- Advanced NMR Techniques and Applications
- Genetic Associations and Epidemiology
- Advanced MRI Techniques and Applications
- Amino Acid Enzymes and Metabolism
- Lanthanide and Transition Metal Complexes
- Genetic and phenotypic traits in livestock
- BRCA gene mutations in cancer
- Cancer Research and Treatments
- Electron Spin Resonance Studies
- Atomic and Subatomic Physics Research
- NMR spectroscopy and applications
- Liver Disease Diagnosis and Treatment
- Nutrition, Genetics, and Disease
- Genetic Mapping and Diversity in Plants and Animals
- Cancer-related molecular mechanisms research
- Phagocytosis and Immune Regulation
- Genomic variations and chromosomal abnormalities
- Chemical Reactions and Isotopes
- Enzyme Structure and Function
- Biomedical Text Mining and Ontologies
- Epigenetics and DNA Methylation
- Folate and B Vitamins Research
- Celiac Disease Research and Management
- Genetic factors in colorectal cancer
- Diabetes, Cardiovascular Risks, and Lipoproteins
23andMe (United States)
2019-2024
Mountain View College
2019
University of California, San Francisco
2012-2016
University of California, Berkeley
2012-2016
University of California System
2016
Graduate Theological Union
2013
Abstract Great efforts are being made to develop advanced polygenic risk scores (PRS) improve the prediction of complex traits and diseases. However, most existing PRS primarily trained on European ancestry populations, limiting their transferability non-European populations. In this article, we propose a novel method for generating multi-ancestry Polygenic Risk scOres based enSemble PEnalized Regression models (PROSPER). PROSPER integrates genome-wide association studies (GWAS) summary...
Polygenic risk scores (PRSs) are now showing promising predictive performance on a wide variety of complex traits and diseases, but there exists substantial gap across populations. We propose MUSSEL, method for ancestry-specific polygenic prediction that borrows information in summary statistics from genome-wide association studies (GWASs) multiple ancestry groups via Bayesian hierarchical modeling ensemble learning. In our simulation data analyses four distinct studies, totaling 5.7 million...
Renal cell carcinomas (RCC) are a heterogeneous group of tumors with wide range aggressiveness. Noninvasive methods to confidently predict the tumor biologic behavior and select appropriate treatment lacking. Here, we investigate dynamic metabolic flux in living RCC cells using hyperpolarized (13)C-pyruvate magnetic resonance spectroscopy (MRS) combined bioreactor platform interrogated biochemical basis MRS data respect cancer have significantly higher pyruvate-to-lactate than normal renal...
<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">13</sup> C steady state free precession (SSFP) magnetic resonance imaging and effective spin-spin relaxation time (T2) mapping were performed using hyperpolarized [ C] urea C, xmlns:xlink="http://www.w3.org/1999/xlink">15</sup> N <sub xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ] injected intravenously in rats. labeling gave large T2 increases both solution vivo due to the elimination of a...
Polygenic risk scores (PRS) increasingly predict complex traits, however, suboptimal performance in non-European populations raise concerns about clinical applications and health inequities. We developed CT-SLEB, a powerful scalable method to calculate PRS using ancestry-specific GWAS summary statistics from multi-ancestry training samples, integrating clumping thresholding, empirical Bayes super learning. evaluate CT-SLEB nine-alternatives methods with large-scale simulated (∼19 million...
Polygenic risk scores (PRS) are now showing promising predictive performance on a wide variety of complex traits and diseases, but there exists substantial gap across different populations. We propose MUSSEL, method for ancestry-specific polygenic prediction that borrows information in the summary statistics from genome-wide association studies (GWAS) multiple ancestry groups. MUSSEL conducts Bayesian hierarchical modeling under MUltivariate Spike-and-Slab model effect-size distribution...
In vivo spin relaxation time (T2) heterogeneity of hyperpolarized [13C,15N2]urea in the rat kidney was investigated. Selective quenching vascular 13C signal with a macromolecular agent revealed that long-T2 component originated from renal extravascular space, thus allowing and filtrate contrast pools to be distinguished via multi-exponential analysis. The T2 response induced diuresis antidiuresis performed two imaging agents: control bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-2H8. Large...
Great efforts are being made to develop advanced polygenic risk scores (PRS) improve the prediction of complex traits and diseases. However, most existing PRS primarily trained on European ancestry populations, limiting their transferability non-European populations. In this article, we propose a novel method for generating multi-ancestry Polygenic Risk scOres based enSemble PEnalized Regression models (PROSPER). PROSPER integrates genome-wide association studies (GWAS) summary statistics...
