Design, Evaluation and Application of Methodology and Software for Time-To-Event Outcomes in Pharmacogenetic Genome-Wide Association Studies
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Assessment of Hematopoietic Failure Due to Rpl11 Deficiency in a Zebrafish Model of Diamond-Blackfan Anemia by Deep Sequencing
Zhang et al. BMC Genomics 2013, 14:896 http://www.biomedcentral.com/1471-2164/14/896 RESEARCH ARTICLE Open Access Assessment of hematopoietic failure due to Rpl11 deficiency in a zebrafish model of Diamond- Blackfan anemia by deep sequencing Zhaojun Zhang1†, Haibo Jia2†, Qian Zhang1, Yang Wan3, Yang Zhou2, Qiong Jia2, Wanguang Zhang4, Weiping Yuan3, Tao Cheng3, Xiaofan Zhu3* and Xiangdong Fang1* Abstract Background: Diamond–Blackfan anemia is a rare congenital red blood cell dysplasia that develops soon after birth. RPL11 mutations account for approximately 4.8% of human DBA cases with defective hematopoietic phenotypes. However, the mechanisms by which RPL11 regulates hematopoiesis in DBA remain elusive. In this study, we analyzed the transcriptome using deep sequencing data from an Rpl11-deficient zebrafish model to identify Rpl11-mediated hematopoietic failure and investigate the underlying mechanisms. Results: We characterized hematological defects in Rpl11-deficient zebrafish embryos by identifying affected hematological genes, hematopoiesis-associated pathways, and regulatory networks. We found that hemoglobin biosynthetic and hematological defects in Rpl11-deficient zebrafish were related to dysregulation of iron metabolism-related genes, including tfa, tfr1b, alas2 and slc25a37, which are involved in heme and hemoglobin biosynthesis. In addition, we found reduced expression of the hematopoietic stem cells (HSC) marker cmyb and HSC transcription factors tal1 and hoxb4a in Rpl11-deficient zebrafish embryos, indicating that the hematopoietic defects may be related to impaired HSC formation, differentiation, and proliferation. However, Rpl11 deficiency did not affect the development of other blood cell lineages such as granulocytes and myelocytes. Conclusion: We identified hematopoietic failure of Rpl11-deficient zebrafish embryos using transcriptome deep sequencing and elucidated potential underlying mechanisms. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Mitoxplorer, a Visual Data Mining Platform To
mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, Cecilia Garcia-Perez, José Villaveces, Salma Gamal, Giovanni Cardone, Fabiana Perocchi, et al. To cite this version: Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, et al.. mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dy- namics and mutations. Nucleic Acids Research, Oxford University Press, 2020, 10.1093/nar/gkz1128. hal-02394433 HAL Id: hal-02394433 https://hal-amu.archives-ouvertes.fr/hal-02394433 Submitted on 4 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Nucleic Acids Research, 2019 1 doi: 10.1093/nar/gkz1128 Downloaded from https://academic.oup.com/nar/advance-article-abstract/doi/10.1093/nar/gkz1128/5651332 by Bibliothèque de l'université la Méditerranée user on 04 December 2019 mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim1,†, Prasanna Koti1,†, Adrien Bonnard2, Fabio Marchiano3, Milena Durrbaum¨ 1, Cecilia Garcia-Perez4, Jose Villaveces1, Salma Gamal1, Giovanni Cardone1, Fabiana Perocchi4, Zuzana Storchova1,5 and Bianca H. -
A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family
Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2018 A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family Linda Molla Follow this and additional works at: https://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Linda Molla June 2018 © Copyright by Linda Molla 2018 A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY Linda Molla, Ph.D. The Rockefeller University 2018 APOBEC2 is a member of the AID/APOBEC cytidine deaminase family of proteins. Unlike most of AID/APOBEC, however, APOBEC2’s function remains elusive. Previous research has implicated APOBEC2 in diverse organisms and cellular processes such as muscle biology (in Mus musculus), regeneration (in Danio rerio), and development (in Xenopus laevis). APOBEC2 has also been implicated in cancer. However the enzymatic activity, substrate or physiological target(s) of APOBEC2 are unknown. For this thesis, I have combined Next Generation Sequencing (NGS) techniques with state-of-the-art molecular biology to determine the physiological targets of APOBEC2. Using a cell culture muscle differentiation system, and RNA sequencing (RNA-Seq) by polyA capture, I demonstrated that unlike the AID/APOBEC family member APOBEC1, APOBEC2 is not an RNA editor. Using the same system combined with enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analyses I showed that, unlike the AID/APOBEC family member AID, APOBEC2 does not act as a 5-methyl-C deaminase. -
Evidences for the Non-Redundant Function of A-Type Proteins ISCA1 and ISCA2 in Iron-Sulfur Cluster Biogenesis Lena Kristina Beilschmidt
