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Your search keyword '"Sandeep Deverasetty"' showing total 6 results
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6 results on '"Sandeep Deverasetty"'

1. The HIVToolbox 2 web system integrates sequence, structure, function and mutation analysis.

Author

David P Sargeant, Sandeep Deverasetty, Christy L Strong, Izua J Alaniz, Alexandria Bartlett, Nicholas R Brandon, Steven B Brooks, Frederick A Brown, Flaviona Bufi, Monika Chakarova, Roxanne P David, Karlyn M Dobritch, Horacio P Guerra, Michael W Hedden, Rma Kumra, Kelvy S Levitt, Kiran R Mathew, Ray Matti, Dorothea Q Maza, Sabyasachy Mistry, Nemanja Novakovic, Austin Pomerantz, Josue Portillo, Timothy F Rafalski, Viraj R Rathnayake, Noura Rezapour, Sarah Songao, Sean L Tuggle, Sandy Yousif, David I Dorsky, and Martin R Schiller

Subjects
Medicine, Science
Abstract

There is enormous interest in studying HIV pathogenesis for improving the treatment of patients with HIV infection. HIV infection has become one of the best-studied systems for understanding how a virus can hijack a cell. To help facilitate discovery, we previously built HIVToolbox, a web system for visual data mining. The original HIVToolbox integrated information for HIV protein sequence, structure, functional sites, and sequence conservation. This web system has been used for almost 40,000 searches. We report improvements to HIVToolbox including new functions and workflows, data updates, and updates for ease of use. HIVToolbox2, is an improvement over HIVToolbox with new functions. HIVToolbox2 has new functionalities focused on HIV pathogenesis including drug-binding sites, drug-resistance mutations, and immune epitopes. The integrated, interactive view enables visual mining to generate hypotheses that are not readily revealed by other approaches. Most HIV proteins form multimers, and there are posttranslational modification and protein-protein interaction sites at many of these multimerization interfaces. Analysis of protease drug binding sites reveals an anatomy of drug resistance with different types of drug-resistance mutations regionally localized on the surface of protease. Some of these drug-resistance mutations have a high prevalence in specific HIV-1 M subtypes. Finally, consolidation of Tat functional sites reveals a hotspot region where there appear to be 30 interactions or posttranslational modifications. A cursory analysis with HIVToolbox2 has helped to identify several global patterns for HIV proteins. An initial analysis with this tool identifies homomultimerization of almost all HIV proteins, functional sites that overlap with multimerization sites, a global drug resistance anatomy for HIV protease, and specific distributions of some DRMs in specific HIV M subtypes. HIVToolbox2 is an open-access web application available at [http://hivtoolbox2.bio-toolkit.com].

Published
2014
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2. The Geogenomic Mutational Atlas of Pathogens (GoMAP) web system.

Author

David P Sargeant, Michael W Hedden, Sandeep Deverasetty, Christy L Strong, Izua J Alaniz, Alexandria N Bartlett, Nicholas R Brandon, Steven B Brooks, Frederick A Brown, Flaviona Bufi, Monika Chakarova, Roxanne P David, Karlyn M Dobritch, Horacio P Guerra, Kelvy S Levit, Kiran R Mathew, Ray Matti, Dorothea Q Maza, Sabyasachy Mistry, Nemanja Novakovic, Austin Pomerantz, Timothy F Rafalski, Viraj Rathnayake, Noura Rezapour, Christian A Ross, Steve G Schooler, Sarah Songao, Sean L Tuggle, Helen J Wing, Sandy Yousif, and Martin R Schiller

Subjects
Medicine, Science
Abstract

We present a new approach for pathogen surveillance we call Geogenomics. Geogenomics examines the geographic distribution of the genomes of pathogens, with a particular emphasis on those mutations that give rise to drug resistance. We engineered a new web system called Geogenomic Mutational Atlas of Pathogens (GoMAP) that enables investigation of the global distribution of individual drug resistance mutations. As a test case we examined mutations associated with HIV resistance to FDA-approved antiretroviral drugs. GoMAP-HIV makes use of existing public drug resistance and HIV protein sequence data to examine the distribution of 872 drug resistance mutations in ∼ 502,000 sequences for many countries in the world. We also implemented a broadened classification scheme for HIV drug resistance mutations. Several patterns for geographic distributions of resistance mutations were identified by visual mining using this web tool. GoMAP-HIV is an open access web application available at http://www.bio-toolkit.com/GoMap/project/

Published
2014
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3. HIVToolbox, an integrated web application for investigating HIV.

