A5037474512- Genetic Associations and Epidemiology
- Mycobacterium research and diagnosis
- Gene expression and cancer classification
- Genomics and Phylogenetic Studies
- Genetic Mapping and Diversity in Plants and Animals
- Antibiotic Resistance in Bacteria
- Cancer Genomics and Diagnostics
- Bacterial Identification and Susceptibility Testing
- Forensic and Genetic Research
- Genomic variations and chromosomal abnormalities
- Fungal Infections and Studies
- Antifungal resistance and susceptibility
- Virus-based gene therapy research
- Evolution and Genetic Dynamics
- Poxvirus research and outbreaks
- Neutropenia and Cancer Infections
- Tuberculosis Research and Epidemiology
- Renal Diseases and Glomerulopathies
- Viral Infections and Vectors
- Vector-borne infectious diseases
- Single-cell and spatial transcriptomics
- Infectious Diseases and Mycology
- Bacillus and Francisella bacterial research
- Gut microbiota and health
- Genetic and phenotypic traits in livestock
Stanford University
2011-2016
Technion – Israel Institute of Technology
2006-2012
Silicon Valley University
2012
DNAnexus (United States)
2011
Microsoft (United States)
2010
Israel Institute
2010
Diagnosis of life-threatening deep-seated infections currently requires invasive sampling the infected tissue to provide a microbiologic diagnosis. These procedures can lead high morbidity in patients and add healthcare costs. Here we describe novel next-generation sequencing assay that was used detect pathogen-derived cell-free DNA peripheral blood with biopsy-proven fungal infections. The noninvasive nature this approach could rapid, actionable treatment information for when biopsy is not possible.
Microbial cell-free DNA (mcfDNA) sequencing is an emerging infectious disease diagnostic tool which enables unbiased pathogen detection and quantification from plasma. The Karius Test, a commercial mcfDNA assay developed by available since 2017 Karius, Inc. (Redwood City, CA), detects quantifies as molecules/μL in sample data results for all tests conducted April 2018 through mid-September 2021 were evaluated laboratory quality metrics, reported pathogens, test requisition forms. A total of...
Abstract Background Pneumonia is a common cause of morbidity and mortality, yet causative pathogen identified in minority cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield immunocompromised patients with pneumonia. Methods In this prospective, multicenter, observational study adults undergoing bronchoscopy to establish pneumonia etiology, plasma was compared standardized usual care testing. etiology adjudicated by blinded independent committee. The primary...
Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether are also in admixed populations differing genomic backgrounds, we genotyped total 1425 and Hispanic American subjects dialysis patients diabetic ESKD controls, using 42 single nucleotide polymorphisms (SNPs) within 40...
Allogeneic hematopoietic stem cell transplant patients are at risk for common and atypical infections. Superior diagnostics can decrease infection-related morbidity mortality. A novel plasma cell-free DNA next-generation sequencing test detected an uncommon presentation of Chlamydia trachomatis recurrent metastatic complications Staphylococcus aureus bacteremia before standard microbiology.
There is an ongoing outbreak of Mycobacterium chimaera infections among patients exposed to contaminated heater-cooler devices used during cardiac surgery. Recognition M. infection hampered by its long latency and non-specific symptoms. Standard diagnostic methods using acid-fast bacilli (AFB) culture often require invasive sampling, have low sensitivity, can take weeks result. We describe the performance a plasma-based next-generation sequencing test (plasma NGS) for diagnosis infection.We...
Abstract Background Laboratory confirmation of early Lyme borreliosis (LB) is challenging. Serology insensitive during the first days to weeks infection, and blood polymerase chain reaction (PCR) offers similarly poor performance. Here, we demonstrate that detection Borrelia burgdorferi (B.b.) cell-free DNA (cfDNA) in plasma can improve diagnosis LB. Methods B.b. samples using unbiased metagenomic cfDNA sequencing performed by a commercial laboratory (Karius Inc) was compared with serology...
The question of a genetic contribution to the higher prevalence and incidence end stage kidney disease (ESKD) among African Americans (AA) remained unresolved, until recent findings using admixture mapping pointed association genomic locus on chromosome 22 with this phenotype. In current study we utilize example demonstrate utility applying multi-step approach.A case only study, consisted following steps was designed: 1) Assembly sample dataset (ESKD AA); 2) Design estimated mutual...
Inferring the ancestral origin of chromosomal segments in admixed individuals is key for genetic applications, ranging from analyzing population demographics and history, to mapping disease genes. Previous methods addressed ancestry inference by using either weak models linkage disequilibrium, or large that make explicit use haplotypes. In this paper we introduce ALLOY, an efficient method incorporates generalized, but highly expressive, disequilibrium models. ALLOY applies a factorial...
