> For the complete documentation index, see [llms.txt](https://knowledge.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://knowledge.illumina.com/microarray/general/microarray-general-reference_material-list/000002186.md). # History of Infinium MethylationEPIC manifest versions The Infinium MethylationEPIC Array manifest file has been updated across v1.0 and v2.0 releases. This article summarizes key changes by manifest version, including new features, improvements, defect fixes, and known considerations, and provides guidance on manifest selection based on BeadChip barcode range. **Manifest Version Overview** **1) Infinium MethylationEPIC v1.0** **Manifest v1.0 B1** * New Features: Added Strand column to the manifest file. * Improvements: None * Defect Repairs: * Removed 1,029 CpG sites originating from legacy Infinium Methylation450K Array content. * Removed two Infinium MethylationEPIC v1.0‑specific CpG sites (cg01962187, cg25909286). * Removed one pair of low intensity green channel Bisulfite Conversion I Controls. There are now five controls per channel for both Converted (C) and Unconverted (U) controls (C1-C5 and U1-U5), compared to six controls of (C) and (U) per channel in the Infinium Methylation450K Array. * Removed 1,031 CpG sites due to underperformance. These sites are listed in the document [1031 CpG Sites Removed from Infinium MethylationEPIC v1.0](https://support.illumina.com/downloads/infinium-methylationepic-v1-0-product-files.html) * Issues: None **Manifest v1.0 B2** * New Features: None * Improvements: None * Defect Repairs: Fixed switch in red/green signal for Infinium I SNP probes. * Issues: None **Manifest v1.0 B3** * New Features: None * Improvements: None * Defect Repairs: * Removed up to 977 CpG sites from DMAP for BeadChips with barcodes ≥ 201172200001, due to a manufacturing process change. These markers have also been removed from the manifest files to streamline comparison of data between the BeadChips before and after the loci removal in the GenomeStudio 2011.1 Analysis Software. The list of the 977 markers removed from the new version of the manifest is available on the [Infinium MethylationEPIC v1.0 Product Files (Legacy BeadChip)](https://support.illumina.com/downloads/infinium-methylationepic-v1-0-product-files.html) page. * Fixed rsID probe sequence swap. * Issues: Potential issues with analyzing data from BeadChips with barcodes ≥ 201172200001 using third-party software tools. Users should ensure the latest versions of those tools are installed prior to analyzing the data. **Markers Removed by BeadChip Lot Number (Manifest v1.0 B3 Context)** Product Quality Notification (pqn0223‑methylation‑epic) states that 977 markershave been removed from the DMAP files. However, the actual number of removed markers varies depending on the BeadChip lot number (first 8 digits of the barcode). * **Lot number ≤ 2011XXXX** * Markers removed: None * **Lot number 2011XXXX to 20150367** * Markers removed: 598 probes * **Lot number ≥ 20150367** * Markers removed: 745 probes **Manifest v1.0 B4** * New Features: None. * Improvements: None. * Defect Repairs: Reformatted the manifest files to address the issue with incorrect gene annotation formatting when viewed in Excel (Gene names were incorrectly displayed as dates). * Issues: None. **Manifest v1.0 B5** * New Features: None * Improvements: None * Defect Repairs: * Identified 998 probes that function with high variability after manufacturing change from all prior Illumina Methylation Array products and provided a new manifest column to identify these probes with the header. “MFG\_CHANGE\_FLAGGED” (Value = 'TRUE' if probe is expected to be discordant when compared with data from earlier manufactured BeadChips). * BeadChips with barcodes ≥ to 204220330001 should be used with the B5 manifest, which notes which probes perform differently compared to prior Infinium Methylation Arrays. * Added GRCh38-aligned columns: * CHR\_hg38: For chromosome alignment * Start\_hg38: For start position alignment * End\_hg38: For end position alignment * Strand\_hg38: For strand alignment * These changes are described in Product Change Notification (pcn2019-019-methylationarray-mfg-change). **Manifest Selection Guidance (v1.0)** * **Barcodes ≥ 204220330001** * Use B5 manifest. * For longitudinal studies, B4 may be used, with the understanding that probes flagged in the B5 manifest under MFG\_CHANGE\_FLAGGED will not be identified in the analysis. * **Barcodes 201172200001-204220330000** * Use B4 manifest. * B3 contains equivalent content but is not recommended due to formatting issues. * B5 may be used for longitudinal studies; however, MFG\_CHANGE\_FLAGGED annotations apply only to BeadChips with barcodes > 204220330001. * **Barcodes < 201172200001** * Use B2 manifest. * B1 is not recommended due to red/green signal issues. * Recommended option\*\*:\*\* Use B4 manifest for consistency, provided barcodes are < 204220330001. ![](/files/duYyuoxpazCJLJ3PxIxv) **Figure 1.