scholarly journals SV-plaudit: A cloud-based framework for manually curating thousands of structural variants

2018 ◽  
Author(s):  
Jonathan R. Belyeu ◽  
Thomas J. Nicholas ◽  
Brent S. Pedersen ◽  
Thomas A. Sasani ◽  
James M. Havrilla ◽  
...  
Keyword(s):  
Web Application ◽  
Variant Calling ◽  
Structural Variants ◽  
Structural Variant ◽  
Link Type ◽  
Cloud Framework ◽  
Demonstration Video ◽  
Client Side ◽  
Proof Of Principle

ABSTRACTSV-plaudit is a framework for rapidly curating structural variant (SVs) predictions. For each SV, we generate an image that visualizes the coverage and alignment signals from a set of samples. Images are uploaded to our cloud framework where users assess the quality of each image using a client-side web application. Reports can then be generated as a tab-delimited file or annotated VCF. As a proof of principle, nine researchers collaborated for one hour to evaluate 1,350 SVs each. We anticipate that SV-plaudit will become a standard step in variant calling pipelines and the crowd-sourced curation of other biological results.Code available at https://github.com/jbelyeu/SV-plauditDemonstration video available at https://www.youtube.com/watch?v=ono8kHMKxDs

scholarly journals IcyTree: Rapid browser-based visualization for phylogenetic trees and networks

2017 ◽  
Author(s):  
Timothy G. Vaughan
Keyword(s):  
Web Application ◽  
Phylogenetic Trees ◽  
Phylogenetic Networks ◽  
Web Browsers ◽  
Network Access ◽  
Online Tool ◽  
Link Type ◽  
Mozilla Firefox ◽  
Ancestral Recombination Graphs ◽  
Client Side

AbstractSummaryIcyTree is an easy-to-use application which can be used to visualize a wide variety of phylogenetic trees and networks. While numerous phylogenetic tree viewers exist already, IcyTree distinguishes itself by being a purely online tool, having a responsive user interface, supporting phylogenetic networks (ancestral recombination graphs in particular), and efficiently drawing trees that include information such as ancestral locations or trait values. IcyTree also provides intuitive panning and zooming utilities that make exploring large phylogenetic trees of many thousands of taxa feasible.Availability and ImplementationIcyTree is a web application and can be accessed directly at http://tgvaughan.github.com/icytree. Currently-supported web browsers include Mozilla Firefox and Google Chrome. IcyTree is written entirely in client-side JavaScript (no plugin required) and, once loaded, does not require network access to run. IcyTree is free software, and the source code is made available at http://github.com/tgvaughan/icytree under version 3 of the GNU General Public [email protected]

scholarly journals LEVIATHAN: efficient discovery of large structural variants by leveraging long-range information from Linked-Reads data

2021 ◽  
Author(s):  
Pierre Morisse ◽  
Fabrice Legeai ◽  
Claire Lemaitre
Keyword(s):  
Long Range ◽  
Model Organism ◽  
Variant Calling ◽  
Simulated Data ◽  
Structural Variants ◽  
Sequencing Data ◽  
High Quality ◽  
Short Reads ◽  
Structural Variant ◽  
Human Data

Linked-Reads technologies, popularized by 10x Genomics, combine the high- quality and low cost of short-reads sequencing with a long-range information by adding barcodes that tag reads originating from the same long DNA fragment. Thanks to their high-quality and long-range information, such reads are thus particularly useful for various applications such as genome scaffolding and structural variant calling. As a result, multiple structural variant calling methods were developed within the last few years. However, these methods were mainly tested on human data, and do not run well on non-human organisms, for which reference genomes are highly fragmented, or sequencing data display high levels of heterozygosity. Moreover, even on human data, most tools still require large amounts of computing resources. We present LEVIATHAN, a new structural variant calling tool that aims to address these issues, and especially better scale and apply to a wide variety of organisms. Our method relies on a barcode index, that allows to quickly compare the similarity of all possible pairs of regions in terms of amount of common barcodes. Region pairs sharing a sufficient number of barcodes are then considered as potential structural variants, and complementary, classical short reads methods are applied to further refine the breakpoint coordinates. Our experiments on simulated data underline that our method compares well to the state-of-the-art, both in terms of recall and precision, and also in terms of resource consumption. Moreover, LEVIATHAN was successfully applied to a real dataset from a non-model organism, while all other tools either failed to run or required unreasonable amounts of resources. LEVIATHAN is implemented in C++, supported on Linux platforms, and available under AGPL-3.0 License at https://github.com/morispi/LEVIATHAN.

