Discovery and genotyping of novel sequence insertions in many sequenced individuals

Kavak, Pınar; Lin, Yen-Yi; Numanagić, Ibrahim; Asghari, Hossein; Güngör, Tunga; Alkan, Can; Hach, Faraz

doi:10.1093/bioinformatics/btx254

Cited by 32 publications

(32 citation statements)

References 37 publications

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“…We have previously developed some of the first tools to discover various types of SV that also incorporate multi-mapping of reads, such as mrCaNaVaR/mrFAST [20], VariationHunter [8], VariationHunter-CR [13], NovelSeq [21], Pamir [22], and Com-monLAW [23]. All of these tools use a similar objective function for SV discovery although they are developed to discover different types of SV under different conditions (e.g.…”

Section: Methodsmentioning

confidence: 99%

Toolkit for automated and rapid discovery of structural variants

Söylev

Koçkan

Hormozdiari

et al. 2017

Methods

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Structural variations (SV) are broadly defined as genomic alterations that affect >50bp of DNA, which are shown to have significant effect on evolution and disease. The advent of high throughput sequencing (HTS) technologies and the ability to perform whole genome sequencing (WGS), makes it feasible to study these variants in depth. However, discovery of all forms of SV using WGS has proven to be challenging as the short reads produced by the predominant HTS platforms (<200bp for current technologies) and the fact that most genomes include large amounts of repeats make it very difficult to unambiguously map and accurately characterize such variants. Furthermore, existing tools for SV discovery are primarily developed for only a few of the SV types, which may have conflicting sequence signatures (i.e. read pairs, read depth, split reads) with other, untargeted SV classes. Here we are introduce a new framework, Tardis, which combines multiple read signatures into a single package to characterize most SV types simultaneously, while preventing such conflicts. Tardis also has a modular structure that makes it easy to extend for the discovery of additional forms of SV.

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Section: Methodsmentioning

confidence: 99%

Toolkit for automated and rapid discovery of structural variants

Söylev

Koçkan

Hormozdiari

et al. 2017

Methods

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“…non-human). If needed, we can perform a contamination removal procedure similar to what was previously done in NovelSeq (Hajirasouliha et al (2010)) and Pamir (Kavak et al (2017)). i.e.…”

Section: Novel Sequence Insertion Assemblymentioning

confidence: 99%

“…Note that we chose these datasets because high coverage PacBio long-reads for these genomes were already publicly available. Furthermore, state-of-the-art short-read tools such as Pamir (Kavak et al (2017)) for novel insertion detection used CHM1 for benchmarking. Unfortunately, Pamir is not designed to handle 10x sequencing data because the mrsFast aligner used inside Pamir's pipeline requires paired reads with equal-length left and right reads.…”

Section: Benchmarking On Haploid Hydatidiform Molesmentioning

confidence: 99%

“…This algorithm was successfully applied to the 1000GP datasets and a number of NovelSeq calls were reported and validated (The 1000 Genomes Project Consortium (2010), Mills et al (2011)). Subsequent short-read methods for this problem such as MindTheGap (Rizk et al (2014)), ANISE and BASIL (Holtgrewe et al (2015)), PopIns (Kehr et al (2016)) or Pamir (Kavak et al (2017)) appended population-based techniques (e.g. allowing multiple low-coverage samples from the same population) or used additional whole genome signals such as split-reads for better breakpoint resolution.…”

Section: Introductionmentioning

confidence: 99%

“…A more recent method, PopIns (Kehr et al (2016)) presents an algorithm that uses information from different samples to find novel insertion sequences common to an ancestral population. The most recent algorithm Pamir (Kavak et al (2017)) also generalizes NovelSeq's approach for handling several low coverage genomes from the same population. Moreover, the accuracy and number of novel sequence insertions discovery were improved due to split-read signature usage and a non-greedy approach to match insertion sequences with their anchors.…”

Section: Introductionmentioning

confidence: 99%

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Detection and assembly of novel sequence insertions using Linked-Read technology

Meleshko

Marks

Williams

et al. 2019

Preprint

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Motivation: Emerging Linked-Read (aka read-cloud) technologies such as the 10x Genomics Chromium system have great potential for accurate detection and phasing of largescale human genome structural variations (SVs). By leveraging the long-range information encoded in Linked-Read sequencing, computational techniques are able to detect and characterize complex structural variations that are previously undetectable by short-read methods. However, there is no available Linked-Read method for detection and assembly of novel sequence insertions, DNA sequences present in a given sequenced sample but missing in the reference genome, without requiring whole genome de novo assembly. In this paper, we propose a novel integrated alignment-based and local-assembly-based algorithm, Novel-X, that effectively uses the barcode information encoded in Linked-Read sequencing datasets to improve detection of such events without the need of whole genome de novo assembly. We evaluated our method on two haploid human genomes, CHM1 and CHM13, sequenced on the 10x Genomics Chromium system. These genomes have been also characterized with high coverage PacBio long-reads recently. We also tested our method on NA12878, the wellknown HapMap CEPH diploid genome and the child genome in a Yoruba trio (NA19240) which was recently studied on multiple sequencing platforms. Detecting insertion events is very challenging using short reads and the only viable available solution is by long-read sequencing (e.g. PabBio or ONT). Our experiments, however, show that Novel-X finds many insertions that cannot be found by state of the art tools using short-read sequencing data but present in PacBio data. Since Linked-Read sequencing is significantly cheaper than long-read sequencing, our method using Linked-Reads enables routine large-scale screenings of sequenced genomes for novel sequence insertions.

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A high-quality cucumber genome assembly enhances computational comparative genomics

et al. 2019

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Genetic variation is expressed by the presence of polymorphisms in compared genomes of individuals that can be transferred to next generations. The aim of this work was to reveal genome dynamics by predicting polymorphisms among the genomes of three individuals of the highly inbred B10 cucumber (Cucumis sativus L.) line. In this study, bioinformatic comparative genomics was used to uncover cucumber genome dynamics (also called real-time evolution). We obtained a new genome draft assembly from long single molecule real-time (SMRT) sequencing reads and used short paired-end read data from three individuals to analyse the polymorphisms. Using this approach, we uncovered differentiation aspects in the genomes of the inbred B10 line. The newly assembled genome sequence (B10v3) has the highest contiguity and quality characteristics among the currently available cucumber genome draft sequences. Standard and newly designed approaches were used to predict single nucleotide and structural variants that were unique among the three individual genomes. Some of the variant predictions spanned protein-coding genes and their promoters, and some were in the neighbourhood of annotated interspersed repetitive elements, indicating that the highly inbred homozygous plants remained genetically dynamic. This is the first bioinformatic comparative genomics study of a single highly inbred plant line. For this project, we developed a polymorphism prediction method with optimized precision parameters, which allowed the effective detection of small nucleotide variants (SNVs). This methodology could significantly improve bioinformatic pipelines for comparative genomics and thus has great practical potential in genomic metadata handling.

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Discovery and genotyping of novel sequence insertions in many sequenced individuals

Cited by 32 publications

References 37 publications

Toolkit for automated and rapid discovery of structural variants

Toolkit for automated and rapid discovery of structural variants

Detection and assembly of novel sequence insertions using Linked-Read technology

A high-quality cucumber genome assembly enhances computational comparative genomics

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