Accurate and comprehensive evaluation of O6‐methylguanine‐DNA methyltransferase promoter methylation by nanopore sequencing Article Swipe
Skarphéðinn Halldórsson
,
Richárd Nagymihály
,
Areeba Patel
,
Petter Brandal
,
Ioannis Panagopoulos
,
Henning Leske
,
Marius Lund‐Iversen
,
Felix Sahm
,
Einar Osland Vik-Mo
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1111/nan.12984
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1111/nan.12984
Aims The methylation status of the O6‐methylguanine‐DNA methyltransferase ( MGMT ) promoter region is essential in evaluating the prognosis and predicting the drug response in patients with glioblastoma. In this study, we evaluated the utility of using nanopore long‐read sequencing as a method for assessing methylation levels throughout the MGMT CpG‐island, compared its performance to established techniques and demonstrated its clinical applicability. Methods We analysed 165 samples from CNS tumours, focusing on the MGMT CpG‐island using nanopore sequencing. Oxford Nanopore Technologies (ONT) MinION and PromethION flow cells were employed for single sample or barcoded assays, guided by a CRISPR/Cas9 protocol, adaptive sampling or as part of a whole genome sequencing assay. Methylation data obtained through nanopore sequencing were compared to results obtained via pyrosequencing and methylation bead arrays. Hierarchical clustering was applied to nanopore sequencing data for patient stratification. Results Nanopore sequencing displayed a strong correlation (R 2 = 0.91) with pyrosequencing results for the four CpGs of MGMT analysed by both methods. The MGMT ‐STP27 algorithm's classification was effectively reproduced using nanopore data. Unsupervised hierarchical clustering revealed distinct patterns in methylated and unmethylated samples, providing comparable survival prediction capabilities. Nanopore sequencing yielded high‐confidence results in a rapid timeframe, typically within hours of sequencing, and extended the analysis to all 98 CpGs of the MGMT CpG‐island. Conclusions This study presents nanopore sequencing as a valid and efficient method for determining MGMT promotor methylation status. It offers a comprehensive view of the MGMT promoter methylation landscape, which enables the identification of potentially clinically relevant subgroups of patients. Further exploration of the clinical implications of patient stratification using nanopore sequencing of MGMT is warranted.
Related Topics
Concepts
Nanopore sequencing
Nanopore
Minion
Methylation
CpG site
Pyrosequencing
DNA sequencing
Methyltransferase
Computational biology
Biology
DNA methylation
DNA
Genetics
Gene
Nanotechnology
Materials science
Gene expression
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1111/nan.12984
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/nan.12984
- OA Status
- hybrid
- Cited By
- 5
- References
- 40
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4398780099
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4398780099Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1111/nan.12984Digital Object Identifier
- Title
-
Accurate and comprehensive evaluation of O6‐methylguanine‐DNA methyltransferase promoter methylation by nanopore sequencingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-05-23Full publication date if available
- Authors
-
Skarphéðinn Halldórsson, Richárd Nagymihály, Areeba Patel, Petter Brandal, Ioannis Panagopoulos, Henning Leske, Marius Lund‐Iversen, Felix Sahm, Einar Osland Vik-MoList of authors in order
- Landing page
-
https://doi.org/10.1111/nan.12984Publisher landing page
- PDF URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/nan.12984Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/nan.12984Direct OA link when available
- Concepts
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Nanopore sequencing, Nanopore, Minion, Methylation, CpG site, Pyrosequencing, DNA sequencing, Methyltransferase, Computational biology, Biology, DNA methylation, DNA, Genetics, Gene, Nanotechnology, Materials science, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
5Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 1Per-year citation counts (last 5 years)
- References (count)
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40Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W4200327950, https://openalex.org/W4211220688, https://openalex.org/W2778283729, https://openalex.org/W2158649478, https://openalex.org/W3180248796, https://openalex.org/W2034535752, https://openalex.org/W2342351330, https://openalex.org/W2082561902, https://openalex.org/W2896789619, https://openalex.org/W4379600627, https://openalex.org/W1911801098, https://openalex.org/W2026770360, https://openalex.org/W2171418517, https://openalex.org/W3158989562, https://openalex.org/W7073872078, https://openalex.org/W2082825869, https://openalex.org/W3004807164, https://openalex.org/W3004226875, https://openalex.org/W4226061119, https://openalex.org/W3035993604, https://openalex.org/W2048796627, https://openalex.org/W6684463743, https://openalex.org/W2282164829, https://openalex.org/W2105100844, https://openalex.org/W2887431954, https://openalex.org/W2103645386, https://openalex.org/W4386216377, https://openalex.org/W4309014876, https://openalex.org/W2121090755, https://openalex.org/W2914759518, https://openalex.org/W2743802042, https://openalex.org/W2903049418, https://openalex.org/W2550586733, https://openalex.org/W1965705450, https://openalex.org/W2168909179, https://openalex.org/W3134360287, https://openalex.org/W2948734763, https://openalex.org/W2982850649, https://openalex.org/W2330247213, https://openalex.org/W4213184163 |
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