Next-generation VariationHunter: combinatorial algorithms for transposon insertion discovery

Hormozdiari, Fereydoun; Hajirasouliha, Iman; Dao, Phuong; Hach, Faraz; Yörükoğlu, Deniz; Alkan, Can; Eichler, Evan E.; Şahinalp, S. Cenk

doi:10.1093/bioinformatics/btq216

Cited by 191 publications

(155 citation statements)

References 29 publications

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“…However, with the advent of next-generation sequencing, the cost of sequencing has dropped precipitously, and now it is feasible to study RDV in detail for large sample populations. Many methods have been developed to discover CNVs using sequencing data (Chen et al 2009;Korbel et al 2009;Lee et al 2009;Sindi et al 2009;Wang et al 2009;Ye et al 2009;Hajirasouliha et al 2010;Hormozdiari et al 2010;Handsaker et al 2011;Zhang et al 2011), but only a few attempted to analyze RDVs (Conrad et al 2009;Karakoc et al 2011;Schrider et al 2011Schrider et al , 2013Ewing et al 2013).…”

Section: Methods Predicting Novel Retroduplicationsmentioning

confidence: 99%

Analysis of variable retroduplications in human populations suggests coupling of retrotransposition to cell division

Abyzov¹,

Iskow

Gökçümen

et al. 2013

Genome Res.

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In primates and other animals, reverse transcription of mRNA followed by genomic integration creates retroduplications. Expressed retroduplications are either “retrogenes” coding for functioning proteins, or expressed “processed pseudogenes,” which can function as noncoding RNAs. To date, little is known about the variation in retroduplications in terms of their presence or absence across individuals in the human population. We have developed new methodologies that allow us to identify “novel” retroduplications (i.e., those not present in the reference genome), to find their insertion points, and to genotype them. Using these methods, we catalogued and analyzed 174 retroduplication variants in almost one thousand humans, which were sequenced as part of Phase 1 of The 1000 Genomes Project Consortium. The accuracy of our data set was corroborated by (1) multiple lines of sequencing evidence for retroduplication (e.g., depth of coverage in exons vs. introns), (2) experimental validation, and (3) the fact that we can reconstruct a correct phylogenetic tree of human subpopulations based solely on retroduplications. We also show that parent genes of retroduplication variants tend to be expressed at the M-to-G1 transition in the cell cycle and that M-to-G1 expressed genes have more copies of fixed retroduplications than genes expressed at other times. These findings suggest that cell division is coupled to retrotransposition and, perhaps, is even a requirement for it.

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Section: Methods Predicting Novel Retroduplicationsmentioning

confidence: 99%

Analysis of variable retroduplications in human populations suggests coupling of retrotransposition to cell division

Abyzov¹,

Iskow

Gökçümen

et al. 2013

Genome Res.

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“…Despite some successes, existing bioinformatics tools such as BreakDancer ), VariationHunter (Hormozdiari et al 2010), CREST (Wang et al 2011), and PRISM (Jiang et al 2012) are hindered by intra-tumor heterogeneity, alignment to repetitive genomic sequences, technical artifacts (i.e., library preparation), poor coverage, and a large number of false-positive calls owing to sequencing errors. The failure to predict some SVs using WGS data would therefore result in the corresponding gene fusion product being missed.…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

INTEGRATE: gene fusion discovery using whole genome and transcriptome data

et al. 2015

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While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping.

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“…Prediction methods for structural variants (SVs) have been developed to annotate diverged regions on the basis of pairedend sequencing (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Unfortunately, these predictions do not include the actual sequence of the variants, and they often miss larger rearrangements, complex changes, and small insertion/ deletions (indels).…”

mentioning

confidence: 99%

Reference-guided assembly of four diverse Arabidopsis thaliana genomes

Schneeberger

Ossowski

Ott

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

232

233

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We present whole-genome assemblies of four divergent Arabidopsis thaliana strains that complement the 125-Mb reference genome sequence released a decade ago. Using a newly developed reference-guided approach, we assembled large contigs from 9 to 42 Gb of Illumina short-read data from the Landsberg erecta (Ler-1), C24, Bur-0, and Kro-0 strains, which have been sequenced as part of the 1,001 Genomes Project for this species. Using alignments against the reference sequence, we first reduced the complexity of the de novo assembly and later integrated reads without similarity to the reference sequence. As an example, half of the noncentromeric C24 genome was covered by scaffolds that are longer than 260 kb, with a maximum of 2.2 Mb. Moreover, over 96% of the reference genome was covered by the reference-guided assembly, compared with only 87% with a complete de novo assembly. Comparisons with 2 Mb of dideoxy sequence reveal that the per-base error rate of the reference-guided assemblies was below 1 in 10,000. Our assemblies provide a detailed, genomewide picture of large-scale differences between A. thaliana individuals, most of which are difficult to access with alignment-consensus methods only. We demonstrate their practical relevance in studying the expression differences of polymorphic genes and show how the analysis of sRNA sequencing data can lead to erroneous conclusions if aligned against the reference genome alone. Genome assemblies, raw reads, and further information are accessible through http://1001genomes.org/projects/assemblies.html.

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Next-generation VariationHunter: combinatorial algorithms for transposon insertion discovery

Cited by 191 publications

References 29 publications

Analysis of variable retroduplications in human populations suggests coupling of retrotransposition to cell division

Analysis of variable retroduplications in human populations suggests coupling of retrotransposition to cell division

INTEGRATE: gene fusion discovery using whole genome and transcriptome data

Reference-guided assembly of four diverse Arabidopsis thaliana genomes

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