Author

David Sargeant, Sandeep Deverasetty, Yang Luo, Angel Villahoz Baleta, Stephanie Zobrist, Viraj Rathnayake, Jacqueline C Russo, Jay Vyas, Mark A Muesing, and Martin R Schiller

Subjects
Medicine, Science
Abstract

Many bioinformatic databases and applications focus on a limited domain of knowledge federating links to information in other databases. This segregated data structure likely limits our ability to investigate and understand complex biological systems. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and allows virologists and structural biologists to access sequence, structure, and functional relationships in an intuitive web application. HIV-1 integrase protein was used as a case study to show the utility of this application. We show how data integration facilitates identification of new questions and hypotheses much more rapid and convenient than current approaches using isolated repositories. Several new hypotheses for integrase were created as an example, and we experimentally confirmed a predicted CK2 phosphorylation site. Weblink: [http://hivtoolbox.bio-toolkit.com].

Published
2011
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4. Genetic screening of a large series of North American sporadic and familial frontotemporal dementia cases

Author

Deepika Dokuru, Victoria Van Berlo, Joanne Taylor, Bruce L. Miller, Giovanni Coppola, Jeremy Syrjanen, Madeline Potter, Alden Y. Huang, Rodney Pearlman, Jamie Fong, Joel H. Kramer, Peter A. Ljubenkov, Yue Qin, Codrin Lungu, Maria Carmela Tartaglia, Alexander Pantelyat, Marka van Blitterswijk, Sandeep Deverasetty, Hilary W. Heuer, Jazmyne L. Jackson, Edward D. Huey, Leah K. Forsberg, Daniel I. Kaufer, Kimiko Domoto-Reilly, Walter K. Kremers, John Q. Trojanowski, Bradford C. Dickerson, Zbigniew K. Wszolek, Katherine P. Rankin, Murray Grossman, Nadine Tatton, Chiadi U. Onyike, Kelley Faber, David S. Knopman, Tatiana Foroud, Erik D. Roberson, Nupur Ghoshal, Eliana Marisa Ramos, Jonathan Graff-Radford, Patrick Brannelly, Bonnie Wong, Mario F. Mendez, Ian R. A. Mackenzie, Brad F. Boeve, Ging-Yuek Robin Hsiung, Q. Wang, Rosa Rademakers, Adam L. Boxer, Neill R. Graff-Radford, David J. Irwin, John Kornak, Irene Litvan, Danielle Brushaber, Ralitza H. Gavrilova, Kejal Kantarci, Yvette Bordelon, Ian Grant, Anna Karydas, Arthur W. Toga, Leslie M. Shaw, Julie A. Fields, Emily Rogalski, Len Petrucelli, Kevin Wojta, Walter A. Kukull, Howard J. Rosen, Sandra Weintraub, Artfl, Brian S. Appleby, Jill Goldman, Diana R. Kerwin, Susan Dickinson, Katya Rascovsky, and ARTFL LEFFTDS Consortium

Subjects
0301 basic medicine, Male, Aging, Epidemiology, Neurodegenerative, Alzheimer's Disease, frontotemporal dementia, 0302 clinical medicine, Progranulins, C9orf72, MAPT, 2.1 Biological and endogenous factors, Aetiology, Alzheimer's Disease Related Dementias (ADRD), Likely pathogenic, media_common, Health Policy, TAR DNA-BINDING PROTEIN, Large series, familial, Frontotemporal lobar degeneration, Art, Middle Aged, Psychiatry and Mental health, Grossman, Frontotemporal Dementia (FTD), Frontotemporal Dementia, Neurological, Female, GRN, Frontotemporal dementia, media_common.quotation_subject, Clinical Sciences, tau Proteins, TARDBP, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Unknown Significance, Rare Diseases, Developmental Neuroscience, Clinical Research, mental disorders, medicine, Genetics, Acquired Cognitive Impairment, Humans, Genetic Predisposition to Disease, Genetic Testing, Biology, C9orf72 Protein, Prevention, Human Genome, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, Brain Disorders, 030104 developmental biology, Geriatrics, sporadic, Dementia, Neurology (clinical), Human medicine, Geriatrics and Gerontology, Humanities, 030217 neurology & neurosurgery, ARTFL/LEFFTDS consortium
Abstract

