Predicting functional gene links from phylogenetic-statistical analyses of whole genomes

An important element of the developing field of proteomics is to understand protein-protein interactions and other functional links amongst genes. Across-species correlation methods for detecting functional links work on the premise that functionally linked proteins will tend to show a common pattern of presence and absence across a range of genomes. We describe a maximum likelihood statistical model for predicting functional gene linkages. The method detects independent instances of the correlated gain or loss of pairs of proteins on phylogenetic trees, reducing the high rates of false positives observed in conventional across-species methods that do not explicitly incorporate a phylogeny. We show, in a dataset of 10,551 protein pairs, that the phylogenetic method improves by up to 35% on across-species analyses at identifying known functionally linked proteins. The method shows that protein pairs with at least two to three correlated events of gain or loss are almost certainly functionally linked. Contingent evolution, in which one gene's presence or absence depends upon the presence of another, can also be detected phylogenetically, and may identify genes whose functional significance depends upon its interaction with other genes. Incorporating phylogenetic information improves the prediction of functional linkages. The improvement derives from having a lower rate of false positives and from detecting trends that across-species analyses miss. Phylogenetic methods can easily be incorporated into the screening of large-scale bioinformatics datasets to identify sets of protein links and to characterise gene networks.

A practical approach to a multi-level analysis with a sparse binary outcome within a large surgical trial

Objectives: To assess the potential source of variation that surgeon may add to patient outcome in a clinical trial of surgical procedures. Methods: Two large (n = 1380) parallel multicentre randomized surgical trials were undertaken to compare laparoscopically assisted hysterectomy with conventional methods of abdominal and vaginal hysterectomy; involving 43 surgeons. The primary end point of the trial was the occurrence of at least one major complication. Patients were nested within surgeons giving the data set a hierarchical structure. A total of 10% of patients had at least one major complication, that is, a sparse binary outcome variable. A linear mixed logistic regression model (with logit link function) was used to model the probability of a major complication, with surgeon fitted as a random effect. Models were fitted using the method of maximum likelihood in SAS((R)). Results: There were many convergence problems. These were resolved using a variety of approaches including; treating all effects as fixed for the initial model building; modelling the variance of a parameter on a logarithmic scale and centring of continuous covariates. The initial model building process indicated no significant 'type of operation' across surgeon interaction effect in either trial, the 'type of operation' term was highly significant in the abdominal trial, and the 'surgeon' term was not significant in either trial. Conclusions: The analysis did not find a surgeon effect but it is difficult to conclude that there was not a difference between surgeons. The statistical test may have lacked sufficient power, the variance estimates were small with large standard errors, indicating that the precision of the variance estimates may be questionable.

Statistical deconvolution of enthalpic energetic contributions to MHC-peptide binding affinity

Background: MHC Class I molecules present antigenic peptides to cytotoxic T cells, which forms an integral part of the adaptive immune response. Peptides are bound within a groove formed by the MHC heavy chain. Previous approaches to MHC Class I-peptide binding prediction have largely concentrated on the peptide anchor residues located at the P2 and C-terminus positions. Results: A large dataset comprising MHC-peptide structural complexes was created by remodelling pre-determined x-ray crystallographic structures. Static energetic analysis, following energy minimisation, was performed on the dataset in order to characterise interactions between bound peptides and the MHC Class I molecule, partitioning the interactions within the groove into van der Waals, electrostatic and total non-bonded energy contributions. Conclusion: The QSAR techniques of Genetic Function Approximation (GFA) and Genetic Partial Least Squares (G/PLS) algorithms were used to identify key interactions between the two molecules by comparing the calculated energy values with experimentally-determined BL50 data. Although the peptide termini binding interactions help ensure the stability of the MHC Class I-peptide complex, the central region of the peptide is also important in defining the specificity of the interaction. As thermodynamic studies indicate that peptide association and dissociation may be driven entropically, it may be necessary to incorporate entropic contributions into future calculations.

Effect of internal partitioning on room air quality with mixing ventilation-statistical analysis

In designing modern office buildings, building spaces are frequently zoned by introducing internal partitioning, which may have a significant influence on the room air environment. This internal partitioning was studied by means of model test, numerical simulation, and statistical analysis as the final stage. In this paper, the results produced from the statistical analysis are summarized and presented.

Achieving quality through statistical prediction for building services systems

The application of prediction theories has been widely practised for many years in many industries such as manufacturing, defence and aerospace. Although these theories are not new, their application has not been widely used within the building services industry. Collectively, the building services industry should take a deeper look at these approaches in comparison with the traditional deterministic approaches currently being practised. By extending the application into this industry, this paper seeks to provide the industry with an overview of how simplified stochastic modelling coupled with availability and reliability predictions using historical data compiled from various sources could enhance the quality of building services systems.

