Functional Phenomics: an Emerging Field Integrating High-Throughput Phenotyping, 2 Physiology, and Bioinformatics
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From Gene to Phene*
T HE JOURNAL OF i NVEST IGATIV E D EHMATO LOGY Vol. 60, N o.6 Copyri ght © 1973 by The Wi lli ams & Wdkms Co. Printed in U. S.A. FROM GENE TO PHENE* JAN H. PORTER, M.D. INTRODUCTION acid. The normal (:J-c hain is made up of 146 a m ino acids a nd as each a mino acid is coded for b y a trio Chromosomes are t he o rgans o f heredity. T hey of DNA bases, the gene determining t he c hain carry t he ge nes, the units of heredity . must contain 438 bases. Since the mutation caus Chromosomes transmit groups o f ge nes fr om one in vo lves the 6th trip let in ge neration to the next, and ge nes mediate the_ ing t he sickl e cell allele 7th, a nd 18th b ases inheri ted m essage by directing t he synt hesiS of the sequence - the 16th, 1 and since adenine has bee n changed for thymine polypept ides. We s hould, t herefore, be a bl ~ to relate a gi ven characteristic (phenotype) of an on one o f the t wo complementary strands of the DNA, it must be t he 17th base t hat is replaced by individual to a s peci fic ge ne (genotype) . Indeed, a e findings in sickle cell full account of a g iven characteristic s hould start another. Alm ost all th disease can be ex plained by the phys ical proper with the type and sequence of t hose d eoxy rib o n~ ties of reduced hemoglobin S, particul arly by i t cl eic ( DNA) bases which m ake up t he ge ne m low solu bili ty at low oxygen tension . -
Proteome-By-Phenome Mendelian Randomisation Detects 38 Proteins with Causal
bioRxiv preprint doi: https://doi.org/10.1101/631747; this version posted May 10, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Proteome-by-phenome Mendelian Randomisation detects 38 proteins with causal 2 roles in human diseases and traits 3 ANDREW D. BRETHERICK1*, ORIOL CANELA-XANDRI1,2, PETER K. JOSHI3, DAVID W. CLARK3, 4 KONRAD RAWLIK2, THIBAUD S. BOUTIN1, YANNI ZENG1,4,5,6, CARMEN AMADOR1, PAU 5 NAVARRO1, IGOR RUDAN3, ALAN F. WRIGHT1, HARRY CAMPBELL3, VERONIQUE VITART1, 6 CAROLINE HAYWARD1, JAMES F. WILSON1,3, ALBERT TENESA1,2, CHRIS P. PONTING1, J. 7 KENNETH BAILLIE2, AND CHRIS HALEY1,2* 8 9 1 MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University 10 of Edinburgh, Western General Hospital, Crewe Road, EH4 2XU, Scotland, UK. 11 2 The Roslin Institute, University of Edinburgh, Easter Bush, EH25 9RG, Scotland, UK. 12 3 Centre for Global Health Research, Usher Institute of Population Health Sciences and 13 Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK. 14 4 Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, 15 74 Zhongshan 2nd Road, Guangzhou 510080, China. 16 5 Guangdong Province Translational Forensic Medicine Engineering Technology 17 Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan 18 2nd Road, Guangzhou 510080, China. 19 6 Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan 20 School of Medicine, Sun Yat-Sen University, 74 Zhongshan 2nd Road, Guangzhou 21 510080, China. -
A Phenome-Wide Association Study (Phewas)
RESEARCH ARTICLE A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans 1 2,3 4 5 Sarah A. PendergrassID , Steven BuyskeID , Janina M. Jeff , Alex Frase , 5 5 6 7 8 a1111111111 Scott DudekID , Yuki Bradford , Jose-Luis AmbiteID , Christy L. Avery , Petra Buzkova , 6 9 10 7,11 a1111111111 Ewa Deelman , Megan D. Fesinmeyer , Christopher Haiman , Gerardo HeissID , Lucia 12 13 14 15 16 a1111111111 A. Hindorff , Chun-Nan HsuID , Rebecca D. Jackson , Yi Lin , Loic Le Marchand , 3 10 17 7,11 a1111111111 Tara C. MatiseID , Kristine R. Monroe , Larry Moreland , Kari E. North , Sungshim a1111111111 L. Park10, Alex Reiner18, Robert Wallace19, Lynne R. Wilkens16, Charles Kooperberg15, 5☯ 20,21☯ Marylyn D. Ritchie , Dana C. CrawfordID * 1 Genentech, Inc., South San Francisco, California, United States of America, 2 Department of Statistics, Rutgers University, Piscataway, New Jersey, United States of America, 3 Department of Genetics, Rutgers University, Piscataway, New Jersey, United States of America, 4 Illumina, Inc., San Diego, California, United OPEN ACCESS States of America, 5 Department of Genetics, Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 6 Information Citation: Pendergrass SA, Buyske S, Jeff JM, Frase Sciences Institute; University of Southern California, Marina del Rey, California, United States of America, A, Dudek S, Bradford -