scholarly journals Curatr: a web application for creating, curating, and sharing a mass spectral library

2017 ◽  
Author(s):  
Andrew Palmer ◽  
Prasad Phapale ◽  
Dominik Fay ◽  
Theodore Alexandrov
Keyword(s):  
Mass Spectrometry ◽  
Web Application ◽  
Mass Spectrometry Analysis ◽  
Supplementary Information ◽  
Spectral Library ◽  
Mass Spectral Fragmentation ◽  
Mass Spectral ◽  
Link Type ◽  
Manual Curation

AbstractMotivationIdentification from metabolomics mass spectrometry experiments requires comparison of fragmentation spectra from experimental samples to spectra from analytical standards. As the quality of identification depends directly on the quality of the reference spectra, manual curation is routine during the selection of reference spectra to include in a spectral library. Whilst building our own in-house spectral library we realised that there is currently no vendor neutral open access tool for for facilitating manual curation of spectra from raw LC-MS data into a custom spectral library.ResultsWe developed a web application curatr for the rapid generation of high quality mass spectral fragmentation libraries for liquid-chromatography mass spectrometry analysis. Curatr handles datasets from single or multiplexed standards, automatically extracting chromatographic profiles and potential fragmentation spectra for multiple adducts. These are presented through an intuitive interface for manual curation before being documented in a custom spectral library. Searchable molecular information and the providence of each standard is stored along with metadata on the experimental protocol. Curatr support the export of spectral libraries in several standard formats for easy use with third party software or submission to community databases, maximising the return on investment for these costly measurements. We demonstrate the use of curatr to generate the EMBL Metabolomics Core Facility spectral library which is publicly available at http://curatr.mcf.embl.de.AvailabilityThe source code is freely available at http://github.com/alexandrovteam/curatr/ along with example data.Supplementary informationA step-by step user manual is available in the supplementary information

scholarly journals GRIDSS, PURPLE, LINX: Unscrambling the tumor genome via integrated analysis of structural variation and copy number

2019 ◽  
Author(s):  
Daniel L. Cameron ◽  
Jonathan Baber ◽  
Charles Shale ◽  
Anthony T. Papenfuss ◽  
Jose Espejo Valle-Inclan ◽  
...  
Keyword(s):  
Copy Number ◽  
Variant Calling ◽  
Genomic Rearrangements ◽  
Whole Genome Sequencing Data ◽  
Integrated Analysis ◽  
Derivative Chromosome ◽  
Structural Variants ◽  
Sequencing Data ◽  
Structural Variant ◽  
Complex Events

AbstractWe have developed a novel, integrated and comprehensive purity, ploidy, structural variant and copy number somatic analysis toolkit for whole genome sequencing data of paired tumor/normal samples. We show that the combination of using GRIDSS for somatic structural variant calling and PURPLE for somatic copy number alteration calling allows highly sensitive, precise and consistent copy number and structural variant determination, as well as providing novel insights for short structural variants and regions of complex local topology. LINX, an interpretation tool, leverages the integrated structural variant and copy number calling to cluster individual structural variants into higher order events and chains them together to predict local derivative chromosome structure. LINX classifies and extensively annotates genomic rearrangements including simple and reciprocal breaks, LINE, viral and pseudogene insertions, and complex events such as chromothripsis. LINX also comprehensively calls genic fusions including chained fusions. Finally, our toolkit provides novel visualisation methods providing insight into complex genomic rearrangements.

scholarly journals Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons

2017 ◽  
Author(s):  
Kemal Eren ◽  
Steven Weaver ◽  
Robert Ketteringham ◽  
Morné Valentyn ◽  
Melissa Laird Smith ◽  
...  
Keyword(s):  
Web Application ◽  
Evolutionary Dynamics ◽  
Full Length ◽  
Viral Population ◽  
Sequencing Data ◽  
Link Type ◽  
Long Read ◽  
Web App ◽  
Client Side ◽  
Hiv 1

