Technical and biological sources of unreliability of Infinium probes on Illumina methylation microarrays.

Autor: Nazarenko T; Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria.; European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Milser Str. 10, 6060, Hall in Tirol, Austria.; Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, Medical School Building, Room 340, 74 Huntley Street, London, WC1E 6AU, UK., Vavourakis CD; Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria.; European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Milser Str. 10, 6060, Hall in Tirol, Austria., Jones A; Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, Medical School Building, Room 340, 74 Huntley Street, London, WC1E 6AU, UK., Evans I; Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, Medical School Building, Room 340, 74 Huntley Street, London, WC1E 6AU, UK., Schreiberhuber L; Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria.; European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Milser Str. 10, 6060, Hall in Tirol, Austria., Kastner C; Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria.; European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Milser Str. 10, 6060, Hall in Tirol, Austria., Ishaq-Parveen I; Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria.; European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Milser Str. 10, 6060, Hall in Tirol, Austria., Redl E; Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria.; European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Milser Str. 10, 6060, Hall in Tirol, Austria., Watson AW; Human Nutrition and Exercise Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK., Brandt K; Human Nutrition and Exercise Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK., Carter C; Transplant and Cellular Immunology Laboratories, Leeds Teaching Hospital NHS Trust, St James's University Hospital, Leeds, LS9 7TF, UK., Zaikin A; Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, Medical School Building, Room 340, 74 Huntley Street, London, WC1E 6AU, UK., Herzog CMS; Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria. Chiara.Herzog@uibk.ac.at.; European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Milser Str. 10, 6060, Hall in Tirol, Austria. Chiara.Herzog@uibk.ac.at., Widschwendter M; Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria. Martin.Widschwendter@uibk.ac.at.; European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Milser Str. 10, 6060, Hall in Tirol, Austria. Martin.Widschwendter@uibk.ac.at.; Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, Medical School Building, Room 340, 74 Huntley Street, London, WC1E 6AU, UK. Martin.Widschwendter@uibk.ac.at.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2024 Sep 18; Vol. 16 (1), pp. 131. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1186/s13148-024-01739-2
Abstrakt: The Illumina Methylation array platform has facilitated countless epigenetic studies on DNA methylation (DNAme) in health and disease, yet relatively few studies have so studied its reliability, i.e., the consistency of repeated measures. Here we investigate the reliability of both type I and type II Infinium probes. We propose a method for excluding unreliable probes based on dynamic thresholds for mean intensity (MI) and 'unreliability', estimated by probe-level simulation of the influence of technical noise on methylation β values using the background intensities of negative control probes. We validate our method in several datasets, including newly generated Illumina MethylationEPIC BeadChip v1.0 data from paired whole blood samples taken six weeks apart and technical replicates spanning multiple sample types. Our analysis revealed that specifically probes with low MI exhibit higher β value variability between repeated samples. MI was associated with the number of C-bases in the respective probe sequence and correlated negatively with unreliability scores. The unreliability scores were substantiated through validation in a new EPIC v1.0 (blood and cervix) and a publicly available 450k (blood) dataset, as they effectively captured the variability observed in β values between technical replicates. Finally, despite promising higher robustness, the newer version v2.0 of the MethylationEPIC BeadChip retained a substantial number of probes with poor unreliability scores. To enhance current pre-processing pipelines, we developed an R package to calculate MI and unreliability scores and provide guidance on establishing optimal dynamic score thresholds for a given dataset.
(© 2024. The Author(s).)
Databáze: MEDLINE
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