Genetic Determinants of Skin Color, Aging, and Cancer Genetische Determinanten Van Huidskleur, Huidveroudering En Huidkanker
Genetic Determinants of Skin Color, Aging, and Cancer Genetische determinanten van huidskleur, huidveroudering en huidkanker Leonie Cornelieke Jacobs Layout and printing: Optima Grafische Communicatie, Rotterdam, The Netherlands Cover design: Annette van Driel - Kluit © Leonie Jacobs, 2015 All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without prior written permission of the author or, when appropriate, of the publishers of the publications. ISBN: 978-94-6169-708-0 Genetic Determinants of Skin Color, Aging, and Cancer Genetische determinanten van huidskleur, huidveroudering en huidkanker Proefschrift Ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van rector magnificus Prof. dr. H.A.P. Pols en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op vrijdag 11 september 2015 om 11:30 uur door Leonie Cornelieke Jacobs geboren te Rotterdam PROMOTIECOMMISSIE Promotoren: Prof. dr. T.E.C. Nijsten Prof. dr. M. Kayser Overige leden: Prof. dr. H.A.M. Neumann Prof. dr. A.G. Uitterlinden Prof. dr. C.M. van Duijn Copromotor: dr. F. Liu COntents Chapter 1 General introduction 7 PART I SKIn COLOR Chapter 2 Perceived skin colour seems a swift, valid and reliable measurement. 29 Br J Dermatol. 2015 May 4; [Epub ahead of print]. Chapter 3 Comprehensive candidate gene study highlights UGT1A and BNC2 37 as new genes determining continuous skin color variation in Europeans. Hum Genet. 2013 Feb; 132(2): 147-58. Chapter 4 Genetics of skin color variation in Europeans: genome-wide association 59 studies with functional follow-up. -
A Review of Automatic Phenotyping Approaches Using Electronic Health Records
electronics Article A Review of Automatic Phenotyping Approaches using Electronic Health Records Hadeel Alzoubi 1,*, Raid Alzubi 2, Naeem Ramzan 3, Daune West 3, Tawfik Al-Hadhrami 4,* and Mamoun Alazab 5 1 School of Computer and Information Technology, Jordan University of Science and Technology, Irbid 22110, Jordan 2 Department of Computer Science, Faculty of Information Technology, Middle East University, Amman 11831, Jordan; [email protected] 3 School of Engineering and Computing, University of the West of Scotland, Paisley PA1 2BE, UK; [email protected] (N.R.); [email protected] (D.W.) 4 School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK 5 College of Engineering, IT and Environment, Charles Darwin University, Darwin 0815, Australia; [email protected] * Correspondences: [email protected] (H.A.); Tawfi[email protected] (T.A.-H.); Tel.: +44-115-848-4818 (T.A.-H.) Received: 27 September 2019; Accepted: 22 October 2019; Published: 29 October 2019 Abstract: Electronic Health Records (EHR) are a rich repository of valuable clinical information that exist in primary and secondary care databases. In order to utilize EHRs for medical observational research a range of algorithms for automatically identifying individuals with a specific phenotype have been developed. This review summarizes and offers a critical evaluation of the literature relating to studies conducted into the development of EHR phenotyping systems. This review describes phenotyping systems and techniques based on structured and unstructured EHR data. Articles published on PubMed and Google scholar between 2013 and 2017 have been reviewed, using search terms derived from Medical Subject Headings (MeSH). -
The Genome and Phenome of the Green Alga Chloroidium Sp