Evidences for the non-redundant function of A-type proteins ISCA1 and ISCA2 in iron-sulfur cluster biogenesis Lena Kristina Beilschmidt To cite this version: Lena Kristina Beilschmidt. Evidences for the non-redundant function of A-type proteins ISCA1 and ISCA2 in iron-sulfur cluster biogenesis. Organisation et fonctions cellulaires [q-bio.SC]. Université de Strasbourg, 2014. Français. NNT : 2014STRAJ031. tel-01297049 HAL Id: tel-01297049 https://tel.archives-ouvertes.fr/tel-01297049 Submitted on 2 Apr 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ DE STRASBOURG Ecole doctorale des Sciences de la Vie et de la Santé Institut de Génetique et de Biologie Moléculaire et Cellulaire THÈSE présentée par : Lena Kristina BEILSCHMIDT soutenue le : 18 Novembre 2014 pour obtenir le grade de : Docteur de l’université de Strasbourg Discipline/ Spécialité : Aspects moléculaires et cellulaires de la biologie Evidences for the non-redundant function of A-type proteins ISCA1 and ISCA2 in iron-sulfur cluster biogenesis THÈSE dirigée par : Dr. PUCCIO Hélène (IGBMC, Illkirch) RAPPORTEURS : Dr. BALK Janneke (University of East Anglia, Norwich UK) Dr. BOUTON Cécile (Institut de Chimie des Substances Naturelles, Gif-sur-Yvette France) AUTRES MEMBRES DU JURY : Dr. -
Amy Elizabeth Defnet Contact Information: [email protected] Degree and Date to Be Conferred: Ph.D
Targeting the Activator Protein-1 Complex to Inhibit Airway Smooth Muscle Cell Hyperproliferation in Asthma Item Type dissertation Authors Defnet, Amy Elizabeth Publication Date 2021 Abstract Hyperproliferation of airway smooth muscle (ASM) cells leads to increased ASM mass causing airway obstruction in inflammatory diseases such as asthma. Currently, there are no effective therapies to modulate ASM cell proliferation that contributes to ... Keywords Activator Protein-1; airway smooth muscle; retinoic acid; Airway Remodeling; Asthma; Protein Kinases; Transcription Factor AP-1; Tretinoin Download date 29/09/2021 14:19:54 Link to Item http://hdl.handle.net/10713/15769 Amy Elizabeth Defnet Contact Information: [email protected] Degree and Date to be Conferred: Ph.D. Pharmaceutical Sciences, May 2021 PROFESSIONAL OBJECTIVE My career objective is to work in academic institution where I can develop myself as an educator and researcher. My research employs a cross-disciplinary training regimen, including frequent opportunities for scientific/public speaking and inter-departmental engagement. In preparation for future teaching responsibilities, I have cultivated core pedagogical techniques through the JHU-UMB Collaborative Teaching Fellowship and Quality Matters Online Teaching Program. Additionally, participation in several societies and volunteer groups have helped cultivate my leadership and communication skills. EDUCATION University of Maryland, Baltimore 2016-present • Ph.D. Pharmaceutical Sciences, anticipated completion 2021 Fairleigh Dickinson University, Florham 2012-2016 • B.S. Biological Sciences with a Minor in Chemistry, 2016 RESEARCH Graduate Research Dr. Paul Shapiro and Dr. Maureen Kane, University of Maryland, Baltimore Fall 2016- Present This study hopes to overcome therapeutic limitations in asthma treatment that lead to bronchoconstriction and airway remodeling through evaluation of a novel function- selective ERK1/2 inhibitor and a RAR agonist. -
Split-Turboid Enables Contact-Dependent Proximity Labeling in Cells
Split-TurboID enables contact-dependent proximity labeling in cells Kelvin F. Choa, Tess C. Branonb,c,d,e, Sanjana Rajeevb, Tanya Svinkinaf, Namrata D. Udeshif, Themis Thoudamg, Chulhwan Kwakh,i, Hyun-Woo Rheeh,j, In-Kyu Leeg,k,l, Steven A. Carrf, and Alice Y. Tingb,c,d,m,1 aCancer Biology Program, Stanford University, Stanford, CA 94305; bDepartment of Genetics, Stanford University, Stanford, CA 94305; cDepartment of Biology, Stanford University, Stanford, CA 94305; dDepartment of Chemistry, Stanford University, Stanford, CA 94305; eDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; fBroad Institute of MIT and Harvard, Cambridge, MA 02142; gResearch Institute of Aging and Metabolism, Kyungpook National University, 37224 Daegu, South Korea; hDepartment of Chemistry, Seoul National University, 08826 Seoul, South Korea; iDepartment of Chemistry, Ulsan National Institute of Science and Technology, 44919 Ulsan, South Korea; jSchool of Biological Sciences, Seoul National University, 08826 Seoul, South Korea; kDepartment of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 41944 Daegu, South Korea; lLeading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University, 41944 Daegu, South Korea; and mChan Zuckerberg Biohub, San Francisco, CA 94158 Edited by Tony Hunter, The Salk Institute for Biological Studies, La Jolla, CA, and approved April 7, 2020 (received for review November 7, 2019) Proximity labeling catalyzed by promiscuous enzymes, such as Split forms of APEX (18) and BioID (19–21) have previously TurboID, have enabled the proteomic analysis of subcellular regions been reported. However, split-APEX (developed by us) has not difficult or impossible to access by conventional fractionation-based ap- been used for proteomics, and the requirement for exogenous proaches. -
Identification of Core Genes Involved in the Progression of Cervical
