A5085693193- RNA and protein synthesis mechanisms
- Cancer Genomics and Diagnostics
- Protein Structure and Dynamics
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Genetics, Bioinformatics, and Biomedical Research
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
- Crystallization and Solubility Studies
- Gene expression and cancer classification
- X-ray Diffraction in Crystallography
- Immune Cell Function and Interaction
- Lipid Membrane Structure and Behavior
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Parkinson's Disease Mechanisms and Treatments
- Epigenetics and DNA Methylation
- Biofuel production and bioconversion
- T-cell and B-cell Immunology
- Advanced Cellulose Research Studies
- Glycosylation and Glycoproteins Research
- vaccines and immunoinformatics approaches
- Enzyme Structure and Function
Enzo Life Sciences (United States)
2022-2024
Yale University
2014-2022
Seven Bridges Genomics (United States)
2017-2018
Whitney Museum of American Art
2014-2016
Los Alamos National Laboratory
2010-2014
University of Illinois Urbana-Champaign
2005-2010
Purdue University West Lafayette
2007
Indian Institute of Technology Bombay
2002
Papillary renal-cell carcinoma, which accounts for 15 to 20% of carcinomas, is a heterogeneous disease that consists various types renal cancer, including tumors with indolent, multifocal presentation and solitary an aggressive, highly lethal phenotype. Little known about the genetic basis sporadic papillary no effective forms therapy advanced exist.We performed comprehensive molecular characterization 161 primary using whole-exome sequencing, copy-number analysis, messenger RNA microRNA...
Community network analysis derived from molecular dynamics simulations is used to identify and compare the signaling pathways in a bacterial glutamyl-tRNA synthetase (GluRS):tRNA(Glu) an archaeal leucyl-tRNA (LeuRS):tRNA(Leu) complex. Although 2 class I synthetases have remarkably different interactions with their cognate tRNAs, allosteric networks for charging tRNA correct amino acid display considerable similarities. A dynamic contact map defines edges connecting nodes (amino acids...
The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide detailed summary this initiative, including technical and biological validations, insights into disease signatures, prediction modelling for various demographic health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping 2,923 proteins that identifies 14,287 primary genetic associations,...
Uniform processing and detailed annotation of human, worm fly RNA-sequencing data reveal ancient, conserved features the transcriptome, shared co-expression modules (many enriched in developmental genes), matched expression patterns across development similar extent non-canonical, non-coding transcription; furthermore, are used to create a single, universal model predict gene-expression levels for all three organisms from chromatin at promoter. In this paper modENCODE consortium reports on...
Abstract ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds cell types, providing a universal annotation for genome interpretation. However, particular applications, it may be advantageous to use customized annotation. Here, we develop such custom by leveraging advanced assays, as eCLIP, Hi-C, whole-genome STARR-seq on number data-rich types. A key aspect this is comprehensive experimentally derived networks both transcription factors RNA-binding...
Abstract The UK Biobank Pharma Proteomics Project (UKB-PPP) is a collaboration between the (UKB) and thirteen biopharmaceutical companies characterising plasma proteomic profiles of 54,306 UKB participants. Here, we describe results from first phase UKB-PPP, including protein quantitative trait loci (pQTL) mapping 1,463 proteins that identifies 10,248 primary genetic associations, which 85% are newly discovered. We also identify independent secondary associations in 92% cis 29% trans loci,...
The Seven Bridges Cancer Genomics Cloud (CGC; www.cancergenomicscloud.org) enables researchers to rapidly access and collaborate on massive public cancer genomic datasets, including Genome Atlas. It provides secure on-demand data, analysis tools, computing resources. Researchers from diverse backgrounds can easily visualize, query, explore datasets visually or programmatically. Data of interest be immediately analyzed in the cloud using more than 200 preinstalled, curated bioinformatics...
Substrate binding is typically one of the rate-limiting steps preceding enzyme catalytic action during homogeneous reactions. However, interfacial-based catalysis on insoluble crystalline substrates, like cellulose, has additional bottlenecks individual biopolymer chain decrystallization from substrate interface followed by its processive depolymerization to soluble sugars. This step ramifications role enzyme–substrate and relationship overall efficiency. We found that altering structure...
Ribosomal signatures, idiosyncrasies in the ribosomal RNA (rRNA) and/or proteins, are characteristic of individual domains life. As such, insight into early evolution can be gained from a comparative analysis their respective signatures translational apparatus. In this work, we identify both sequence and structure rRNA analyze contributions to universal phylogenetic tree using sequence- structure-based methods. Domain-specific proteins considered own right. Although it is commonly assumed...
