Wurst: a protein threading server with a structural scoring function, sequence profiles and optimized substitution matrices

Wurst is a protein threading program with an emphasis on high quality sequence to structure alignments (http://www.zbh.uni-hamburg.de/wurst). Submitted sequences are aligned to each of about 3000 templates with a conventional dynamic programming algorithm, but using a score function with sophisticated structure and sequence terms. The structure terms are a log-odds probability of sequence to structure fragment compatibility, obtained from a Bayesian classification procedure. A simplex optimization was used to optimize the sequence-based terms for the goal of alignment and model quality and to balance the sequence and structural contributions against each other. Both sequence and structural terms operate with sequence profiles.

Statistical tests of load-unload response ratio signals by lattice solid model: Implication to tidal triggering and earthquake prediction

Statistical tests of Load-Unload Response Ratio (LURR) signals are carried in order to verify statistical robustness of the previous studies using the Lattice Solid Model (MORA et al., 2002b). In each case 24 groups of samples with the same macroscopic parameters (tidal perturbation amplitude A, period T and tectonic loading rate k) but different particle arrangements are employed. Results of uni-axial compression experiments show that before the normalized time of catastrophic failure, the ensemble average LURR value rises significantly, in agreement with the observations of high LURR prior to the large earthquakes. In shearing tests, two parameters are found to control the correlation between earthquake occurrence and tidal stress. One is, A/(kT) controlling the phase shift between the peak seismicity rate and the peak amplitude of the perturbation stress. With an increase of this parameter, the phase shift is found to decrease. Another parameter, AT/k, controls the height of the probability density function (Pdf) of modeled seismicity. As this parameter increases, the Pdf becomes sharper and narrower, indicating a strong triggering. Statistical studies of LURR signals in shearing tests also suggest that except in strong triggering cases, where LURR cannot be calculated due to poor data in unloading cycles, the larger events are more likely to occur in higher LURR periods than the smaller ones, supporting the LURR hypothesis.

Determinants of functional capacity in patients with chronic heart failure: Role of filling pressure and systolic and diastolic function

Background Previous work suggesting a better correlation of diastolic than systolic function with exercise capacity in heart failure may reflect the -relative insensitivity and load-dependence of ejection fraction (EF). We sought the correlation of new and more sensitive methods of quantifying systolic and diastolic function and filling pressure with functional capacity. Methods We studied 155 consecutive exercise tests on 95 patients with congestive heart failure (81 male, aged 62 +/- 10 years), who underwent resting 2-climensional echocardiography and tissue Doppler imaging before and after measurement of maximum oxygen uptake (peak VO2)Results The resting EF was 3 1 % 10% and a peak VO(2)was 13 +/- 5 mL/kg/min; the majority of these patients (80%) had an ischemic cardiornyopathy. Resting EF (r 0.14, P =.09) correlated poorly with peak VO2 and mean systolic (r = 0.23, P =.004) and diastolic tissue velocities (r 0.18, P =.02). Peak EF was weakly correlated with the mean systolic (r = 0.18, P =.02) and diastolic velocities (r = 0.16, P <.04). The mean sum of systolic and diastolic velocities in both annuli (r = 0.30, P <.001) and E/Ea ratio (r 0.31, P <.001) were better correlated with peak VO2 Prediction of peak VO2 was similar with models based on models of filling pressure (R = 0.61), systolic factors (R = 0.63), and diastolic factors (R 0.59), although a composite model of filling pressure, systolic and diastolic function was a superior predictor of peak VO2 (R 0.69; all P<.001). Conclusions The reported association of diastolic rather than systolic function with functional capacity may have reflected the limitations of EF. Functional capacity appears related not only to diastolic function, but also to systolic function and filling pressure, and is most closely associated with a combination of these factors.

