A5041658734- Prion Diseases and Protein Misfolding
- T-cell and B-cell Immunology
- Antifungal resistance and susceptibility
- Fungal and yeast genetics research
- Immune Cell Function and Interaction
- Neurological diseases and metabolism
- Evolution and Genetic Dynamics
- Genomics and Phylogenetic Studies
- Interdisciplinary Research and Collaboration
- Gene Regulatory Network Analysis
- Genetic Associations and Epidemiology
- Amino Acid Enzymes and Metabolism
- Bioinformatics and Genomic Networks
- Biomedical and Engineering Education
- Immunotherapy and Immune Responses
- Academic Publishing and Open Access
- Genetics, Bioinformatics, and Biomedical Research
- Fermentation and Sensory Analysis
- Computational Physics and Python Applications
- Antibiotic Resistance in Bacteria
- scientometrics and bibliometrics research
- Gene expression and cancer classification
- Genomics and Rare Diseases
- Biochemical Acid Research Studies
- Scientific Computing and Data Management
Institute for Globally Distributed Open Research and Education
2024
Ronin Institute
2014-2024
University of Tennessee at Martin
2019
Whitehead Institute for Biomedical Research
2010-2017
Beth Israel Deaconess Medical Center
2014-2015
Harvard University
2014-2015
Boston University
2015
Center for Systems Biology
2014-2015
University of Massachusetts Chan Medical School
2014
Howard Hughes Medical Institute
2014
Summary: Prions are self-templating protein aggregates that stably perpetuate distinct biological states and of keen interest to researchers in both evolutionary biomedical science. The best understood prions from yeast have a prion-forming domain with strongly biased amino acid composition, most notably enriched for Q or N. PLAAC is web application scans sequences domains prion-like composition. Users can upload sequence files, paste directly into textbox. ranks the input by several summary...
The evolution of drug resistance in microbial pathogens provides a paradigm for investigating evolutionary dynamics with important consequences human health. Candida albicans, the leading fungal pathogen humans, rapidly evolves to two major antifungal classes, triazoles and echinocandins. In contrast, third used clinic, amphotericin B (AmB), remains extremely rare despite 50 years use as monotherapy. We sought understand this long-standing puzzle. whole genome sequencing AmB-resistant...
α-Synuclein (α-syn) is a small lipid-binding protein implicated in several neurodegenerative diseases, including Parkinson's disease, whose pathobiology conserved from yeast to man. There are no therapies targeting these underlying cellular pathologies, or indeed those of any major disease. Using unbiased phenotypic screens as an alternative target-based approaches, we discovered N-aryl benzimidazole (NAB) that strongly and selectively protected diverse cell types α-syn toxicity. Three...
Significance Prion proteins provide the best-understood mode for protein-based molecular memory. Since their discovery in mammals, prions have been identified diverse organisms including fungi, Aplysia , and Drosophila but not plant kingdom. Applying methods we used to uncover yeast prions, nearly 500 Arabidopsis that harbor potential prion-like domains (PrDs). At least one of these domains, Luminidependens PrD, had some classical characteristics prion when tested experimentally yeast,...
Abstract Population genetic statistics from multilocus genotype data inform our understanding of the patterns variation and their implications for evolutionary studies, generally, human disease studies in particular. In any given population one can estimate haplotype frequencies, identify deviation Hardy–Weinberg equilibrium, test balancing or directional selection, investigate linkage disequilibrium. Existing software packages are oriented primarily toward computation such on a...
The allelic and haplotypic diversity of the HLA-A, HLA-B, HLA-C loci was investigated in 852 subjects from five sub-Saharan populations Kenya (Nandi Luo), Mali (Dogon), Uganda, Zambia. Distributions genotypes at all fit Hardy-Weinberg equilibrium expectations. There not a single allele predominant any these populations, with exception A*3002 [allele frequency (AF) = 0.233] Zambians Cw*1601 (AF 0.283) Malians. This distribution consistent balancing selection for class I which evidenced by...
