Evidence map›Paper›PMID 33742045›Full record

ArticleScientific reports2021

Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma.

Hannah E Roberts, Maria Lopopolo, Alistair T Pagnamenta, Eshita Sharma, Duncan Parkes, Lorne Lonie, Colin Freeman, Samantha J L Knight, Gerton Lunter, Helene Dreau and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 24 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

Hannah E Roberts *Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Maria Lopopolo *Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Alistair T Pagnamenta *Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Eshita SharmaWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Duncan ParkesWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Lorne LonieWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Colin FreemanWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Samantha J L KnightNational Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK.
Gerton LunterMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Helene DreauOxford University Hospitals NHS Trust, Oxford, UK.
Helen LockstoneWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Jenny C TaylorWellcome Centre for Human Genetics, University of Oxford, Oxford, UK. jenny.taylor@well.ox.ac.uk.
Anna SchuhNational Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK. anna.schuh@oncology.ox.ac.uk.
Rory BowdenWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
David BuckWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
University of Oxford · GBNational Institute for Health Research · GBCentre for Human Genetics · GBMRC Weatherall Institute of Molecular Medicine · GB

Funding

Wellcome Trust 203141/Z/16/Z
6 · The paper itself

Abstract

Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.

Indexed as

Genome, HumanGerm CellsPolymorphism, Single NucleotideAlgorithmsBase SequenceChromosome MappingChromosomes, HumanComputational BiologyDNA Copy Number VariationsGenes, p53GenomicsHigh-Throughput Nucleotide SequencingHumansLymphoma, Large B-Cell, DiffuseMutationNanopore SequencingTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID33742045
PMCPMC7979876
OpenAlexW3138634498

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.