Hitting emissions targets with (statistical) confidence in multi-instrument Emissions Trading Schemes

A means of assessing, monitoring and controlling aggregate emissions from multi-instrument Emissions Trading Schemes is proposed. The approach allows contributions from different instruments with different forms of emissions targets to be integrated. Where Emissions Trading Schemes are helping meet specific national targets, the approach allows the entry requirements of new participants to be calculated and set at a level that will achieve these targets. The approach is multi-levelled, and may be extended downwards to support pooling of participants within instruments, or upwards to embed Emissions Trading Schemes within a wider suite of policies and measures with hard and soft targets. Aggregate emissions from each instrument are treated stochastically. Emissions from the scheme as a whole are then the joint probability distribution formed by integrating the emissions from its instruments. Because a Bayesian approach is adopted, qualitative and semi-qualitative data from expert opinion can be used where quantitative data is not currently available, or is incomplete. This approach helps government retain sufficient control over emissions trading scheme targets to allow them to meet their emissions reduction obligations, while minimising the need for retrospectively adjusting existing participants’ conditions of entry. This maintains participant confidence, while providing the necessary policy levers for good governance.

Rapid quality assessment of wheat cultivars registered in Poland using the 2-g mixograph and multivariate statistical analysis

Baking and 2-g mixograph analyses were performed for 55 cultivars (19 spring and 36 winter wheat) from various quality classes from the 2002 harvest in Poland. An instrumented 2-g direct-drive mixograph was used to study the mixing characteristics of the wheat cultivars. A number of parameters were extracted automatically from each mixograph trace and correlated with baking volume and flour quality parameters (protein content and high molecular weight glutenin subunit [HMW-GS] composition by SDS-PAGE) using multiple linear regression statistical analysis. Principal component analysis of the mixograph data discriminated between four flour quality classes, and predictions of baking volume were obtained using several selected mixograph parameters, chosen using a best subsets regression routine, giving R-2 values of 0.862-0.866. In particular, three new spring wheat strains (CHD 502a-c) recently registered in Poland were highly discriminated and predicted to give high baking volume on the basis of two mixograph parameters: peak bandwidth and 10-min bandwidth.

Ranald Macdonald and statistical inference

Ranald Roderick Macdonald (1945-2007) was an important contributor to mathematical psychology in the UK, as a referee and action editor for British Journal of Mathematical and Statistical Psychology and as a participant and organizer at the British Psychological Society's Mathematics, statistics and computing section meetings. This appreciation argues that his most important contribution was to the foundations of significance testing, where his concern about what information was relevant in interpreting the results of significance tests led him to be a persuasive advocate for the 'Weak Fisherian' form of hypothesis testing.

The development of convergence and accommodation

Aim: To review current literature on the development of convergence and accommodation. The accommodation and vergence systems provide the foundation upon which bifoveal binocular single vision develops. Deviations from their normal development not only are implicated in the aetiology of convergence anomalies, accommodative anomalies and strabismus, but may also be implicated in failure of the emmetropisation process. Method: This review considers the problems of researching the development of accommodation and vergence in infants and how infant research has had to differ from adult methods. It then reviews and discusses the implications of current research into the development of both systems and their linkages. Results: Vergence and accommodation develop rapidly in the first months of life, with accommodation changing from relatively fixed myopic focus in the neonatal period to adult-like responses by 4 months of age. Vergence develops gradually and becomes more accurate after 4 months of age, but has been demonstrated in infants well before the age that binocular disparity detection mechanisms are thought to develop. Hypotheses for this early vergence mechanism are discussed. The relationship between accommodation and vergence shows much more variability in infants than adult literature has found, but this apparent adult/infant difference may be partly attributed to methodological differences rather than maturational change alone. Conclusions: Variability and flexibility characterise infant responses. This variability may enable infants to develop a flexible and robust binocular system for later life. Studies of infant visual cue use may give clues to the aetiology of strabismus and refractive error.

Inverse effectiveness, multisensory integration, and the bodily self: some statistical considerations

A recent report in Consciousness and Cognition provided evidence from a study of the rubber hand illusion (RHI) that supports the multisensory principle of inverse effectiveness (PoIE). I describe two methods of assessing the principle of inverse effectiveness ('a priori' and 'post-hoc'), and discuss how the post-hoc method is affected by the statistical artefact of,regression towards the mean'. I identify several cases where this artefact may have affected particular conclusions about the PoIE, and relate these to the historical origins of 'regression towards the mean'. Although the conclusions of the recent report may not have been grossly affected, some of the inferential statistics were almost certainly biased by the methods used. I conclude that, unless such artefacts are fully dealt with in the future, and unless the statistical methods for assessing the PoIE evolve, strong evidence in support of the PoIE will remain lacking. (C) 2009 Elsevier Inc. All rights reserved.

Unsupervised segmentation using Gabor wavelets and statistical features in LIDAR data analysis

In this paper, we address issues in segmentation Of remotely sensed LIDAR (LIght Detection And Ranging) data. The LIDAR data, which were captured by airborne laser scanner, contain 2.5 dimensional (2.5D) terrain surface height information, e.g. houses, vegetation, flat field, river, basin, etc. Our aim in this paper is to segment ground (flat field)from non-ground (houses and high vegetation) in hilly urban areas. By projecting the 2.5D data onto a surface, we obtain a texture map as a grey-level image. Based on the image, Gabor wavelet filters are applied to generate Gabor wavelet features. These features are then grouped into various windows. Among these windows, a combination of their first and second order of statistics is used as a measure to determine the surface properties. The test results have shown that ground areas can successfully be segmented from LIDAR data. Most buildings and high vegetation can be detected. In addition, Gabor wavelet transform can partially remove hill or slope effects in the original data by tuning Gabor parameters.