International Journal of Molecular Sciences Article Identification of Core Genes Involved in the Progression of Cervical Cancer Using an Integrative mRNA Analysis Marina Dudea-Simon 1, Dan Mihu 1, Alexandru Irimie 2,3, Roxana Cojocneanu 4, Schuyler S. Korban 5, Radu Oprean 6, Cornelia Braicu 4,* and Ioana Berindan-Neagoe 4,7 1 2nd Obstetrics and Gynecology Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; [email protected] (M.D.-S.); [email protected] (D.M.) 2 Department of Surgery, “Prof. Dr. Ion Chiricuta” Oncology Institute, 400015 Cluj-Napoca, Romania; [email protected] 3 Department of Surgical Oncology and Gynecological Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania 4 Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania; [email protected] (R.C.); [email protected] (I.B.-N.) 5 Department of Natural and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; [email protected] 6 Analytical Chemistry Department, Iuliu Hatieganu University of Medicine and Pharmacy, 4, Louis Pasteur Street, 400349 Cluj-Napoca, Romania; [email protected] 7 Department of Functional Genomics and Experimental Pathology, “Prof. Dr. Ion Chiricu¸tă” Oncology Institute, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania * Correspondence: [email protected] Received: 5 September 2020; Accepted: 1 October 2020; Published: 3 October 2020 Abstract: In spite of being a preventable disease, cervical cancer (CC) remains at high incidence, and it has a significant mortality rate. Although hijacking of the host cellular pathway is fundamental for developing a better understanding of the human papillomavirus (HPV) pathogenesis, a major obstacle is identifying the central molecular targets involved in HPV-driven CC. -
Content Based Search in Gene Expression Databases and a Meta-Analysis of Host Responses to Infection
Content Based Search in Gene Expression Databases and a Meta-analysis of Host Responses to Infection A Thesis Submitted to the Faculty of Drexel University by Francis X. Bell in partial fulfillment of the requirements for the degree of Doctor of Philosophy November 2015 c Copyright 2015 Francis X. Bell. All Rights Reserved. ii Acknowledgments I would like to acknowledge and thank my advisor, Dr. Ahmet Sacan. Without his advice, support, and patience I would not have been able to accomplish all that I have. I would also like to thank my committee members and the Biomed Faculty that have guided me. I would like to give a special thanks for the members of the bioinformatics lab, in particular the members of the Sacan lab: Rehman Qureshi, Daisy Heng Yang, April Chunyu Zhao, and Yiqian Zhou. Thank you for creating a pleasant and friendly environment in the lab. I give the members of my family my sincerest gratitude for all that they have done for me. I cannot begin to repay my parents for their sacrifices. I am eternally grateful for everything they have done. The support of my sisters and their encouragement gave me the strength to persevere to the end. iii Table of Contents LIST OF TABLES.......................................................................... vii LIST OF FIGURES ........................................................................ xiv ABSTRACT ................................................................................ xvii 1. A BRIEF INTRODUCTION TO GENE EXPRESSION............................. 1 1.1 Central Dogma of Molecular Biology........................................... 1 1.1.1 Basic Transfers .......................................................... 1 1.1.2 Uncommon Transfers ................................................... 3 1.2 Gene Expression ................................................................. 4 1.2.1 Estimating Gene Expression ............................................ 4 1.2.2 DNA Microarrays ...................................................... -
MTFR2, a Potential Biomarker for Prognosis and Immune Infiltrates
Journal of Cancer 2021, Vol. 12 3611 Ivyspring International Publisher Journal of Cancer 2021; 12(12): 3611-3625. doi: 10.7150/jca.58158 Research Paper MTFR2, A Potential Biomarker for Prognosis and Immune Infiltrates, Promotes Progression of Gastric Cancer Based on Bioinformatics Analysis and Experiments Hai Zhu1*, Gang Wang2*, Haixing Zhu3, Aman Xu1, 2 1. Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230001, People’s Republic of China. 2. Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230001, People’s Republic of China. 3. Department of Gastrointestinal Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230031, People’s Republic of China. * These authors contributed equally to this work. Corresponding author: Aman Xu, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230001, People’s Republic of China. Tel: +86 5162885159; E-mail: [email protected]. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2021.01.13; Accepted: 2021.04.15; Published: 2021.04.26 Abstract Background: Mitochondrial fission regulator 2 (MTFR2) which can promote mitochondrial fission, has recently been reported to be involved in tumorigenesis. However, little is known about its expression levels and function in gastric cancer (GC). This study aims to clarify the role of MTFR2 in GC.