Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits

Beard, Diana C.; Zhang, Xiyun; Wu, Dennis Y.; Martin, Jenna R.; Erickson, Alyssa; Boua, Jane Valeriane; Hamagami, Nicole; Swift, Raylynn G.; McCullough, Katherine B.; Ge, Xia; Bell-Hensley, Austin; Zheng, Hongjun; Palmer, Cory W.; Fuhler, Nicole A.; Lawrence, Austin B.; Hill, Cheryl A.; Papouin, Thomas; Noguchi, Kevin K.; McAlinden, Audrey; Garbow, Joel R.; Dougherty, Joseph D.; Maloney, Susan E.; Gabel, Harrison W.

doi:10.1016/j.celrep.2023.113411

Cited by 6 publications

(1 citation statement)

References 83 publications

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“…Further, environmental factors can induce DNA methylation changes, which also modify gene expression. Genome-wide DNA methylation pattern is also altered in various chronic diseases such as chronic kidney diseases (CKD), diabetic nephropathy, many cancers, hematopoietic malignancies, and neurodevelopmental diseases ( Lyst and Bird 2015 , Pagliaroli et al 2016 , Jeong et al 2018 , Gluck et al 2019 , Skvortsova et al 2019 , Tulstrup et al 2021 , Beard et al 2023 ). These methylation changes can be diagnostic, prognostic, and used as biomarkers, and even some of these diseases are treated by methyltransferase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Improve-RRBS: a novel tool to correct the 3′ trimming of reduced representation sequencing reads

Fóthi,

Liu,

Susztak

et al. 2024

Bioinformatics Advances

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Motivation Reduced Representation Bisulfite Sequencing (RRBS) is a popular approach to determine DNA methylation of the CpG-rich regions of the genome. However, we observed that false positive differentially methylated sites (DMS) are also identified using the standard computational analysis. Results During RRBS library preparation the MspI digested DNA undergo end-repair by a cytosine at the 3’ end of the fragments. After sequencing, Trim Galore cuts these end-repaired nucleotides. However, Trim Galore fails to detect end-repair when it overlaps with the 3’ end of the sequencing reads. We found that these non-trimmed cytosines bias methylation calling, thus can identify DMS erroneously. To circumvent this problem, we developed improve-RRBS, which efficiently identifies and hides these cytosines from methylation calling with a false positive rate of maximum 0.5%. To test improve-RRBS, we investigated four datasets from four laboratories and two different species. We found non-trimmed 3’ cytosines in all datasets analyzed and as much as > 50% of false positive DMS under certain conditions. By applying improve-RRBS, these DMS completely disappeared from all comparisons. Availability improve-RRBS is a freely available python package https://pypi.org/project/iRRBS/ or https://github.com/fothia/improve-RRBS to be implemented in RRBS pipelines. Supplementary information Supplementary data are available at Bioinformatics Advances online.

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