Epigenetically inherited aggregates of the yeast prion [PSI+] cause genomewide readthrough translation that sometimes increases evolvability in certain harsh environments. The effects natural selection on modifiers appearance have been subject much debate. It seems likely would be at least mildly deleterious most environments, but this may counteracted by its properties rare occasions. Indirect is predicted to depend primarily spontaneous rate, critical parameter has not previously...
In fungi, the anchoring of proteins to plasma membrane via their covalent attachment glycosylphosphatidylinositol (GPI) is essential and thus provides a valuable point attack for development antifungal therapeutics. Unfortunately, studying underlying biology GPI-anchor synthesis difficult, especially in medically relevant fungal pathogens because they are not genetically tractable. Compounding difficulties, many genes this pathway Saccharomyces cerevisiae. Here, we report discovery new small...
Spiders (Order Araneae) are essential predators in every terrestrial ecosystem largely because they have evolved potent arsenals of silk and venom. Spider silks high performance materials made almost entirely proteins, thus represent an ideal system for investigating genome level evolution novel protein functions. However, genomic resources remain limited spiders. We de novo assembled a transcriptome the Western black widow (Latrodectus hesperus) from deeply sequenced cDNAs three tissue...
Abstract Sequence‐based typing was used to identify human leukocyte antigen (HLA)‐A, ‐B, ‐C, and ‐DRB1 alleles from 558 consecutively recruited US volunteers with Eastern European ancestry for an unrelated hematopoietic stem cell registry. Four of 31 HLA‐A alleles, 29 HLA‐C 59 HLA‐B 42 HLA‐DRB1 identified (A*0325, B*440204, Cw*0332, *0732N) are novel. The HLA‐A*02010101g allele observed at a frequency 0.28. Two‐, three‐, four‐locus haplotypes were estimated using the expectation‐maximization...
Abstract Sequence‐based typing was used to identify human leukocyte antigen (HLA)‐A, ‐B, ‐C, and ‐DRB1 alleles from 564 consecutively recruited African American volunteers for an unrelated hematopoietic stem cell registry. The number of known identified at each locus 42 HLA‐A, HLA‐B 67, HLA‐C 33, HLA‐DRB1 44. Six novel (A*260104, A*7411, Cw*0813, Cw*1608, Cw*1704, DRB1*130502) not observed in the initial sequence‐specific oligonucleotide probe testing were characterized. action balancing...
Reversible phenotypic switching can be caused by a number of different mechanisms including epigenetic inheritance systems and DNA-based contingency loci. Previous work has shown that reversible may favored natural selection. Many switches characterized as "on/off" where the "off" state constitutes temporary loss function. Loss-of-function phenotypes corresponding to produced in many ways, all yielding identical fitness short term. In long term, however, switch-induced function reversed,...
Abstract Summary: Efficient workflows to shepherd clinically generated genomic data through the multiple stages of a next-generation sequencing pipeline are critical importance in translational biomedical science. Here we present COSMOS, Python library for workflow management that allows formal description pipelines and partitioning jobs. In addition, it includes user interface tracking progress jobs, abstraction queuing system fine-grained control over workflow. Workflows can be created on...
While next-generation sequencing (NGS) costs have plummeted in recent years, cost and complexity of computation remain substantial barriers to the use NGS routine clinical care. The potential will not be realized until robust whole genome data can accurately rendered medically actionable reports within a time window hours at scales economy 10’s dollars. We take step towards addressing this challenge, by using COSMOS, cloud-enabled workflow management system, develop GenomeKey, an analysis...
Python for Population Genomics (PyPop) is a software package that processes genotype and allele data performs large-scale population genetic analyses on highly polymorphic multi-locus data. In particular, PyPop tests conformity to Hardy-Weinberg equilibrium expectations, Ewens-Watterson selection, estimates haplotype frequencies, measures linkage disequilibrium, significance. Standardized means of performing these key contemporary studies evolutionary biology genetics, are central disease...