The genome and phenome of the green alga Chloroidium sp. UTEX 3007 reveal adaptive traits for desert acclimati- zation David R. Nelson1,2,*, Basel Khraiwesh1,2, Weiqi Fu1, Saleh Alseekh3, Ashish Jaiswal1, Amphun Chaiboonchoe1, Khaled M. Hazzouri2, Matthew J. O’Connor4, Glenn L. Butterfoss2, Nizar Drou2, Jil- lian D. Rowe2, Jamil Harb3,5, Alisdair R. Fernie3, Kristin C. Gunsalus2,6, Kourosh Salehi-Ashtiani1,2,* 1Laboratory of Algal, Systems, and Synthetic Biology, Division of Science and Math, New York Uni- versity Abu Dhabi, Abu Dhabi, UAE 2Center for Genomics and Systems Biology, New York University Abu Dhabi, Abu Dhabi, UAE 3Max Planck Institute of Molecular Plant Physiology, D-14476 Potsdam-Golm, Germany 4Core Technology Platform, New York University Abu Dhabi, Abu Dhabi, UAE 5Department of Biology and Biochemistry, Birzeit University, Birzeit, West Bank, Palestine 6Center for Genomics & Systems Biology and Department of Biology, New York University, New York, NY, USA *Correspondence and requests for materials should be addressed to D.R.N. ([email protected]) or K.S.- A ([email protected]) Abstract To investigate the phenomic and genomic traits that allow green algae to survive in deserts, we characterized a ubiquitous species, Chloroidium sp. UTEX 3007, which we isolated from multiple locations in the United Arab Emirates (UAE). Metabolomic analyses of Chloroidium sp. UTEX 3007 indicated that the alga accumulates a broad range of carbon sources, including several desiccation tolerance-promoting sugars and unusually large stores of palmitate. Growth assays re- vealed capacities to grow in salinities from zero to 60 g/L and to grow heterotrophically on >40 distinct carbon sources. -
Phenome-Wide Mendelian Randomization Mapping The
5 6 Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex 7 diseases 8 9 Jie Zheng*§1, Valeriia Haberland*1, Denis Baird*1, Venexia Walker*1, Philip C. Haycock*1, Mark R. Hurle2, Alex Gutteridge3, Pau Erola1, Yi Liu1, 10 Shan Luo1,4, Jamie Robinson1, Tom G. Richardson1, James R. Staley1,5, Benjamin Elsworth1, Stephen Burgess5, Benjamin B. Sun5, John 11 Danesh5,6,7,8,9,10, Heiko Runz11, Joseph C. Maranville12, Hannah M. Martin13, James Yarmolinsky1, Charles Laurin1, Michael V. Holmes1,14,15,16, 12 Jimmy Z. Liu11, Karol Estrada11, Rita Santos17, Linda McCarthy3, Dawn Waterworth2, Matthew R. Nelson2, George Davey Smith*1,18, Adam S. 13 Butterworth*5,6,7,8,9, Gibran Hemani*1, Robert A. Scott*§3, and Tom R. Gaunt*§1,18 14 15 1MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Bristol, UK. 16 2Human Genetics, GlaxoSmithKline, Collegeville, PA, USA. 17 3Human Genetics, GlaxoSmithKline, Stevenage, Hertfordshire, UK. 18 4School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China. 19 5BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. 20 6BHF Centre of Research Excellence, School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, UK. 21 7NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, 22 Cambridge, UK. 23 8NIHR Cambridge Biomedical Research Centre, School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, UK. 24 9Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Hinxton, UK. -
Epigenome and Phenome Study Reveals Circulating Markers Pertinent to Brain Health
medRxiv preprint doi: https://doi.org/10.1101/2021.09.03.21263066; this version posted September 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Epigenome and phenome study reveals circulating markers pertinent to brain health Danni A Gadd1,, Robert F Hillary1, Daniel L McCartney1, Liu Shi2, Robert I McGeachan3, Aleks Stolicyn4, Stewart W Morris1, Rosie M Walker5, Archie Campbell1, Miruna C Barbu4, Mathew A Harris4, Ellen V Backhouse5, Joanna M Wardlaw5,6,7,8, J Douglas Steele9, Diego A Oyarzún10, Graciela Muniz-Terrera12, Craig Ritchie12, Alejo Nevado-Holgado2, Caroline Hayward1,13, Kathryn L Evans1, David J Porteous1, Simon R Cox14,15, Heather C Whalley4, Andrew M McIntosh4, Riccardo E Marioni1,† 1 Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU 2 Department of Psychiatry, University of Oxford, UK, OX3 7JX 3 Centre for Discovery Brain Sciences, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK 4 Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, UK 5 Centre for Clinical Brain Sciences, Chancellor’s Building, 49 Little France Crescent, Edinburgh BioQuarter, Edinburgh, EH16 4SB 6 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK 7 Edinburgh Imaging, University of -
