Proteomic applications of automated GPCR classification

The G-protein coupled receptor (GPCR) superfamily fulfils various metabolic functions and interacts with a diverse range of ligands. There is a lack of sequence similarity between the six classes that comprise the GPCR superfamily. Moreover, most novel GPCRs found have low sequence similarity to other family members which makes it difficult to infer properties from related receptors. Many different approaches have been taken towards developing efficient and accurate methods for GPCR classification, ranging from motif-based systems to machine learning as well as a variety of alignment-free techniques based on the physiochemical properties of their amino acid sequences. This review describes the inherent difficulties in developing a GPCR classification algorithm and includes techniques previously employed in this area.

Optimizing amino acid groupings for GPCR classification

MOTIVATION: There is much interest in reducing the complexity inherent in the representation of the 20 standard amino acids within bioinformatics algorithms by developing a so-called reduced alphabet. Although there is no universally applicable residue grouping, there are numerous physiochemical criteria upon which one can base groupings. Local descriptors are a form of alignment-free analysis, the efficiency of which is dependent upon the correct selection of amino acid groupings. RESULTS: Within the context of G-protein coupled receptor (GPCR) classification, an optimization algorithm was developed, which was able to identify the most efficient grouping when used to generate local descriptors. The algorithm was inspired by the relatively new computational intelligence paradigm of artificial immune systems. A number of amino acid groupings produced by this algorithm were evaluated with respect to their ability to generate local descriptors capable of providing an accurate classification algorithm for GPCRs.

Outlier detection with partial information:Application to emergency mapping

This paper, addresses the problem of novelty detection in the case that the observed data is a mixture of a known 'background' process contaminated with an unknown other process, which generates the outliers, or novel observations. The framework we describe here is quite general, employing univariate classification with incomplete information, based on knowledge of the distribution (the 'probability density function', 'pdf') of the data generated by the 'background' process. The relative proportion of this 'background' component (the 'prior' 'background' 'probability), the 'pdf' and the 'prior' probabilities of all other components are all assumed unknown. The main contribution is a new classification scheme that identifies the maximum proportion of observed data following the known 'background' distribution. The method exploits the Kolmogorov-Smirnov test to estimate the proportions, and afterwards data are Bayes optimally separated. Results, demonstrated with synthetic data, show that this approach can produce more reliable results than a standard novelty detection scheme. The classification algorithm is then applied to the problem of identifying outliers in the SIC2004 data set, in order to detect the radioactive release simulated in the 'oker' data set. We propose this method as a reliable means of novelty detection in the emergency situation which can also be used to identify outliers prior to the application of a more general automatic mapping algorithm. © Springer-Verlag 2007.

Efficient training of RBF networks for classification.

Radial Basis Function networks with linear outputs are often used in regression problems because they can be substantially faster to train than Multi-layer Perceptrons. For classification problems, the use of linear outputs is less appropriate as the outputs are not guaranteed to represent probabilities. We show how RBFs with logistic and softmax outputs can be trained efficiently using the Fisher scoring algorithm. This approach can be used with any model which consists of a generalised linear output function applied to a model which is linear in its parameters. We compare this approach with standard non-linear optimisation algorithms on a number of datasets.

Gaussian processes for classification: mean field algorithms:mean-field algorithms

We derive a mean field algorithm for binary classification with Gaussian processes which is based on the TAP approach originally proposed in Statistical Physics of disordered systems. The theory also yields an approximate leave-one-out estimator for the generalization error which is computed with no extra computational cost. We show that from the TAP approach, it is possible to derive both a simpler 'naive' mean field theory and support vector machines (SVM) as limiting cases. For both mean field algorithms and support vectors machines, simulation results for three small benchmark data sets are presented. They show 1. that one may get state of the art performance by using the leave-one-out estimator for model selection and 2. the built-in leave-one-out estimators are extremely precise when compared to the exact leave-one-out estimate. The latter result is a taken as a strong support for the internal consistency of the mean field approach.

The use of context in the classification of urban aerial imagery

Urban regions present some of the most challenging areas for the remote sensing community. Many different types of land cover have similar spectral responses, making them difficult to distinguish from one another. Traditional per-pixel classification techniques suffer particularly badly because they only use these spectral properties to determine a class, and no other properties of the image, such as context. This project presents the results of the classification of a deeply urban area of Dudley, West Midlands, using 4 methods: Supervised Maximum Likelihood, SMAP, ECHO and Unsupervised Maximum Likelihood. An accuracy assessment method is then developed to allow a fair representation of each procedure and a direct comparison between them. Subsequently, a classification procedure is developed that makes use of the context in the image, though a per-polygon classification. The imagery is broken up into a series of polygons extracted from the Marr-Hildreth zero-crossing edge detector. These polygons are then refined using a region-growing algorithm, and then classified according to the mean class of the fine polygons. The imagery produced by this technique is shown to be of better quality and of a higher accuracy than that of other conventional methods. Further refinements are suggested and examined to improve the aesthetic appearance of the imagery. Finally a comparison with the results produced from a previous study of the James Bridge catchment, in Darleston, West Midlands, is made, showing that the Polygon classified ATM imagery performs significantly better than the Maximum Likelihood classified videography used in the initial study, despite the presence of geometric correction errors.

