MLiftOver: Harmonizing Data Across Infinium DNA Methylation Platforms

Overview

Journal Bioinformatics

Publisher Oxford University Press

Specialty Biology

Date 2024 Jul 4

PMID 38963309

Authors

Brian H Chen

Wanding Zhou

Affiliations

Soon will be listed here.

Abstract

Motivation: Infinium DNA methylation BeadChips are widely used for genome-wide DNA methylation profiling at the population scale. Recent updates to probe content and naming conventions in the EPIC version 2 (EPICv2) arrays have complicated integrating new data with previous Infinium array platforms, such as the MethylationEPIC (EPIC) and the HumanMethylation450 (HM450) BeadChip.

Results: We present mLiftOver, a user-friendly tool that harmonizes probe ID, methylation level, and signal intensity data across different Infinium platforms. It manages probe replicates, missing data imputation, and platform-specific bias for accurate data conversion. We validated the tool by applying HM450-based cancer classifiers to EPICv2 cancer data, achieving high accuracy. Additionally, we successfully integrated EPICv2 healthy tissue data with legacy HM450 data for tissue identity analysis and produced consistent copy number profiles in cancer cells.

Availability And Implementation: mLiftOver is implemented R and available in the Bioconductor package SeSAMe (version 1.21.13+): https://bioconductor.org/packages/release/bioc/html/sesame.html. Analysis of EPIC and EPICv2 platform-specific bias and high-confidence mapping is available at https://github.com/zhou-lab/InfiniumAnnotationV1/raw/main/Anno/EPICv2/EPICv2ToEPIC_conversion.tsv.gz. The source code is available at https://github.com/zwdzwd/sesame/blob/devel/R/mLiftOver.R under the MIT license.

Citing Articles

Discrepancies in readouts between Infinium MethylationEPIC v2.0 and v1.0 reflected in DNA methylation-based tools: implications and considerations for human population epigenetic studies.

Zhuang B, Jude M, Konwar C, Yusupov N, Ryan C, Engelbrecht H bioRxiv. 2024; .

PMID: 39005299 PMC: 11245009. DOI: 10.1101/2024.07.02.600461.

References

Maden S, Thompson R, Hansen K, Nellore A . Human methylome variation across Infinium 450K data on the Gene Expression Omnibus. NAR Genom Bioinform. 2021; 3(2):lqab025. PMC: 8061458. DOI: 10.1093/nargab/lqab025. View

Mannens M, Lombardi M, Alders M, Henneman P, Bliek J . Further Introduction of DNA Methylation (DNAm) Arrays in Regular Diagnostics. Front Genet. 2022; 13:831452. PMC: 9289263. DOI: 10.3389/fgene.2022.831452. View

Zhou W, Triche Jr T, Laird P, Shen H . SeSAMe: reducing artifactual detection of DNA methylation by Infinium BeadChips in genomic deletions. Nucleic Acids Res. 2018; 46(20):e123. PMC: 6237738. DOI: 10.1093/nar/gky691. View

Hawe J, Wilson R, Schmid K, Zhou L, Lakshmanan L, Lehne B . Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function. Nat Genet. 2022; 54(1):18-29. PMC: 7617265. DOI: 10.1038/s41588-021-00969-x. View

Zhou B, Ho S, Greer S, Zhu X, Bell J, Arthur J . Comprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562. Genome Res. 2019; 29(3):472-484. PMC: 6396411. DOI: 10.1101/gr.234948.118. View

Noguera-Castells A, Garcia-Prieto C, Alvarez-Errico D, Esteller M . Validation of the new EPIC DNA methylation microarray (900K EPIC v2) for high-throughput profiling of the human DNA methylome. Epigenetics. 2023; 18(1):2185742. PMC: 9988339. DOI: 10.1080/15592294.2023.2185742. View