** Manifest selection guidance by BeadChip barcode lot **2) Infinium MethylationEPIC v2.0** **Manifest v2.0 A1** * New Features (from MethylationEPIC v1.0): 1. - Expanded manifest to 49 column headings. Column designations are described in the [Infinium MethylationEPIC v2.0 Manifest Column Headings](https://github.com/illumina-swi/illumina-knowledge/tree/master/articles/Knowledge/Infinium-MethylationEPIC-v2-0-Manifest-Column-Headings/README.md) file. * The logic for how the IlmnID is determined, is further described in the [Description of suffixes in the cg probes ID in Infinium MethylationEPIC v2.0](https://github.com/illumina-swi/illumina-knowledge/tree/master/articles/Knowledge/Infinium-MethylationEPIC-v2-0-Description-of-suffixes-in-the-cg-probes-ID/README.md). * Updated Genome Build to hg38. * Updated GenCode version to v41. * \*\*Flagged probes:\*\*Approximately 49,000 probes did not meet performance expectations based on internal Illumina probe-level analysis. The evaluation took into account two measures of performance: 1. Technical replicate sample reproducibility within <0.2 beta-value 2. Methylation titration control sample sensitivity against expected beta-value metrics. The list of Illumina-flagged probes are listed in [EPIC-8v2-0\_A1-FlaggedProbes](https://support.illumina.com/downloads/infinium-methylationepic-v2-0-product-files.html). 2. * \*\*Probes with mapping inaccuracies:\*\*A subset of approximately 190 probes were identified with mapping inaccuracies. The effort to resolve these errors in mapping is currently in progress by the Illumina bioinformatics team. The complete list is in [EPIC-8v2-0\_A1-190Mapping Inaccuracies](https://support.illumina.com/downloads/infinium-methylationepic-v2-0-product-files.html) . * Improvements (from MethylationEPIC v1.0): * Removed non-functional probes due to underlying SNPs near the 3’ end of probes, cross-hybridization, and multi-mapping from this paper:[Zhou, W., Shen, H. & Laird, P. W. Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes. *Nucleic Acids Res.* **45**, e22 (2017)](https://pubmed.ncbi.nlm.nih.gov/27924034/). * Addition of 186K new probes, bringing total number of assays to 936K. More information about new content is listed on the Product Datasheet. * Ability to interrogate common cancer driver mutations through SNP probes. * Defect Repairs: None * Issues: None **Manifest v2.0 A2** * New Features: Added GRCh37 coordinates to the manifest under columns ‘CHR\_37’ and ‘MAPINFO\_37. * Improvements: Removed ‘chr’ prefix from the CHR column. * Defect Repairs: None * Issues: None **Note:** Contact Illumina Technical Support at for a copy of the Product Quality Notification (pqn0223‑methylation‑epic) and Product Change Notification (pcn2019-019-methylationarray-mfg-change). **References:** * [Infinium MethylationEPIC v1.0 Array Manifest File Downloads](https://support.illumina.com/array/array_kits/infinium-methylationepic-beadchip-kit/downloads.html) * [Infinium MethylationEPIC B5 Manifest Release Notes](https://support.illumina.com/content/dam/illumina-support/documents/downloads/productfiles/methylationepic/infinium-methylationepic-v1-0-b5-customer-release-notes.pdf) * [Infinium MethylationEPIC GenomeStudio v2.0 Manifest File Release Notes v2.0 A1](https://support.illumina.com/downloads/infinium-methylationepic-v2-0-product-files.html) * [Infinium MethylationEPIC GenomeStudio v2.0 Manifest File Release Notes v2.0 A2](https://support.illumina.com/downloads/infinium-methylationepic-v2-0-product-files.html) \ \ \
| | | :---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------: | | *For any feedback or questions regarding this article (Illumina Knowledge Article #2186), contact Illumina Technical Support* [*techsupport@illumina.com*](mailto:techsupport@illumina.com?subject=Question%2FFeedback%20Regarding%20Illumina%20Knowledge%20Article%20#000008344%20-%20Microarray%20\&body=Dear%20Illumina%20Technical%20Support,%0D%0A%0D%0A)*.* | --- # Agent Instructions This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. Learn more at gitbook.com. ## Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. Perform an HTTP GET request on the current page URL with the `ask` query parameter, and the optional `goal` query parameter: ``` GET https://knowledge.illumina.com/microarray/general/microarray-general-reference_material-list/000002186.md?ask=&goal= ``` `ask` is the immediate question: it should be specific, self-contained, and written in natural language. `goal` is optional and describes the broader end goal you are ultimately trying to accomplish on behalf of the user. GitBook uses it to tailor the answer towards what is most useful for that goal. The response will contain a direct answer to the question and relevant excerpts and sources from the documentation. Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.