Validation of the new EPIC DNA methylation microarray (900K EPIC v2) for high-throughput profiling of the human DNA methylome

Noguera‐Castells, Aleix; García-Prieto, Carlos A.; Álvarez-Errico, Damiana; Esteller, Manel

doi:10.1080/15592294.2023.2185742

Cited by 18 publications

(20 citation statements)

References 30 publications

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“…We overcome this limitation by employing iSCORED method to concatenate small digested genomic fragments in one reaction, significantly improving sequencing efficiency and achieving molecular analysis within craniotomy surgical windows (3-4 hours). In contrast to other sequencing platforms 17 and hybridization-based arrays 23,39 , the low cost per sample, a mere $125 USD, and the ease of setting up the infrastructure with a budget of $6,000-8,000 USD for MinION and $14,000-16,000 USD for PromethION make it an economical option for clinical applications (Additional table 3). Notably, the unmatched turnaround time of 120-140 minutes further positions our method as a robust and invaluable tool for widespread implementation in clinical settings (Additional table 1).…”

Section: Discussionmentioning

confidence: 99%

iSCORED: nanopore-based random genomic sampling for intraoperative molecular diagnosis

Emiliani,

Ould Ismail,

Hughes

et al. 2023

Preprint

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Copy number variations (CNVs) are almost ubiquitous in cancer. In many cases, somatic CNV analysis has led to the identification of oncogenic pathways and suggested molecular-defined therapeutic targets. Here, we develop iSCORED, a one-step random genomic DNA reconstruction method that enables efficient, unbiased quantification of CNVs using a real-time Nanopore sequencer. By leveraging the long concatenated reads, we generate approximately 1-2 million genomic fragments within one hour of MinION sequencing, allowing for high-resolution genomic dosage comparisons. In our cohort of 26 malignant brain tumors, we demonstrated 100% concordance in CNV detections, including chromosomal alterations and oncogene amplifications when compared to clinically validated next generation sequencing and chromosomal microarray results. In addition, iSCORED allows concurrent brain tumor methylation classification without additional tissue preparation. The integrated methylation information revealed promoter hypomethylation in all detected amplified oncogenes. The entire workflow, including the automatic generation of CNV and methylation reports, can be accomplished within 120-140 minutes. Ultrafast molecular analysis can enhance clinical decision-making, optimize surgical planning and identify potential molecular therapies within surgical timeframes.

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Section: Discussionmentioning

confidence: 99%

iSCORED: nanopore-based random genomic sampling for intraoperative molecular diagnosis

Emiliani,

Ould Ismail,

Hughes

et al. 2023

Preprint

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Section: Practical Utilization Of Dna Methylome‐based Classificationmentioning

confidence: 99%

“…The EPIC array is particularly notable for its expanded coverage of regulatory regions, high reproducibility, and reliability, encompassing approximately 90% of the CpG sites included in the 450 K. 71 The Infinium Methylation EPIC v2.0 BeadChip (EPICv2, 900 K), the latest version of the microarray includes >935 000 CpG sites, further incorporates additional DNA cis-regulatory regions, such as enhancers, super-enhancers, and CCTCT-binding factor regions. 72 The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) discloses a web platform for the DNA methylation-based classifier (referred to as the "DKFZ classifier" in this review article) for CNS tumors, sarcomas, and skin tumors (http://molecularneuropathology.org/). 17 Built upon a machine-learning technique, predicted results intriguingly correlate tumor types and subtypes with the morphological or morpho-genetic features of CNS tumors, eliminating the need for DNA sequencing or fusion analysis.…”

Section: Tumor Subtypingmentioning

confidence: 99%

Decoding the DNA methylome of central nervous system tumors: An emerging modality for integrated diagnosis

Satomi,

Ichimura,

Shibahara

2024

Pathology International

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The definitive diagnosis and classification of individual cancers are crucial for patient care and cancer research. To achieve a robust diagnosis of central nervous system (CNS) tumors, a genotype‐phenotype integrated diagnostic approach was introduced in recent versions of the World Health Organization classification, followed by the incorporation of a genome‐wide DNA methylome‐based classification. Microarray‐based platforms are widely used to obtain DNA methylome data, and the German Cancer Research Center (Deutsches Krebsforschungszentrum [DKFZ]) has a webtool for a DNA methylation‐based classifier (DKFZ classifier). Integration of DNA methylome will further enhance the precision of CNS tumor classification, especially in diagnostically challenging cases. However, in the clinical application of DNA methylome‐based classification, challenges related to data interpretation persist, in addition to technical caveats, regulations, and limited accessibility. Dimensionality reduction (DMR) can complement integrated diagnosis by visualizing a profile and comparing it with other known samples. Therefore, DNA methylome‐based classification is a highly useful research tool for auxiliary analysis in challenging diagnostic and rare disease cases, and for establishing novel tumor concepts. Decoding the DNA methylome, especially by DMR in addition to DKFZ classifier, emphasizes the capability of grasping the fundamental biological principles that provide new perspectives on CNS tumors.

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Illumina DNA methylation arrays are frequently used for the discovery of methylation signatures associated with aging and disease [2]. With the latest InfiniumMethylation EPIC BeadChips v1.0 and v2.0 covering 850-900K CpG sites across the human

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mentioning

confidence: 99%

“… Summary Illumina DNA methylation arrays are frequently used for the discovery of methylation signatures associated with aging and disease [2]. With the latest InfiniumMethylation EPIC BeadChips v1.0 and v2.0 covering 850-900K CpG sites across the human genome, one of the major hurdles to overcome when training trait prediction models is the high dimensionality of the data, with the number of features (target CpGs) greatly exceeding the typical number of samples assessed.…”

mentioning

confidence: 99%

Devising reliable and accurate epigenetic predictors: choosing the optimal computational solution

Vavourakis,

Herzog,

Widschwendter

2023

Preprint

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ARISING FROM A.T. Higgins-Chen et al. Nature Aging https://doi.org/10.1038/s43587-022-00248-2 (2022) [1] Illumina DNA methylation arrays are frequently used for the discovery of methylation signatures associated with aging and disease [2]. With the latest Infinium Methylation EPIC BeadChips v1.0 and v2.0 covering 850-900K CpG sites across the human genome, one of the major hurdles to overcome when training trait prediction models is the high dimensionality of the data, with the number of features (target CpGs) greatly exceeding the typical number of samples assessed. In addition, most large-scale DNA methylation-based studies do not include replicate measurements for a given sample, making it impossible to estimate the degree of measurement uncertainty. Hence, the robustness of the assay and reliability of the prediction models are critical to ensure potential clinical utility. Recently, Higgins-Chen et al [1] proposed that training models on principal components (PCs) calculated from the data rather than directly on a selection of original features, results in more reliable age predictions. We found that dimension reduction with PCA consistently improves the reliability of age prediction models but may compromise their predictive accuracy. Our model projections further suggest that the balance in the trade-off between accuracy and precision we observed, may tip over in favor of PC-based models with increasing training sample numbers.

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Validation of the new EPIC DNA methylation microarray (900K EPIC v2) for high-throughput profiling of the human DNA methylome

Cited by 18 publications

References 30 publications

iSCORED: nanopore-based random genomic sampling for intraoperative molecular diagnosis

iSCORED: nanopore-based random genomic sampling for intraoperative molecular diagnosis

Decoding the DNA methylome of central nervous system tumors: An emerging modality for integrated diagnosis

Devising reliable and accurate epigenetic predictors: choosing the optimal computational solution

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