A Natural Language Interface Plug-In for Cooperative Query Answering in Biological Databases Hasan M
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Small Cell Ovarian Carcinoma: Genomic Stability and Responsiveness to Therapeutics
Gamwell et al. Orphanet Journal of Rare Diseases 2013, 8:33 http://www.ojrd.com/content/8/1/33 RESEARCH Open Access Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics Lisa F Gamwell1,2, Karen Gambaro3, Maria Merziotis2, Colleen Crane2, Suzanna L Arcand4, Valerie Bourada1,2, Christopher Davis2, Jeremy A Squire6, David G Huntsman7,8, Patricia N Tonin3,4,5 and Barbara C Vanderhyden1,2* Abstract Background: The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer. Method: The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested. Results: BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. -
Impact of a Cis-Associated Gene Expression SNP on Chromosome
The British Journal of Psychiatry (2016) 208, 128–137. doi: 10.1192/bjp.bp.114.156976 Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance Ming Li,* Xiong-jian Luo,* Mikael Lande´ n, Sarah E. Bergen, Christina M. Hultman, Xiao Li, Wen Zhang, Yong-Gang Yao, Chen Zhang, Jiewei Liu, Manuel Mattheisen, Sven Cichon, Thomas W. Mu¨ hleisen, Franziska A. Degenhardt, Markus M. No¨ then, Thomas G. Schulze, Maria Grigoroiu-Serbanescu, Hao Li, Chris K. Fuller, Chunhui Chen, Qi Dong, Chuansheng Chen, Ste´ phane Jamain, Marion Leboyer, Frank Bellivier, Bruno Etain, Jean-Pierre Kahn, Chantal Henry, Martin Preisig, Zolta´ n Kutalik, Enrique Castelao, Adam Wright, Philip B. Mitchell, Janice M. Fullerton, Peter R. Schofield, Grant W. Montgomery, Sarah E. Medland, Scott D. Gordon, Nicholas G. Martin, MooDS Consortium,a The Swedish Bipolar Study Group,a Marcella Rietschel, Chunyu Liu, Joel E. Kleinman, Thomas M. Hyde, Daniel R. Weinberger and Bing Su Background Bipolar disorder is a highly heritable polygenic disorder. between a brain eQTL rs6088662 on chromosome 20q11.22 Recent enrichment analyses suggest that there may and bipolar disorder (log Bayes factor = 5.48; bipolar disorder be true risk variants for bipolar disorder in the expression P = 5.8561075). Follow-up studies across multiple quantitative trait loci (eQTL) in the brain. independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar Aims disorder susceptibility (P = 3.5461078). Further exploratory We sought to assess the impact of eQTL variants on bipolar analysis revealed that rs6088662 is also associated with disorder risk by combining data from both bipolar disorder hippocampal volume and cognitive performance in healthy genome-wide association studies (GWAS) and brain eQTL. -
A Study of Alterations in DNA Epigenetic Modifications (5Mc and 5Hmc) and Gene Expression Influenced by Simulated Microgravity I
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Digital Repository @ Iowa State University Genome Informatics Facility Publications Genome Informatics Facility 1-28-2016 A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells Basudev Chowdhury Purdue University Arun S. Seetharam Iowa State University, [email protected] Zhiping Wang Indiana University School of Medicine Yunlong Liu Indiana University School of Medicine Amy C. Lossie Purdue University See next page for additional authors Follow this and additional works at: https://lib.dr.iastate.edu/genomeinformatics_pubs Part of the Bioinformatics Commons, Genetics Commons, and the Genomics Commons Recommended Citation Chowdhury, Basudev; Seetharam, Arun S.; Wang, Zhiping; Liu, Yunlong; Lossie, Amy C.; Thimmapuram, Jyothi; and Irudayaraj, Joseph, "A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells" (2016). Genome Informatics Facility Publications. 4. https://lib.dr.iastate.edu/genomeinformatics_pubs/4 This Article is brought to you for free and open access by the Genome Informatics Facility at Iowa State University Digital Repository. It has been accepted for inclusion in Genome Informatics Facility Publications by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells Abstract Cells alter their gene expression in response to exposure to various environmental changes. Epigenetic mechanisms such as DNA methylation are believed to regulate the alterations in gene expression patterns. -
Common Variants in the GDF5-UQCC Region Are Associated with Variation in Human Height
