45 research outputs found

    MuSERA: Multiple sample enriched region assessment

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    Enriched region (ER) identification is a fundamental step in several next-generation sequencing (NGS) experiment types. Yet, although NGS experimental protocols recommend producing replicate samples for each evaluated condition and their consistency is usually assessed, typically pipelines for ER identification do not consider available NGS replicates. This may alter genome-wide descriptions of ERs, hinder significance of subsequent analyses on detected ERs and eventually preclude biological discoveries that evidence in replicate could support. MuSERA is a broadly useful stand-alone tool for both interactive and batch analysis of combined evidence from ERs in multiple ChIP-seq or DNase-seq replicates. Besides rigorously combining sample replicates to increase statistical significance of detected ERs, it also provides quantitative evaluations and graphical features to assess the biological relevance of each determined ER set within its genomic context; they include genomic annotation of determined ERs, nearest ER distance distribution, global correlation assessment of ERs and an integrated genome browser.We review MuSERA rationale and implementation, and illustrate how sets of significant ERs are expanded by applying MuSERA on replicates for several types of NGS data, including ChIP-seq of transcription factors or histone marks and DNase-seq hypersensitive sites. We show that MuSERA can determine a new, enhanced set of ERs for each sample by locally combining evidence on replicates, and prove how the easy-to-use interactive graphical displays and quantitative evaluations that MuSERA provides effectively support thorough inspection of obtained results and evaluation of their biological content, facilitating their understanding and biological interpretations. MuSERA is freely available at http://www.bioinformatics.deib.polimi.it/MuSERA/

    Using combined evidence from replicates to evaluate ChIP-seq peaks

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    Motivation: Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) detects genome-wide DNA–protein interactions and chromatin modifications, returning enriched regions (ERs), usually associated with a significance score. Moderately significant interactions can correspond to true, weak interactions, or to false positives; replicates of a ChIP-seq experiment can provide co-localised evidence to decide between the two cases. We designed a general methodological framework to rigorously combine the evidence of ERs in ChIP-seq replicates, with the option to set a significance threshold on the repeated evidence and a minimum number of samples bearing this evidence. Results: We applied our method to Myc transcription factor ChIP-seq datasets in K562 cells available in the ENCODE project. Using replicates, we could extend up to 3 times the ER number with respect to single-sample analysis with equivalent significance threshold. We validated the ‘rescued’ ERs by checking for the overlap with open chromatin regions and for the enrichment of the motif that Myc binds with strongest affinity; we compared our results with alternative methods (IDR and jMOSAiCS), obtaining more validated peaks than the former and less peaks than latter, but with a better validation. Availability and implementation: An implementation of the proposed method and its source code under GPLv3 license are freely available at http://www.bioinformatics.deib.polimi.it/MSPC/ and http://mspc.codeplex.com/, respectively. Contact: [email protected] Supplementary information: Supplementary Material are available at Bioinformatics online

    Next Generation Indexing for Genomic Intervals

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    Di4 (1D intervals incremental inverted index) is a multi-resolution, single-dimension indexing framework for efficient, scalable, and extensible computation of genomic interval expressions. The framework has a tri-layer architecture: the semantic layer provides orthogonal and generic means (including the support of user-defined function) of sense-making and higher-lever reasoning from region-based datasets; the logical layer provides building blocks for region calculus and topological relations between intervals; the physical layer abstracts from persistence technology and makes the model adaptable to variety of persistence technologies, spanning from small-scale (e.g., B+tree) to large-scale (e.g., LevelDB). The extensibility of Di4 to application scenarios is shown with an example of comparative evaluation of ChIP-seq and DNase-Seq replicates. Performance of Di4 is benchmarked for small and large scale scenarios under common bioinformatics application scenarios. Di4 is freely available from https://genometric.github.io/Di4

    Explorative visual analytics on interval-based genomic data and their metadata

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    Background: With the wide-spreading of public repositories of NGS processed data, the availability of user-friendly and effective tools for data exploration, analysis and visualization is becoming very relevant. These tools enable interactive analytics, an exploratory approach for the seamless "sense-making" of data through on-the-fly integration of analysis and visualization phases, suggested not only for evaluating processing results, but also for designing and adapting NGS data analysis pipelines. Results: This paper presents abstractions for supporting the early analysis of NGS processed data and their implementation in an associated tool, named GenoMetric Space Explorer (GeMSE). This tool serves the needs of the GenoMetric Query Language, an innovative cloud-based system for computing complex queries over heterogeneous processed data. It can also be used starting from any text files in standard BED, BroadPeak, NarrowPeak, GTF, or general tab-delimited format, containing numerical features of genomic regions; metadata can be provided as text files in tab-delimited attribute-value format. GeMSE allows interactive analytics, consisting of on-the-fly cycling among steps of data exploration, analysis and visualization that help biologists and bioinformaticians in making sense of heterogeneous genomic datasets. By means of an explorative interaction support, users can trace past activities and quickly recover their results, seamlessly going backward and forward in the analysis steps and comparative visualizations of heatmaps. Conclusions: GeMSE effective application and practical usefulness is demonstrated through significant use cases of biological interest. GeMSE is available at http://www.bioinformatics.deib.polimi.it/GeMSE/ , and its source code is available at https://github.com/Genometric/GeMSEunder GPLv3 open-source license

    The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update

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    Galaxy (homepage: https://galaxyproject.org, main public server: https://usegalaxy.org) is a web-based scientific analysis platform used by tens of thousands of scientists across the world to analyze large biomedical datasets such as those found in genomics, proteomics, metabolomics and imaging. Started in 2005, Galaxy continues to focus on three key challenges of data-driven biomedical science: making analyses accessible to all researchers, ensuring analyses are completely reproducible, and making it simple to communicate analyses so that they can be reused and extended. During the last two years, the Galaxy team and the open-source community around Galaxy have made substantial improvements to Galaxy's core framework, user interface, tools, and training materials. Framework and user interface improvements now enable Galaxy to be used for analyzing tens of thousands of datasets, and >5500 tools are now available from the Galaxy ToolShed. The Galaxy community has led an effort to create numerous high-quality tutorials focused on common types of genomic analyses. The Galaxy developer and user communities continue to grow and be integral to Galaxy's development. The number of Galaxy public servers, developers contributing to the Galaxy framework and its tools, and users of the main Galaxy server have all increased substantially

    The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

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    Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe
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