Improvement of 3D protein models using multiple templates guided by single-template model quality assessment

Motivation: Modelling the 3D structures of proteins can often be enhanced if more than one fold template is used during the modelling process. However, in many cases, this may also result in poorer model quality for a given target or alignment method. There is a need for modelling protocols that can both consistently and significantly improve 3D models and provide an indication of when models might not benefit from the use of multiple target-template alignments. Here, we investigate the use of both global and local model quality prediction scores produced by ModFOLDclust2, to improve the selection of target-template alignments for the construction of multiple-template models. Additionally, we evaluate clustering the resulting population of multi- and single-template models for the improvement of our IntFOLD-TS tertiary structure prediction method. Results: We find that using accurate local model quality scores to guide alignment selection is the most consistent way to significantly improve models for each of the sequence to structure alignment methods tested. In addition, using accurate global model quality for re-ranking alignments, prior to selection, further improves the majority of multi-template modelling methods tested. Furthermore, subsequent clustering of the resulting population of multiple-template models significantly improves the quality of selected models compared with the previous version of our tertiary structure prediction method, IntFOLD-TS.

High Resolution Melt (HRM) analysis is an efficient tool to genotype EMS mutants in complex crop genomes

Background: Targeted Induced Loci Lesions IN Genomes (TILLING) is increasingly being used to generate and identify mutations in target genes of crop genomes. TILLING populations of several thousand lines have been generated in a number of crop species including Brassica rapa. Genetic analysis of mutants identified by TILLING requires an efficient, high-throughput and cost effective genotyping method to track the mutations through numerous generations. High resolution melt (HRM) analysis has been used in a number of systems to identify single nucleotide polymorphisms (SNPs) and insertion/deletions (IN/DELs) enabling the genotyping of different types of samples. HRM is ideally suited to high-throughput genotyping of multiple TILLING mutants in complex crop genomes. To date it has been used to identify mutants and genotype single mutations. The aim of this study was to determine if HRM can facilitate downstream analysis of multiple mutant lines identified by TILLING in order to characterise allelic series of EMS induced mutations in target genes across a number of generations in complex crop genomes. Results: We demonstrate that HRM can be used to genotype allelic series of mutations in two genes, BraA.CAX1a and BraA.MET1.a in Brassica rapa. We analysed 12 mutations in BraA.CAX1.a and five in BraA.MET1.a over two generations including a back-cross to the wild-type. Using a commercially available HRM kit and the Lightscanner™ system we were able to detect mutations in heterozygous and homozygous states for both genes. Conclusions: Using HRM genotyping on TILLING derived mutants, it is possible to generate an allelic series of mutations within multiple target genes rapidly. Lines suitable for phenotypic analysis can be isolated approximately 8-9 months (3 generations) from receiving M3 seed of Brassica rapa from the RevGenUK TILLING service.

An improved algorithm for generating global window brightness temperatures from multiple satellite infrared imagery

An improved algorithm for the generation of gridded window brightness temperatures is presented. The primary data source is the International Satellite Cloud Climatology Project, level B3 data, covering the period from July 1983 to the present. The algorithm rakes window brightness, temperatures from multiple satellites, both geostationary and polar orbiting, which have already been navigated and normalized radiometrically to the National Oceanic and Atmospheric Administration's Advanced Very High Resolution Radiometer, and generates 3-hourly global images on a 0.5 degrees by 0.5 degrees latitude-longitude grid. The gridding uses a hierarchical scheme based on spherical kernel estimators. As part of the gridding procedure, the geostationary data are corrected for limb effects using a simple empirical correction to the radiances, from which the corrected temperatures are computed. This is in addition to the application of satellite zenith angle weighting to downweight limb pixels in preference to nearer-nadir pixels. The polar orbiter data are windowed on the target time with temporal weighting to account for the noncontemporaneous nature of the data. Large regions of missing data are interpolated from adjacent processed images using a form of motion compensated interpolation based on the estimation of motion vectors using an hierarchical block matching scheme. Examples are shown of the various stages in the process. Also shown are examples of the usefulness of this type of data in GCM validation.

