ArticleNature genetics2025
Synchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Phenotyping and hierarchical clustering in genetically unresolved DSD identifies distinct multisystem clinical subgroups-a DSDgene study.Journal of the Endocrine Society · 2026Article
- A practical guide to studying genome function using single-molecule genomics.Nature reviews. Molecular cell biology · 2026Review
- Long-read transcriptome analysis using IsoRanker for identifying pathogenic variants in Mendelian conditions.American journal of human genetics · 2026Article
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Native yeast kinetochore structures identify an essential inner kinetochore interaction.Nature communications · 2026Article
- Near-perfect genome sequencing in medical genetics.Nature genetics · 2026Review
- Genetic diversity and regulatory features of human-specific NOTCH2NL duplications.Cell genomics · 2026Article
- Epigenetic conditioning improves sequence-based modeling of gene regulation across cell types and alleles.bioRxiv : the preprint server for biology · 2026Article
- Mapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learning.Nature communications · 2026Article
- Haplotype-resolved genome assemblies of BJ and IMR-90 human fibroblast cell lines reveal extensive structural variation and enable reanalysis of historical sequencing data.Nucleic acids research · 2026Article
- Targeted long-read RNA sequencing for rare disease diagnosis and variant interpretation.Science advances · 2026Article
- Identification of de novo variants from parent-proband duos via long-read sequencing.American journal of human genetics · 2026Article
- Elucidating the coordination of RNA processing using short-read and long-read RNA-sequencing methods.Nature reviews. Molecular cell biology · 2026Review
- Native yeast kinetochore structures identify an essential inner kinetochore interaction.bioRxiv : the preprint server for biology · 2026Article
- Article
- isoSeQL: comparing long-read isoforms across multiple datasets.Bioinformatics (Oxford, England) · 2026Article
- Long-read transcriptome analysis using IsoRanker for identifying pathogenic variants in Mendelian conditions.medRxiv : the preprint server for health sciences · 2025Article
- Oxford Nanopore Technologies [ONT] Sequencing: Clinical Validation in Genetically Heterogeneous Disorders.Genes · 2025Article
- GREGoR: accelerating genomics for rare diseases.Nature · 2025Article
- Shaping Precision Medicine: The Journey of Sequencing Technologies Across Human Solid Tumors.Biomedicines · 2025Review
Corrections and comments
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39 authors.
Funding
Abstract
Resolving the molecular basis of a Mendelian condition remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion and structural variant calling and diploid de novo genome assembly. This permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network participant with a chromosome X;13-balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four separate genes (NBEA, PDK3, MAB21L1 and RB1) previously associated with single-gene Mendelian conditions. Notably, the function of each gene was disrupted via a distinct mechanism that required integration of the four 'omes' to resolve. These included fusion transcript formation, enhancer adoption, transcriptional readthrough silencing and inappropriate X-chromosome inactivation of autosomal genes. Overall, this highlights the utility of synchronized long-read multi-omic profiling for mechanistically resolving complex phenotypes.
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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.