Better prediction of protein contact number using a support vector regression analysis of amino acid sequence

Background: Protein tertiary structure can be partly characterized via each amino acid's contact number measuring how residues are spatially arranged. The contact number of a residue in a folded protein is a measure of its exposure to the local environment, and is defined as the number of C-beta atoms in other residues within a sphere around the C-beta atom of the residue of interest. Contact number is partly conserved between protein folds and thus is useful for protein fold and structure prediction. In turn, each residue's contact number can be partially predicted from primary amino acid sequence, assisting tertiary fold analysis from sequence data. In this study, we provide a more accurate contact number prediction method from protein primary sequence. Results: We predict contact number from protein sequence using a novel support vector regression algorithm. Using protein local sequences with multiple sequence alignments (PSI-BLAST profiles), we demonstrate a correlation coefficient between predicted and observed contact numbers of 0.70, which outperforms previously achieved accuracies. Including additional information about sequence weight and amino acid composition further improves prediction accuracies significantly with the correlation coefficient reaching 0.73. If residues are classified as being either contacted or non-contacted, the prediction accuracies are all greater than 77%, regardless of the choice of classification thresholds. Conclusion: The successful application of support vector regression to the prediction of protein contact number reported here, together with previous applications of this approach to the prediction of protein accessible surface area and B-factor profile, suggests that a support vector regression approach may be very useful for determining the structure-function relation between primary sequence and higher order consecutive protein structural and functional properties.

Accurate prediction of scorpion toxin functional properties from primary structures

Scorpion toxins are common experimental tools for studies of biochemical and pharmacological properties of ion channels. The number of functionally annotated scorpion toxins is steadily growing, but the number of identified toxin sequences is increasing at much faster pace. With an estimated 100,000 different variants, bioinformatic analysis of scorpion toxins is becoming a necessary tool for their systematic functional analysis. Here, we report a bioinformatics-driven system involving scorpion toxin structural classification, functional annotation, database technology, sequence comparison, nearest neighbour analysis, and decision rules which produces highly accurate predictions of scorpion toxin functional properties. (c) 2005 Elsevier Inc. All rights reserved.

Benefits of all work and no play: The relationship between neuroticism and performance as a function of resource allocation

The authors evaluate a model suggesting that the performance of highly neurotic individuals, relative to their stable counterparts, is more strongly influenced by factors relating to the allocation of attentional resources. First, an air traffic control simulation was used to examine the interaction between effort intensity and scores on the Anxiety subscale of Eysenck Personality Profiler Neuroticism in the prediction of task performance. Overall effort intensity enhanced performance for highly anxious individuals more so than for individuals with low anxiety. Second, a longitudinal field study was used to examine the interaction between office busyness and Eysenck Personality Inventory Neuroticism in the prediction of telesales performance. Changes in office busyness were associated with greater performance improvements for highly neurotic individuals compared with less neurotic individuals. These studies suggest that highly neurotic individuals outperform their stable counterparts in a busy work environment or if they are expending a high level of effort.

Prediction of vapor-moisture equilibriums for a wood-moisture system using a modified UNIQUAC model

A modified UNIQUAC model has been extended to describe and predict the equilibrium relative humidity and moisture content for wood. The method is validated over a range of moisture content from oven-dried state to fiber saturation point, and over a temperature range of 20-70 degrees C. Adjustable parameters and binary interaction parameters of the UNIQUAC model were estimated from experimental data for Caribbean pine and Hoop pine as well as data available in the literature. The two group-interaction parameters for the wood-moisture system were consistent with using function group contributions for H2O, -OH and -CHO. The result reconfirms that the main contributors to water adsorption in cell walls are the hydroxyl groups of the carbohydrates in cellulose and hemicelluloses. This provides some physical insight into the intermolecular force and energy between bound water and the wood material. (c) 2006 Elsevier Ltd. All rights reserved.

Prediction of HLA-DQ3.2 beta ligands: evidence of multiple registers in class II binding peptides

Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models. Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2 beta complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2 beta receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2 beta binding and non-binding peptides obtained from biochemical and functional studies. Results: Our model predicts DQ3.2 beta binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve A(ROC) > 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2 beta peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.