Intrinsic disorder prediction from the analysis of multiple protein fold recognition models

Motivation: Intrinsic protein disorder is functionally implicated in numerous biological roles and is, therefore, ubiquitous in proteins from all three kingdoms of life. Determining the disordered regions in proteins presents a challenge for experimental methods and so recently there has been much focus on the development of improved predictive methods. In this article, a novel technique for disorder prediction, called DISOclust, is described, which is based on the analysis of multiple protein fold recognition models. The DISOclust method is rigorously benchmarked against the top.ve methods from the CASP7 experiment. In addition, the optimal consensus of the tested methods is determined and the added value from each method is quantified. Results: The DISOclust method is shown to add the most value to a simple consensus of methods, even in the absence of target sequence homology to known structures. A simple consensus of methods that includes DISOclust can significantly outperform all of the previous individual methods tested.

Optimal foraging when regulating intake of multiple nutrients

There is growing evidence that, rather than maximizing energy intake subject to constraints, many animals attempt to regulate intake of multiple nutrients independently. In the complex diets of animals such as herbivores, the consumption of nutritionally imbalanced foods is sometimes inevitable, forcing trade-offs between eating too much of nutrients present in the foods in relative excess against too little of those in deficit. Such situations are not adequately represented in existing formulations of foraging theory. Here we provide the necessary theory to fit this case, using an approach that combines state-space models of nutrition with Tilman's models of resource exploitation (Tilman 1982, Resource Competition and Community Structure, Princeton: Princeton University Press). Our approach was to construct a smooth fitness landscape over nutrient space, centred on a 'target' intake at which no fitness cost is incurred, and this leads to a natural classification of the simple possible fitness landscapes based on Taylor series approximations of landscape shape. We next examined how needs for multiple nutrients can be assessed experimentally using direct measures of animal performance as the common currency, so that the nutritional strategies of animals can be mapped on to the performance surface, including the position of regulated points of intake and points of nutrient balance when fed suboptimal foods. We surveyed published data and conducted an experiment to map out the performance landscape of a generalist leaf-feeding caterpillar, Spodoptera littoralis. (C) 2004 Tire Association for the Study of Animal Behaviour. Poblished by Elsevier Ltd. All rights reserved.

Binaural prediction of speech intelligibility in reverberant rooms with multiple noise sources

When speech is in competition with interfering sources in rooms, monaural indicators of intelligibility fail to take account of the listener’s abilities to separate target speech from interfering sounds using the binaural system. In order to incorporate these segregation abilities and their susceptibility to reverberation, Lavandier and Culling [J. Acoust. Soc. Am. 127, 387–399 (2010)] proposed a model which combines effects of better-ear listening and binaural unmasking. A computationally efficient version of this model is evaluated here under more realistic conditions that include head shadow, multiple stationary noise sources, and real-room acoustics. Three experiments are presented in which speech reception thresholds were measured in the presence of one to three interferers using real-room listening over headphones, simulated by convolving anechoic stimuli with binaural room impulse-responses measured with dummy-head transducers in five rooms. Without fitting any parameter of the model, there was close correspondence between measured and predicted differences in threshold across all tested conditions. The model’s components of better-ear listening and binaural unmasking were validated both in isolation and in combination. The computational efficiency of this prediction method allows the generation of complex “intelligibility maps” from room designs. © 2012 Acoustical Society of America

The effect of multiple haptic distractors on the performance of motion-impaired users

The effect of multiple haptic distractors on target selection performance was examined in terms of times to select the target and the associated cursor movement patterns. Two experiments examined: a) The effect of multiple haptic distractors around a single target and b) the effect of inter-item spacing in a linear selection task. It was found that certain target-distractor arrangements hindered performance and that this could be associated with specific, explanatory cursor patterns. In particular, it was found that the presence of distractors along the task axis in front of the target was detrimental to performance, and that there was evidence to suggest that this could sometimes be associated with consequent cursor oscillation between distractors adjacent to a desired target. A further experiment examined the effect of target-distractor spacing in two orientations on a user’s ability to select a target when caught in the gravity well of a distractor. Times for movements in the vertical direction were found to be faster than those in the horizontal direction. In addition, although times for the vertical direction appeared equivalent across five target-distractor distances, times for the horizontal direction exhibited peaks at certain distances. The implications of these results for the design and implementation of haptically enhanced interfaces using the force feedback mouse are discussed.

