A5066000877- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- Biomedical Text Mining and Ontologies
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Machine Learning in Healthcare
- Gene expression and cancer classification
- Genetics, Bioinformatics, and Biomedical Research
- Machine Learning in Bioinformatics
- Cancer Genomics and Diagnostics
- Protein Structure and Dynamics
- Artificial Intelligence in Healthcare
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- Digital Mental Health Interventions
- Metabolism and Genetic Disorders
- Artificial Intelligence in Healthcare and Education
- Genetic Associations and Epidemiology
- Scientific Computing and Data Management
- Genomic variations and chromosomal abnormalities
- Chronic Kidney Disease and Diabetes
- Radiomics and Machine Learning in Medical Imaging
- CRISPR and Genetic Engineering
- Genetics, Aging, and Longevity in Model Organisms
University of Washington Medical Center
2015-2025
University of Washington
2016-2025
Center for Information Technology
2024-2025
National Institutes of Health
2024-2025
Seattle University
2018-2024
Alzheimer’s Disease Neuroimaging Initiative
2023
Lund University
2022
Institute of Translational Health Sciences
2021
Trinity College Dublin
2021
Landscape Research Group
2021
Abstract Motivation: Advances in high-throughput genotyping and next generation sequencing have generated a vast amount of human genetic variation data. Single nucleotide substitutions within protein coding regions are particular importance owing to their potential give rise amino acid that affect structure function which may ultimately lead disease state. Over the last decade, number computational methods been developed predict whether such result an altered phenotype. Although these useful...
Abstract Identifying pathogenic variants and underlying functional alterations is challenging. To this end, we introduce MutPred2, a tool that improves the prioritization of amino acid substitutions over existing methods, generates molecular mechanisms potentially causative disease, returns interpretable pathogenicity score distributions on individual genomes. Whilst its performance state-of-the-art, distinguishing feature MutPred2 probabilistic modeling variant impact specific aspects...
Large-scale proteomic approaches have identified numerous mitochondrial acetylated proteins; however in most cases, their regulation by acetyltransferases and deacetylases remains unclear. Sirtuin 3 (SIRT3) is an NAD + -dependent protein deacetylase that has been shown to regulate a limited number of enzymes key metabolic pathways. Here, we use rigorous label-free quantitative MS approach (called MS1 Filtering) analyze changes lysine acetylation from mouse liver mitochondria the absence...
Digital technologies such as smartphones are transforming the way scientists conduct biomedical research. Several remotely conducted studies have recruited thousands of participants over a span few months allowing researchers to collect real-world data at scale and fraction cost traditional Unfortunately, remote been hampered by substantial participant attrition, calling into question representativeness collected including generalizability outcomes. We report findings regarding recruitment...
Metazoan genes are encrypted with at least two superimposed codes: the genetic code to specify primary structure of proteins and splicing expand their proteomic output via alternative splicing. Here, we define specificity a central regulator pre-mRNA splicing, conserved, essential factor SFRS1. Cross-linking immunoprecipitation high-throughput sequencing (CLIP-seq) identified 23,632 binding sites for SFRS1 in transcriptome cultured human embryonic kidney cells. was found engage many...
Recommendations from the American College of Medical Genetics and Genomics Association for Molecular Pathology (ACMG/AMP) interpreting sequence variants specify use computational predictors as "supporting" level evidence pathogenicity or benignity using criteria PP3 BP4, respectively. However, score intervals defined by tool developers, ACMG/AMP recommendations that require consensus multiple predictors, lack quantitative support. Previously, we described a probabilistic framework quantified...
Rapamycin has been shown to extend lifespan in numerous model organisms including mice, with the most dramatic longevity effects reported females. However, little is known about functional ramifications of this longevity-enhancing paradigm mammalian tissues. We treated 24-month-old female C57BL/6J mice rapamycin for 3 months and determined health outcomes via a variety noninvasive measures cardiovascular, skeletal, metabolic individual mice. that while mild transient effects, there are...
Natural language computer applications are becoming increasingly sophisticated and, with the recent release of Generative Pre-trained Transformer 3, they could be deployed in healthcare-related contexts that have historically comprised human-to-human interaction. However, for GPT-3 and similar to considered use health-related contexts, possibilities pitfalls need thoughtful exploration. In this article, we briefly introduce some opportunities cautions would accompany advanced Language...
The rapid development of genomic sequencing technologies has decreased the cost genetic analysis to extent that it seems plausible genome-scale could have widespread availability in pediatric care. Genomic provides a powerful diagnostic modality for patients who manifest symptoms monogenic disease and an opportunity detect health conditions before their development. However, many technical, clinical, ethical, societal challenges should be addressed such technology is widely deployed...