Ding W, Kaur D, Horvath S, Zhou W . Comparative epigenome analysis using Infinium DNA methylation BeadChips. Brief Bioinform. 2023; 24(1). PMC: 10147478. DOI: 10.1093/bib/bbac617. View

Bibikova M, Lin Z, Zhou L, Chudin E, Garcia E, Wu B . High-throughput DNA methylation profiling using universal bead arrays. Genome Res. 2006; 16(3):383-93. PMC: 1415217. DOI: 10.1101/gr.4410706. View

Thompson M, Hill B, Rakocz N, Chiang J, Geschwind D, Sankararaman S . Methylation risk scores are associated with a collection of phenotypes within electronic health record systems. NPJ Genom Med. 2022; 7(1):50. PMC: 9411568. DOI: 10.1038/s41525-022-00320-1. View

10.

Zhou L, Ng H, Drautz-Moses D, Schuster S, Beck S, Kim C . Systematic evaluation of library preparation methods and sequencing platforms for high-throughput whole genome bisulfite sequencing. Sci Rep. 2019; 9(1):10383. PMC: 6637168. DOI: 10.1038/s41598-019-46875-5. View

11.

Haghani A, Li C, Robeck T, Zhang J, Lu A, Ablaeva J . DNA methylation networks underlying mammalian traits. Science. 2023; 381(6658):eabq5693. PMC: 11180965. DOI: 10.1126/science.abq5693. View

12.

Zhou W, Laird P, Shen H . Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes. Nucleic Acids Res. 2016; 45(4):e22. PMC: 5389466. DOI: 10.1093/nar/gkw967. View

13.

Xiong Z, Li M, Yang F, Ma Y, Sang J, Li R . EWAS Data Hub: a resource of DNA methylation array data and metadata. Nucleic Acids Res. 2019; 48(D1):D890-D895. PMC: 6943079. DOI: 10.1093/nar/gkz840. View

14.

Pasolli E, Schiffer L, Manghi P, Renson A, Obenchain V, Truong D . Accessible, curated metagenomic data through ExperimentHub. Nat Methods. 2017; 14(11):1023-1024. PMC: 5862039. DOI: 10.1038/nmeth.4468. View

15.

Kaur D, Lee S, Goldberg D, Spix N, Hinoue T, Li H . Comprehensive Evaluation of The Infinium Human MethylationEPIC v2 BeadChip. Epigenetics Commun. 2024; 3(1). PMC: 10919401. DOI: 10.1186/s43682-023-00021-5. View

16.

Bibikova M, Le J, Barnes B, Saedinia-Melnyk S, Zhou L, Shen R . Genome-wide DNA methylation profiling using Infinium® assay. Epigenomics. 2011; 1(1):177-200. DOI: 10.2217/epi.09.14. View

17.

Battram T, Yousefi P, Crawford G, Prince C, Sheikhali Babaei M, Sharp G . The EWAS Catalog: a database of epigenome-wide association studies. Wellcome Open Res. 2022; 7:41. PMC: 9096146. DOI: 10.12688/wellcomeopenres.17598.2. View

18.

Li H, Xu L, Weisenberger D, Li M, Zhou W, Peng C . Characterizing DNA methylation signatures of retinoblastoma using aqueous humor liquid biopsy. Nat Commun. 2022; 13(1):5523. PMC: 9492718. DOI: 10.1038/s41467-022-33248-2. View

19.

Lee S, Loo C, Prasasya R, Bartolomei M, Kohli R, Zhou W . Low-input and single-cell methods for Infinium DNA methylation BeadChips. Nucleic Acids Res. 2024; 52(7):e38. PMC: 11040145. DOI: 10.1093/nar/gkae127. View

20.

Aref-Eshghi E, Kerkhof J, Pedro V, Barat-Houari M, Ruiz-Pallares N, Andrau J . Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders. Am J Hum Genet. 2020; 106(3):356-370. PMC: 7058829. DOI: 10.1016/j.ajhg.2020.01.019. View