ReviewAmerican journal of human genetics2021
Anatomy of DNA methylation signatures: Emerging insights and applications.
Review in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- From chromatin dynamics to brain disease: Polycomb-Trithorax mechanisms in neurodevelopment.Trends in neurosciences · 2026Review
- How Epigenetics Bridges Genes and Environment: A Multiomics Evidence Chain in Congenital Diaphragmatic Hernia.Birth defects research · 2026Review
- Genome-wide methylation detection and episignature analysis using PacBio long-read sequencing.Genome medicine · 2026Article
- Analysis Methods for Diagnosing Rare Neurodevelopmental Diseases with Episignatures: A Systematic Review of the Literature.Biomedicines · 2025Review
- Biallelic loss-of-function variants in ZNF142 are associated with a robust DNA methylation signature affecting a limited number of genomic loci.European journal of human genetics : EJHG · 2025Article
- Artificial intelligence-driven genotype-epigenotype-phenotype approaches to resolve challenges in syndrome diagnostics.EBioMedicine · 2025Article
- Evolution of genome-wide methylation profiling technologies.Genome research · 2025Review
- Navigating Genetic Testing in Nephrology: Options and Decision-Making Strategies.Kidney international reports · 2025Review
- Diagnostic utility of single-locus DNA methylation mark in Sotos syndrome developed by nanopore sequencing-based episignature.Clinical epigenetics · 2025Article
- Expanding Upon Genomics in Rare Diseases: Epigenomic Insights.International journal of molecular sciences · 2024Review
- Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes.American journal of human genetics · 2024Article
- DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism.European journal of human genetics : EJHG · 2024Article
- Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.Genome research · 2024Article
- Cuproptosis-related DNA methylation signature predict prognosis and immune microenvironment in cutaneous melanoma.Discover oncology · 2024Article
- DNA methylation signatures for chromatinopathies: current challenges and future applications.Human genetics · 2024Article
- The omics era: a nexus of untapped potential for Mendelian chromatinopathies.Human genetics · 2024Review
- Episignatures in practice: independent evaluation of published episignatures for the molecular diagnostics of ten neurodevelopmental disorders.European journal of human genetics : EJHG · 2024Article
- Comprehensive evaluation of the implementation of episignatures for diagnosis of neurodevelopmental disorders (NDDs).Human genetics · 2023Article
- Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.American journal of human genetics · 2023Article
- Peripheral blood DNA methylation and neuroanatomical responses to HDACi treatment that rescues neurological deficits in a Kabuki syndrome mouse model.Clinical epigenetics · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
DNA methylation (DNAm) signatures are unique patterns of DNAm alterations defined for rare disorders caused by pathogenic variants in epigenetic regulatory genes. The potential of DNAm signatures (also known as "episignatures") is just beginning to emerge as there are >300 known epigenetic regulatory genes, ∼100 of which are linked to neurodevelopmental disorders. To date, approximately 50 signatures have been identified, which have proven unexpectedly successful as predictive tools for classifying variants of uncertain significance as pathogenic or benign. The molecular basis of these signatures is poorly understood. Furthermore, their relationships to primary disease pathophysiology have yet to be adequately investigated, despite clear demonstrations of potential connections. There are currently no published guidelines for signature development. As signatures are highly dependent on the samples and methods used to derive them, we propose a framework for consideration in signature development including sample size, statistical parameters, cell type of origin, and the value of detailed clinical and molecular information. We illustrate the relationship between signature output/efficacy and sample size by generating and testing 837 DNAm signatures of Kleefstra syndrome using downsampling analysis. Our findings highlight that no single DNAm signature encompasses all DNAm alterations present in a rare disorder, and that a substandard study design can generate a DNAm signature that misclassifies variants. Finally, we discuss the importance of further investigating DNAm signatures to inform disease pathophysiology and broaden their scope as a functional assay.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.