Emmanouil Viennas

Updates of the HbVar database of human hemoglobin variants and thalassemia mutations

HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Database records include extensive phenotypic descriptions, biochemical and hematological effects, associated pathology and ethnic occurrence, accompanied by mutation frequencies and references. Here, we report updates to >600 HbVar entries, inclusion of population-specific data for 28 populations and 27 ethnic groups for α-, and β-thalassemias and additional querying options in the HbVar query page. HbVar content was also inter-connected with two other established genetic databases, namely FINDbase (http://www.findbase.org) and Leiden Open-Access Variation database (http://www.lovd.nl), which allows comparative data querying and analysis. HbVar data content has contributed to the realization of two collaborative projects to identify genomic variants that lie on different globin paralogs. Most importantly, HbVar data content has contributed to demonstrate the microattribution concept in practice. These updates significantly enriched the database content and querying potential, enhanced the database profile and data quality and broadened the inter-relation of HbVar with other databases, which should increase the already high impact of this resource to the globin and genetic database community.

Population-specific documentation of pharmacogenomic markers and their allelic frequencies in FINDbase

AIMS Population and ethnic group-specific allele frequencies of pharmacogenomic markers are poorly documented and not systematically collected in structured data repositories. We developed the Frequency of Inherited Disorders Pharmacogenomics database (FINDbase-PGx), a separate module of the FINDbase, aiming to systematically document pharmacogenomic allele frequencies in various populations and ethnic groups worldwide. MATERIALS & METHODS We critically collected and curated 214 scientific articles reporting pharmacogenomic markers allele frequencies in various populations and ethnic groups worldwide. Subsequently, in order to host the curated data, support data visualization and data mining, we developed a website application, utilizing Microsoft™ PivotViewer software. RESULTS Curated allelic frequency data pertaining to 144 pharmacogenomic markers across 14 genes, representing approximately 87,000 individuals from 150 populations worldwide, are currently included in FINDbase-PGx. A user-friendly query interface allows for easy data querying, based on numerous content criteria, such as population, ethnic group, geographical region, gene, drug and rare allele frequency. CONCLUSION FINDbase-PGx is a comprehensive database, which, unlike other pharmacogenomic knowledgebases, fulfills the much needed requirement to systematically document pharmacogenomic allelic frequencies in various populations and ethnic groups worldwide.

Developments in FINDbase worldwide database for clinically relevant genomic variation allele frequencies

FINDbase (http://www.findbase.org) aims to document frequencies of clinically relevant genomic variations, namely causative mutations and pharmacogenomic markers, worldwide. Each database record includes the population, ethnic group or geographical region, the disorder name and the related gene, accompanied by links to any related databases and the genetic variation together with its frequency in that population. Here, we report, in addition to the regular data content updates, significant developments in FINDbase, related to data visualization and querying, data submission, interrelation with other resources and a new module for genetic disease summaries. In particular, (i) we have developed new data visualization tools that facilitate data querying and comparison among different populations, (ii) we have generated a new FINDbase module, built around Microsoft’s PivotViewer (http://www.getpivot.com) software, based on Microsoft Silverlight technology (http://www.silverlight.net), that includes 259 genetic disease summaries from five populations, systematically collected from the literature representing the documented genetic makeup of these populations and (iii) the implementation of a generic data submission tool for every module currently available in FINDbase.

FINDbase: a worldwide database for genetic variation allele frequencies updated

Frequency of INherited Disorders database (FIND base; http://www.findbase.org) records frequencies of causative genetic variations worldwide. Database records include the population and ethnic group or geographical region, the disorder name and the related gene, accompanied by links to any related external resources and the genetic variation together with its frequency in that population. In addition to the regular data content updates, we report the following significant advances: (i) the systematic collection and thorough documentation of population/ethnic group-specific pharmacogenomic markers allele frequencies for 144 markers in 14 genes of pharmacogenomic interest from different classes of drug-metabolizing enzymes and transporters, representing 150 populations and ethnic groups worldwide; (ii) the development of new data querying and visualization tools in the expanded FINDbase data collection, built around Microsoft’s PivotViewer software (http://www.getpivot.com), based on Microsoft Silverlight technology (http://www.silverlight.net) that facilitates querying of large data sets and visualizing the results; and (iii) the establishment of the first database journal, by affiliating FINDbase with Human Genomics and Proteomics, a new open-access scientific journal, which would serve as a prime example of a non-profit model for sustainable database funding.