BACKGROUND Metabolic shifts in disease are of great interest for the development novel therapeutics. In cancer treatment, these therapies exploit metabolic phenotype associated with oncogenesis and progression. One recent strategy involves depletion cofactors needed to maintain high rate glycolysis seen Warburg effect. Specifically, blocking nicotinamide adenine dinucleotide (NAD) biosynthesis via phosphoribosyltransferase (NAMPT) inhibition depletes cells NAD glycolysis. To characterize...
We combined the high MR signal enhancement achieved using dissolution dynamic nuclear polarization (DNP) with a pulsed gradient double spin echo diffusion sequence to rapidly and accurately measure coefficients of various hyperpolarized 13C molecules in solution. Furthermore, diffusion-weighted imaging we generate coefficient maps multiple metabolites simultaneously. While experiments can rapid, non-equilibrium processes by avoiding averaging, continuous loss due longitudinal relaxation (T1)...
Purpose Hyperpolarized 13 C magnetic resonance allows for the study of real‐time metabolism in vivo, including significant hyperpolarized lactate production many tumors. Other studies have shown that aggressive and highly metastatic tumors rapidly transport out cells. Thus, ability to not only measure but also understand its compartmentalization using diffusion‐weighted MR will provide unique information improved tumor characterization. Methods We used a bipolar, pulsed‐gradient, double spin...
A substantial proportion of the adult United States population with type 2 diabetes (T2D) are undiagnosed, calling into question comprehensiveness current screening practices, which primarily rely on age, family history, and body mass index (BMI). We hypothesized that a polygenic score (PGS) may serve as complementary tool to identify high-risk individuals. The T2D maintained predictive utility after adjusting for history combining genetics led even more improved disease risk prediction....
Abstract Current guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants — 185delAG (c.68_69delAG), 5382insC (c.5266dupC), 6174delT (c.5946delT) are common in the Ashkenazi Jewish population. We characterized cohort more than 2,800 research participants 23andMe database who carry one three variants, evaluating two characteristics that typically used to BRCA testing: self-reported ancestry...
Abstract Background Human genetics provides opportunities for enhancing disease prediction through polygenic risk scores (PRS). Method We used a dataset from 23andMe (6.77M European, 1.30M Latine, and 0.45M African American individuals). Using cross-sectional data PRS construction prospective cohort evaluation, we estimated PRS-associated cumulative incidences after one year of follow-up 12 clinical endpoints. Results The incidence at was consistently higher among individuals in the top 10%...
Reliability of prostate cancer (PCa) genetic risk score (GRS), that is, the concordance between its estimated and observed risk, is required for testing at individual level. data are lacking non-European racial/ethnic populations, which hinders clinical use exacerbates racial disparity.To calibrate PCa ancestry-specific GRS in four populations.PCa GRSs, calculated from published risk-associated single-nucleotide polymorphisms corresponding were evaluated men who participated 23andMe, Inc....
With the rise in prevalence of type 2 diabetes (T2D), as well undiagnosed cases T2D and prediabetes (25% 90%, respectively), early detection is imperative to minimize individual societal burden. highly heritable, personal genetic information increasingly available general public. Studies have suggested that risk reduction strategies may be more effective for individuals with high risk, supporting use genetics a screening tool inform cost-effective interventions. We trained polygenic score...
\textit{In vivo} spin relaxation time ($T_2$) heterogeneity of hyperpolarized \textsuperscript{13}C urea in the rat kidney was investigated. Selective quenching vascular signal with a macromolecular agent revealed that long-$T_2$ component originated from renal extravascular space, thus allowing and filtrate contrast pools to be distinguished via multi-exponential analysis. The $T_2$ response induced diuresis antidiuresis performed two imaging agents: control...
Purpose: To demonstrate an increase spin‐spin relaxation time (T2) of hyperpolarized carbon‐13 urea by nitrogen‐15 labeling its amide groups, and to show how this enables background‐free perfusion MRI at 1 mm in‐plane resolution with SNR > 300. Methods: In vivo dual‐labeled [C13,N‐15]urea singly‐labeled [C13]urea images were acquired dynamically in a rat using steady state free precession (SSFP) fast low angle shot (FLASH) acquisitions on clinical 3T scanner. Dynamic fit pixel‐wise...
<p>PDF file-63KB, Representative 31P spectra of HK-2, UMRC6 and UOK262 cell lines.</p>