LETTERS Common variants in the GDF5-UQCC region are associated with variation in human height Serena Sanna1,2,19, Anne U Jackson1,19, Ramaiah Nagaraja3, Cristen J Willer1, Wei-Min Chen1,4, Lori L Bonnycastle5, Haiqing Shen6, Nicholas Timpson7,8, Guillaume Lettre9, Gianluca Usala2, Peter S Chines5, Heather M Stringham1, Laura J Scott1, Mariano Dei2, Sandra Lai2, Giuseppe Albai2, Laura Crisponi2, Silvia Naitza2, Kimberly F Doheny10, Elizabeth W Pugh10, Yoav Ben-Shlomo7, Shah Ebrahim11, Debbie A Lawlor7,8, Richard N Bergman12, Richard M Watanabe12,13, Manuela Uda2, Jaakko Tuomilehto14, Josef Coresh15, Joel N Hirschhorn9, Alan R Shuldiner6,16, David Schlessinger3, Francis S Collins5, George Davey Smith7,8, Eric Boerwinkle17, Antonio Cao2, Michael Boehnke1, Gonc¸alo R Abecasis1 & http://www.nature.com/naturegenetics Karen L Mohlke18 Identifying genetic variants that influence human height be genetically determined3,4. Rare mutations with large effects on will advance our understanding of skeletal growth and height in mendelian syndromes have been identified in the genes development. Several rare genetic variants have been FBN1, FGFR3, GH1, EVC, EVC2 and GPC3 (MIM 154700, 100800, convincingly and reproducibly associated with height in 262400, 225500 and 312870 (corresponding syndromes, respectively)). mendelian syndromes, and common variants in the Despite the high heritability, numerous candidate gene and linkage transcription factor gene HMGA2 are associated with variation studies to identify loci influencing height in individuals of ‘normal in height in the general population1. Here we report genome- stature’ have been inconclusive5. Overall, variation in human height is Nature Publishing Group Group Nature Publishing wide association analyses, using genotyped and imputed likely to be polygenic and heterogeneous. -
Quantitative Trait Loci Mapping of Macrophage Atherogenic Phenotypes
QUANTITATIVE TRAIT LOCI MAPPING OF MACROPHAGE ATHEROGENIC PHENOTYPES BRIAN RITCHEY Bachelor of Science Biochemistry John Carroll University May 2009 submitted in partial fulfillment of requirements for the degree DOCTOR OF PHILOSOPHY IN CLINICAL AND BIOANALYTICAL CHEMISTRY at the CLEVELAND STATE UNIVERSITY December 2017 We hereby approve this thesis/dissertation for Brian Ritchey Candidate for the Doctor of Philosophy in Clinical-Bioanalytical Chemistry degree for the Department of Chemistry and the CLEVELAND STATE UNIVERSITY College of Graduate Studies by ______________________________ Date: _________ Dissertation Chairperson, Johnathan D. Smith, PhD Department of Cellular and Molecular Medicine, Cleveland Clinic ______________________________ Date: _________ Dissertation Committee member, David J. Anderson, PhD Department of Chemistry, Cleveland State University ______________________________ Date: _________ Dissertation Committee member, Baochuan Guo, PhD Department of Chemistry, Cleveland State University ______________________________ Date: _________ Dissertation Committee member, Stanley L. Hazen, MD PhD Department of Cellular and Molecular Medicine, Cleveland Clinic ______________________________ Date: _________ Dissertation Committee member, Renliang Zhang, MD PhD Department of Cellular and Molecular Medicine, Cleveland Clinic ______________________________ Date: _________ Dissertation Committee member, Aimin Zhou, PhD Department of Chemistry, Cleveland State University Date of Defense: October 23, 2017 DEDICATION I dedicate this work to my entire family. In particular, my brother Greg Ritchey, and most especially my father Dr. Michael Ritchey, without whose support none of this work would be possible. I am forever grateful to you for your devotion to me and our family. You are an eternal inspiration that will fuel me for the remainder of my life. I am extraordinarily lucky to have grown up in the family I did, which I will never forget. -
New Genetic Loci Link Adipose and Insulin Biology to Body Fat Distribution
This is a repository copy of New genetic loci link adipose and insulin biology to body fat distribution.. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/107870/ Version: Accepted Version Article: Shungin, D, Winkler, TW, Croteau-Chonka, DC et al. (416 more authors) (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature, 518 (7538). pp. 187-196. ISSN 0028-0836 https://doi.org/10.1038/nature14132 Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version - refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher’s website. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Europe PMC Funders Group Author Manuscript Nature. Author manuscript; available in PMC 2015 August 12. Published in final edited form as: Nature. 2015 February 12; 518(7538): 187– 196. doi:10.1038/nature14132. Europe PMC Funders Author Manuscripts New genetic loci link adipose and insulin biology to body fat distribution A full list of authors and affiliations appears at the end of the article. -
Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Fall 2010 Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Renuka Nayak University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Computational Biology Commons, and the Genomics Commons Recommended Citation Nayak, Renuka, "Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress" (2010). Publicly Accessible Penn Dissertations. 1559. https://repository.upenn.edu/edissertations/1559 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1559 For more information, please contact [email protected]. Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Abstract Genes interact in networks to orchestrate cellular processes. Here, we used coexpression networks based on natural variation in gene expression to study the functions and interactions of human genes. We asked how these networks change in response to stress. First, we studied human coexpression networks at baseline. We constructed networks by identifying correlations in expression levels of 8.9 million gene pairs in immortalized B cells from 295 individuals comprising three independent samples. The resulting networks allowed us to infer interactions between biological processes. We used the network to predict the functions of poorly-characterized human genes, and provided some experimental support. Examining genes implicated in disease, we found that IFIH1, a diabetes susceptibility gene, interacts with YES1, which affects glucose transport. Genes predisposing to the same diseases are clustered non-randomly in the network, suggesting that the network may be used to identify candidate genes that influence disease susceptibility. -
Integrative Multi-Omic Analysis Identifies New Drivers and Pathways
www.nature.com/scientificreports OPEN Integrative multi-omic analysis identifes new drivers and pathways in molecularly distinct subtypes of Received: 16 October 2018 Accepted: 4 June 2019 ALS Published: xx xx xxxx Giovanna Morello1, Maria Guarnaccia1, Antonio Gianmaria Spampinato1, Salvatore Salomone2, Velia D’Agata 3, Francesca Luisa Conforti6, Eleonora Aronica4,5 & Sebastiano Cavallaro1 Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease. Increasing the chances of success for future clinical strategies requires more in-depth knowledge of the molecular basis underlying disease heterogeneity. We recently laid the foundation for a molecular taxonomy of ALS by whole-genome expression profling of motor cortex from sporadic ALS (SALS) patients. Here, we analyzed copy number variants (CNVs) occurring in the same patients, by using a customized exon-centered comparative genomic hybridization array (aCGH) covering a large panel of ALS-related genes. A large number of novel and known disease-associated CNVs were detected in SALS samples, including several subgroup-specifc loci, suggestive of a great divergence of two subgroups at the molecular level. Integrative analysis of copy number profles with their associated transcriptomic data revealed subtype-specifc genomic perturbations and candidate driver genes positively correlated with transcriptional signatures, suggesting a strong interaction between genomic and transcriptomic events in ALS pathogenesis. The functional analysis confrmed our previous pathway-based characterization of SALS subtypes and identifed 24 potential candidates for genomic-based patient stratifcation. To our knowledge, this is the frst comprehensive “omics” analysis of molecular events characterizing SALS pathology, providing a road map to facilitate genome-guided personalized diagnosis and treatments for this devastating disease. -
Detection of Selection Signatures in Piemontese and Marchigiana Cattle, Two Breeds with Similar Production Aptitudes but Differe
et al. Genetics Selection Evolution Sorbolini (2015) 47:52 Genetics DOI 10.1186/s12711-015-0128-2 Selection Evolution RESEARCH ARTICLE Open Access Detection of selection signatures in Piemontese and Marchigiana cattle, two breeds with similar production aptitudes but different selection histories Silvia Sorbolini1*, Gabriele Marras1, Giustino Gaspa1, Corrado Dimauro1, Massimo Cellesi1, Alessio Valentini2 and Nicolò PP Macciotta1 Abstract Background: Domestication and selection are processes that alter the pattern of within- and between-population genetic variability. They can be investigated at the genomic level by tracing the so-called selection signatures. Recently, sequence polymorphisms at the genome-wide level have been investigated in a wide range of animals. A common approach to detect selection signatures is to compare breeds that have been selected for different breeding goals (i.e. dairy and beef cattle). However, genetic variations in different breeds with similar production aptitudes and similar phenotypes can be related to differences in their selection history. Methods: In this study, we investigated selection signatures between two Italian beef cattle breeds, Piemontese and Marchigiana, using genotyping data that was obtained with the Illumina BovineSNP50 BeadChip. The comparison was based on the fixation index (Fst), combined with a locally weighted scatterplot smoothing (LOWESS) regression and a control chart approach. In addition, analyses of Fst were carried out to confirm candidate genes. In particular, data were processed using the varLD method, which compares the regional variation of linkage disequilibrium between populations. Results: Genome scans confirmed the presence of selective sweeps in the genomic regions that harbour candidate genes that are known to affect productive traits in cattle such as DGAT1, ABCG2, CAPN3, MSTN and FTO. -
