A5055797335- Metabolism and Genetic Disorders
- Genomics and Rare Diseases
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- Genomics and Phylogenetic Studies
- Advanced biosensing and bioanalysis techniques
- Folate and B Vitamins Research
- Molecular Biology Techniques and Applications
- Forensic and Genetic Research
- Diet and metabolism studies
- Fungal and yeast genetics research
- Bioinformatics and Genomic Networks
- Microfluidic and Bio-sensing Technologies
- Genetic diversity and population structure
- CRISPR and Genetic Engineering
- Genomic variations and chromosomal abnormalities
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Biosensors and Analytical Detection
- Microbial Metabolic Engineering and Bioproduction
- Gene expression and cancer classification
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Genomics and Chromatin Dynamics
- Parvovirus B19 Infection Studies
Yale University
2017-2025
RELX Group (Netherlands)
2017
Stanford University
2004-2016
Stanford Medicine
2016
Cardiovascular Institute of the South
2015
Walter and Eliza Hall Institute of Medical Research
2012
University of California, Berkeley
2012
Ludwig-Maximilians-Universität München
1997-2003
Max Planck Institute of Psychiatry
2003
München Klinik Schwabing
2003
High-throughput screens have begun to reveal the protein interaction network that underpins most cellular functions in yeast Saccharomyces cerevisiae. How organization of this affects evolution proteins compose it is a fundamental question molecular evolution. We show connectivity well-conserved negatively correlated with their rate Proteins more interactors evolve slowly not because they are important organism, but greater proportion directly involved its function. At sites for between...
High mutation rate in mammalian mitochondrial DNA generates a highly divergent pool of alleles even within species that have dispersed and expanded size recently. Phylogenetic analysis 277 human genomes revealed significant (P < 0.01) excess rRNA nonsynonymous base substitutions among hotspots recurrent mutation. Most involved transitions from guanine to adenine that, with thymine-to-cytosine transitions, illustrate the asymmetric bias codon usage at synonymous sites on heavy-strand DNA. The...
In this study yeast mitochondria were used as a model system to apply, evaluate, and integrate different genomic approaches define the proteins of an organelle. Liquid chromatography mass spectrometry applied purified identified 546 proteins. By expression analysis comparison other proteome studies, we demonstrate that proteomic approach identifies primarily highly abundant expanding our evaluation types approaches, including systematic deletion phenotype screening, profiling, subcellular...
Significance Uniquely human biology is the result of genetic differences between humans and other primates, but identifying critical changes still poses a major challenge. We screened >32,000 human-specific substitutions in two classes putative transcriptional enhancers implicated evolution for their effects on enhancer activity neural stem cells, cell type fundamental cortical development expansion. identify hundreds that modify either alone or combination with variants. find different...
Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse debilitating clinical disorders. To date, 1,200 of these have been recorded, while no standardized catalog exists the associated phenotypes. Such a would be useful to develop methods analyze human phenotypic data, determine genotype-phenotype relations among many diseases, support diagnosis Here we establish phenotype 174 disease study associations diseases genes. Phenotypic features such as signs symptoms...
The accurate and complete selection of candidate genomic regions from a DNA sample before sequencing is critical in molecular diagnostics. Several recently developed technologies await substantial improvements performance, cost, multiplex processing. Here we present the utility long padlock probes (LPPs) for targeted exon capture followed by array-based sequencing. We found that on average 92% 5,471 exons 524 nuclear-encoded mitochondrial genes were successfully amplified 63 individuals....
Next-generation sequencing is revolutionizing genomic analysis, but this analysis can be compromised by high rates of missing true variants. To develop a robust statistical method capable identifying variants that would otherwise not called, we conducted sequence data simulations and both whole-genome targeted 28 families. Our (Family-Based Sequencing Program, FamSeq) integrates Mendelian transmission information raw reads. Sequence using FamSeq reduced the number false negative 14–33% as...
Newborn screening (NBS) for inborn metabolic disorders is a highly successful public health program that by design accompanied false-positive results. Here we trained Random Forest machine learning classifier on data to improve prediction of true and false positives. Data included 39 analytes detected tandem mass spectrometry clinical variables such as gestational age birth weight. Analytical performance was evaluated cohort 2777 screen positives reported the California NBS program, which...
Determining nucleic acid concentrations in a sample is an important step prior to proceeding with downstream analysis molecular diagnostics. Given the need for testing DNA amounts and its purity many samples, including samples very small input DNA, there utility of novel machine learning approaches accurate high-throughput quantification. Here, we demonstrated ability neural network predict coupled paramagnetic beads. To this end, custom-made microfluidic chip applied detect molecules bound...