AbstractNext generation sequencing of viral populations has advanced our understanding of viral population dynamics, the development of drug resistance, and escape from host immune responses. Many applications require complete gene sequences, which can be impossible to reconstruct from short reads. HIV-1 env, the protein of interest for HIV vaccine studies, is exceptionally challenging for long-read sequencing and analysis due to its length, high substitution rate, and extensive indel variation. While long-read sequencing is attractive in this setting, the analysis of such data is not well handled by existing methods. To address this, we introduce FLEA (Full-Length Envelope Analyzer), which performs end-to-end analysis and visualization of long-read sequencing data.FLEA consists of both a pipeline (optionally run on a high-performance cluster), and a client-side web application that provides interactive results. The pipeline transforms FASTQ reads into high-quality consensus sequences (HQCSs) and uses them to build a codon-aware multiple sequence alignment. The resulting alignment is then used to infer phylogenies, selection pressure, and evolutionary dynamics. The web application provides publication-quality plots and interactive visualizations, including an annotated viral alignment browser, time series plots of evolutionary dynamics, visualizations of gene-wide selective pressures (such as dN /dS) across time and across protein structure, and a phylogenetic tree browser.We demonstrate how FLEA may be used to process Pacific Biosciences HIV-1 env data and describe recent examples of its use. Simulations show how FLEA dramatically reduces the error rate of this sequencing platform, providing an accurate portrait of complex and variable HIV-1 env populations.A public instance of FLEA is hosted at http://flea.datamonkey.org. The Python source code for the FLEA pipeline can be found at https://github.com/veg/flea-pipeline. The client-side application is available at https://github.com/veg/flea-web-app. A live demo of the P018 results can be found at http://flea.murrell.group/view/P018.

scholarly journals Whisper 2: indel-sensitive short read mapping

2019 ◽  
Author(s):  
Sebastian Deorowicz ◽  
Adam Gudyś
Keyword(s):  
Web Site ◽  
Variant Calling ◽  
Supplementary Information ◽  
Supplementary Data ◽  
Read Mapping ◽  
Short Read ◽  
Short Read Mapping ◽  
Link Type ◽  
Mapping Software

AbstractSummaryWhisper 2 is a short-read-mapping software providing superior quality of indel variant calling. Its running times place it among the fastest existing tools.Availability and Implementationhttps://github.com/refresh-bio/[email protected] informationSupplementary data are available at publisher’s Web site.

scholarly journals SimFFPE and FilterFFPE: improving structural variant calling in FFPE samples

GigaScience ◽  
2021 ◽  
Vol 10 (9) ◽  
Author(s):  
Lanying Wei ◽  
Martin Dugas ◽  
Sarah Sandmann
Keyword(s):  
Next Generation Sequencing ◽  
Variant Calling ◽  
Real Data ◽  
Next Generation Sequencing Data ◽  
Next Generation ◽  
Structural Variants ◽  
Sequencing Data ◽  
Structural Variant ◽  
Ffpe Samples ◽  
Generation Sequencing

Abstract Background Artifact chimeric reads are enriched in next-generation sequencing data generated from formalin-fixed paraffin-embedded (FFPE) samples. Previous work indicated that these reads are characterized by erroneous split-read support that is interpreted as evidence of structural variants. Thus, a large number of false-positive structural variants are detected. To our knowledge, no tool is currently available to specifically call or filter structural variants in FFPE samples. To overcome this gap, we developed 2 R packages: SimFFPE and FilterFFPE. Results SimFFPE is a read simulator, specifically designed for next-generation sequencing data from FFPE samples. A mixture of characteristic artifact chimeric reads, as well as normal reads, is generated. FilterFFPE is a filtration algorithm, removing artifact chimeric reads from sequencing data while keeping real chimeric reads. To evaluate the performance of FilterFFPE, we performed structural variant calling with 3 common tools (Delly, Lumpy, and Manta) with and without prior filtration with FilterFFPE. After applying FilterFFPE, the mean positive predictive value improved from 0.27 to 0.48 in simulated samples and from 0.11 to 0.27 in real samples, while sensitivity remained basically unchanged or even slightly increased. Conclusions FilterFFPE improves the performance of SV calling in FFPE samples. It was validated by analysis of simulated and real data.