Graph Analytics for Phenome-Genome Associations Inference
bioRxiv preprint doi: https://doi.org/10.1101/682229; this version posted June 26, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Graph analytics for phenome-genome associations inference Davide Cirillo1,*, Dario Garcia-Gasulla1,*, Ulises Cortés1,3, Alfonso Valencia1,2 1 Barcelona Supercomputing Center (BSC), C/ Jordi Girona 29, 08034, Barcelona, Spain 2 ICREA, Pg. Lluís Companys 23, 08010, Barcelona, Spain. 3 Universitat Politècnica de Catalunya (UPC), C/ Jordi Girona 31, 08034, Barcelona, Spain * corresponding authors: [email protected]; [email protected] Abstract Motivation: Biological ontologies, such as the Human Phenotype Ontology (HPO) and the Gene Ontology (GO), are extensively used in biomedical research to find enrichment in the annotations of specific gene sets. However, the interpretation of the encoded information would greatly benefit from methods that effectively interoperate between multiple ontologies providing molecular details of disease-related features. Results: In this work, we present a statistical framework based on graph theory to infer direct associations between HPO and GO terms that do not share co-annotated genes. The method enables to map genotypic features to phenotypic features thus providing a valid tool for bridging functional and pathological annotations. We validated the results by (a) supporting evidence of known drug-target associations (PanDrugs), protein-protein physical and functional interactions (BioGRID and STRING), and common pathways (Reactome); (b) comparing relationships inferred from early ontology releases with knowledge contained in the latest versions. Applications: We applied our method to improve the interpretation of molecular processes involved in pathological conditions, illustrating the applicability of our predictions with a number of biological examples. -
Phenome-Wide Association Studies in Diverse Populations
Genomic Research in Action: Phenome-Wide Association Studies in Diverse Populations Sarah A. Pendergrass PhD, MS Assistant Professor Biomedical and Translational Informatics Geisinger Health System October 14, 2016 How Did I Get Here? MathUndergraduate and analytical thinking in Physics and programming, from Smith never College ending problem setsMasters in Biomedical Engineering from Thayer School of Working on disease based problems with computational solutions Engineering at Dartmouth PhD in Genetics from Dartmouth College Emerging world of bioinformatics and using these tools to study disease Postdoctoral work at Vanderbilt University Genetic Staff epidemiology Scientist atand Penn bioinformatics State – how can we leverage complex multifaceted data for discovery?? Investigator at Geisinger Health System PheWAS What are Phenome Wide Association Studies (PheWAS)? . Genome Wide Association Studies (GWAS) . Single Nucleotide Polymorphisms (SNPs) . One phenotype, or a limited phenotypic domain Phenome Wide Association Studies (PheWAS) . Comprehensively calculating the association between . Small to large number of SNPs . Diverse range of phenotypes from phenotypically rich datasets We can also use other data types too! . Other genetic variants: copy number variants, rare variants, mitochondrial variants . Quantitative lab variables instead of SNPs for biomarker identification PheWAS Phenome Wide Association Studies . Datasets with thousands of collected phenotypes . Unlikely that time would be spent to carefully investigate each phenotype for use . Hypothesis generation . Can we identify SNPs and/or phenotypes for further research ? Also exploring cross-phenotype associations . Exploring the relationship between associations for the same genetic variant and multiple phenotypes MegaPheWAS Performed a comprehensive genome-wide PheWAS . 632,574 genetic variants, MAF > 1% . 38,662 EA . 541 ICD-9 derived case-control diagnoses and a series of clinical lab measures Anurag Verma, Anastasia Lucas MegaPheWAS Performed a comprehensive genome-wide PheWAS . -
