Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma
| Autor: | Samantha J. L. Knight, Hannah E. Roberts, Helene Dreau, Helen Lockstone, Maria Lopopolo, Alistair T. Pagnamenta, David Buck, D. E. Parkes, Jenny C. Taylor, Lorne Lonie, Eshita Sharma, Colin Freeman, Gerton Lunter, Rory Bowden, Anna Schuh |
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| Přispěvatelé: | Life Course Epidemiology (LCE) |
| Rok vydání: | 2020 |
| Předmět: |
DNA Copy Number Variations
Somatic cell Science Computational biology Biology Genome informatics medicine.disease_cause Polymorphism Single Nucleotide Sensitivity and Specificity Genome Article DNA sequencing Germline 03 medical and health sciences 0302 clinical medicine medicine Chromosomes Human Humans Clinical genetics Cancer genetics 030304 developmental biology Haematological cancer 0303 health sciences Mutation Multidisciplinary Base Sequence Whole Genome Sequencing Genome Human Chromosome Mapping Computational Biology High-Throughput Nucleotide Sequencing Structural variant Genomics Genes p53 medicine.disease Nanopore Sequencing Germ Cells 030220 oncology & carcinogenesis Medicine Lymphoma Large B-Cell Diffuse Nanopore sequencing Tumor Suppressor Protein p53 Diffuse large B-cell lymphoma Algorithms |
| Zdroj: | Scientific Reports, 11(1):6408. Nature Publishing Group Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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