Present perspectives on the automated classification of the G-protein coupled receptors (GPCRs) at the protein sequence level.

The G-protein coupled receptors--or GPCRs--comprise simultaneously one of the largest and one of the most multi-functional protein families known to modern-day molecular bioscience. From a drug discovery and pharmaceutical industry perspective, the GPCRs constitute one of the most commercially and economically important groups of proteins known. The GPCRs undertake numerous vital metabolic functions and interact with a hugely diverse range of small and large ligands. Many different methodologies have been developed to efficiently and accurately classify the GPCRs. These range from motif-based techniques to machine learning as well as a variety of alignment-free techniques based on the physiochemical properties of sequences. We review here the available methodologies for the classification of GPCRs. Part of this work focuses on how we have tried to build the intrinsically hierarchical nature of sequence relations, implicit within the family, into an adaptive approach to classification. Importantly, we also allude to some of the key innate problems in developing an effective approach to classifying the GPCRs: the lack of sequence similarity between the six classes that comprise the GPCR family and the low sequence similarity to other family members evinced by many newly revealed members of the family.

GPCRTree: online hierarchical classification of GPCR function.

BACKGROUND: G protein-coupled receptors (GPCRs) play important physiological roles transducing extracellular signals into intracellular responses. Approximately 50% of all marketed drugs target a GPCR. There remains considerable interest in effectively predicting the function of a GPCR from its primary sequence. FINDINGS: Using techniques drawn from data mining and proteochemometrics, an alignment-free approach to GPCR classification has been devised. It uses a simple representation of a protein's physical properties. GPCRTree, a publicly-available internet server, implements an algorithm that classifies GPCRs at the class, sub-family and sub-subfamily level. CONCLUSION: A selective top-down classifier was developed which assigns sequences within a GPCR hierarchy. Compared to other publicly available GPCR prediction servers, GPCRTree is considerably more accurate at every level of classification. The server has been available online since March 2008 at URL: http://igrid-ext.cryst.bbk.ac.uk/gpcrtree/.

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.

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.

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.

Highly scalable video compression with scalable motion coding.

A scalable video coder cannot be equally efficient over a wide range of bit rates unless both the video data and the motion information are scalable. We propose a wavelet-based, highly scalable video compression scheme with rate-scalable motion coding. The proposed method involves the construction of quality layers for the coded sample data and a separate set of quality layers for the coded motion parameters. When the motion layers are truncated, the decoder receives a quantized version of the motion parameters used to code the sample data. The effect of motion parameter quantization on the reconstructed video distortion is described by a linear model. The optimal tradeoff between the motion and subband bit rates is determined after compression. We propose two methods to determine the optimal tradeoff, one of which explicitly utilizes the linear model. This method performs comparably to a brute force search method, reinforcing the validity of the linear model itself. Experimental results indicate that the cost of scalability is small. In addition, considerable performance improvements are observed at low bit rates, relative to lossless coding of the motion information.

Lifting-based invertible motion adaptive transform (LIMAT) framework for highly scalable video compression.

We propose a new framework for highly scalable video compression, using a lifting-based invertible motion adaptive transform (LIMAT). We use motion-compensated lifting steps to implement the temporal wavelet transform, which preserves invertibility, regardless of the motion model. By contrast, the invertibility requirement has restricted previous approaches to either block-based or global motion compensation. We show that the proposed framework effectively applies the temporal wavelet transform along a set of motion trajectories. An implementation demonstrates high coding gain from a finely embedded, scalable compressed bit-stream. Results also demonstrate the effectiveness of temporal wavelet kernels other than the simple Haar, and the benefits of complex motion modeling, using a deformable triangular mesh. These advances are either incompatible or difficult to achieve with previously proposed strategies for scalable video compression. Video sequences reconstructed at reduced frame-rates, from subsets of the compressed bit-stream, demonstrate the visually pleasing properties expected from low-pass filtering along the motion trajectories. The paper also describes a compact representation for the motion parameters, having motion overhead comparable to that of motion-compensated predictive coders. Our experimental results compare favorably to others reported in the literature, however, our principal objective is to motivate a new framework for highly scalable video compression.