QueryOR: a comprehensive web platform for genetic variant analysis and prioritization

Background: Whole genome and exome sequencing are contributing to the extraordinary progress in the study of human genetic variants. In this fast developing field, appropriate and easily accessible tools are required to facilitate data analysis. Results: Here we describe QueryOR, a web platform suitable for searching among known candidate genes as well as for finding novel gene-disease associations. QueryOR combines several innovative features that make it comprehensive, flexible and easy to use. Instead of being designed on specific datasets, it works on a general XML schema specifying formats and criteria of each data source. Thanks to this flexibility, new criteria can be easily added for future expansion. Currently, up to 70 user-selectable criteria are available, including a wide range of gene and variant features. Moreover, rather than progressively discarding variants taking one criterion at a time, the prioritization is achieved by a global positive selection process that considers all transcript isoforms, thus producing reliable results. QueryOR is easy to use and its intuitive interface allows to handle different kinds of inheritance as well as features related to sharing variants in different patients. QueryOR is suitable for investigating single patients, families or cohorts. Conclusions: QueryOR is a comprehensive and flexible web platform eligible for an easy user-driven variant prioritization. It is freely available for academic institutions at http://queryor.cribi.unipd.it/

Forecasting Recharging Demand to Integrate Electric Vehicle Fleets in Smart Grids

Electric vehicle fleets and smart grids are two growing technologies. These technologies provided new possibilities to reduce pollution and increase energy efficiency. In this sense, electric vehicles are used as mobile loads in the power grid. A distributed charging prioritization methodology is proposed in this paper. The solution is based on the concept of virtual power plants and the usage of evolutionary computation algorithms. Additionally, the comparison of several evolutionary algorithms, genetic algorithm, genetic algorithm with evolution control, particle swarm optimization, and hybrid solution are shown in order to evaluate the proposed architecture. The proposed solution is presented to prevent the overload of the power grid

Search based software engineering: Trends, techniques and applications

© ACM, 2012. This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version is available from the link below.In the past five years there has been a dramatic increase in work on Search-Based Software Engineering (SBSE), an approach to Software Engineering (SE) in which Search-Based Optimization (SBO) algorithms are used to address problems in SE. SBSE has been applied to problems throughout the SE lifecycle, from requirements and project planning to maintenance and reengineering. The approach is attractive because it offers a suite of adaptive automated and semiautomated solutions in situations typified by large complex problem spaces with multiple competing and conflicting objectives. This article provides a review and classification of literature on SBSE. The work identifies research trends and relationships between the techniques applied and the applications to which they have been applied and highlights gaps in the literature and avenues for further research.EPSRC and E

Understanding requirements dependency in requirements prioritization: a systematic literature review

Requirement prioritization (RP) is a crucial task in managing requirements as it determines the order of implementation and, thus, the delivery of a software system. Improper RP may cause software project failures due to over budget and schedule as well as a low-quality product. Several factors influence RP. One of which is requirements dependency. Handling inappropriate handling of requirements dependencies can lead to software development failures. If a requirement that serves as a prerequisite for other requirements is given low priority, it affects the overall project completion time. Despite its importance, little is known about requirements dependency in RP, particularly its impacts, types, and techniques. This study, therefore, aims to understand the phenomenon by analyzing the existing literature. It addresses three objectives, namely, to investigate the impacts of requirements dependency on RP, to identify different types of requirements dependency, and to discover the techniques used for requirements dependency problems in RP. To fulfill the objectives, this study adopts the Systematic Literature Review (SLR) method. Applying the SLR protocol, this study selected forty primary articles, which comprise 58% journal papers, 32% conference proceedings, and 10% book sections. The results of data synthesis indicate that requirements dependency has significant impacts on RP, and there are a number of requirements dependency types as well as techniques for addressing requirements dependency problems in RP. This research discovered various techniques employed, including the use of Graphs for RD visualization, Machine Learning for handling large-scale RP, decision making for multi-criteria handling, and optimization techniques utilizing evolutionary algorithms. The study also reveals that the existing techniques have encountered serious limitations in terms of scalability, time consumption, interdependencies of requirements, and limited types of requirement dependencies

MutationDistiller: user-driven identification of pathogenic DNA variants

MutationDistiller is a freely available online tool for user-driven analyses of Whole Exome Sequencing data. It offers a user-friendly interface aimed at clinicians and researchers, who are not necessarily bioinformaticians. MutationDistiller combines Mutation- Taster’s pathogenicity predictions with a phenotypebased approach. Phenotypic information is not limited to symptoms included in the Human Phenotype Ontology (HPO), but may also comprise clinical diagnoses and the suspected mode of inheritance. The search can be restricted to lists of candidate genes (e.g. virtual gene panels) and by tissue-specific gene expression. The inclusion of GeneOntology (GO) and metabolic pathways facilitates the discovery of hitherto unknown disease genes. In a novel approach, we trained MutationDistiller’s HPO-based prioritization on authentic genotype–phenotype sets obtained from ClinVar and found it to match or outcompete current prioritization tools in terms of accuracy. In the output, the program provides a list of potential disease mutations ordered by the likelihood of the affected genes to cause the phenotype. MutationDistiller provides links to gene-related information from various resources. It has been extensively tested by clinicians and their suggestions have been valued in many iterative cycles of revisions. The tool, a comprehensive documentation and examples are freely available at https://www.mutationdistiller.org

