Structural Variation Detection from Next Generation Sequencing

Ye, Kai; Hall, George T.; Ning, Zemin

doi:10.4172/2469-9853.s1-007

Cited by 12 publications

(9 citation statements)

References 49 publications

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“…As no single informatics tool can detect the full range of SVs regarding size and subtype [5], integrated methods have been proposed [6, 7], with de novo assembly of tumor genomes remaining a challenge. While long-read (up to thousands of bases) sequencing methods, such as single-molecule sequencing from Pacific Biosystems (PacBio) and Oxford Nanopore, are improving SV detection [8, 9], they are still limited by relatively high costs, low throughput and relatively high error rates.…”

Section: Introductionmentioning

confidence: 99%

Next generation mapping reveals novel large genomic rearrangements in prostate cancer

et al. 2017

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Complex genomic rearrangements are common molecular events driving prostate carcinogenesis. Clinical significance, however, has yet to be fully elucidated. Detecting the full range and subtypes of large structural variants (SVs), greater than one kilobase in length, is challenging using clinically feasible next generation sequencing (NGS) technologies. Next generation mapping (NGM) is a new technology that allows for the interrogation of megabase length DNA molecules outside the detection range of single-base resolution NGS. In this study, we sought to determine the feasibility of using the Irys (Bionano Genomics Inc.) nanochannel NGM technology to generate whole genome maps of a primary prostate tumor and matched blood from a Gleason score 7 (4 + 3), ETS-fusion negative prostate cancer patient. With an effective mapped coverage of 35X and sequence coverage of 60X, and an estimated 43% tumor purity, we identified 85 large somatic structural rearrangements and 6,172 smaller somatic variants, respectively. The vast majority of the large SVs (89%), of which 73% are insertions, were not detectable ab initio using high-coverage short-read NGS. However, guided manual inspection of single NGS reads and de novo assembled scaffolds of NGM-derived candidate regions allowed for confirmation of 94% of these large SVs, with over a third impacting genes with oncogenic potential. From this single-patient study, the first cancer study to integrate NGS and NGM data, we hypothesise that there exists a novel spectrum of large genomic rearrangements in prostate cancer, that these large genomic rearrangements are likely early events in tumorigenesis, and they have potential to enhance taxonomy.

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Section: Introductionmentioning

confidence: 99%

Next generation mapping reveals novel large genomic rearrangements in prostate cancer

et al. 2017

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“…Medical conditions that are genetically determined or have a strong genetic component arise from a variety of DNA alterations. These molecular events include SNV [referred to as single nucleotide polymorphism (SNP)] if they occur to some appreciable degree (>1%) in a population) and structural DNA changes, such as copy number variation (CNV), short insertions and deletions (indels), repetitions, large insertions and deletions, translocations (can result in fusion genes), inversions, aneuploidy, and ploidy (Ye et al, 2016). WES is primarily used for the detection of SNV/SNPs and indels within the coding regions of a genome.…”

Section: New Generation Of Big Data Analyticsmentioning

confidence: 99%

Advancing Personalized Medicine Through the Application of Whole Exome Sequencing and Big Data Analytics

et al. 2019

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There is a growing attention toward personalized medicine. This is led by a fundamental shift from the ‘one size fits all’ paradigm for treatment of patients with conditions or predisposition to diseases, to one that embraces novel approaches, such as tailored target therapies, to achieve the best possible outcomes. Driven by these, several national and international genome projects have been initiated to reap the benefits of personalized medicine. Exome and targeted sequencing provide a balance between cost and benefit, in contrast to whole genome sequencing (WGS). Whole exome sequencing (WES) targets approximately 3% of the whole genome, which is the basis for protein-coding genes. Nonetheless, it has the characteristics of big data in large deployment. Herein, the application of WES and its relevance in advancing personalized medicine is reviewed. WES is mapped to Big Data “10 Vs” and the resulting challenges discussed. Application of existing biological databases and bioinformatics tools to address the bottleneck in data processing and analysis are presented, including the need for new generation big data analytics for the multi-omics challenges of personalized medicine. This includes the incorporation of artificial intelligence (AI) in the clinical utility landscape of genomic information, and future consideration to create a new frontier toward advancing the field of personalized medicine.

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“…A loss-of-function retrotransposon insertion led to adaptation to cultivation at high latitudes in a photoperiod-insensitive soybean landrace [86]. The de novo detection of SVs requires a deeper sequence coverage compared with the low-fold approaches usually employed in resequencing [87,88]. To overcome some of these limitations, a metagenome-like assembly strategy based on a low-coverage population sequencing data was employed for the construction of the dispensable rice genome as a more cost-and labor-effective strategy [89].…”

Section: Genomic Scans Of Local Adaptation In Landracesmentioning

confidence: 99%

Towards the Genomic Basis of Local Adaptation in Landraces

Corrado

Rao

2017

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Landraces are key elements of agricultural biodiversity that have long been considered a source of useful traits. Their importance goes beyond subsistence agriculture and the essential need to preserve genetic diversity, because landraces are farmer-developed populations that are often adapted to environmental conditions of significance to tackle environmental concerns. It is therefore increasingly important to identify adaptive traits in crop landraces and understand their molecular basis. This knowledge is potentially useful for promoting more sustainable agricultural techniques, reducing the environmental impact of high-input cropping systems, and diminishing the vulnerability of agriculture to global climate change. In this review, we present an overview of the opportunities and limitations offered by landraces' genomics. We discuss how rapid advances in DNA sequencing techniques, plant phenotyping, and recombinant DNA-based biotechnology encourage both the identification and the validation of the genomic signature of local adaptation in crop landraces. The integration of 'omics' sciences, molecular population genetics, and field studies can provide information inaccessible with earlier technological tools. Although empirical knowledge on the genetic and genomic basis of local adaptation is still fragmented, it is predicted that genomic scans for adaptation will unlock an intraspecific molecular diversity that may be different from that of modern varieties.Keywords: genomics; differentiation; genome-environment association Crop LandracesPublic awareness on the importance of biodiversity conservation is strengthening over time [1]. Climate change, pollution, environmental disasters, loss of natural habitats, environmental degradation, and overexploitation of resources regularly make front-page news. Without taking into consideration the impact of the measures implemented to avoid biodiversity loss, large attention is generally given to wild species, especially those at risk of extinction [1,2]. Agricultural biodiversity (i.e., the variety and variability of animals, plants, and microorganisms that are used directly or indirectly for food and agriculture [3]) is largely regarded as a subset of biodiversity. However, agriculture and biodiversity are closely tied. Their mutual dependence is crucial not only to ensure yield today, but also to contribute to a more resilient, sustainable agriculture. This includes the development of solutions for water-saving technologies and for minimizing the detrimental effects of global climate change on crops [4,5].Plant genetic resources for food and agriculture (PGRFA) are the central components of agricultural biodiversity because they constitute the primary elements of the production process. Crop improvement relies on genetic diversity. Taking into account the trends and efforts of modern breeding, the main part of genetic diversity of cultivated species is expected to be found in traditional varieties, also known as landraces. It is not easy to provide an all-p...

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Structural Variation Detection from Next Generation Sequencing

Cited by 12 publications

References 49 publications

Next generation mapping reveals novel large genomic rearrangements in prostate cancer

Next generation mapping reveals novel large genomic rearrangements in prostate cancer

Advancing Personalized Medicine Through the Application of Whole Exome Sequencing and Big Data Analytics

Towards the Genomic Basis of Local Adaptation in Landraces

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