Abstract Diffuse idiopathic skeletal hyperostosis (DISH) is a condition where adjacent vertebrae become fused through formation of osteophytes. The genetic and epidemiological etiology this not well understood. Here, we implemented machine learning algorithm to assess the prevalence severity pathology in ~40,000 lateral DXA scans UK Biobank Imaging cohort. We find that DISH highly prevalent, above age 45, ~20% men ~8% women having multiple Surprisingly, strong phenotypic association with...
We have combined equilibrium and steered molecular dynamics (SMD) simulations with principal component correlation analyses to probe the mechanism of allosteric regulation in imidazole glycerol phosphate (IGP) synthase. An evolutionary analysis IGP synthase revealed a conserved network interactions leading from effector binding site glutaminase active site, forming communication pathways between remote sites. SMD undocking ribonucleotide N1-[(5'-phosphoribulosyl)-formino]-5'-aminoimidazole...
A steady increase in knowledge of the molecular and antigenic structure gp120 gp41 HIV-1 envelope glycoproteins (Env) is yielding important new insights for vaccine design, but it has been difficult to translate this information an immunogen that elicits broadly neutralizing antibodies. To help bridge gap, we used phylogenetically corrected statistical methods identify amino acid signature patterns Envs derived from people who have made potently antibodies, with hypothesis these may share...
The HIV-1 envelope (Env) spike, which consists of a compact, heterodimeric trimer the glycoproteins gp120 and gp41, is target neutralizing antibodies. However, high mutation rate plasticity Env facilitates viral evasion from antibodies through various mechanisms. Mutations that are distant antibody binding site can lead to escape, probably by changing conformation or dynamics Env; however, these changes difficult identify define mechanistically. Here we describe network analysis-based...
Calcification of large arteries is a high-risk factor in the development cardiovascular diseases, however, due to lack routine monitoring, pathology remains severely under-diagnosed and prevalence general population not known. We have developed set machine learning methods quantitate levels abdominal aortic calcification (AAC) UK Biobank imaging cohort carried out largest to-date analysis genetic, biochemical, epidemiological risk factors associated with pathology. In genetic association...
The recent discovery of an alternate pathway for indirectly charging tRNA(Cys) has stimulated a re-examination the evolutionary history Cys-tRNA(Cys) formation. In first step pathway, O-phosphoseryl-tRNA synthetase charges with O-phosphoserine (Sep), precursor cognate amino acid. following step, Sep-tRNA:Cys-tRNA synthase (SepCysS) converts Sep to Cys in tRNA-dependent reaction. existence such raises several questions, including whether indirect is invention, as might be implied from its...
High-titer autologous neutralizing antibody responses have been demonstrated during early subtype C human immunodeficiency virus type 1 (HIV-1) infection. However, characterization of this response against at the monoclonal (MAb) level has only recently begun to be elucidated. Here we describe five antibodies derived from a C-infected seroconverter and their activities pseudoviruses that carry envelope glycoproteins 48 days (0 month), 2 months, 8 months after estimated time Sequence analysis...
Antibodies that neutralize (nAbs) genetically diverse HIV-1 strains have been recovered from a subset of infected subjects during chronic infection. Exact mechanisms expand the otherwise narrow neutralization capacity observed early infection are, however, currently undefined. Here we characterized earliest nAb responses in subtype A Rwandan seroconverter who later developed moderate cross-clade breadth, using (i) envelope (Env) glycoproteins transmitted/founder virus and twenty longitudinal...
Abstract Background Degradation of cellulose to glucose requires the cooperative action three classes enzymes, collectively known as cellulases. Endoglucanases randomly bind surfaces and generate new chain ends by hydrolyzing β-1,4-D-glycosidic bonds. Exoglucanases free hydrolyze glycosidic bonds in a processive manner releasing cellobiose units. Then, β-glucosidases soluble glucose. Optimal synergistic these enzymes is essential for efficient digestion cellulose. Experiments show that...
Abstract In complex physiological systems, causal associations between protein concentration and outcomes can be difficult to determine, as proteins both effectors of responders. This problem becomes especially when the outcome interest is death because this often preceded by failure multiple systems. Our aim in study was determine extent which variation plasma abundance predict all-cause disease-specific mortality, assess potential nature any observed associations. To identify biomarkers...