scholarly journals A decoupled, modular and scriptable architecture for tools to curate data platforms

2020 ◽  
Author(s):  
Moritz Langenstein ◽  
Henning Hermjakob ◽  
Manuel Bernal Llinares
Keyword(s):  
Web Application ◽  
Production Systems ◽  
Source Code ◽  
Black Box ◽  
Command Line ◽  
Web Interface ◽  
Link Type ◽  
Data Platform ◽  
The Web

AbstractMotivationCuration is essential for any data platform to maintain the quality of the data it provides. Existing databases, which require maintenance, and the amount of newly published information that needs to be surveyed, are growing rapidly. More efficient curation is often vital to keep up with this growth, requiring modern curation tools. However, curation interfaces are often complex and difficult to further develop. Furthermore, opportunities for experimentation with curation workflows may be lost due to a lack of development resources, or a reluctance to change sensitive production systems.ResultsWe propose a decoupled, modular and scriptable architecture to build curation tools on top of existing platforms. Instead of modifying the existing infrastructure, our architecture treats the existing platform as a black box and relies only on its public APIs and web application. As a decoupled program, the tool’s architecture gives more freedom to developers and curators. This added flexibility allows for quickly prototyping new curation workflows as well as adding all kinds of analysis around the data platform. The tool can also streamline and enhance the curator’s interaction with the web interface of the platform. We have implemented this design in cmd-iaso, a command-line curation tool for the identifiers.org registry.AvailabilityThe cmd-iaso curation tool is implemented in Python 3.7+ and supports Linux, macOS and Windows. Its source code and documentation are freely available from https://github.com/identifiers-org/cmd-iaso. It is also published as a Docker container at https://hub.docker.com/r/identifiersorg/[email protected]

scholarly journals Structural variants identified by Oxford Nanopore PromethION sequencing of the human genome

2018 ◽  
Author(s):  
De Coster Wouter ◽  
De Roeck Arne ◽  
De Pooter Tim ◽  
D’Hert Svenn ◽  
De Rijk Peter ◽  
...  
Keyword(s):  
Variant Calling ◽  
High Sensitivity ◽  
Structural Variants ◽  
Computationally Efficient ◽  
Sequencing Platform ◽  
Structural Variant ◽  
Oxford Nanopore ◽  
Sequencing Studies ◽  
Long Read

AbstractWe sequenced the Yoruban NA19240 genome on the long read sequencing platform Oxford Nanopore PromethION for benchmarking and evaluation of recently published aligners and structural variant calling tools. In this work, we determined the precision and recall, present high confidence and high sensitivity call sets of variants and discuss optimal parameters. The aligner Minimap2 and structural variant caller Sniffles are both the most accurate and the most computationally efficient tools in our study. We describe our scalable workflow for identification, annotation, and characterization of tens of thousands of structural variants from long read genome sequencing of an individual or population. By discussing the results of this genome we provide an approximation of what can be expected in future long read sequencing studies aiming for structural variant identification.

scholarly journals State-of-the-art structural variant calling: What went conceptually wrong and how to fix it?

2021 ◽  
Author(s):  
Markus Schmidt ◽  
Arne Kutzner
Keyword(s):  
Open Source ◽  
State Of The Art ◽  
Graph Model ◽  
Variant Calling ◽  
Genomic Rearrangements ◽  
Prototype Implementation ◽  
Structural Variant ◽  
Link Type ◽  
Adjacency Matrices ◽  
Yeast Genomes

AbstractStructural variant (SV) calling belongs to the standard tools of modern bioinformatics for identifying and describing alterations in genomes. Initially, this work presents several complex genomic rearrangements that reveal conceptual ambiguities inherent to the SV representations of state-of-the-art SV callers. We contextualize these ambiguities theoretically as well as practically and propose a graph-based approach for resolving them. Our graph model unifies both genomic strands by using the concept of skew-symmetry; it supports graph genomes in general and pan genomes in specific. Instances of our model are inferred directly from seeds instead of the commonly used alignments that conflict with various types of SV as reported here. For yeast genomes, we practically compute adjacency matrices of our graph model and demonstrate that they provide highly accurate descriptions of one genome in terms of another. An open-source prototype implementation of our approach is available under the MIT license at https://github.com/ITBE-Lab/MA.

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