A Review and Characterization of Progressive Visual Analytics

Progressive Visual Analytics (PVA) has gained increasing attention over the past years. It brings the user into the loop during otherwise long-running and non-transparent computations by producing intermediate partial results. These partial results can be shown to the user for early and continuous interaction with the emerging end result even while it is still being computed. Yet as clear-cut as this fundamental idea seems, the existing body of literature puts forth various interpretations and instantiations that have created a research domain of competing terms, various definitions, as well as long lists of practical requirements and design guidelines spread across different scientific communities. This makes it more and more difficult to get a succinct understanding of PVA’s principal concepts, let alone an overview of this increasingly diverging field. The review and discussion of PVA presented in this paper address these issues and provide (1) a literature collection on this topic, (2) a conceptual characterization of PVA, as well as (3) a consolidated set of practical recommendations for implementing and using PVA-based visual analytics solutions

Towards Utility-Based Prioritization of Requirements in Open Source Environments

Peer reviewe

Semantic-enabled Hybrid Genetic Disease Diagnostics in Next-Generation Sequenced Data

Next Generation Sequencing is a technology for genome sequencing used in genetics for diseased diagnosis. NGS provides the list of all mutations in a genome, so identifying the one which causes a disease is not trivial. A number of applications for variant prioritization was developed, but the data they provide is rather a suggestion than a diagnosis, moreover they suffer from issues as identifying nonpathogenic variant as a causal one or inability to identify the causal gene. These issues inspired us to create a strategy for variant prioritization which includes the use of Exomiser and OmimExplorer result sets improved by semantic analysis of abstracts and articles freely available from PubMed and PubMed Central databases. For the wider scope of scientific articles Google Scholar repository will be used. Described approach enables to present latest and most accurate information about potential pathogenic variants

Scheduling Refactoring Opportunities Using Computational Search

Maintaining a high-level code quality can be extremely expensive since time and monetary pressures force programmers to neglect improving the quality of their source code. Refactoring is an extremely important solution to reduce and manage the growing complexity of software systems. Developers often need to make trade-offs between code quality, available resources and delivering a product on time, and such management support is beyond the scope and capability of existing refactoring engines. The problem of finding the optimal sequence in which the refactoring opportunities, such as bad smells, should be ordered is rarely studied. Due to the large number of possible scheduling solutions to explore, software engineers cannot manually find an optimal sequence of refactoring opportunities that may reduce the effort and time required to efficiently improve the quality of software systems. In this paper, we use bi-level multi-objective optimization to the refactoring opportunities management problem. The upper level generates a population of solutions where each solution is defined as an ordered list of code smells to fix which maximize the benefits in terms of quality improvements and minimize the cost in terms of number of refactorings to apply. The lower level finds the best sequence of refactorings that fixes the maximum number of code smells with a minimum number of refactorings for each solution (code smells sequence) in the upper level. The statistical analysis of our experiments over 30 runs on 6 open source systems and 1 industrial project shows a significant reduction in effort and better improvements of quality when compared to state-of-art bad smells prioritization techniques. The manual evaluation performed by software engineers also confirms the relevance of our refactoring opportunities scheduling solutions.Master of ScienceComputer Science, College of Engineering and Computer ScienceUniversity of Michigan-Dearbornhttp://deepblue.lib.umich.edu/bitstream/2027.42/136063/1/Scheduling Refactoring Opportunities Using Computational Search.pd

A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics

Background: Genome-wide data are increasingly important in the clinical evaluation of human disease. However, the large number of variants observed in individual patients challenges the efficiency and accuracy of diagnostic review. Recent work has shown that systematic integration of clinical phenotype data with genotype information can improve diagnostic workflows and prioritization of filtered rare variants. We have developed visually interactive, analytically transparent analysis software that leverages existing disease catalogs, such as the Online Mendelian Inheritance in Man database (OMIM) and the Human Phenotype Ontology (HPO), to integrate patient phenotype and variant data into ranked diagnostic alternatives. Methods: Our tool, “OMIM Explorer” (http://www.omimexplorer.com), extends the biomedical application of semantic similarity methods beyond those reported in previous studies. The tool also provides a simple interface for translating free-text clinical notes into HPO terms, enabling clinical providers and geneticists to contribute phenotypes to the diagnostic process. The visual approach uses semantic similarity with multidimensional scaling to collapse high-dimensional phenotype and genotype data from an individual into a graphical format that contextualizes the patient within a low-dimensional disease map. The map proposes a differential diagnosis and algorithmically suggests potential alternatives for phenotype queries—in essence, generating a computationally assisted differential diagnosis informed by the individual’s personal genome. Visual interactivity allows the user to filter and update variant rankings by interacting with intermediate results. The tool also implements an adaptive approach for disease gene discovery based on patient phenotypes. Results: We retrospectively analyzed pilot cohort data from the Baylor Miraca Genetics Laboratory, demonstrating performance of the tool and workflow in the re-analysis of clinical exomes. Our tool assigned to clinically reported variants a median rank of 2, placing causal variants in the top 1 % of filtered candidates across the 47 cohort cases with reported molecular diagnoses of exome variants in OMIM Morbidmap genes. Our tool outperformed Phen-Gen, eXtasy, PhenIX, PHIVE, and hiPHIVE in the prioritization of these clinically reported variants. Conclusions: Our integrative paradigm can improve efficiency and, potentially, the quality of genomic medicine by more effectively utilizing available phenotype information, catalog data, and genomic knowledge