Network-Based Identification and Prioritization of Key Regulators of Coronary Artery Disease Loci
Translational Sciences Network-Based Identification and Prioritization of Key Regulators of Coronary Artery Disease Loci Yuqi Zhao, Jing Chen, Johannes M. Freudenberg, Qingying Meng, CARDIoGRAM Consortium, Deepak K. Rajpal, Xia Yang Objective—Recent genome-wide association studies of coronary artery disease (CAD) have revealed 58 genome-wide significant and 148 suggestive genetic loci. However, the molecular mechanisms through which they contribute to CAD and the clinical implications of these findings remain largely unknown. We aim to retrieve gene subnetworks of the 206 CAD loci and identify and prioritize candidate regulators to better understand the biological mechanisms underlying the genetic associations. Approach and Results—We devised a new integrative genomics approach that incorporated (1) candidate genes from the top CAD loci, (2) the complete genetic association results from the 1000 genomes-based CAD genome-wide association studies from the Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus the Coronary Artery Disease consortium, (3) tissue-specific gene regulatory networks that depict the potential relationship and interactions between genes, and (4) tissue-specific gene expression patterns between CAD patients and controls. The networks and top-ranked regulators according to these data-driven criteria were further queried against literature, experimental evidence, and drug information to evaluate their disease relevance and potential as drug targets. Our analysis uncovered several potential novel regulators of CAD such as LUM and STAT3, which possess properties suitable as drug targets. We also revealed molecular relations and potential mechanisms through which the top CAD loci operate. Furthermore, we found that multiple CAD-relevant biological processes such as extracellular matrix, inflammatory and immune pathways, complement and coagulation cascades, and lipid metabolism interact in the CAD networks. -
New Genetic Loci Link Adipose and Insulin Biology to Body Fat Distribution
New genetic loci link adipose and insulin biology to body fat distribution The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Shungin, D., T. W. Winkler, D. C. Croteau-Chonka, T. Ferreira, A. E. Locke, R. Mägi, R. J. Strawbridge, et al. 2014. “New genetic loci link adipose and insulin biology to body fat distribution.” Nature 518 (7538): 187-196. doi:10.1038/nature14132. http://dx.doi.org/10.1038/ nature14132. Published Version doi:10.1038/nature14132 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:21459269 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Europe PMC Funders Group Author Manuscript Nature. Author manuscript; available in PMC 2015 August 12. Published in final edited form as: Nature. 2015 February 12; 518(7538): 187–196. doi:10.1038/nature14132. Europe PMC Funders Author Manuscripts New genetic loci link adipose and insulin biology to body fat distribution A full list of authors and affiliations appears at the end of the article. # These authors contributed equally to this work. Abstract Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. -
Genome-Wide Meta-Analysis of Muscle Weakness Identifies 15
ARTICLE https://doi.org/10.1038/s41467-021-20918-w OPEN Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women Garan Jones 1,58, Katerina Trajanoska 2,3,58, Adam J. Santanasto 4,58, Najada Stringa 5,58, Chia-Ling Kuo6,58, Janice L. Atkins 1,58, Joshua R. Lewis 7,8,9, ThuyVy Duong10, Shengjun Hong11, Mary L. Biggs12, Jian’an Luan 13, Chloe Sarnowski 14, Kathryn L. Lunetta 14, Toshiko Tanaka15, Mary K. Wojczynski16, Ryan Cvejkus 4, Maria Nethander 17,18, Sahar Ghasemi19,20, Jingyun Yang 21, M. Carola Zillikens2, Stefan Walter 22,23, Kamil Sicinski24, Erika Kague 25, Cheryl L. Ackert-Bicknell26, 1234567890():,; Dan E. Arking10, B. Gwen Windham27, Eric Boerwinkle28,29, Megan L. Grove28, Misa Graff 30, Dominik Spira31,32, Ilja Demuth31,32,33, Nathalie van der Velde34, Lisette C. P. G. M. de Groot 35, Bruce M. Psaty36,37, Michelle C. Odden38, Alison E. Fohner39, Claudia Langenberg 13, Nicholas J. Wareham 13, Stefania Bandinelli40, Natasja M. van Schoor5, Martijn Huisman5, Qihua Tan 41, Joseph Zmuda4, Dan Mellström17,42, Magnus Karlsson43, David A. Bennett21, Aron S. Buchman 21, Philip L. De Jager 44,45, Andre G. Uitterlinden 2, Uwe Völker 46, Thomas Kocher 47, Alexander Teumer 20, Leocadio Rodriguéz-Mañas48,23, Francisco J. García49,23, José A. Carnicero23, Pamela Herd50, Lars Bertram 11, Claes Ohlsson17,51, Joanne M. Murabito52, David Melzer 1, George A. Kuchel 53,59, Luigi Ferrucci 54,59, David Karasik 55,56,59, Fernando Rivadeneira 2,3,59, ✉ Douglas P. Kiel 57,59 & Luke C. Pilling 1,59 Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people.