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.

Integrating OpenMI and Uncertweb:managing uncertainty in OpenMI models

OpenMI is a widely used standard allowing exchange of data between integrated models, which has mostly been applied to dynamic, deterministic models. Within the FP7 UncertWeb project we are developing mechanisms and tools to support the management of uncertainty in environmental models. In this paper we explore the integration of the UncertWeb framework with OpenMI, to assess the issues that arise when propagating uncertainty in OpenMI model compositions, and the degree of integration possible with UncertWeb tools. In particular we develop an uncertainty-enabled model for a simple Lotka-Volterra system with an interface conforming to the OpenMI standard, exploring uncertainty in the initial predator and prey levels, and the parameters of the model equations. We use the Elicitator tool developed within UncertWeb to identify the initial condition uncertainties, and show how these can be integrated, using UncertML, with simple Monte Carlo propagation mechanisms. The mediators we develop for OpenMI models are generic and produce standard Web services that expose the OpenMI models to a Web based framework. We discuss what further work is needed to allow a more complete system to be developed and show how this might be used practically.

Models@run.time:foundations, applications, and roadmaps

Traditionally, research on model-driven engineering (MDE) has mainly focused on the use of models at the design, implementation, and verification stages of development. This work has produced relatively mature techniques and tools that are currently being used in industry and academia. However, software models also have the potential to be used at runtime, to monitor and verify particular aspects of runtime behavior, and to implement self-* capabilities (e.g., adaptation technologies used in self-healing, self-managing, self-optimizing systems). A key benefit of using models at runtime is that they can provide a richer semantic base for runtime decision-making related to runtime system concerns associated with autonomic and adaptive systems. This book is one of the outcomes of the Dagstuhl Seminar 11481 on models@run.time held in November/December 2011, discussing foundations, techniques, mechanisms, state of the art, research challenges, and applications for the use of runtime models. The book comprises four research roadmaps, written by the original participants of the Dagstuhl Seminar over the course of two years following the seminar, and seven research papers from experts in the area. The roadmap papers provide insights to key features of the use of runtime models and identify the following research challenges: the need for a reference architecture, uncertainty tackled by runtime models, mechanisms for leveraging runtime models for self-adaptive software, and the use of models at runtime to address assurance for self-adaptive systems.

Summary of the 9th Workshop on Models@run.time

The Models@run.time workshop (MRT) series offers a discussion forum for the rising need to leverage modeling techniques at runtime for the software of the future. MRT has become a mature research topic, which is, e.g., reflected in separate sessions at conferences covering MRT approaches only. The target venues of the workshops audience changed from workshops to conferences. Hence, new topics in the area of MRT need to be identified, which are not yet mature enough for conferences. In consequence, the main goal of this edition was to reflect on the past decade of the workshop's history and to identify new future directions for the workshop.

Comparison of software developed for FHR extraction from PCG signals

A valuable alternative to US cardiotocography, for fetal surveillance, can be offered by phonocardiography, a passive and low cost acoustic recording of fetal heart sounds. A crucial point is the exact recognizing of the fetal heart sounds, associated to each fetal heart beat, and then the estimation of FHR signal. In this work, software for FHR assessment from phonocardiographic signals was developed. To check the reliability of the software, obtained results were compared with those of simultaneously recorded cardiotocographic signals. Results seemed to be satisfying, as provided FHR series were almost all confined within FHR-CTG +/- 3 bpm, where FHR-CTG were FHR series provided by commercial US cardiotocographic devices, currently employed in clinical routine.

Reliability of retinal vessel calibre measurements using a retinal oximeter

Background: Summarised retinal vessel diameters are linked to systemic vascular pathology. Monochromatic images provide best contrast to measure vessel calibres. However, when obtaining images with a dual wavelength oximeter the red-free image can be extracted as the green channel information only which in turn will reduce the number of photographs taken at a given time. This will reduce patient exposure to the camera flash and could provide sufficient quality images to reliably measure vessel calibres. Methods: We obtained retinal images of one eye of 45 healthy participants. Central retinal arteriolar and central retinal venular equivalents (CRAE and CRVE, respectively) were measured using semi-automated software from two monochromatic images: one taken with a red-free filter and one extracted from the green channel of a dual wavelength oximetry image. Results: Participants were aged between 21 and 62 years, all were normotensive (SBP: 115 (12) mmHg; DBP: 72 (10) mmHg) and had normal intra-ocular pressures (12 (3) mmHg). Bland-Altman analysis revealed good agreement of CRAE and CRVE as obtained from both images (mean bias CRAE = 0.88; CRVE = 2.82). Conclusions: Summarised retinal vessel calibre measurements obtained from oximetry images are in good agreement to those obtained using red-free photographs.

Introduction to performance improvement management software (PIM-DEA)

This chapter provides information on the use of Performance Improvement Management Software (PIMDEA). This advanced DEA software enables users to make the best possible analysis of the data, using the latest theoretical developments in Data Envelopment Analysis (DEA). PIM-DEA software gives full capacity to assess efficiency and productivity, set targets, identify benchmarks, and much more, allowing users to truly manage the performance of organizational units. PIM-DEA is easy to use and powerful, and it has an extensive range of the most up-to-date DEA models and which can handle large sets of data.

Implementing an agent-based model with a spatial visual display in discrete-event simulation software

There has been an increasing interest in the use of agent-based simulation and some discussion of the relative merits of this approach as compared to discrete-event simulation. There are differing views on whether an agent-based simulation offers capabilities that discrete-event cannot provide or whether all agent-based applications can at least in theory be undertaken using a discrete-event approach. This paper presents a simple agent-based NetLogo model and corresponding discrete-event versions implemented in the widely used ARENA software. The two versions of the discrete-event model presented use a traditional process flow approach normally adopted in discrete-event simulation software and also an agent-based approach to the model build. In addition a real-time spatial visual display facility is provided using a spreadsheet platform controlled by VBA code embedded within the ARENA model. Initial findings from this investigation are that discrete-event simulation can indeed be used to implement agent-based models and with suitable integration elements such as VBA provide the spatial displays associated with agent-based software.

Preface to Models@run.time 2016

The complexity of adapting software during runtime has spawned interest in how models can be used to validate, monitor and adapt runtime behaviour. The use of models during runtime extends the use of modeling techniques beyond the design and implementation phases. The goal of this workshop is to look at issues related to developing appropriate modeldriven approaches to managing and monitoring the execution of systems and, also, to allow the system to reason about itself. We aim to continue the discussion of research ideas and proposals from researchers who work in relevant areas such as MDE, software architectures, reflection, and autonomic and self-adaptive systems, and provide a 'state-of-the-art' research assessment expressed in terms of challenges and achievements.