SCORPION2: A database for structure-function analysis of scorpion toxins

Scorpion toxins are important experimental tools for characterization of vast array of ion channels and serve as scaffolds for drug design. General public database entries contain limited annotation whereby rich structure-function information from mutation studies is typically not available. SCORPION2 contains more than 800 records of native and mutant toxin sequences enriched with binding affinity and toxicity information, 624 three-dimensional structures and some 500 references. SCORPION2 has a set of search and prediction tools that allow users to extract and perform specific queries: text searches of scorpion toxin records, sequence similarity search, extraction of sequences, visualization of scorpion toxin structures, analysis of toxic activity, and functional annotation of previously uncharacterized scorpion toxins. The SCORPION2 database is available at http://sdmc.i2r.a-star.edu.sg/scorpion/. (c) 2006 Elsevier Ltd. All rights reserved.

A misspelt youth: Spelling and orthographic learning in university students as a function of spelling-sound consistency

Pseudowords with inconsistent vs. consistent spellings (e.g., nurch, with rhyme neighbours search, lurch & perch, vs. mish, with neighbours dish, wish) were presented with definitions for naming either twice or 6 times. In an oral spelling test, there were main and interactive effects of consistency and the number of training trials on accuracy and main effects only on response latency, with the improvement in accuracy from 2 to 6 training trials greater for the more poorly learned inconsistent items. Of most interest, the smaller effect of training on accuracy in the consistent condition was reliable; contrary to the most obvious prediction of dual route spelling models that the sublexical procedure should produce correct spellings for consistent items early in training. In a second task students wrote spellings of multisyllabic words containing unstressed indeterminate (schwa) vowels. In their errors on the schwa vowel, students showed sensitivity to the most common spelling overall but also they were influenced by differences in schwa spellings in English words as a function of the number of syllables and schwa position. These results indicate that dual route models of spelling will need to accommodate the consistency of spellings within categories defined by lexical structure variables.

Evaluation and comparison of mammalian subcellular localization prediction methods

Background: Determination of the subcellular location of a protein is essential to understanding its biochemical function. This information can provide insight into the function of hypothetical or novel proteins. These data are difficult to obtain experimentally but have become especially important since many whole genome sequencing projects have been finished and many resulting protein sequences are still lacking detailed functional information. In order to address this paucity of data, many computational prediction methods have been developed. However, these methods have varying levels of accuracy and perform differently based on the sequences that are presented to the underlying algorithm. It is therefore useful to compare these methods and monitor their performance. Results: In order to perform a comprehensive survey of prediction methods, we selected only methods that accepted large batches of protein sequences, were publicly available, and were able to predict localization to at least nine of the major subcellular locations (nucleus, cytosol, mitochondrion, extracellular region, plasma membrane, Golgi apparatus, endoplasmic reticulum (ER), peroxisome, and lysosome). The selected methods were CELLO, MultiLoc, Proteome Analyst, pTarget and WoLF PSORT. These methods were evaluated using 3763 mouse proteins from SwissProt that represent the source of the training sets used in development of the individual methods. In addition, an independent evaluation set of 2145 mouse proteins from LOCATE with a bias towards the subcellular localization underrepresented in SwissProt was used. The sensitivity and specificity were calculated for each method and compared to a theoretical value based on what might be observed by random chance. Conclusion: No individual method had a sufficient level of sensitivity across both evaluation sets that would enable reliable application to hypothetical proteins. All methods showed lower performance on the LOCATE dataset and variable performance on individual subcellular localizations was observed. Proteins localized to the secretory pathway were the most difficult to predict, while nuclear and extracellular proteins were predicted with the highest sensitivity.

