A5007090026- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- Molecular Biology Techniques and Applications
- Genetic Associations and Epidemiology
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Respiratory viral infections research
- Genomic variations and chromosomal abnormalities
- Genetics, Bioinformatics, and Biomedical Research
- Cardiomyopathy and Myosin Studies
- RNA modifications and cancer
- SARS-CoV-2 and COVID-19 Research
- Cardiovascular Function and Risk Factors
- Physiological and biochemical adaptations
- Bioinformatics and Genomic Networks
- Neurological diseases and metabolism
- RNA and protein synthesis mechanisms
- Biomedical and Engineering Education
- Animal Behavior and Reproduction
- Innovative Microfluidic and Catalytic Techniques Innovation
- Genetic factors in colorectal cancer
- Evolution and Paleontology Studies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Microbial infections and disease research
Stanford University
2020-2025
Stanford Medicine
2024
Neurosciences Institute
2024
Washington University in St. Louis
2024
Quantitative BioSciences
2024
University of Utah
2010
Abstract Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for and analysis has been a barrier to its use in acutely ill patients. In present study, we develop an approach ultra-rapid nanopore WGS combines optimized sample preparation protocol, distributing over 48 flow cells, near real-time base calling alignment, accelerated variant fast filtration efficient manual review. Application two example clinical cases identified candidate <8...
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,...
Background Xenotropic murine leukemia-related retrovirus (XMRV) is a recently discovered that has been linked to human prostate cancer and chronic fatigue syndrome (CFS). Both diseases affect large fraction of the world population, with affecting one in six men, CFS an estimated 0.4 1% population. Principal Findings Forty-five compounds, including twenty-eight drugs approved for use humans, were evaluated against XMRV replication vitro. We found retroviral integrase inhibitor, raltegravir,...
Abstract Long-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and rapid genetic diagnosis clinical settings. Rapidly evolving third-generation platforms like Pacific Biosciences (PacBio) Oxford Nanopore Technologies (ONT) are introducing newer data types. It been demonstrated that calling methods based on deep neural networks can use local haplotyping information with long-reads to improve genotyping accuracy. However, using haplotype...
Single nucleotide variants near
Single-nucleotide variants near TMEM106B associate with the risk of frontotemporal lobar dementia TDP-43 inclusions (FTLD-TDP) and Alzheimer disease (AD) in genome-wide association studies (GWASs), but causal variant at this locus remains unclear. Here, we asked whether a novel structural on is variant.
Summary The ε4 allele of apolipoprotein E ( APOE ) is the strongest genetic risk factor for sporadic Alzheimer’s Disease (AD). Knockdown this may provide a therapeutic strategy AD, but effect loss-of-function (LoF) on AD pathogenesis unknown. We searched LoF variants in large cohort older controls and patients with identified six heterozygote carriers variants. Five were (ages 71-90) one was an case unremarkable age-at-onset between 75-79. Two ε3/ε4 (Subjects 1 2) carried stop-gain affecting...
Long read sequencing offers benefits for the detection of structural variation in Mendelian disease. Here, we applied a new technology that generates contiguous long reads via tagmentation and by synthesis to small cohort patients with undiagnosed disease from Undiagnosed Diseases Network. We first compare HG002 benchmark sample Genome In A Bottle using nanopore (R10.4.1, duplex reads, Oxford Nanopore), single molecule real time (Revio SMRT cell, Pacific Biosciences) complete (S4 flowcell,...
The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk multi-ancestry genomes. We leverage tracking strategy in which we sequence viral host genomes transcriptomes from nasopharyngeal swabs of 1049 individuals (736 positive 313 negative) integrate them with digital phenotypes electronic health records diverse catchment area Northern California. Genome-wide association disaggregated by...
During COVID19 and other viral pandemics, rapid generation of host pathogen genomic data is critical to tracking infection informing therapies. There an urgent need for efficient approaches this at scale. We have developed a scalable, high throughput approach generate fidelity low pass whole genome HLA sequencing, genomes, representation human transcriptome from single nasopharyngeal swabs patients.
Long-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and rapid genetic diagnosis clinical settings. Rapidly evolving third-generation platforms like Pacific Biosciences (PacBio) Oxford nanopore technologies (ONT) are introducing newer data types. It been demonstrated that calling methods based on deep neural networks can use local haplotyping information with long-reads to improve genotyping accuracy. However, using haplotype creates an...
Although the gross morphology of heart is conserved across mammals, subtle interspecific variations exist in cardiac phenotype, which may reflect evolutionary divergence among closely-related species. Here, we compare left ventricle (LV) all extant members Hominidae taxon, using 2D echocardiography, to gain insight into evolution human heart. We present compelling evidence that LV has diverged away from a more trabeculated phenotype other great apes, towards ventricular wall with...
Abstract Background Alzheimer’s disease (AD) is the most common form of dementia. Neuropathologically, AD stands out as a mixed proteinopathy. Beta‐amyloid and tau biomarkers can now add in‐vivo support to diagnosis. Rarely, patient with confirmed at autopsy may have negative amyloid PET. Here we describe pedigree in whom index case was PET‐negative. We performed genetic sequencing two affected siblings identify set candidate single nucleotide variants (SNVs) structural (SVs) associated rare...
Abstract Background Alzheimer's disease (AD) is the most common form of dementia. Neuropathologically, AD stands out as a mixed proteinopathy. Beta‐amyloid and tau biomarkers can now add in‐vivo support to diagnosis. Rarely, patient with confirmed at autopsy may have negative amyloid PET. Here we describe pedigree in whom index case was PET‐negative. We performed genetic sequencing two affected siblings identify set candidate single nucleotide variants (SNVs) structural (SVs) associated rare...
ABSTRACT The SARS-CoV-2 pandemic has differentially impacted populations of varied race, ethnicity and socioeconomic status. Admixture mapping local ancestry inference represent powerful tools to examine genetic risk within multi-ancestry genomes independent these confounding social constructs. Here, we leverage a tracking strategy in which sequence viral host transcriptomes from 1,327 nasopharyngeal swab residuals integrate them with digital phenotypes electronic health records. We...
Aim: To prepare an ONT non-barcoded library using LSK109, to be distributed over 48 flow cells from 2ml of whole blood.
Abstract The sustainability of zoo populations is dependent on maintaining genetic diversity and controlling heritable disease. Here, we explore the integration whole genome sequencing data in management international zoological population western lowland gorillas, focusing diseases. By comparing kinship values derived from classical pedigree mapping sequencing, demonstrate that genomic provides a more sensitive measure relatedness. Our analysis reveals decrease due to closed breeding,...
Abstract Background Alzheimer’s disease (AD) is up to 60‐80% heritable, but less than ∼20% explained by studies analyzing single nucleotide variants (SNVs). One limitation of short‐read whole‐genome sequencing (SRS) the standard read length 150 base pairs, which does not enable detection longer structural (SVs). Here we sequenced individuals using long‐read (LRS), can sequence reads with an average ∼20 kilobases, allowing us identify SVs previously uncaptured. Method All participants...