Efficient tools for data management and integration are essential many aspects of high-throughput biology. In particular, annotations genes human genetic variants commonly used but highly fragmented across resources. Here, we describe MyGene.info MyVariant.info, high-performance web services querying gene variant annotation information. These currently accessed more than three million times permonth. They also demonstrate a generalizable cloud-based model organizing biological MyVariant.info...
Abstract We introduce MutPred2, a tool that improves the prioritization of pathogenic amino acid substitutions, generates molecular mechanisms potentially causative disease, and returns interpretable pathogenicity score distributions on individual genomes. While its performance is state-of-the-art, novel distinguishing feature MutPred2 probabilistic modeling variant impact specific aspects protein structure function can serve to guide experimental studies phenotype-altering variants....
Gain-of-function mutations in fibroblast growth factor-23 (FGF23) are responsible for autosomal dominant hypophosphatemic rickets, a disorder of isolated renal phosphate wasting. Patients with the display hypophosphatemia normocalcemia as well inappropriately normal 1,25-dihydroxyvitamin D [1,25(OH)2D3] concentrations. Reciprocally tumoral calcinosis (TC) patients often hyperphosphatemic or elevated serum 1,25(OH)2D3 levels and have ectopic vascular calcifications, phenotype similar to that...
Abstract One of the most important tasks modern bioinformatics is development computational tools that can be used to understand and treat human disease. To date, a variety methods have been explored algorithms for candidate gene prioritization are gaining in their usefulness. Here, we propose an algorithm detecting gene–disease associations based on protein–protein interaction network, known associations, protein sequence, functional information at molecular level. Our method, PhenoPred,...
While it is generally recognized that misfolding of specific proteins can cause late-onset disease, the contribution protein aggregation to normal aging process less well understood. To address this issue, a mass spectrometry-based proteomic analysis was performed identify adopt sodium dodecyl sulfate (SDS)-insoluble conformations during in Caenorhabditis elegans. SDS-insoluble extracted from young and aged C. elegans were chemically labeled by isobaric tagging for relative absolute...
Summary A decline in skeletal muscle mass and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report for first time a genome‐wide study of DNA methylation dynamics healthy male individuals during normal human aging. We predominantly observed hypermethylation throughout genome within aged group as compared to young subjects. Differentially methylated CpG (dmCpG) nucleotides tend arise intragenically are underrepresented promoters...
We have developed a novel machine-learning approach, MutPred Splice, for the identification of coding region substitutions that disrupt pre-mRNA splicing. Applying Splice to human disease-causing exonic mutations suggests 16% causing inherited disease and 10 14% somatic in cancer may For disease, main mechanism responsible splicing defect is splice site loss, whereas predominant disruption predicted be exon skipping via loss enhancers or gain silencer elements. available at...
Most people with mental health disorders fail to receive timely access adequate care. US Hispanic/Latino individuals are particularly underrepresented in care and historically a very difficult population recruit into clinical trials; however, they have increasing mobile technology, over 75% owning smartphone. This technology has the potential overcome known barriers accessing utilizing traditional assessment treatment approaches.This study aimed compare recruitment engagement fully remote...
Cellular senescence irreversibly arrests cell proliferation, accompanied by a multi-component senescence-associated secretory phenotype (SASP) that participates in several age-related diseases. Using stable isotope labeling with amino acids (SILACs) and cultured cells, we identify 343 SASP proteins senescent human fibroblasts secrete at 2-fold or higher levels compared quiescent counterparts. Bioinformatic analysis reveals 44 of these participate hemostasis, process not previously linked...
Background Smartphones provide a low-cost and efficient means to collect population level data. Several small studies have shown promise in predicting mood variability from smartphone-based sensor usage data, but not been generalized nationally recruited samples. This study used passive smartphone demographic characteristics, baseline depressive symptoms predict prospective daily mood. Method Daily phone data were collected passively 271 Android users participating fully remote randomized...
We utilized induced pluripotent stem cells (iPSCs) derived from Huntington's disease (HD) patients as a human model of HD and determined that the phenotypes only manifest in differentiated neural cell (NSC) stage, not iPSCs. To understand molecular basis for CAG repeat expansion-dependent NSCs, we performed transcriptomic analysis iPSCs NSCs compared to isogenic controls. Differential gene expression pathway pointed transforming growth factor β (TGF-β) netrin-1 top dysregulated pathways....