A5056645115- Genomics and Rare Diseases
- Infective Endocarditis Diagnosis and Management
- Bacterial Identification and Susceptibility Testing
- Bacterial Infections and Vaccines
- Cancer Genomics and Diagnostics
- Pneumonia and Respiratory Infections
- Cancer Treatment and Pharmacology
- Genetic factors in colorectal cancer
- Genomic variations and chromosomal abnormalities
- Monoclonal and Polyclonal Antibodies Research
- Genetics and Neurodevelopmental Disorders
- COVID-19 epidemiological studies
- Microbial Natural Products and Biosynthesis
- Hematological disorders and diagnostics
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- Mycobacterium research and diagnosis
- Antimicrobial Resistance in Staphylococcus
- Metabolism and Genetic Disorders
- Chemotherapy-related skin toxicity
- Prenatal Screening and Diagnostics
- Cystic Fibrosis Research Advances
- Biosensors and Analytical Detection
- Gut microbiota and health
- Dysphagia Assessment and Management
University of California, San Diego
2011-2023
Rady Children's Hospital-San Diego
2018-2023
Children’s Institute
2017-2021
Office of Infectious Diseases
2021
The University of Kansas Health System
2015
University of California San Diego Medical Center
2015
Scripps Institution of Oceanography
2011-2013
Scripps Research Institute
2000-2005
Yale University
2000
Genetic diseases are leading causes of childhood mortality. Whole-genome sequencing (WGS) and whole-exome (WES) relatively new methods for diagnosing genetic diseases, whereas chromosomal microarray (CMA) is well established. Here we compared the diagnostic utility (rate causative, pathogenic, or likely pathogenic genotypes in known disease genes) clinical (proportion whom medical surgical management was changed by diagnosis) WGS, WES, CMA children with suspected systematic review literature...
Abstract Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid whole-genome sequencing (rWGS) can diagnose genetic time to change acute medical or surgical management (clinical utility) improve outcomes acutely ill We report retrospective cohort study inpatient infants regional children’s hospital from July 2016–March 2017. Forty-two families received rWGS for etiologic diagnosis disorders. Probands also standard testing as clinically indicated. Primary...
Automated phenotyping and interpretation of rapid whole-genome sequencing improve time to diagnosis genetic diseases in hospitalized children.
Whole-genome sequencing (WGS) shows promise as a first-line genetic test for acutely ill infants, but widespread adoption and implementation requires evidence of an effect on clinical management.To determine the WGS management in racially ethnically diverse geographically distributed population infants US.This randomized, time-delayed trial enrolled participants from September 11, 2017, to April 30, 2019, with observation period extending July 2, 2019. The study was conducted at 5 US...
Genetic disorders are a leading contributor to mortality in the neonatal ICU and PICU United States. Although individually rare, there over 6,200 single-gene diseases, which may preclude genetic diagnosis prior admission. Rapid whole genome sequencing is an emerging method of diagnosing conditions time affect management neonates; however, its clinical utility has yet be adequately demonstrated critically ill children. This study evaluates next-generation pediatric critical care.Retrospective...
Community-acquired pneumonia (CAP) is a common cause of pediatric hospital admission. Empiric antibiotic therapy for hospitalized children with serious CAP now targets the most likely pathogen(s), including those that may demonstrate significant resistance. Cell-free plasma next-generation sequencing (CFPNGS) was first made available Pediatric Infectious Diseases physicians in June 1, 2017, to supplement standard-of-care diagnostic techniques. A retrospective chart review performed between...
The diagnostic and clinical utility of rapid whole genome sequencing (rWGS) for critically ill children in the intensive care unit (ICU) has been substantiated by multiple studies, but comprehensive cost-effectiveness evaluation rWGS ICU outside neonatal age group is lacking. In this study, we examined cost data retrospectively a cohort 38 regional pediatric (PICU) who received rWGS. We identified seven 17 patients molecular diagnoses had resultant changes management with sufficient clarity...
The microbial production, isolation, and structure elucidation of four new napyradiomycin congeners (1–4) is reported. structures these compounds, which are additions to the marine-derived meroterpenoids, were defined by comprehensive spectroscopic analysis X-ray crystallography. Using fluorescence-activated cell sorting (FACS) analysis, napyradiomycins 1–4 observed induce apoptosis in colon adenocarcinoma line HCT-116, indicating possibility a specific biochemical target for this class cytotoxins.
Pediatric infective endocarditis incurs significant morbidity and generally occurs among children with underlying heart disease. Identification of a pathogen is critical in determining appropriate therapy. However, standard diagnostic testing has limited sensitivity. We describe case series whom plasma next-generation sequencing (Karius, Redwood, CA) identified an organism 8 10 cases.
Abstract Background Children affected by infectious diseases may not always have a detectable etiology. Diagnostic uncertainty can lead to prolonged hospitalizations, inappropriately broad or extended courses of antibiotics, invasive diagnostic procedures, and difficulty predicting the clinical course outcome. Cell-free plasma next-generation sequencing (cfNGS) identify viral, bacterial, fungal infections detecting pathogen DNA in peripheral blood. This testing modality offers ability test...
Osteoarticular infections (OAIs) are frequently encountered in children. Treatment may be guided by isolation of a pathogen; however, operative cultures often negative. Metagenomic next-generation sequencing (mNGS) allows for broad and sensitive pathogen detection that is culture-independent. We sought to evaluate the diagnostic utility mNGS comparison culture usual care testing detect pathogens acute osteomyelitis and/or septic arthritis children.This was single-site study use pediatric...
Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management characterizing prognosis. Usual care testing by culture polymerase chain reaction often unable to identify pathogen. We examined the systematic application metagenomic next-generation sequencing (mNGS) for detecting organisms transcriptomic analysis cerebrospinal fluid (CSF) children with...
An increasing number of studies suggest the importance antibodies in pathogenesis most systemic and organ-specific autoimmune diseases, although there is considerable controversy over precise role autoantibodies involved. In humans, a major obstacle to progress identification cloning relevant autoantigens. Here, an approach based on sequential use antibody phage display antigen expression libraries developed applied donor suffering from rheumatoid arthritis (RA), splenomegaly, peripheral...
A 9-mo-old infant was admitted with infantile spasms that improved on administration of topiramate and steroids. He also had developmental delay, esotropia, hypsarrhythmia interictal electroencephalogram (EEG), normal brain magnetic resonance imaging (MRI). West syndrome is the triad spasms, hypsarrhythmia, mental retardation. Rapid trio whole-genome sequencing (WGS) revealed a novel, likely pathogenic, de novo variant in gene encoding γ-aminobutyric acid (GABA) type receptor, α1 polypeptide...
There is an urgent need for new antibiotics to treat hospital- and community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections. Previous work has indicated that both terrestrial marine-derived members of the napyradiomycin class possess potential anti-staphylococcal activities. These compounds are unique meroterpenoids with unusual levels halogenation. In this paper we report evaluation two previously described derivatives, A80915A (1) A80915B (2) produced by...
X-linked agammaglobulinemia (XLA, OMIM#300300) is a rare monogenic primary immunodeficiency caused by mutations in the Bruton tyrosine kinase (BTK) gene. XLA characterized insufficient immunoglobulin levels and susceptibility to life-threatening bacterial infections. We report on patient that presented with ecthyma gangrenosum septicemia. Rapid trio whole-genome sequencing (rWGS) revealed an apparently de novo hemizygous pathogenic variant (c.726dupT; p.Ile243TyrfsTer15) BTK Metagenomic...