ArticleAmerican journal of human genetics2025
Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.
Article in American journal of human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Diagnostic yield of long-read sequencing for rare diseases: a systematic review.Frontiers in genetics · 2026Pooled it
- Nanopore long-read sequencing facilitates accurate diagnosis of KMT2B-related dystonia.Clinical epigenetics · 2026Article
- Long-Read Sequencing in CKD Diagnostics: Breaking Genomic Barriers and Expanding Global Inclusion.Kidney international reports · 2026Review
- Artificial Intelligence and Genomic Data Analysis: New Frontiers in Precision Medicine.International journal of molecular sciences · 2026Review
- Best practice recommendations for bioinformatics approaches applied to high-throughput sequencing for rare disease and cancer diagnosis within the UK National Health Service.Journal of medical genetics · 2026Article
- HPRC2: A human pangenome reference with near-complete coverage of common genetic variation.bioRxiv : the preprint server for biology · 2026Article
- Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing.medRxiv : the preprint server for health sciences · 2026Article
- Nanopore direct RNA sequencing and the epitranscriptome: Advances in mapping native RNA landscapes.iMeta · 2026Review
- Article
- From Spatial Epigenomes to Clinical Diagnostics: Integrative Methylomics Across Scales and Modalities.International journal of molecular sciences · 2026Review
- Association of Seasonal Hyperacute Panuveitis Syndrome withOphthalmology science · 2026Article
- Strand-seq and the future of personalized genomics.Nature genetics · 2026Review
- Mapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learning.Nature communications · 2026Article
- Paternal age effect in autosomal dominant or X-linked de novo variants identified by genome-wide sequencing.HGG advances · 2026Article
- Proof-of-concept study for the detection of somatic structural variant driver alterations using HiFi long-read sequencing in a pediatric leukemia cohort.NPJ genomic medicine · 2026Article
- Targeted long-read genomic and epigenomic profiling enhances timely comprehensive variant discovery in hypotonia and muscle weakness.BMC medicine · 2026Article
- Advances in SRNS Gene Research: From Precision Classification to Precision Diagnosis and Treatment.Biomedicines · 2026Review
- Identification of de novo variants from parent-proband duos via long-read sequencing.American journal of human genetics · 2026Article
- Evaluating genome assemblies with HMM-Flagger.bioRxiv : the preprint server for biology · 2026Article
- Breakpoint-resolved balanced t(2;12)(q35;q24.31) disruptingMetabolism open · 2026Article
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23 authors.
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Abstract
More than 50% of families with suspected rare monogenic diseases remain unsolved after whole-genome analysis by short-read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing and providing haplotype-resolved methylation profiling. To evaluate LRS's additional diagnostic yield, we sequenced a rare-disease cohort of 98 samples from 41 families, using nanopore sequencing, achieving per sample ∼36× average coverage and 32-kb read N50 from a single flow cell. Our Napu pipeline generated assemblies, phased variants, and methylation calls. LRS covered, on average, coding exons in ∼280 genes and ∼5 known Mendelian disease-associated genes that were not covered by SRS. In comparison to SRS, LRS detected additional rare, functionally annotated variants, including structural variants (SVs) and tandem repeats, and completely phased 87% of protein-coding genes. LRS detected additional de novo variants and could be used to distinguish postzygotic mosaic variants from prezygotic de novos. Diagnostic variants were established by LRS in 11 probands, with diverse underlying genetic causes including de novo and compound heterozygous variants, large-scale SVs, and epigenetic modifications. Our study demonstrates LRS's potential to enhance diagnostic yield for rare monogenic diseases, implying utility in future clinical genomics workflows.
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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.