Author(s): Ramos, Eliana Marisa; Dokuru, Deepika Reddy; Van Berlo, Victoria; Wojta, Kevin; Wang, Qing; Huang, Alden Y; Deverasetty, Sandeep; Qin, Yue; van Blitterswijk, Marka; Jackson, Jazmyne; Appleby, Brian; Bordelon, Yvette; Brannelly, Patrick; Brushaber, Danielle E; Dickerson, Bradford; Dickinson, Susan; Domoto-Reilly, Kimiko; Faber, Kelley; Fields, Julie; Fong, Jamie; Foroud, Tatiana; Forsberg, Leah K; Gavrilova, Ralitza; Ghoshal, Nupur; Goldman, Jill; Graff-Radford, Jonathan; Graff-Radford, Neill; Grant, Ian; Grossman, Murray; Heuer, Hilary W; Hsiung, Ging-Yuek R; Huey, Edward; Irwin, David; Kantarci, Kejal; Karydas, Anna; Kaufer, Daniel; Kerwin, Diana; Knopman, David; Kornak, John; Kramer, Joel H; Kremers, Walter; Kukull, Walter; Litvan, Irene; Ljubenkov, Peter; Lungu, Codrin; Mackenzie, Ian; Mendez, Mario F; Miller, Bruce L; Onyike, Chiadi; Pantelyat, Alexander; Pearlman, Rodney; Petrucelli, Len; Potter, Madeline; Rankin, Katherine P; Rascovsky, Katya; Roberson, Erik D; Rogalski, Emily; Shaw, Leslie; Syrjanen, Jeremy; Tartaglia, Maria Carmela; Tatton, Nadine; Taylor, Joanne; Toga, Arthur; Trojanowski, John Q; Weintraub, Sandra; Wong, Bonnie; Wszolek, Zbigniew; Rademakers, Rosa; Boeve, Brad F; Rosen, Howard J; Boxer, Adam L; ARTFL/LEFFTDS consortium; Coppola, Giovanni | Abstract: IntroductionThe Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) consortia are two closely connected studies, involving multiple North American centers that evaluate both sporadic and familial frontotemporal dementia (FTD) participants and study longitudinal changes.MethodsWe screened the major dementia-associated genes in 302 sporadic and 390 familial (symptomatic or at-risk) participants enrolled in these studies.ResultsAmong the sporadic patients, 16 (5.3%) carried chromosome 9 open reading frame 72 (C9orf72), microtubule-associated protein tau (MAPT), and progranulin (GRN) pathogenic variants, whereas in the familial series we identified 207 carriers from 146 families. Of interest, one patient was found to carry a homozygous C9orf72 expansion, while another carried both a C9orf72 expansion and a GRN pathogenic variant. We also identified likely pathogenic variants in the TAR DNA binding protein (TARDBP), presenilin 1 (PSEN1), and valosin containing protein (VCP) genes, and a subset of variants of unknown significance in other rare FTD genes.DiscussionOur study reports the genetic characterization of a large FTD series and supports an unbiased sequencing screen, irrespective of clinical presentation or family history.

