPI-2, crambin and CPI respectively. Unbiased sampling of the conformational space consistent with the restraints was achieved by varying the random number seed used to assign the initial velocities. This ensures that the different trajectories diverge during the early stages of the simulations and only converge later as more and more interproton distance restraints are satisfied. The average backbone atomic r.m.s. difference between the converged structures is 2.2 +/- 0.3 A for crambin (nine structures), 2.4 +/- 0.3 A for CPI (eight structures) and 2.5 +/- 0.2 A for BSPI-2 (five structures). The backbone atomic r.m.s. difference between the mean structures derived by averaging the coordinates of the converged structures and the corresponding X-ray structures is 1.2 A for crambin, 1.6 A for CPI and 1.7 A for BSPI-2.

Hordeum↗

Distance stereopsis as a screening device.

PURPOSE: To determine the efficacy of distance stereotesting as a screening device. METHODS: Distance stereoacuity using the global Random Dot and contour Circle test of the Mentor BVAT II-SG computerized testing system was measured for 216 patients, ages 6 to 18 years, before the clinical examination. Patients were classified into pass/fail groups in the areas of refractive error change (REC), ocular deviation (DEV), visual acuity (VA), and all three together (EXAM). Legitimate cutoff scores were obtained when patients were classified as 'pass' as follows: REC if the change was 0.50 D or less in sphere or cylinder relative to the habitual correction or to emmetropia if no habitual correction; DEV if there was no heterophoria or strabismus at distance (criteria of heterophoria of < 6 prism diopters and heterophorias of any magnitude were also tested); VA if the acuity at distance was better than or equal to 20/25 in the poorer eye and better than or equal to 20/20 in the better eye; EXAM if they were pass in REC, DEV, and VA. Optimal pass/fail cutoff values for the stereopsis measurements were determined by finding the maximum chi2 value from contingency tables constructed using pass/fail levels for the screening test at each of the observed levels. RESULTS: The pass rates for REC, DEV, VA, and EXAM were 45%, 72%, 42%, and 24%, respectively. Patients passed the BVAT at the analytically determined optimal cutoff values of less than or equal to 120 sec arc for global and less than or equal to 30 sec arc for contour stereopsis. The sensitivity and specificity for global stereopsis were 0.90 and 0.40 for REC, 0.89 and 0.30 for DEV, 0.93 and 0.51 for VA, and 0.87 and 0.63 for EXAM. For contour stereopsis, the corresponding values were 0.85 and 0.42, 0.89 and 0.34, 0.91 and 0.53, and 0.84 and 0.62. CONCLUSION: Distance stereotesting is highly sensitive to small refractive error changes, heterophorias and strabismus, visual acuities < 20/25, or any of the three. Global stereopsis is only slightly better than contour stereopsis at classifying patients. Distance stereotesting has potential as an effective screening test.

Adolescent↗

Distance telescopes: a survey of user success.

The distance telescope has a historical reputation for causing difficulties in prescribing and adaptation. Hence, we considered that a retrospective survey of patients at Nottingham Low Vision Clinic might elucidate specific attributes that influence an individual patient's success in using a distance telescope. From 142 patients prescribed distance telescopes since the Clinic's inception, 133 apparently remained users and were mailed a preliminary three-question enquiry about usage of their distance telescopes. The 87 respondents were followed up with questionnaire 2, requesting explicit information about usage, namely frequency, degree of ease or difficulty, and purpose. Older patients required higher magnification (p < 0.025). Seventeen of 74 respondents to questionnaire 2 had various adaptational problems, which are discussed; 57 of 74 patients found their distance telescopes easy to use, and 49 of 57 were frequent users. Thus, ease and frequency are linked (p < 0.05). People tended to use their distance telescopes outdoors and indoors with similar frequency (p > or = 0.29). Adaptation was found to be unrelated to visual acuity, binocularity/monocularity, ocular pathology, or restricted mobility; magnification seemed to be influential, although not significantly. Aging did not significantly impede adaptation. We infer that the universal criterion for selecting treatable patients seems to be personality type. We conclude that adaptation to a device is dependent upon active recognition of its benefits, paralleled with a tolerance of its constraints, which combine to make usage easy and regular on at least one common task.

Adaptation, Physiological↗

Hip abductor weakness in distance runners with iliotibial band syndrome.

