Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity:in silico bioinformatic step-by-step guide using quantitative structure-activity relationships

Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method is available commercially in the SYBYL molecular modeling software package. The resulting models, which can be used for accurate T-cell epitope prediction, will be made are freely available online at the URL http://www.jenner.ac.uk/MHCPred.

A comparison of denoising methods for X-ray fluoroscopic images

Fluoroscopic images exhibit severe signal-dependent quantum noise, due to the reduced X-ray dose involved in image formation, that is generally modelled as Poisson-distributed. However, image gray-level transformations, commonly applied by fluoroscopic device to enhance contrast, modify the noise statistics and the relationship between image noise variance and expected pixel intensity. Image denoising is essential to improve quality of fluoroscopic images and their clinical information content. Simple average filters are commonly employed in real-time processing, but they tend to blur edges and details. An extensive comparison of advanced denoising algorithms specifically designed for both signal-dependent noise (AAS, BM3Dc, HHM, TLS) and independent additive noise (AV, BM3D, K-SVD) was presented. Simulated test images degraded by various levels of Poisson quantum noise and real clinical fluoroscopic images were considered. Typical gray-level transformations (e.g. white compression) were also applied in order to evaluate their effect on the denoising algorithms. Performances of the algorithms were evaluated in terms of peak-signal-to-noise ratio (PSNR), signal-to-noise ratio (SNR), mean square error (MSE), structural similarity index (SSIM) and computational time. On average, the filters designed for signal-dependent noise provided better image restorations than those assuming additive white Gaussian noise (AWGN). Collaborative denoising strategy was found to be the most effective in denoising of both simulated and real data, also in the presence of image gray-level transformations. White compression, by inherently reducing the greater noise variance of brighter pixels, appeared to support denoising algorithms in performing more effectively. © 2012 Elsevier Ltd. All rights reserved.

From marine ecology to crime analysis: improving the detection of serial sexual offences using a taxonomic similarity measure

Jaccard has been the choice similarity metric in ecology and forensic psychology for comparison of sites or offences, by species or behaviour. This paper applies a more powerful hierarchical measure - taxonomic similarity (s), recently developed in marine ecology - to the task of behaviourally linking serial crime. Forensic case linkage attempts to identify behaviourally similar offences committed by the same unknown perpetrator (called linked offences). s considers progressively higher-level taxa, such that two sites show some similarity even without shared species. We apply this index by analysing 55 specific offence behaviours classified hierarchically. The behaviours are taken from 16 sexual offences by seven juveniles where each offender committed two or more offences. We demonstrate that both Jaccard and s show linked offences to be significantly more similar than unlinked offences. With up to 20% of the specific behaviours removed in simulations, s is equally or more effective at distinguishing linked offences than where Jaccard uses a full data set. Moreover, s retains significant difference between linked and unlinked pairs, with up to 50% of the specific behaviours removed. As police decision-making often depends upon incomplete data, s has clear advantages and its application may extend to other crime types. Copyright © 2007 John Wiley & Sons, Ltd.

Regrouping metric-space search index for search engine size adaptation

This work contributes to the development of search engines that self-adapt their size in response to fluctuations in workload. Deploying a search engine in an Infrastructure as a Service (IaaS) cloud facilitates allocating or deallocating computational resources to or from the engine. In this paper, we focus on the problem of regrouping the metric-space search index when the number of virtual machines used to run the search engine is modified to reflect changes in workload. We propose an algorithm for incrementally adjusting the index to fit the varying number of virtual machines. We tested its performance using a custom-build prototype search engine deployed in the Amazon EC2 cloud, while calibrating the results to compensate for the performance fluctuations of the platform. Our experiments show that, when compared with computing the index from scratch, the incremental algorithm speeds up the index computation 2–10 times while maintaining a similar search performance.