VaxiJen:a server for prediction of protective antigens, tumour antigens and subunit vaccines

Background - Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. Despite the obvious advantages of this approach – such as speed and cost efficiency – its success remains dependent on the accuracy of antigen prediction. Most approaches use sequence alignment to identify antigens. This is problematic for several reasons. Some proteins lack obvious sequence similarity, although they may share similar structures and biological properties. The antigenicity of a sequence may be encoded in a subtle and recondite manner not amendable to direct identification by sequence alignment. The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC) transformation of protein sequences into uniform vectors of principal amino acid properties. Results - Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The derived models were tested by internal leave-one-out cross-validation and external validation using test sets. An additional five training sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The models performed well in both validations showing prediction accuracy of 70% to 89%. The models were implemented in a server, which we call VaxiJen. Conclusion - VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. The server can be used on its own or in combination with alignment-based prediction methods.

LIPPRED:a web server for accurate prediction of lipoprotein signal sequences and cleavage sites

Bacterial lipoproteins have many important functions and represent a class of possible vaccine candidates. The prediction of lipoproteins from sequence is thus an important task for computational vaccinology. Naïve-Bayesian networks were trained to identify SpaseII cleavage sites and their preceding signal sequences using a set of 199 distinct lipoprotein sequences. A comprehensive range of sequence models was used to identify the best model for lipoprotein signal sequences. The best performing sequence model was found to be 10-residues in length, including the conserved cysteine lipid attachment site and the nine residues prior to it. The sensitivity of prediction for LipPred was 0.979, while the specificity was 0.742. Here, we describe LipPred, a web server for lipoprotein prediction; available at the URL: http://www.jenner.ac.uk/LipPred/. LipPred is the most accurate method available for the detection of SpaseIIcleaved lipoprotein signal sequences and the prediction of their cleavage sites.

BPROMPT:a consensus server for membrane protein prediction

Protein structure prediction is a cornerstone of bioinformatics research. Membrane proteins require their own prediction methods due to their intrinsically different composition. A variety of tools exist for topology prediction of membrane proteins, many of them available on the Internet. The server described in this paper, BPROMPT (Bayesian PRediction Of Membrane Protein Topology), uses a Bayesian Belief Network to combine the results of other prediction methods, providing a more accurate consensus prediction. Topology predictions with accuracies of 70% for prokaryotes and 53% for eukaryotes were achieved. BPROMPT can be accessed at http://www.jenner.ac.uk/BPROMPT.

EpiJen:a server for multistep T cell epitope prediction

Background - The main processing pathway for MHC class I ligands involves degradation of proteins by the proteasome, followed by transport of products by the transporter associated with antigen processing (TAP) to the endoplasmic reticulum (ER), where peptides are bound by MHC class I molecules, and then presented on the cell surface by MHCs. The whole process is modeled here using an integrated approach, which we call EpiJen. EpiJen is based on quantitative matrices, derived by the additive method, and applied successively to select epitopes. EpiJen is available free online. Results - To identify epitopes, a source protein is passed through four steps: proteasome cleavage, TAP transport, MHC binding and epitope selection. At each stage, different proportions of non-epitopes are eliminated. The final set of peptides represents no more than 5% of the whole protein sequence and will contain 85% of the true epitopes, as indicated by external validation. Compared to other integrated methods (NetCTL, WAPP and SMM), EpiJen performs best, predicting 61 of the 99 HIV epitopes used in this study. Conclusion - EpiJen is a reliable multi-step algorithm for T cell epitope prediction, which belongs to the next generation of in silico T cell epitope identification methods. These methods aim to reduce subsequent experimental work by improving the success rate of epitope prediction.

MHCPred : a server for quantitative prediction of peptide-MHC binding

Accurate T-cell epitope prediction is a principal objective of computational vaccinology. As a service to the immunology and vaccinology communities at large, we have implemented, as a server on the World Wide Web, a partial least squares-base multivariate statistical approach to the quantitative prediction of peptide binding to major histocom-patibility complexes (MHC), the key checkpoint on the antigen presentation pathway within adaptive,cellular immunity. MHCPred implements robust statistical models for both Class I alleles (HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203,HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3301, HLA-A*6801, HLA-A*6802 and HLA-B*3501) and Class II alleles (HLA-DRB*0401, HLA-DRB*0401and HLA-DRB* 0701).

