Prediction of protein-protein interactions using one-class classification methods and integrating diverse data

This research addresses the problem of prediction of protein-protein interactions (PPI) when integrating diverse kinds of biological information. This task has been commonly viewed as a binary classification problem (whether any two proteins do or do not interact) and several different machine learning techniques have been employed to solve this task. However the nature of the data creates two major problems which can affect results. These are firstly imbalanced class problems due to the number of positive examples (pairs of proteins which really interact) being much smaller than the number of negative ones. Secondly the selection of negative examples can be based on some unreliable assumptions which could introduce some bias in the classification results. Here we propose the use of one-class classification (OCC) methods to deal with the task of prediction of PPI. OCC methods utilise examples of just one class to generate a predictive model which consequently is independent of the kind of negative examples selected; additionally these approaches are known to cope with imbalanced class problems. We have designed and carried out a performance evaluation study of several OCC methods for this task, and have found that the Parzen density estimation approach outperforms the rest. We also undertook a comparative performance evaluation between the Parzen OCC method and several conventional learning techniques, considering different scenarios, for example varying the number of negative examples used for training purposes. We found that the Parzen OCC method in general performs competitively with traditional approaches and in many situations outperforms them. Finally we evaluated the ability of the Parzen OCC approach to predict new potential PPI targets, and validated these results by searching for biological evidence in the literature

Transforming specifications of observable behaviour into programs

A methodology for deriving programs from specifications of observable behaviour is described. The class of processes to which this methodology is applicable includes those whose state changes are fully definable by labelled transition systems, for example communicating processes without internal state changes. A logic program representation of such labelled transition systems is proposed, interpreters based on path searching techniques are defined, and the use of partial evaluation techniques to derive the executable programs is described

Domain discovery method for topological profile searches in protein structures

We describe a method for automated domain discovery for topological profile searches in protein structures. The method is used in a system TOPStructure for fast prediction of CATH classification for protein structures (given as PDB files). It is important for profile searches in multi-domain proteins, for which the profile method by itself tends to perform poorly. We also present an O(C(n)k +nk2) time algorithm for this problem, compared to the O(C(n)k +(nk)2) time used by a trivial algorithm (where n is the length of the structure, k is the number of profiles and C(n) is the time needed to check for a presence of a given motif in a structure of length n). This method has been developed and is currently used for TOPS representations of protein structures and prediction of CATH classification, but may be applied to other graph-based representations of protein or RNA structures and/or other prediction problems. A protein structure prediction system incorporating the domain discovery method is available at http://bioinf.mii.lu.lv/tops/

A computer system to perform structure comparison using TOPS representations of protein structure

We describe the design and implementation of a fast topology–based method for protein structure comparison. The approach uses the TOPS topological representation of protein structure, aligning two structures using a common discovered pattern and generating measure of distance derived from an insert score. Heavy use is made of a constraint-based pattern matching algorithm for TOPS diagrams that we have designed and described elsewhere Gilbert et al. (1999). The comparison system is maintained at the European Bioinformatics Institute and is available over the Web via the at tops.ebi.ac.uk/tops. Users submit a structure description in Protein Data Bank (PDB) format and can compare it with structures in the entire PDB or a representative subset of protein domains, receiving the results by email

Field Driven Thermostated System : A Non-Linear Multi-Baker Map

In this paper, we discuss a simple model for a field driven, thermostated random walk that is constructed by a suitable generalization of a multi-baker map. The map is a usual multi-baker, but perturbed by a thermostated external field that has many of the properties of the fields used in systems with Gaussian thermostats. For small values of the driving field, the map is hyperbolic and has a unique SRB measure that we solve analytically to first order in the field parameter. We then compute the positive and negative Lyapunov exponents to second order and discuss their relation to the transport properties. For higher values of the parameter, this system becomes non-hyperbolic and posseses an attractive fixed point.Comment: 6 pages + 5 figures, to appear in Phys. Rev.

Reduction of alternator apparent-power requirements and harmonic distortion caused by phase-controlled parasitic loads

Reduction of alternator apparent power requirements and harmonic distortion caused by phase-controlled parasitic load

The new scramble for Africa: towards a human-rights based approach to large-scale land acquisitions in the Southern African Development Community (SADC) sub-region

The chapter examines the implications of a contemporary ‘land grab’ in the SADC region, or the growing acquisition of lands by foreign investors at the behest of Asian or Middle Eastern states, to produce crops for their own consumption and security in the wake of the global food crisis. The analysis provides a rights-based approach to large-scale land acquisition, particularly looking at the right to food and land rights for the local communities, including an exploration of the meaning and reach of customary land rights. It also examines the right to development, which is used as a justification for leasing lands, and highlights that this right concurrently confers obligations on SADC states to protect the rights of peoples to control decisions which affect their economic and social development. Overall the aim is to signal the alarming move towards large-scale land acquisitions in the SADC region, and the potential for human rights to provide a regulatory framework. It is suggested that the issue could galvanise the international movement towards non-state actor accountability, which has been evolving for several decades

Lipid Coated Gold Nanoparticle Cores: Synthesis and Characterization

Including environmental, industrial, and biomedical sciences, applications of gold nanoparticles are on the forefront of research in many areas. By altering the surface treatment of spherical gold nanoparticle cores, particularly those smaller than 100 nm (nanometers), one can influence their potential use in a number of ways. Lipid coated nanoparticles with specifically selected surface ligands can be used for multiple biomedical functions, including medical imaging, for use as colorimetric and plasmonic sensors within the body, and as cell or organelle specific targets for therapeutic drug delivery or cancer treatment. Here, spherical gold nanoparticles ranging in size from 8-40 nm (avg. diameter 23-48 nm) have been synthesized and coated with poly(allylamine hydrochloride) (PAH) and a mixed lipid solution of 1:1 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS) and lysophosphatidylcholine (LPC), two of the four major types of lipids found in the human body. Characterization was performed using a NanoSight LM10HS particle sizer, and shows a gradual increase in size after each step in the coating process for nanoparticle cores ranging in size from 16-27 nm. The thickness of these purified and lipid coated nanoparticles was consistently 2-3 times that of the PAH coated sample it was layered onto, suggesting a successful, multi-layered coat that ranges in size based on the PAH coated core size. UV-Vis spectroscopy shows a slight red shift, indicating an increase in size and change in refractive index, which supports the presence of lipid coating on the PAH coated gold nanoparticle cores