Abstract Background Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying in plasma. However, data are needed to define clinical scenarios where this tool offers highest benefit. Methods We conducted a prospective multicenter observational study that evaluated impact plasma mcfDNA compared with usual care testing among adults hematologic malignancies. This is secondary analysis an expanded cohort utility across...
Abstract Motivation: Association analysis is the method of choice for studying complex multifactorial diseases. The premise this that affected persons contain some common genomic regions with similar SNP alleles and such areas will be found in analysis. An important disadvantage GWA studies it does not distinguish between are inherited from a ancestor [identical by descent (IBD)] identical merely state (IBS)]. Clearly, can marked higher probability as IBD have same correlation disease status...
Metagenomic data enables the study of microbes and viruses through their DNA as retrieved directly from environment in which they live. Functional analysis metagenomes explores abundance gene families, pathways, systems, rather than taxonomy. Through such analysis, researchers are able to identify those functional capabilities most important organisms examined environment. Recently, a statistical framework for was described that focuses on families. Here we describe two pathway level...
ABSTRACT Microbial cell-free DNA (mcfDNA) sequencing is an emerging infectious disease diagnostic tool which enables unbiased pathogen detection from plasma. The Karius Test®, a commercial mcfDNA assay developed by and available since 2017 Karius, Inc. (Redwood City, CA), detects quantifies as molecules/μl in sample data results for all tests conducted April 2018 through mid-September 2021 were evaluated laboratory performance metrics, reported pathogens, test requisition forms. A total of...
Host inflammatory responses predict worse outcome in severe pneumonia, yet little is known about what drives dysregulated inflammation. We performed metagenomic sequencing of microbial cell-free DNA (mcfDNA) 83 mechanically ventilated patients (26 culture-positive, 41 culture-negative 16 uninfected controls). Culture-positive had higher levels mcfDNA than those with pneumonia and controls (p<0.005). Plasma biomarkers (fractalkine, procalcitonin, pentraxin-3 suppression tumorigenicity-2)...
Identity-by-descent (IBD) inference is the problem of establishing a genetic connection between two individuals through genomic segment that inherited by both from recent common ancestor. IBD an important preceding step in variety population studies, ranging demographic studies to linking variation with phenotype and disease. The accurate detection has become increasingly challenging availability large collections human genotypes genomes: Given cohort’s size, quadratic number pairwise genome...
Background Chorioamnionitis has been linked to spontaneous preterm labor and complications such as neonatal sepsis. We hypothesized that microbial cell-free (cf) DNA would be detectable in maternal plasma patients with chorioamnionitis could the basis for a non-invasive method detect fetal exposure microorganisms. Objective The purpose of this study was determine whether next generation sequencing cfDNA chorioamnionitis. Study design Maternal (n = 94) umbilical cord 120) were collected...
Abstract Motivation: Accurate inference of genealogical relationships between pairs individuals is paramount in association studies, forensics and evolutionary analyses wildlife populations. Current methods for relationship consider only a small set close have limited to no power distinguish with the same number meioses separating under consideration (e.g. aunt–niece versus niece–aunt or first cousins great aunt–niece). Results: We present CARROT (ClAssification Relationships ROTations),...
Population low-coverage whole-genome sequencing is rapidly emerging as a prominent approach for discovering genomic variation and genotyping cohort. This combines substantially lower cost than full-coverage with discovery of low-allele frequency variants, to an extent that not possible array or exome sequencing. However, challenging computational problem arises jointly variants the entire Variant are relatively straightforward tasks on single individual has been sequenced at high coverage,...
Mapping by admixture linkage disequilibrium (MALD) is an economical and powerful approach for the identification of genomic regions harboring disease susceptibility genes in recently admixed populations. We develop information-theory-based measure, called expected mutual information (EMI), which computes impact a set markers on ability to infer ancestry at each chromosomal location. then present simple effective algorithm selection panels that strives maximize EMI score. Finally, we...
We used a next-generation sequencing platform to characterize microbial cell-free DNA (mcfDNA) in plasma samples from patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). In this observational study, we sought mcfDNA order explore its potential association with the immunologic complications of transplantation. compared serially collected patient healthy control subjects. observed changes total burden after transplantation, which was most striking during early...
Much effort has recently been invested in developing methods for determining the ancestral origin of chromosomal segments admixed individuals. Motivations this task are study population history such as bottleneck effects and migration, assessment stratification adequate adjustment association studies, enhancement mapping by admixture linkage disequilibrium (MALD). In article, we present a novel framework inference ancestry at each location. The uniqueness our method stems from ability to...