Published
2020

5. Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice

Author

Fuying Gao, Giovanni Coppola, Sandeep Deverasetty, Andreas Tebbe, Xiao-Hong Lu, Christoph Schaab, Peter Langfelder, X. William Yang, Eliana Marisa Ramos, Nan Wang, Jeffrey P. Cantle, Juan Botas, Ismael Al-Ramahi, Daniel J. Lavery, Jeffrey S. Aaronson, Doxa Chatzopoulou, Yining Zhao, Jim Rosinski, David Howland, Karla El-Zein, Steve Horvath, and Seung Kwak

Subjects
0301 basic medicine, Huntington's Disease, Male, Proteomics, congenital, hereditary, and neonatal diseases and abnormalities, Huntingtin, Protocadherin, Nerve Tissue Proteins, Biology, Neurodegenerative, Medium spiny neuron, Inbred C57BL, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Rare Diseases, Huntington's disease, Gene expression, mental disorders, Huntingtin Protein, medicine, Genetics, Psychology, Animals, Gene Regulatory Networks, Gene Knock-In Techniques, Cerebral Cortex, Neurology & Neurosurgery, General Neuroscience, Neurosciences, Nuclear Proteins, Genomics, medicine.disease, Molecular biology, Corpus Striatum, Brain Disorders, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, nervous system, Cerebral cortex, Neurological, Cognitive Sciences, Female, 030217 neurology & neurosurgery, Biotechnology
Abstract

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington’s disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We find repeat length dependent transcriptional signatures are prominent in the striatum, less so in cortex, and minimal in the liver. Co-expression network analyses reveal 13 striatal and 5 cortical modules that are highly correlated with CAG length and age, and that are preserved in HD models and some in the patients. Top striatal modules implicate mHtt CAG length and age in graded impairment of striatal medium spiny neuron identity gene expression and in dysregulation of cAMP signaling, cell death, and protocadherin genes. Importantly, we used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at both RNA and protein levels, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo.

Published
2015

6. The Geogenomic Mutational Atlas of Pathogens (GoMAP) web system

Author

Viraj Rathnayake, Monika Chakarova, Nemanja Novakovic, Frederick A. Brown, Sarah Songao, Dorothea Q. Maza, Kelvy S. Levit, Helen J. Wing, Martin R. Schiller, Nicholas R. Brandon, Steve G. Schooler, David P. Sargeant, Ray Matti, Christy Strong, Horacio P. Guerra, Roxanne P. David, Sabyasachy Mistry, Michael W. Hedden, Sandeep Deverasetty, Kiran R. Mathew, Flaviona Bufi, Christian A. Ross, Izua J. Alaniz, Sean L. Tuggle, Alexandria Bartlett, Karlyn M. Dobritch, Timothy F. Rafalski, Noura Rezapour, Steven B. Brooks, Sandy Yousif, and Austin Pomerantz

Subjects
Viral Diseases, lcsh:Medicine, Social Sciences, HIV Infections, Drug resistance, Web Browser, medicine.disease_cause, Global Health, Genome, Computer Applications, Immunodeficiency Viruses, Databases, Genetic, Global health, Medicine and Health Sciences, lcsh:Science, Genetics, Mutation, Multidisciplinary, Geography, Antimicrobials, Genomics, Antivirals, 3. Good health, Infectious Diseases, Biogeography, Medical Microbiology, Population Surveillance, Viral Pathogens, Web-Based Applications, HIV drug resistance, Research Article, Computer and Information Sciences, Biology, Communicable Diseases, Microbiology, Antibiotic resistance, Microbial Control, Virology, medicine, Web application, Humans, Microbial Pathogens, Evolutionary Biology, business.industry, lcsh:R, Biology and Life Sciences, Computational Biology, HIV, Genome, Microbial, Earth Sciences, lcsh:Q, business, Population Genetics
Abstract

We present a new approach for pathogen surveillance we call Geogenomics. Geogenomics examines the geographic distribution of the genomes of pathogens, with a particular emphasis on those mutations that give rise to drug resistance. We engineered a new web system called Geogenomic Mutational Atlas of Pathogens (GoMAP) that enables investigation of the global distribution of individual drug resistance mutations. As a test case we examined mutations associated with HIV resistance to FDA-approved antiretroviral drugs. GoMAP-HIV makes use of existing public drug resistance and HIV protein sequence data to examine the distribution of 872 drug resistance mutations in ∼ 502,000 sequences for many countries in the world. We also implemented a broadened classification scheme for HIV drug resistance mutations. Several patterns for geographic distributions of resistance mutations were identified by visual mining using this web tool. GoMAP-HIV is an open access web application available at http://www.bio-toolkit.com/GoMap/project/

Published
2013

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