The interactive responses of water quality and hydrology to changes in multiple stressors, and implications for the long-term effective management of phosphorus

Soluble reactive phosphorus (SRP) plays a key role in eutrophication, a global problem decreasing habitat quality and in-stream biodiversity. Mitigation strategies are required to prevent SRP fluxes from exceeding critical levels, and must be robust in the face of potential changes in climate, land use and a myriad of other influences. To establish the longevity of these strategies it is therefore crucial to consider the sensitivity of catchments to multiple future stressors. This study evaluates how the water quality and hydrology of a major river system in the UK (the River Thames) respond to alterations in climate, land use and water resource allocations, and investigates how these changes impact the relative performance of management strategies over an 80-year period. In the River Thames, the relative contributions of SRP from diffuse and point sources vary seasonally. Diffuse sources of SRP from agriculture dominate during periods of high runoff, and point sources during low flow periods. SRP concentrations rose under any future scenario which either increased a) surface runoff or b) the area of cultivated land. Under these conditions, SRP was sourced from agriculture, and the most effective single mitigation measures were those which addressed diffuse SRP sources. Conversely, where future scenarios reduced flow e.g. during winters of reservoir construction, the significance of point source inputs increased, and mitigation measures addressing these issues became more effective. In catchments with multiple point and diffuse sources of SRP, an all-encompassing effective mitigation approach is difficult to achieve with a single strategy. In order to attain maximum efficiency, multiple strategies might therefore be employed at different times and locations, to target the variable nature of dominant SRP sources and pathways.

The identity of crop pollinators helps target conservation for improved ecosystem services

Insect pollinated mass flowering crops are becoming more widespread and there is a need to understand which insects are primarily responsible for the pollination of these crops so conservation measures can be appropriately targeted in the face of pollinator declines. This study used field surveys in conjunction with cage manipulations to identify the relative contributions of different pollinator taxa to the pollination of two widespread flowering crops, field beans and oilseed rape. Flower visiting pollinator communities observed in the field were distinct for each crop; while field beans were visited primarily by a few bumblebee species, multiple pollinator taxa visited oilseed, and the composition of this pollinator community was highly variable spatially and temporally. Neither pollinator community, however, appears to be meeting the demands of crops in our study regions. Cage manipulations showed that multiple taxa can effectively pollinate both oilseed and field beans, but bumblebees are particularly effective bean pollinators. Combining field observations and cage manipulations demonstrated that the pollination demands of these two mass flowering crops are highly contrasting, one would benefit from management to increase the abundance of some key taxa, whilst for the other, boosting overall pollinator abundance and diversity would be more appropriate. Our findings highlight the need for crop specific mitigation strategies that are targeted at conserving specific pollinator taxa (or group of taxa) that are both active and capable of crop pollination in order to reduce pollination deficits and meet the demands of future crop production.

Extending the Lincoln–Petersen estimator for multiple identifications in one source

The Lincoln–Petersen estimator is one of the most popular estimators used in capture–recapture studies. It was developed for a sampling situation in which two sources independently identify members of a target population. For each of the two sources, it is determined if a unit of the target population is identified or not. This leads to a 2 × 2 table with frequencies f11, f10, f01, f00 indicating the number of units identified by both sources, by the first but not the second source, by the second but not the first source and not identified by any of the two sources, respectively. However, f00 is unobserved so that the 2 × 2 table is incomplete and the Lincoln–Petersen estimator provides an estimate for f00. In this paper, we consider a generalization of this situation for which one source provides not only a binary identification outcome but also a count outcome of how many times a unit has been identified. Using a truncated Poisson count model, truncating multiple identifications larger than two, we propose a maximum likelihood estimator of the Poisson parameter and, ultimately, of the population size. This estimator shows benefits, in comparison with Lincoln–Petersen’s, in terms of bias and efficiency. It is possible to test the homogeneity assumption that is not testable in the Lincoln–Petersen framework. The approach is applied to surveillance data on syphilis from Izmir, Turkey.