Mapping and phasing of structural variation in patient genomes using nanopore sequencing

Stancu, Mircea Cretu; Roosmalen, Markus J. van; Renkens, Ivo; Nieboer, Marleen M.; Middelkamp, Sjors; Ligt, Joep de; Pregno, Giulia; Giachino, Daniela; Mandrile, Giorgia; Valle-Inclán, Jose Espejo; Korzelius, Jerome; Bruijn, Ewart de; Cuppen, Edwin; Talkowski, Michael E.; Marschall, Tobias; Ridder, Jeroen de; Kloosterman, Wigard P.

doi:10.1038/s41467-017-01343-4

Cited by 336 publications

(240 citation statements)

References 53 publications

(86 reference statements)

Supporting

Mentioning

236

Contrasting

Unclassified

Order By: Relevance

“…Notably, long reads are critical in structural variation analysis and the complete sequencing of repetitive DNA contents of clinical utility. Another group developed a new bioinformatics tool, NanoSV, for structural variation detection with nanopore data using split read mapping (Cretu Stancu et al, 2017). Another group developed a new bioinformatics tool, NanoSV, for structural variation detection with nanopore data using split read mapping (Cretu Stancu et al, 2017).…”

Section: Ultr A-long Re Ads -" Whale Watching"mentioning

confidence: 99%

“…Norris and colleagues demonstrated that nanopore sequencers could detect large-scale structural variations, including large deletions, inversions, and translocations related to the inactivation of tumor suppressor genes in pancreatic cancer, with very few reads (Norris, Workman, Fan, Eshleman, & Timp, 2016). Another group developed a new bioinformatics tool, NanoSV, for structural variation detection with nanopore data using split read mapping (Cretu Stancu et al, 2017). Mitsuhashi and colleagues successfully identified a full-length microsatellite repeat spanning 49,877 bp in the D4Z4 array responsible for facioscapulohumeral muscular dystrophy .…”

Section: Ultr A-long Re Ads -" Whale Watching"mentioning

confidence: 99%

“…Long reads also allow the study of structural variations within the genome (Cretu Stancu et al, 2017). The extremely long reads are also useful to determine sequences of genomic region containing long repetitive sequences, which is difficult with short read sequencing.…”

mentioning

confidence: 99%

“…A successor of PBcR(Miller et al, 2008) (Koren et al, 2017) SMARTdenovo Fast and reasonably accurate OLC assembler for long reads without prior error correction step(Giordano et al, 2017) TULIP Efficient assembler for large and complex genome using seed extension(Jansen et al, 2017) Falcon Long read assembler for phased diploid genome(Chin et al, 2016) Miniasm Efficient assembler for SMRT and ONT reads without an error correction(Li, 2016) NanoSV Breakpoint junction detection of structural variant using mapping BAM file produced by LAST(Cretu Stancu et al, 2017) Sniffles Structural variation caller using automatic filtering of false events based on coverage data(Sedlazeck et al, 2018) npInv Specially designed tool for non-allelic homologous recombination (NAHR) inversions BWA-MEM Leading short read mapping tool tuned to work with ONT recently https://github.com/lh3/bwa Others NanoPipe Interactive web-based tool for fast and easy processing and analysis of the ONT data(Shabardina et al, 2019) BulkVis Visualization tool for bulk FAST5 files obtained from ONT sequencing A successor of PBcR(Miller et al, 2008) (Koren et al, 2017) SMARTdenovo Fast and reasonably accurate OLC assembler for long reads without prior error correction step(Giordano et al, 2017) TULIP Efficient assembler for large and complex genome using seed extension(Jansen et al, 2017) Falcon Long read assembler for phased diploid genome(Chin et al, 2016) Miniasm Efficient assembler for SMRT and ONT reads without an error correction(Li, 2016) NanoSV Breakpoint junction detection of structural variant using mapping BAM file produced by LAST(Cretu Stancu et al, 2017) Sniffles Structural variation caller using automatic filtering of false events based on coverage data(Sedlazeck et al, 2018) npInv Specially designed tool for non-allelic homologous recombination (NAHR) inversions BWA-MEM Leading short read mapping tool tuned to work with ONT recently https://github.com/lh3/bwa Others NanoPipe Interactive web-based tool for fast and easy processing and analysis of the ONT data(Shabardina et al, 2019) BulkVis Visualization tool for bulk FAST5 files obtained from ONT sequencing…”

mentioning

confidence: 99%

“…The extremely long reads are also useful to determine sequences of genomic region containing long repetitive sequences, which is difficult with short read sequencing. Long reads also allow the study of structural variations within the genome (Cretu Stancu et al, 2017). Moreover, detection of the ionic current changes shifted by the nucleotides passing through the nanopore is not limited to the canonical four nucleobases of adenine, guanine, cytosine and thymine.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Nanopore sequencing: Review of potential applications in functional genomics