Classification and contextual enhancement of remotely sensed data

The aims of the project were twofold: 1) To investigate classification procedures for remotely sensed digital data, in order to develop modifications to existing algorithms and propose novel classification procedures; and 2) To investigate and develop algorithms for contextual enhancement of classified imagery in order to increase classification accuracy. The following classifiers were examined: box, decision tree, minimum distance, maximum likelihood. In addition to these the following algorithms were developed during the course of the research: deviant distance, look up table and an automated decision tree classifier using expert systems technology. Clustering techniques for unsupervised classification were also investigated. Contextual enhancements investigated were: mode filters, small area replacement and Wharton's CONAN algorithm. Additionally methods for noise and edge based declassification and contextual reclassification, non-probabilitic relaxation and relaxation based on Markov chain theory were developed. The advantages of per-field classifiers and Geographical Information Systems were investigated. The conclusions presented suggest suitable combinations of classifier and contextual enhancement, given user accuracy requirements and time constraints. These were then tested for validity using a different data set. A brief examination of the utility of the recommended contextual algorithms for reducing the effects of data noise was also carried out.

A smart sensing platform for the classification of ambulatory patterns

This paper describes an innovative sensing approach allowing capture, discrimination, and classification of transients automatically in gait. A walking platform is described, which offers an alternative design to that of standard force plates with advantages that include mechanical simplicity and less restriction on dimensions. The scope of the work is to investigate as an experiment the sensitivity of the distributive tactile sensing method with the potential to address flexibility on gait assessment, including patient targeting and the extension to a variety of ambulatory applications. Using infrared sensors to measure plate deflection, gait patterns are compared with stored templates using a pattern recognition algorithm. This information is input into a neural network to classify normal and affected walking events, with a classification accuracy of just under 90 per cent achieved. The system developed has potential applications in gait analysis and rehabilitation, whereby it can be used as a tool for early diagnosis of walking disorders or to determine changes between pre- and post-operative gait.

Protein-protein interactions classification from text via local learning with class priors

Text classification is essential for narrowing down the number of documents relevant to a particular topic for further pursual, especially when searching through large biomedical databases. Protein-protein interactions are an example of such a topic with databases being devoted specifically to them. This paper proposed a semi-supervised learning algorithm via local learning with class priors (LL-CP) for biomedical text classification where unlabeled data points are classified in a vector space based on their proximity to labeled nodes. The algorithm has been evaluated on a corpus of biomedical documents to identify abstracts containing information about protein-protein interactions with promising results. Experimental results show that LL-CP outperforms the traditional semisupervised learning algorithms such as SVMand it also performs better than local learning without incorporating class priors.

On the hierarchical classification of G protein-coupled receptors

MOTIVATION: G protein-coupled receptors (GPCRs) play an important role in many physiological systems by transducing an extracellular signal into an intracellular response. Over 50% of all marketed drugs are targeted towards a GPCR. There is considerable interest in developing an algorithm that could effectively predict the function of a GPCR from its primary sequence. Such an algorithm is useful not only in identifying novel GPCR sequences but in characterizing the interrelationships between known GPCRs. RESULTS: An alignment-free approach to GPCR classification has been developed using techniques drawn from data mining and proteochemometrics. A dataset of over 8000 sequences was constructed to train the algorithm. This represents one of the largest GPCR datasets currently available. A predictive algorithm was developed based upon the simplest reasonable numerical representation of the protein's physicochemical properties. A selective top-down approach was developed, which used a hierarchical classifier to assign sequences to subdivisions within the GPCR hierarchy. The predictive performance of the algorithm was assessed against several standard data mining classifiers and further validated against Support Vector Machine-based GPCR prediction servers. The selective top-down approach achieves significantly higher accuracy than standard data mining methods in almost all cases.

The design and validation of an optical coherence tomography-based classification system for focal vitreomacular traction

PurposeTo develop and validate a classification system for focal vitreomacular traction (VMT) with and without macular hole based on spectral domain optical coherence tomography (SD-OCT), intended to aid in decision-making and prognostication.MethodsA panel of retinal specialists convened to develop this system. A literature review followed by discussion on a wide range of cases formed the basis for the proposed classification. Key features on OCT were identified and analysed for their utility in clinical practice. A final classification was devised based on two sequential, independent validation exercises to improve interobserver variability.ResultsThis classification tool pertains to idiopathic focal VMT assessed by a horizontal line scan using SD-OCT. The system uses width (W), interface features (I), foveal shape (S), retinal pigment epithelial changes (P), elevation of vitreous attachment (E), and inner and outer retinal changes (R) to give the acronym WISPERR. Each category is scored hierarchically. Results from the second independent validation exercise indicated a high level of agreement between graders: intraclass correlation ranged from 0.84 to 0.99 for continuous variables and Fleiss' kappa values ranged from 0.76 to 0.95 for categorical variables.ConclusionsWe present an OCT-based classification system for focal VMT that allows anatomical detail to be scrutinised and scored qualitatively and quantitatively using a simple, pragmatic algorithm, which may be of value in clinical practice as well as in future research studies.