The ModFOLD server for the quality assessment of protein structural models

The reliable assessment of the quality of protein structural models is fundamental to the progress of structural bioinformatics. The ModFOLD server provides access to two accurate techniques for the global and local prediction of the quality of 3D models of proteins. Firstly ModFOLD, which is a fast Model Quality Assessment Program (MQAP) used for the global assessment of either single or multiple models. Secondly ModFOLDclust, which is a more intensive method that carries out clustering of multiple models and provides per-residue local quality assessment.

Estimation of Hidden Markov Models parameters using differential evolution

Hidden Markov Models (HMMs) have been successfully applied to different modelling and classification problems from different areas over the recent years. An important step in using HMMs is the initialisation of the parameters of the model as the subsequent learning of HMM’s parameters will be dependent on these values. This initialisation should take into account the knowledge about the addressed problem and also optimisation techniques to estimate the best initial parameters given a cost function, and consequently, to estimate the best log-likelihood. This paper proposes the initialisation of Hidden Markov Models parameters using the optimisation algorithm Differential Evolution with the aim to obtain the best log-likelihood.

Estimation of optimal gravity wave parameters for climate models using data assimilation

There is a current need to constrain the parameters of gravity wave drag (GWD) schemes in climate models using observational information instead of tuning them subjectively. In this work, an inverse technique is developed using data assimilation principles to estimate gravity wave parameters. Because mostGWDschemes assume instantaneous vertical propagation of gravity waves within a column, observations in a single column can be used to formulate a one-dimensional assimilation problem to estimate the unknown parameters. We define a cost function that measures the differences between the unresolved drag inferred from observations (referred to here as the ‘observed’ GWD) and the GWD calculated with a parametrisation scheme. The geometry of the cost function presents some difficulties, including multiple minima and ill-conditioning because of the non-independence of the gravity wave parameters. To overcome these difficulties we propose a genetic algorithm to minimize the cost function, which provides a robust parameter estimation over a broad range of prescribed ‘true’ parameters. When real experiments using an independent estimate of the ‘observed’ GWD are performed, physically unrealistic values of the parameters can result due to the non-independence of the parameters. However, by constraining one of the parameters to lie within a physically realistic range, this degeneracy is broken and the other parameters are also found to lie within physically realistic ranges. This argues for the essential physical self-consistency of the gravity wave scheme. A much better fit to the observed GWD at high latitudes is obtained when the parameters are allowed to vary with latitude. However, a close fit can be obtained either in the upper or the lower part of the profiles, but not in both at the same time. This result is a consequence of assuming an isotropic launch spectrum. The changes of sign in theGWDfound in the tropical lower stratosphere, which are associated with part of the quasi-biennial oscillation forcing, cannot be captured by the parametrisation with optimal parameters.

Bayesian estimation of co-integrating thresholds in the term structure of interest rates.

Threshold Error Correction Models are used to analyse the term structure of interest Rates. The paper develops and uses a generalisation of existing models that encompasses both the Band and Equilibrium threshold models of [Balke and Fomby ((1997) Threshold cointegration. Int Econ Rev 38(3):627–645)] and estimates this model using a Bayesian approach. Evidence is found for threshold effects in pairs of longer rates but not in pairs of short rates. The Band threshold model is supported in preference to the Equilibrium model.

Vegetation dynamics in abandoned crop fields on a Mediterranean island: Development of succession model and estimation of disturbance thresholds

This case study on the Sifnos island, Greece, assesses the main factors controlling vegetation succession following crop abandonment and describes the vegetation dynamics of maquis and phrygana formations in relation to alternative theories of secondary succession. Field survey data were collected and analysed at community as well as species level. The results show that vegetation succession on abandoned crop fields is determined by the combined effects of grazing intensity, soil and geological characteristics and time. The analysis determines the quantitative grazing thresholds that modify the successional pathway. Light grazing leads to dominance by maquis vegetation while overgrazing leads to phryganic vegetation. The proposed model shows that vegetation succession following crop abandonment is a complex multi-factor process where the final or the stable stage of the process is not predefined but depends on the factors affecting succession. An example of the use of succession models and disturbance thresholds as a policy assessment tool is presented by evaluating the likely vegetation impacts of the recent reform of the Common Agricultural Policy on Sifnos island over a 20-30-year time horizon. (c) 2006 Elsevier B.V. All rights reserved.