DruGeVar: An Online Resource Triangulating Drugs with Genes and Genomic Biomarkers for Clinical Pharmacogenomics

Background/Aims: Pharmacogenomics aims to rationalize drug use by minimizing drug toxicity and/or by increasing drug efficacy. A large number of genomic markers have been correlated with variable drug responses and severity of adverse drug reactions. Although a number of these drugs bear pharmacogenomic information in their labels - approved by regulatory agencies - and comprehensive drug/gene lists exist online, information related to the respective pharmacogenomic biomarkers is currently missing from such lists. Methods: We extracted information from the published literature and online resources and developed DruGeVar (http://drugevar.genomicmedicinealliance.org), an online resource triangulating drugs with genes and pharmacogenomic biomarkers in an effort to build a comprehensive database that could serve clinical pharmacogenomics. Results and Conclusions: A user-friendly data querying and visualization interface allows users to formulate simple and complex queries. Such a database would be readily applicable as a stand-alone resource or a plug-in module for other databases.

Population-ethnic group specific genome variation allele frequency data: a querying and visualization journey.

National/ethnic mutation databases aim to document the genetic heterogeneity in various populations and ethnic groups worldwide. We have previously reported the development and upgrade of FINDbase (www.findbase.org), a database recording causative mutations and pharmacogenomic marker allele frequencies in various populations around the globe. Although this database has recently been upgraded, we continuously try to enhance its functionality by providing more advanced visualization tools that would further assist effective data querying and comparisons. We are currently experimenting in various visualization techniques on the existing FINDbase causative mutation data collection aiming to provide a dynamic research tool for the worldwide scientific community. We have developed an interactive web-based application for population-based mutation data retrieval. It supports sophisticated data exploration allowing users to apply advanced filtering criteria upon a set of multiple views of the underlying data collection and enables browsing the relationships between individual datasets in a novel and meaningful way.

Expanded national database collection and data coverage in the FINDbase worldwide database for clinically relevant genomic variation allele frequencies

FINDbase (http://www.findbase.org) is a comprehensive data repository that records the prevalence of clinically relevant genomic variants in various populations worldwide, such as pathogenic variants leading mostly to monogenic disorders and pharmacogenomics biomarkers. The database also records the incidence of rare genetic diseases in various populations, all in well-distinct data modules. Here, we report extensive data content updates in all data modules, with direct implications to clinical pharmacogenomics. Also, we report significant new developments in FINDbase, namely (i) the release of a new version of the ETHNOS software that catalyzes development curation of national/ethnic genetic databases, (ii) the migration of all FINDbase data content into 90 distinct national/ethnic mutation databases, all built around Microsofts PivotViewer (http://www.getpivot.com) software (iii) new data visualization tools and (iv) the interrelation of FINDbase with DruGeVar database with direct implications in clinical pharmacogenomics. The abovementioned updates further enhance the impact of FINDbase, as a key resource for Genomic Medicine applications.

Intelligent Mobile Recommendations for Exhibitions Using Indoor Location Services

Information and Communication Technologies (ICTs) are utilized in an increasing number of museums and collection exhibitions world-wide. In this chapter, we present novel fully-automatic mobile assistant with indoor recommendation services. We will discuss novel efficient techniques in order to provide within a single software solution (a) typical, (b) semi automatic and (c) seamless-no human interaction tour guidance and recommendations during an exhibition tour. We have designed, developed, deployed and evaluated the solution at a real case exhibition to provide at a users’ level an intelligent personalized virtual guide. The provided solution aims to assist visitors and to provide full automatic multimedia or audio guidance during exhibition visits using Wi-Fi based indoor and outdoor positioning, mobile messaging and wireless data provisioning. In the proposed chapter we will discuss the design, implementation, deployment and outcomes of the research and development endeavor for the integration of mobile multimedia, positioning and messaging services into a novel automatic personalized exhibition recommender-assistant. Deployment and evaluation issues of the proposed solution will be discussed for the case of the Museum “Digital Exhibition of History of Olympic Games in Antiquity” in Ancient Olympia (Greece, EU).

Exposing click-fraud using a burst detection algorithm

The explosive growth in the size and use of the World Wide Web continuously creates new great challenges and needs. One such need is dealing with click fraud, which aims at increasing clicks on certain ads and thus the profit of the websites which display them. In this work, we extend the concept of click fraud and redefine it as any pattern of clicks whose goal is to alternate the normal operation of a website in order to produce specific results. An indication of a click fraud may be a burst of clicks that can be simulated by an automated program or script. We deal with the problem of efficient real-time Click Fraud detection utilizing advanced data structures and exploiting their advantages concerning space and time required.

Improving Search Engines’ Document Ranking Employing Semantics and an Inference Network

The users search mainly diverse information from several topics and their needs are difficult to be satisfied from the techniques currently employed in commercial search engines and without intervention from the user. In this paper, a novel framework is presented for performing re-ranking in the results of a search engine based on feedback from the user. The proposed scheme combines smoothly techniques from the area of Inference Networks and data from semantic knowledge bases. The novelty lies in the construction of a probabilistic network for each query which takes as input the belief of the user to each result (initially, all are equivalent) and produces as output a new ranking for the search results. We have constructed an implemented prototype that supports different Web search engines and it can be extended to support any search engine. Finally extensive experiments were performed using the proposed methods depicting the improvement of the ranking of the search engines results.