How to Use a Desktop Version of a DBMS for Client-Server Applications

DBMS (Data base management systems) still have a very high price for small and middle enterprises in Bulgaria. Desktop versions are free but they cannot function in multi-user environment. We will try to make an application server which will make a Desktop version of a DBMS open to many users. Thus, this approach will be appropriate for client-server applications. The author of the article gives a concise observation of the problem and a possible way of solution.

Algorithmic Background of the Host Recommendation in the Adaptive Distributed Multimedia Server

Partial support of the Hungarian State Eötvös Scholarship, the Hungarian National Science Fund (Grant No. OTKA 42559 and 42706) and the Mobile Innovation Center, Hungary is gratefully acknowledged.

AllerTOP v.2 - a server for in silico prediction of allergens

Allergy is an overreaction by the immune system to a previously encountered, ordinarily harmless substance - typically proteins - resulting in skin rash, swelling of mucous membranes, sneezing or wheezing, or other abnormal conditions. The use of modified proteins is increasingly widespread: their presence in food, commercial products, such as washing powder, and medical therapeutics and diagnostics, makes predicting and identifying potential allergens a crucial societal issue. The prediction of allergens has been explored widely using bioinformatics, with many tools being developed in the last decade; many of these are freely available online. Here, we report a set of novel models for allergen prediction utilizing amino acid E-descriptors, auto- and cross-covariance transformation, and several machine learning methods for classification, including logistic regression (LR), decision tree (DT), naïve Bayes (NB), random forest (RF), multilayer perceptron (MLP) and k nearest neighbours (kNN). The best performing method was kNN with 85.3% accuracy at 5-fold cross-validation. The resulting model has been implemented in a revised version of the AllerTOP server (http://www.ddg-pharmfac.net/AllerTOP). © Springer-Verlag 2014.

Single-Server Queueing System with Markov-Modulated Arrivals and Service Times

Key words: Markov-modulated queues, waiting time, heavy traffic.

AllerTOP - a server for in silico prediction of allergens

Background: Allergy is a form of hypersensitivity to normally innocuous substances, such as dust, pollen, foods or drugs. Allergens are small antigens that commonly provoke an IgE antibody response. There are two types of bioinformatics-based allergen prediction. The first approach follows FAO/WHO Codex alimentarius guidelines and searches for sequence similarity. The second approach is based on identifying conserved allergenicity-related linear motifs. Both approaches assume that allergenicity is a linearly coded property. In the present study, we applied ACC pre-processing to sets of known allergens, developing alignment-independent models for allergen recognition based on the main chemical properties of amino acid sequences.Results: A set of 684 food, 1,156 inhalant and 555 toxin allergens was collected from several databases. A set of non-allergens from the same species were selected to mirror the allergen set. The amino acids in the protein sequences were described by three z-descriptors (z1, z2 and z3) and by auto- and cross-covariance (ACC) transformation were converted into uniform vectors. Each protein was presented as a vector of 45 variables. Five machine learning methods for classification were applied in the study to derive models for allergen prediction. The methods were: discriminant analysis by partial least squares (DA-PLS), logistic regression (LR), decision tree (DT), naïve Bayes (NB) and k nearest neighbours (kNN). The best performing model was derived by kNN at k = 3. It was optimized, cross-validated and implemented in a server named AllerTOP, freely accessible at http://www.pharmfac.net/allertop. AllerTOP also predicts the most probable route of exposure. In comparison to other servers for allergen prediction, AllerTOP outperforms them with 94% sensitivity.Conclusions: AllerTOP is the first alignment-free server for in silico prediction of allergens based on the main physicochemical properties of proteins. Significantly, as well allergenicity AllerTOP is able to predict the route of allergen exposure: food, inhalant or toxin. © 2013 Dimitrov et al.; licensee BioMed Central Ltd.

Manager's Perceptions of Alcohol Server Staffing and Training Methods

Over-consumption of alcoholic beverages is a concern of managers of hotels and motels with a club/lounge, restaurant, and tavern. The authors surveyed members of two industry associations in Oklahoma to ascertain alcohol server training methods and managers' perception of the value of such programs.