Extending Zelterman’s approach for robust estimation of population size to zero-truncated clustered data

Estimation of population size with missing zero-class is an important problem that is encountered in epidemiological assessment studies. Fitting a Poisson model to the observed data by the method of maximum likelihood and estimation of the population size based on this fit is an approach that has been widely used for this purpose. In practice, however, the Poisson assumption is seldom satisfied. Zelterman (1988) has proposed a robust estimator for unclustered data that works well in a wide class of distributions applicable for count data. In the work presented here, we extend this estimator to clustered data. The estimator requires fitting a zero-truncated homogeneous Poisson model by maximum likelihood and thereby using a Horvitz-Thompson estimator of population size. This was found to work well, when the data follow the hypothesized homogeneous Poisson model. However, when the true distribution deviates from the hypothesized model, the population size was found to be underestimated. In the search of a more robust estimator, we focused on three models that use all clusters with exactly one case, those clusters with exactly two cases and those with exactly three cases to estimate the probability of the zero-class and thereby use data collected on all the clusters in the Horvitz-Thompson estimator of population size. Loss in efficiency associated with gain in robustness was examined based on a simulation study. As a trade-off between gain in robustness and loss in efficiency, the model that uses data collected on clusters with at most three cases to estimate the probability of the zero-class was found to be preferred in general. In applications, we recommend obtaining estimates from all three models and making a choice considering the estimates from the three models, robustness and the loss in efficiency. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Bayesian estimation of recent migration rates after a spatial expansion

Approximate Bayesian computation (ABC) is a highly flexible technique that allows the estimation of parameters under demographic models that are too complex to be handled by full-likelihood methods. We assess the utility of this method to estimate the parameters of range expansion in a two-dimensional stepping-stone model, using samples from either a single deme or multiple demes. A minor modification to the ABC procedure is introduced, which leads to an improvement in the accuracy of estimation. The method is then used to estimate the expansion time and migration rates for five natural common vole populations in Switzerland typed for a sex-linked marker and a nuclear marker. Estimates based on both markers suggest that expansion occurred < 10,000 years ago, after the most recent glaciation, and that migration rates are strongly male biased.

Likelihood-based estimation of microsatellite mutation rates

Microsatellites are widely used in genetic analyses, many of which require reliable estimates of microsatellite mutation rates, yet the factors determining mutation rates are uncertain. The most straightforward and conclusive method by which to study mutation is direct observation of allele transmissions in parent-child pairs, and studies of this type suggest a positive, possibly exponential, relationship between mutation rate and allele size, together with a bias toward length increase. Except for microsatellites on the Y chromosome, however, previous analyses have not made full use of available data and may have introduced bias: mutations have been identified only where child genotypes could not be generated by transmission from parents' genotypes, so that the probability that a mutation is detected depends on the distribution of allele lengths and varies with allele length. We introduce a likelihood-based approach that has two key advantages over existing methods. First, we can make formal comparisons between competing models of microsatellite evolution; second, we obtain asymptotically unbiased and efficient parameter estimates. Application to data composed of 118,866 parent-offspring transmissions of AC microsatellites supports the hypothesis that mutation rate increases exponentially with microsatellite length, with a suggestion that contractions become more likely than expansions as length increases. This would lead to a stationary distribution for allele length maintained by mutational balance. There is no evidence that contractions and expansions differ in their step size distributions.

Fermentation of resistant starches: influence of in vitro models on colon carcinogenesis

Resistant starch type 2 (RS2) and type 3 (RS3) containing preparations were digested using a batch (a) and a dynamic in vitro model (b). Furthermore, in vivo obtained indigestible fractions from ileostomy patients were used (c). Subsequently these samples were fermented with human feces with a batch and a dynamic in vitro method. The fermentation supernatants were used to treat CAC02 cells. Cytotoxicity, anti-genotoxicity against hydrogen peroxide (comet assay) and the effect on barrier function measured by trans-epithelial electrical resistance were determine. Dynamically fermented samples led to high cytotoxic activity, probably due to additional compounds added during in vitro fermentation. As a consequence only batch fermented samples were investigated further. Batch fermentation of RS resulted in an anti-genotoxic activity ranging from 9-30% decrease in DNA damage for all the samples, except for RS2-b. It is assumed that the changes in RS2 structures due to dynamic digestion resulted in a different fermentation profile not leading to any anti-genotoxic effect. Additionally, in vitro batch fermentation of RS caused an improvement in integrity across the intestinal barrier by approximately 22% for all the samples. We have demonstrated that batch in vitro fermentation of RS2 and RS3 preparations differently pre-digested are capable of inhibiting the initiation and promotion stage in colon carcinogenesis in vitro.

Predictive control using feedback linearization based on dynamic neural models

This paper presents a hybrid control strategy integrating dynamic neural networks and feedback linearization into a predictive control scheme. Feedback linearization is an important nonlinear control technique which transforms a nonlinear system into a linear system using nonlinear transformations and a model of the plant. In this work, empirical models based on dynamic neural networks have been employed. Dynamic neural networks are mathematical structures described by differential equations, which can be trained to approximate general nonlinear systems. A case study based on a mixing process is presented.