2019

View full text Add to dashboard Cite

Molecular biology has been led by various measurement technologies, and increased throughput has developed omics analysis. The development of massively parallel sequencing technology has enabled access to fundamental molecular data and revealed genomic and transcriptomic signatures. Nanopore sequencers have driven such evolution to the next stage. Oxford Nanopore Technologies Inc. provides a new type of single molecule sequencer using protein nanopore that realizes direct sequencing without DNA synthesizing or amplification. This nanopore sequencer can sequence an ultra‐long read limited by the input nucleotide length, or can determine DNA/RNA modifications. Recently, many fields such as medicine, epidemiology, ecology, and education have benefited from this technology. In this review, we explain the features and functions of the nanopore sequencer, introduce various situations where it has been used as a critical technology, and expected future applications.

show abstract

Section: Ultr A-long Re Ads -" Whale Watching"mentioning

confidence: 99%

Section: Ultr A-long Re Ads -" Whale Watching"mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Nanopore sequencing: Review of potential applications in functional genomics

2019

View full text Add to dashboard Cite

show abstract

Diagnostic capabilities of nanopore long‐read sequencing in muscular dystrophy

Bruels

Littel

Daugherty

et al. 2022

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Many individuals with muscular dystrophies remain genetically undiagnosed despite clinical diagnostic testing, including exome sequencing. Some may harbor previously undetected structural variants (SVs) or cryptic splice sites. We enrolled 10 unrelated families: nine had muscular dystrophy but lacked complete genetic diagnoses and one had an asymptomatic DMD duplication. Nanopore genomic long‐read sequencing identified previously undetected pathogenic variants in four individuals: an SV in DMD, an SV in LAMA2, and two single nucleotide variants in DMD that alter splicing. The DMD duplication in the asymptomatic individual was in tandem. Nanopore sequencing may help streamline genetic diagnostic approaches for muscular dystrophy.

show abstract

Long‐read sequencing and optical genome mapping identify causative gene disruptions in noncoding sequence in two patients with neurologic disease and known chromosome abnormalities

Sund,

Liu,

Lee

et al. 2024

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Despite advances in next generation sequencing (NGS), genetic diagnoses remain elusive for many patients with neurologic syndromes. Long‐read sequencing (LRS) and optical genome mapping (OGM) technologies improve upon existing capabilities in the detection and interpretation of structural variation in repetitive DNA, on a single haplotype, while also providing enhanced breakpoint resolution. We performed LRS and OGM on two patients with known chromosomal rearrangements and inconclusive Sanger or NGS. The first patient, who had epilepsy and developmental delay, had a complex translocation between two chromosomes that included insertion and inversion events. The second patient, who had a movement disorder, had an inversion on a single chromosome disrupted by multiple smaller inversions and insertions. Sequence level resolution of the rearrangements identified pathogenic breaks in noncoding sequence in or near known disease‐causing genes with relevant neurologic phenotypes (MBD5, NKX2‐1). These specific variants have not been reported previously, but expected molecular consequences are consistent with previously reported cases. As the use of LRS and OGM technologies for clinical testing increases and data analyses become more standardized, these methods along with multiomic data to validate noncoding variation effects will improve diagnostic yield and increase the proportion of probands with detectable pathogenic variants for known genes implicated in neurogenetic disease.

show abstract

Mapping and phasing of structural variation in patient genomes using nanopore sequencing

Cited by 336 publications

References 53 publications

Nanopore sequencing: Review of potential applications in functional genomics

Nanopore sequencing: Review of potential applications in functional genomics

Diagnostic capabilities of nanopore long‐read sequencing in muscular dystrophy

Long‐read sequencing and optical genome mapping identify causative gene disruptions in noncoding sequence in two patients with neurologic disease and known chromosome abnormalities

Contact Info

Product

Resources

About