Newborn screening identifies rare diseases that result from the recessive inheritance of pathogenic variants in both copies a gene. Long-read genome sequencing (LRS) is used for identifying and phasing genomic variants, but further efforts are needed to develop LRS applications using low-yield DNA samples. In this study, with high molecular weight was obtained 2 cystic fibrosis patients, comprising whole-blood sample (CF1) newborn dried blood spot (CF2). Library preparation (30-fold...
Clinical genetic testing often takes days to weeks, but rapid, affordable tests during outpatient visits could significantly benefit patients. This is crucial for detecting common, actionable point mutations, such as those linked hereditary transthyretin (TTR) amyloidosis, which underdiagnosed in individuals of West African ancestry with congestive heart failure. Here we developed a method known DNA variants using allele-specific polymerase chain reaction (ASPCR) and electrical impedance....
The mitochondrial outer membrane mediates numerous interactions between the metabolic and genetic systems of mitochondria rest eukaryotic cell. We performed a proteomic study to discover novel functions components membrane. Proteins highly pure vesicles (OMV) from Neurospora crassa were identified by combination LC-MS/MS tryptic peptide digests gel electrophoresis solubilized OMV proteins, followed their identification using MALDI-MS PMF. Among 30 proteins found in at least three four...
The thiamine transporter gene<i>SLC19A2</i> was recently found to be mutated in responsive megaloblastic anaemia with diabetes and deafness (TRMA, Rogers syndrome), an early onset autosomal recessive disorder. We now report a novel G1074A transition mutation exon 4 of the<i>SLC19A2</i> gene, predicting Trp358 ter change, girl consanguineous parents. In addition the typical triad syndrome, presented short stature, hepatosplenomegaly, retinal degeneration, brain MRI lesion. Both muscle skin...
PurposeImproved second-tier tools are needed to reduce false-positive outcomes in newborn screening (NBS) for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP).MethodsWe designed an assay multiplex sequencing of 72 genes (RUSPseq) from dried blood spots. Analytical and clinical performance was evaluated 60 screen-positive newborns methylmalonic acidemia (MMA) reported by California Department Public Health NBS program. Additionally, we trained a Random Forest...
Microhaplotypes (MH) are comprised of multiple single nucleotide polymorphisms (SNPs) that located within 300 bases genomic sequence. Improved tools needed to facilitate broader application microhaplotypes in a diverse range populations and forensic settings. We designed an assay for multiplex sequencing 90 (mMHseq) include 46 MH loci with high Effective Number Alleles (Ae) from previous studies [[1]Kidd K.K. Pakstis A.J. Speed W.C. Lagace R. Wootton S. Chang J. Selecting optimized different...
Abstract Improved second‐tier assays are needed to reduce the number of false positives in newborn screening (NBS) for inherited metabolic disorders including those on Recommended Uniform Screening Panel (RUSP). We developed an expanded metabolite panel testing dried blood spot (DBS) samples from screen‐positive cases reported by California NBS program, consisting true‐ and false‐positives four disorders: glutaric acidemia type I (GA1), methylmalonic (MMA), ornithine transcarbamylase...
Rapid advances in the screening, diagnosis, and treatment of genetic disorders have increased number conditions that can be detected through universal newborn screening (NBS). However, addition to Recommended Uniform Screening Panel (RUSP) implementation nationwide has been a slow process taking several years accomplish for individual conditions. Here, we describe web-based tools resources developed implemented by translational research network (NBSTRN) advance support NBS stakeholders...
MITOP (http://www.mips.biochem.mpg.de/proj/medgen/ mitop/ ) is a comprehensive database for genetic and functional information on both nuclear- mitochondrial-encoded proteins their genes. The five species files—Saccharomyces cerevisiae, Mus musculus, Caenorhabditis elegans, Neurospora crassa Homo sapiens—include annotated data derived from variety of online resources the literature. A wide spectrum search facilities given in overlapping sections 'Gene catalogues', 'Protein 'Homologies',...
Thousands of mutations across >50 genes have been implicated in inherited cardiomyopathies. However, options for sequencing this rapidly evolving gene set are limited because many services and off-the-shelf kits suffer from slow turnaround, inefficient capture genomic DNA, high cost. Furthermore, customization these assays to cover emerging targets that suit individual needs is often expensive time consuming.We sought develop a custom throughput, clinical-grade next-generation assay...