Phene Analysis, Overdominance, Variability
Hereditas 86: 251-266 (1977) Effects of the Pallas gene in barley: phene analysis, overdominance, variability AKE GUSTAFSSON, GUNNAR EKMAN AND INGEGERD DORMLING Institute of Genetics, University of Lund Semka AB, Sundbyberg The Phytotron, Swedish University of Agriculture, Stockholm, Sweden GUSTAFSSON,A., EKMAN,G. and DORMLING,I. 1977. Effects of the Pallas gene in barley: phene analysis, overdominance, variability. - Hereditas 86: 251 -266 Lund, Sweden. JSSN 001 8-0661. Received May 1, 1977 Pallas barley is a high-yielding mutant induced by X-rays in Bonus barley and was among the first cereal mutants released into practice. It is characterized by a high lodging resistance and surpassed its parent variety Bonus, under good soil conditions, in yielding capacity. It has been widely cultivated in several European countries. It wasconsidered worth while to analyse the phene reactions of the mutant, its parent strain Bonus and their F,-hybrid (Pallas x Bonus) in the Stockholm phytotron under varied climatic conditions. Three photoperiods and two thermoperiods were chosen for study. Fifteen phenotypic traits (phenes) were analysed concerning generative and vegetative production, occur- rence and expression of dominance and overdominance, as well as phene variability (flexibility). Overdominance was common and often highly significant. Variability of individual phenes changed widely. In generative traits Pallas was more variable than Bonus and the F,-hybrid. Under certain climatic conditions, the hybrid, in its turn, was definitely less variable than the parents. An evident interaction of genotype and climatic condition on productivity and variability was found. Ake Gustafsson, Institute of Genetics, S-223 62 Lund, Sweden The barley mutant erectoides 32 (ert-k3’)was isolated In the year 1974, cross materials of Pallas x Pallas, in 1947 from Svalov’s Bonus barley. -
Effects of a Temperature-Sensitive Minute Mutation on Gene Expression in Drosophila Melanogaster
Qenet. Res., Camb. (1984), 43, pp. 257-275 257 With 1 plate and 4 text-figures Printed in Great Britain Effects of a temperature-sensitive Minute mutation on gene expression in Drosophila melanogaster BY DONALD A. R. SINCLAIR*, THOMAS A. GRIGLIATTI* AND THOMAS C. KAUFMANf ^Department of Zoology, University of British Columbia, Vancouver, B.C. V6T 2A9 Canada. ^Department of Biology, Indiana University, Bloomington, Indiana, U.S.A. (Received 21 November 1983 and in revised form 21 January 1984) SUMMARY Minute (M) lesions exhibit a striking propensity for interacting with many different mutations. In the past, few attempts have been made to explain these diverse phenomena. This study describes a variety of temperature-sensitive (ts) interactions exhibited by the ts third chromo- some Minute mutation M(3)LS4Qin (Q-III). Most of these interactions (i.e. those involving vg, cp, Dl, Dfd or Ly) reflect ^-///-induced enhance- ment of the respective mutant phenotypes at the restrictive temperature. However, Q-III also suppresses the extra-sex-comb phenotypes of Pc and Msc at 29 °C and evokes lethal and bristle traits when combined with J34e at the restrictive temperature. All of these interactions are character- istic of non-ts Minute lesions and thus they appear to be correlated with general physiological perturbations associated with the M syndrome. In addition, our findings show that mutations that affect ribosome produc- tion and/or function, namely su{f)tse7g and bb18'1, exhibit interactions comparable to those elicited by Q-III. Hence, in accordance with previous findings, we argue that most of the Q-III interactions can be attributed to reduced translational capacity at the restrictive temperature.