A5031147468- Genomics and Phylogenetic Studies
- Genomics and Rare Diseases
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Telomeres, Telomerase, and Senescence
- RNA and protein synthesis mechanisms
- Genetic Associations and Epidemiology
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Genetic Mapping and Diversity in Plants and Animals
- Genomic variations and chromosomal abnormalities
- Gene expression and cancer classification
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
Johns Hopkins University
2020-2025
Genome in a Bottle benchmarks are widely used to help validate clinical sequencing pipelines and develop variant calling methods. Here we use accurate linked long reads expand 7 samples include difficult-to-map regions segmental duplications that challenging for short reads. These add more than 300,000 SNVs 50,000 insertions or deletions (indels) 16% exonic variants, many challenging, clinically relevant genes not covered previously, such as PMS2. For HG002, 92% of the autosomal GRCh38...
Rare structural variants (SVs)-insertions, deletions, and complex rearrangements-can cause Mendelian disease, yet they remain difficult to accurately detect interpret. We sequenced analyzed Oxford Nanopore Technologies long-read genomes of 68 individuals from the undiagnosed disease network (UDN) with no previously identified diagnostic mutations short-read sequencing. Using our optimized SV detection pipelines 571 control genomes, we detected 716 rare (MAF < 0.01) alleles per genome on...
Rare structural variants (SVs) – insertions, deletions, and complex rearrangements can cause Mendelian disease, yet they remain difficult to accurately detect interpret. We sequenced analyzed Oxford Nanopore long-read genomes of 68 individuals from the Undiagnosed Disease Network (UDN) with no previously identified diagnostic mutations short-read sequencing. Using our optimized SV detection pipelines 571 control genomes, we detected 716 rare (MAF < 0.01) alleles per genome on average,...
Summary Genome in a Bottle (GIAB) benchmarks have been widely used to help validate clinical sequencing pipelines and develop new variant calling methods. Here, we use accurate linked reads long expand the prior 7 samples include difficult-to-map regions segmental duplications that are not readily accessible short reads. Our benchmark adds more than 300,000 SNVs, 50,000 indels, 16 % exonic variants, many challenging, clinically relevant genes previously covered (e.g., PMS2 ). For HG002, 92%...
Abstract The increasing availability of long-reads is revolutionizing studies structural variants (SVs). However, because SVs vary across individuals and are discovered through imprecise read technologies methods, they can be difficult to compare. Addressing this, we present Jasmine ( https://github.com/mkirsche/Jasmine ), a fast accurate method for SV refinement, comparison, population analysis. Using an proximity graph, outperforms five widely-used comparison including reducing the rate...
Abstract ReadUntil sequencing allows nanopore devices to selectively eject individual reads from the pore in real-time. This could enable purely computational targeted sequencing, however most mapping methods require basecalling, which is computationally intensive. Here we present UNCALLED ( github.com/skovaka/UNCALLED ), an open-source mapper that rapidly matches streaming current signals a reference sequence. probabilistically considers k-mers signal represent, and then prunes candidates...
Each human genome has tens of thousands rare genetic variants; however, identifying impactful variants remains a major challenge. We demonstrate how use personal multi-omics can enable identification by using the Multi-Ethnic Study Atherosclerosis, which included several hundred individuals, with whole-genome sequencing, transcriptomes, methylomes, and proteomes collected across two time points, 10 years apart. evaluated each phenotype's ability to separately jointly inform functional...
Abstract Telomere length genome-wide association studies (GWAS) have become well-powered to detect novel genes in telomere regulation. However, no prior work has validated these putative confirm the contribution of GWAS loci We conducted a trans-ancestry meta-analysis 211,369 individuals. Through enrichment analyses chromatin state and cell-type heritability we identified blood immune cells as most relevant cell type examine signals. specific associations by overexpressing KBTBD6 , component...
Abstract Each human genome has tens of thousands rare genetic variants; however, identifying impactful variants remains a major challenge. We demonstrate how use personal multi-omics can enable identification by using the Multi-Ethnic Study Atherosclerosis (MESA) which included several hundred individuals with whole sequencing, transcriptomes, methylomes, and proteomes collected across two time points, ten years apart. evaluated each multi-omic phenotype’s ability to separately jointly...