An Efficient Parameterization of Dynamic Neural Networks for Nonlinear System Identification

Dynamic neural networks (DNNs), which are also known as recurrent neural networks, are often used for nonlinear system identification. The main contribution of this letter is the introduction of an efficient parameterization of a class of DNNs. Having to adjust less parameters simplifies the training problem and leads to more parsimonious models. The parameterization is based on approximation theory dealing with the ability of a class of DNNs to approximate finite trajectories of nonautonomous systems. The use of the proposed parameterization is illustrated through a numerical example, using data from a nonlinear model of a magnetic levitation system.

Estimation of distances in virtual environments using size constancy

It is reported in the literature that distances from the observer are underestimated more in virtual environments (VEs) than in physical world conditions. On the other hand estimation of size in VEs is quite accurate and follows a size-constancy law when rich cues are present. This study investigates how estimation of distance in a CAVETM environment is affected by poor and rich cue conditions, subject experience, and environmental learning when the position of the objects is estimated using an experimental paradigm that exploits size constancy. A group of 18 healthy participants was asked to move a virtual sphere controlled using the wand joystick to the position where they thought a previously-displayed virtual cube (stimulus) had appeared. Real-size physical models of the virtual objects were also presented to the participants as a reference of real physical distance during the trials. An accurate estimation of distance implied that the participants assessed the relative size of sphere and cube correctly. The cube appeared at depths between 0.6 m and 3 m, measured along the depth direction of the CAVE. The task was carried out in two environments: a poor cue one with limited background cues, and a rich cue one with textured background surfaces. It was found that distances were underestimated in both poor and rich cue conditions, with greater underestimation in the poor cue environment. The analysis also indicated that factors such as subject experience and environmental learning were not influential. However, least square fitting of Stevens’ power law indicated a high degree of accuracy during the estimation of object locations. This accuracy was higher than in other studies which were not based on a size-estimation paradigm. Thus as indirect result, this study appears to show that accuracy when estimating egocentric distances may be increased using an experimental method that provides information on the relative size of the objects used.

Advancements in the estimation of ice particle fall speeds using laboratory and field measurements

Accurate estimates for the fall speed of natural hydrometeors are vital if their evolution in clouds is to be understood quantitatively. In this study, laboratory measurements of the terminal velocity vt for a variety of ice particle models settling in viscous fluids, along with wind-tunnel and field measurements of ice particles settling in air, have been analyzed and compared to common methods of computing vt from the literature. It is observed that while these methods work well for a number of particle types, they fail for particles with open geometries, specifically those particles for which the area ratio Ar is small (Ar is defined as the area of the particle projected normal to the flow divided by the area of a circumscribing disc). In particular, the fall speeds of stellar and dendritic crystals, needles, open bullet rosettes, and low-density aggregates are all overestimated. These particle types are important in many cloud types: aggregates in particular often dominate snow precipitation at the ground and vertically pointing Doppler radar measurements. Based on the laboratory data, a simple modification to previous computational methods is proposed, based on the area ratio. This new method collapses the available drag data onto an approximately universal curve, and the resulting errors in the computed fall speeds relative to the tank data are less than 25% in all cases. Comparison with the (much more scattered) measurements of ice particles falling in air show strong support for this new method, with the area ratio bias apparently eliminated.

Predicting metal-binding site residues in low-resolution structural models

The accurate prediction of the biochemical function of a protein is becoming increasingly important, given the unprecedented growth of both structural and sequence databanks. Consequently, computational methods are required to analyse such data in an automated manner to ensure genomes are annotated accurately. Protein structure prediction methods, for example, are capable of generating approximate structural models on a genome-wide scale. However, the detection of functionally important regions in such crude models, as well as structural genomics targets, remains an extremely important problem. The method described in the current study, MetSite, represents a fully automatic approach for the detection of metal-binding residue clusters applicable to protein models of moderate quality. The method involves using sequence profile information in combination with approximate structural data. Several neural network classifiers are shown to be able to distinguish metal sites from non-sites with a mean accuracy of 94.5%. The method was demonstrated to identify metal-binding sites correctly in LiveBench targets where no obvious metal-binding sequence motifs were detectable using InterPro. Accurate detection of metal sites was shown to be feasible for low-resolution predicted structures generated using mGenTHREADER where no side-chain information was available. High-scoring predictions were observed for a recently solved hypothetical protein from Haemophilus influenzae, indicating a putative metal-binding site.