Returning to Server-Centric Hospitality System Applications

Application service provider models represent an alternative to in-house information systems and are gaining favor within the hospitality industry: The models, which place technical system components at a remote site, are described as server-centric. ASPs allow hospitality management to share investment dollars, system costs, and technical staff expenditure with an ASP operator, thereby concentrating on providing enhanced guest services. Although considered a viable alternative to in-house processing, not everyone agrees this is a favorable trend.

Alcohol Server Liability Law Suits Result From Dram Shop Statutes

The country is experiencing a trend of alcohol server liability law suits resulting from dram shop statutes and common law liability, relatively recent developments in the field of tort law. The author, an expert on liquor liability law, explores the meaning of this trend for the hospitality industry.

Algorithms for efficient transaction management and consistent queries in client -server semantic object-oriented parallel databases

Large read-only or read-write transactions with a large read set and a small write set constitute an important class of transactions used in such applications as data mining, data warehousing, statistical applications, and report generators. Such transactions are best supported with optimistic concurrency, because locking of large amounts of data for extended periods of time is not an acceptable solution. The abort rate in regular optimistic concurrency algorithms increases exponentially with the size of the transaction. The algorithm proposed in this dissertation solves this problem by using a new transaction scheduling technique that allows a large transaction to commit safely with significantly greater probability that can exceed several orders of magnitude versus regular optimistic concurrency algorithms. A performance simulation study and a formal proof of serializability and external consistency of the proposed algorithm are also presented.^ This dissertation also proposes a new query optimization technique (lazy queries). Lazy Queries is an adaptive query execution scheme which optimizes itself as the query runs. Lazy queries can be used to find an intersection of sub-queries in a very efficient way, which does not require full execution of large sub-queries nor does it require any statistical knowledge about the data.^ An efficient optimistic concurrency control algorithm used in a massively parallel B-tree with variable-length keys is introduced. B-trees with variable-length keys can be effectively used in a variety of database types. In particular, we show how such a B-tree was used in our implementation of a semantic object-oriented DBMS. The concurrency control algorithm uses semantically safe optimistic virtual "locks" that achieve very fine granularity in conflict detection. This algorithm ensures serializability and external consistency by using logical clocks and backward validation of transactional queries. A formal proof of correctness of the proposed algorithm is also presented. ^

Development of a new client -server architecture for context aware mobile computing

This dissertation studies the context-aware application with its proposed algorithms at client side. The required context-aware infrastructure is discussed in depth to illustrate that such an infrastructure collects the mobile user’s context information, registers service providers, derives mobile user’s current context, distributes user context among context-aware applications, and provides tailored services. The approach proposed tries to strike a balance between the context server and mobile devices. The context acquisition is centralized at the server to ensure the reusability of context information among mobile devices, while context reasoning remains at the application level. Hence, a centralized context acquisition and distributed context reasoning are viewed as a better solution overall. The context-aware search application is designed and implemented at the server side. A new algorithm is proposed to take into consideration the user context profiles. By promoting feedback on the dynamics of the system, any prior user selection is now saved for further analysis such that it may contribute to help the results of a subsequent search. On the basis of these developments at the server side, various solutions are consequently provided at the client side. A proxy software-based component is set up for the purpose of data collection. This research endorses the belief that the proxy at the client side should contain the context reasoning component. Implementation of such a component provides credence to this belief in that the context applications are able to derive the user context profiles. Furthermore, a context cache scheme is implemented to manage the cache on the client device in order to minimize processing requirements and other resources (bandwidth, CPU cycle, power). Java and MySQL platforms are used to implement the proposed architecture and to test scenarios derived from user’s daily activities. To meet the practical demands required of a testing environment without the impositions of a heavy cost for establishing such a comprehensive infrastructure, a software simulation using a free Yahoo search API is provided as a means to evaluate the effectiveness of the design approach in a most realistic way. The integration of Yahoo search engine into the context-aware architecture design proves how context aware application can meet user demands for tailored services and products in and around the user’s environment. The test results show that the overall design is highly effective, providing new features and enriching the mobile user’s experience through a broad scope of potential applications.