ArticleNature communications2023
Direct haplotype-resolved 5-base HiFi sequencing for genome-wide profiling of hypermethylation outliers in a rare disease cohort.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 39 citations in OpenAlex.
- Accurate characterization of CRISPR-Cas9 genome editing outcomes and mosaicism with near-perfect long reads.Genome medicine · 2026Article
- No Evidence for an Association Between DIP2B Repeat Expansion and Neurological Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- HPRC2: A human pangenome reference with near-complete coverage of common genetic variation.bioRxiv : the preprint server for biology · 2026Article
- Near-perfect genome sequencing in medical genetics.Nature genetics · 2026Review
- Haplotype-resolved methylomes reveal parent-of-origin DNA methylation imbalance in autism spectrum disorder.Science advances · 2026Article
- Population-scale detection of methylation outliers from long-read genome sequencing.medRxiv : the preprint server for health sciences · 2026Article
- From Spatial Epigenomes to Clinical Diagnostics: Integrative Methylomics Across Scales and Modalities.International journal of molecular sciences · 2026Review
- Integrative Genomic and AI Approaches to Lung Cancer and Implications for Disease Prevention in Former Smokers.International journal of molecular sciences · 2026Review
- 5mC and 5hmC methylation sequencing: the power of 6-base sequencing in a multiomic era.Epigenomics · 2026Review
- Analysis Methods for Diagnosing Rare Neurodevelopmental Diseases with Episignatures: A Systematic Review of the Literature.Biomedicines · 2025Review
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- Structural variation, selection, and diversification of the NPIP gene family from the human pangenome.Cell genomics · 2025Article
- Long and Accurate: How HiFi Sequencing is Transforming Genomics.Genomics, proteomics & bioinformatics · 2025Review
- Expanded methylome and quantitative trait loci detection by long-read profiling of personal DNA.Genome research · 2025Article
- The impact of long-read sequencing on human population-scale genomics.Genome research · 2025Review
- Evolution of genome-wide methylation profiling technologies.Genome research · 2025Review
- The additional diagnostic yield of long-read sequencing in undiagnosed rare diseases.Genome research · 2025Review
- Assessing DNA methylation detection for primary human tissue using Nanopore sequencing.Genome research · 2025Article
- Genome assembly resources of genitourinary cancers for chromosomal aberration at the single nucleotide level.Scientific data · 2025Article
- Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.American journal of human genetics · 2025Article
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Authors and funding
25 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory element activity directly in HiFi reads. We present a comprehensive haplotype resolved 5-base HiFi genome sequencing dataset from a rare disease cohort of 276 samples in 152 families to identify rare (~0.5%) hypermethylation events. We find that 80% of these events are allele-specific and predicted to cause loss of regulatory element activity. We demonstrate heritability of extreme hypermethylation including rare cis variants associated with short (~200 bp) and large hypermethylation events (>1 kb), respectively. We identify repeat expansions in proximal promoters predicting allelic gene silencing via hypermethylation and demonstrate allelic transcriptional events downstream. On average 30-40 rare hypermethylation tiles overlap rare disease genes per patient, providing indications for variation prioritization including a previously undiagnosed pathogenic allele in DIP2B causing global developmental delay. We propose that use of HiFi genome sequencing in unsolved rare disease cases will allow detection of unconventional diseases alleles due to loss of regulatory element activity.
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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.