Central Cardiovascular Anatomy and Function in Crocodilia

Abstract: Among the vertebrates, crocodilians have the most complex anatomy of the heart and outflow channels. Their cardiovascular anatomy may also be the most func­tionally sophisticated, combining as it does the best features of both reptilian and mammalian (and avian) systems. The puzzlingly complex "plumbing" of crocodilians has fascinated ana­tomists and physiologists for a very long time, the first paper being that by Panizza (1833). Gradually, with the application of successive techniques of investigation as they became available, its functional significance has become reasonably clear, and the complexity is now revealed as a cardiovascular system of considerable elegance. In this paper I will review the main anatomical features of the heart and outflow channels, discuss what is known about the way they work, and speculate about the probable functional significance.

The prediction of disease risk in genomic medicine

In recent years, the phrase 'genomic medicine' has increasingly been used to describe a new development in medicine that holds great promise for human health. This new approach to health care uses the knowledge of an individual's genetic make-up to identify those that are at a higher risk of developing certain diseases and to intervene at an earlier stage to prevent these diseases. Identifying genes that are involved in disease aetiology will provide researchers with tools to develop better treatments and cures. A major role within this field is attributed to 'predictive genomic medicine', which proposes screening healthy individuals to identify those who carry alleles that increase their susceptibility to common diseases, such as cancers and heart disease. Physicians could then intervene even before the disease manifests and advise individuals with a higher genetic risk to change their behaviour - for instance, to exercise or to eat a healthier diet - or offer drugs or other medical treatment to reduce their chances of developing these diseases. These promises have fallen on fertile ground among politicians, health-care providers and the general public, particularly in light of the increasing costs of health care in developed societies. Various countries have established databases on the DNA and health information of whole populations as a first step towards genomic medicine. Biomedical research has also identified a large number of genes that could be used to predict someone's risk of developing a certain disorder. But it would be premature to assume that genomic medicine will soon become reality, as many problems remain to be solved. Our knowledge about most disease genes and their roles is far from sufficient to make reliable predictions about a patient’s risk of actually developing a disease. In addition, genomic medicine will create new political, social, ethical and economic challenges that will have to be addressed in the near future.

Measurement Function Design for Visual Tracking Applications

Extracting human postural information from video sequences has proved a difficult research question. The most successful approaches to date have been based on particle filtering, whereby the underlying probability distribution is approximated by a set of particles. The shape of the underlying observational probability distribution plays a significant role in determining the success, both accuracy and efficiency, of any visual tracker. In this paper we compare approaches used by other authors and present a cost path approach which is commonly used in image segmentation problems, however is currently not widely used in tracking applications.

Prediction of the chemical composition of lamb carcasses from multi-frequency impedance data

Multi-frequency bioimpedance analysis (MFBIA) was used to determine the impedance, reactance and resistance of 103 lamb carcasses (17.1-34.2 kg) immediately after slaughter and evisceration. Carcasses were halved, frozen and one half subsequently homogenized and analysed for water, crude protein and fat content. Three measures of carcass length were obtained. Diagonal length between the electrodes (right side biceps femoris to left side of neck) explained a greater proportion of the variance in water mass than did estimates of spinal length and was selected for use in the index L-2/Z to predict the mass of chemical components in the carcass. Use of impedance (Z) measured at the characteristic frequency (Z(c)) instead of 50 kHz (Z(50)) did not improve the power of the model to predict the mass of water, protein or fat in the carcass. While L-2/Z(50) explained a significant proportion of variation in the masses of body water (r(2) 0.64), protein (r(2) 0.34) and fat (r(2) 0.35), its inclusion in multi-variate indices offered small or no increases in predictive capacity when hot carcass weight (HCW) and a measure of rib fat-depth (GR) were present in the model. Optimized equations were able to account for 65-90 % of the variance observed in the weight of chemical components in the carcass. It is concluded that single frequency impedance data do not provide better prediction of carcass composition than can be obtained from measures of HCW and GR. Indices of intracellular water mass derived from impedance at zero frequency and the characteristic frequency explained a similar proportion of the variance in carcass protein mass as did the index L-2/Z(50).