OBJECTIVE: To examine hip abductor strength in long-distance runners with iliotibial band syndrome (ITBS), comparing their injured-limb strength to their nonaffected limb and to the limbs of a control group of healthy long-distance runners; and to determine whether correction of strength deficits in the hip abductors of the affected runners through a rehabilitation program correlates with a successful return to running. DESIGN: Case series. SETTING: Stanford University Sports Medicine Clinics. PARTICIPANTS: 24 distance runners with ITBS (14 female, 10 male) were randomly selected from patients presenting to our Runners' Injury Clinic with history and physical examination findings typical for ITBS. The control group of 30 distance runners (14 females, 16 males) were randomly selected from the Stanford University Cross-Country and Track teams. MAIN OUTCOME MEASURES: Group differences in hip abductor strength, as measured by torque generated, were analyzed using separate two-tailed t-tests between the injured limb, non-injured limb, and the noninjured limbs of the control group. Prerehabilitation hip abductor torque for the injured runners was then compared with postrehabilitation torque after a 6-week rehabilitation program. RESULTS: Hip abductor torque was measured with the Nicholas Manual Muscle Tester (kg), and normalized for differences in height and weight among subjects to units of percent body weight times height (%BWh). Average prerehabilitation hip abductor torque of the injured females was 7.82%BWh versus 9.82%BWh for their noninjured limb and 10.19%BWh for the control group of female runners. Average prerehabilitation hip abductor torque of the injured males was 6.86%BWh versus 8.62%BWh for their noninjured limb and 9.73%BWh for the control group of male runners. All prerehabilitation group differences were statistically significant at the p < 0.05 level. The injured runners were then enrolled in a 6-week standardized rehabilitation protocol with special attention directed to strengthening the gluteus medius. After rehabilitation, the females demonstrated an average increase in hip abductor torque of 34.9% in the injured limb, and the males an average increase of 51.4%. After 6 weeks of rehabilitation, 22 of 24 athletes were pain free with all exercises and able to return to running, and at 6-months follow-up there were no reports of recurrence. CONCLUSIONS: Long distance runners with ITBS have weaker hip abduction strength in the affected leg compared with their unaffected leg and unaffected long-distance runners. Additionally, symptom improvement with a successful return to the preinjury training program parallels improvement in hip abductor strength.

Adolescent↗

Influence of training loads on patterns of illness in elite distance runners.

OBJECTIVE: To investigate relationships between training mileage and intensity, and the type, incidence, severity, and duration of respiratory illness in distance runners, and the impact of illness on submaximal and maximal running performance. DESIGN: A longitudinal observational study of distance runners with serial monitoring of training loads and clinical patterns of illness. SETTING: A 4-month winter training period in the Southern Hemisphere. PARTICIPANTS: A total of 20 highly trained (elite) male middle-distance and distance runners competing at the national and international levels. MAIN OUTCOME MEASURES: Training was quantified by mileage (km), intensity (scale, 1-5), and load (volume x intensity). Symptoms and signs of respiratory illness (type, duration, and severity) were verified by a physician at a weekly review. Performance was monitored by measuring submaximal and maximal oxygen uptake and time to exhaustion on a incremental treadmill test. RESULTS: A majority of subjects (15/20) experienced 1 or more episodes of respiratory illness (mean, 2.5 episodes; range, 1-5), with 79% of symptoms classified as upper respiratory in origin. There were no significant differences in mean weekly mileage (P = 0.43), training intensity (P = 0.85), or training load (P = 0.45) between healthy runners and those affected by illness. Mean weekly (88 +/- 46 km) and mean monthly (373 +/- 163 km) mileages prior to each episode of illness were similar to the overall study means (95.5 +/- 36.4 km and 382 +/- 146 km). There were no substantial relationships between mean weekly training mileage, intensity, or training load and the number of illnesses reported (all r < 0.20). Neither submaximal nor maximal running performance was significantly affected by the presence of illness. CONCLUSIONS: Differences in training mileage, intensity, and load were not associated with the incidence of respiratory illness in highly trained middle-distance and distance runners. Runners with mild illness can be reassured that symptoms will not necessarily impair submaximal and maximal performance.

Adult↗

Numerical distance effect in the N240 component in a number-matching task.

The event-related potential technique was used to investigate the time course and scalp-potential topography for the numerical distance effect in a number-matching task. Twenty undergraduates judged whether a number matched or did not match another number presented 1.5 s earlier. Compared with number pairs with a 'small' numerical distance (distance=1), number pairs with a 'large' numerical distance (greater than 2) showed a longer latency and a greater positive amplitude in the N240 component. This numerical distance effect was limited to fronto-central electrodes. These results were discussed in terms of the neural bases of the numerical distance effect during the automatic processing of numbers.

Adult↗

Deriving dispersal distances from genetic data.

Dispersal is one of the most important factors determining the genetic structure of a population, but good data on dispersal distances are rare because it is difficult to observe a large sample of dispersal events. However, genetic data contain unbiased information about the average dispersal distances in species with a strong sex bias in their dispersal rates. By plotting the genetic similarity between members of the philopatric sex against some measure of the distance between them, the resulting regression line can be used for estimating how far dispersing individuals of the opposite sex have moved before settling. Dispersers showing low genetic similarity to members of the opposite sex will on average have originated from further away. Applying this method to a microsatellite dataset from lions (Panthera leo) shows that their average dispersal distance is 1.3 home ranges with a 95% confidence interval of 0.4-3.0 home ranges. These results are consistent with direct observations of dispersal from our study population and others. In this case, direct observations of dispersal distance were not detectably biased by a failure to detect long-range dispersal, which is thought to be a common problem in the estimation of dispersal distance.

Animal Migration↗