DOCSLIB.ORG

Global and Quantitative Gene Expression Analysis of the Effects of Drinking Water Exposure to Lead Acetate in Fisher 344 Male Rats Liver

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Western Michigan University ScholarWorks at WMU Dissertations Graduate College 4-2007 Global and Quantitative Gene Expression Analysis of the Effects of Drinking Water Exposure to Lead Acetate in Fisher 344 Male Rats Liver Worlanyo Eric Gato Western Michigan University Follow this and additional works at: https://scholarworks.wmich.edu/dissertations Part of the Chemistry Commons Recommended Citation Gato, Worlanyo Eric, "Global and Quantitative Gene Expression Analysis of the Effects of Drinking Water Exposure to Lead Acetate in Fisher 344 Male Rats Liver" (2007). Dissertations. 863. https://scholarworks.wmich.edu/dissertations/863 This Dissertation-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Dissertations by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. GLOBAL AND QUANTITATIVE GENE EXPRESSION ANALYSIS OF THE EFFECTS OF DRINKING WATER EXPOSURE TO LEAD ACETATE IN FISHER 344 MALE RATS LIVER by Worlanyo Eric Gato A Dissertation Submitted to the Faculty of The Graduate College in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Department of Chemistry Dr. Jay Means, Advisor Western Michigan University Kalamazoo, Michigan April 2007 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. GLOBAL AND QUANTITATIVE GENE EXPRESSION ANALYSIS OF THE EFFECTS OF DRINKING WATER EXPOSURE TO LEAD ACETATE IN FISHER 344 MALE RATS LIVER Worlanyo Eric Gato, Ph.D. Western Michigan University, 2007 The primary objective of this research is to analyze global gene expression patterns occuring in Fisher 344 rat livers exposed to varying levels of lead and times. The hypotheses were that: 1) effects associated with Pb exposure are both dose and time dependent and 2) several genes will be over-expressed or repressed including transcripts associated with calcium signaling. Initially, the effects of Pb exposures upon morphometric indices, liver and kidney tissue histology, Pb distribution, Pb interaction with other trace metals including Zn, Cu, Co, Fe, Ni and Ca were assessed. Results showed a significant accumulation of lead in blood, liver, kidney and bone marrow in lead exposed groups with the kidney demonstrating greater damage compared to the liver. Potential interactions of calcium, iron, cobalt, copper, zinc and nickel and lead examined showed positive and negative correlation for 30 and 90 days treatment period respectively. Differentially expressed genes included genes cited in the literature and several not previously reported to be affected by lead toxicity. Expression profiles were clustered and gene ontology (GO) revealed 15 GO categories affected by chronic (90d) exposure, while 3 GO categories were affected during (30d) exposures. Pathways emphasized the importance of Pb in modulating various cellular events in a manner similar to calcium regulation, including phosphorylation and dephosphorylation, calcium Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. signaling, histone acetylation and deacetylation. Conclusions include: 1. Pb controls mammalian protein synthesis via regulating phosphorylation or dephosphorylation events of eukaryotic elongation/initiation factors 2. Pb regulates gene expression through the regulation of histone acetylases 3. Pb regulates calcium dependent transcription factor myocyte enhance factor-2 Quantitative PCR was employed in validating the microarray result and showed that Microarrays and qRT-PCR yield comparable results. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: 3259739 Copyright 2007 by Gato, Worlanyo Eric All rights reserved. INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. ® UMI UMI Microform 3259739 Copyright 2007 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Copyright by Worlanyo Eric Gato 2007 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGEMENTS I am indebted to my late grandmother Malwine Adzoa Boateng, my wife Vivian Mawuse Gato and children Worlanyo Eric Gato, Jr. and Elikem Winifred Gato, to whom I dedicate this dissertation. I want to thank the Chemistry Department of Western Michigan University for giving me the opportunity to study for a doctoral degree in Chemistry. I also want to thank Dr. Jay C. Means for allowing me to work in his laboratory and supporting me financially. I am grateful to my committee members Drs. David Huffman and Robert Eversole for their thoughtful comments and support in various ways. Also, I want to express my deep appreciation to Dr. Michael Barcelona for the various ways in which he has helped me through this program. This Chemistry program has given me the opportunity to meet and interact with people from diverse cultural, ethnic and intellectual backgrounds. I am glad to meet colleagues from Sri Lanka - Thushara Ghunasinghe, Kumar Tilak, Nayane Prasange, Piyardasha and Arana Weerasinghe, China - Minghong Liu, Wen Guo, Luchin Lin, Wend, Kenya - Wilson Okumu, David Achila, Patrick Ochieng, Joshua Muia, Paul Oshule and Joy Mwalimu; U.S. - Jenny Powell, Elizabeth Sodt and Elizabeth Semkiw, Brian Zeider and William Lizik, India - Shankar Varangati, Swapna Katram, Pramod Thekkat, Suhitha Meka and Sandhya Nair. I appreciate the friendship of these guys and a host of others. I appreciate the friendship provided by Paul Knoll and Trisha Basford my ii Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Acknowledgements - Continued laboratory colleagues. Thank you, Trisha Basford for helping me to learn the techniques required for this project. Drs. David Reinhold, Susan Stapleton and Sherine Obare have provided mentoring and references for me. Pam McCartney and Annie Dobbs have been helpful in many ways. For these, I say thank you and I appreciate your kindness very much. Finally, I want to express my deep thanks to the members of Westwood Baptist Church for being a family to us. Worlanyo Eric Gato iii Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS ACKNOWLEGEMENTS............................ ............................................... ii LIST OF TABLES......................................................................................... ix LIST OF FIGURES....................................................................................... x CHAPTER I. INTRODUCTION....................................................................................... 1 II. LITERATURE REVIEW........................................................................... 9 Lead Background Information ............................................................. 9 Historical Background ............................................................. 9 What is Lead?........................................................................... 11 Sources of Lead in the Environment ....................................... 12 Lead Use History ...................................................................... 14 Production, Disposal and Regulations .................................... 16 Mode of Toxicity .................................................................................. 18 Lead in Air ................................................................................ 18 Lead in Soil ............................................................................... 20 Lead in Aquatic Systems ......................................................... 22 Lead Cycling in Soils and Surface Waters ............................ 23 Human Lead Exposure Routes ............................................... 27 Lead Remediation .................................................................... 28 iv Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table of Contents - Continued CHAPTER Lead Absorption, Distribution and Excretion ......................... 29 Lead T oxicokinetics ................................................................ 35 Health Effects Associated With Pb2+ Exposure.. ............................. 42 N eurobehavioral Effects .......................................................... 42 Developmental Effects ............................................................. 44 Lead Carcinogenicity ............................................................... 46 Immunological Effects ............................................................. 48 Reproductive Effects ...............................................................
Recommended publications
  • Deregulated Gene Expression Pathways in Myelodysplastic Syndrome Hematopoietic Stem Cells

    Deregulated Gene Expression Pathways in Myelodysplastic Syndrome Hematopoietic Stem Cells

    Leukemia (2010) 24, 756–764 & 2010 Macmillan Publishers Limited All rights reserved 0887-6924/10 $32.00 www.nature.com/leu ORIGINAL ARTICLE Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells A Pellagatti1, M Cazzola2, A Giagounidis3, J Perry1, L Malcovati2, MG Della Porta2,MJa¨dersten4, S Killick5, A Verma6, CJ Norbury7, E Hellstro¨m-Lindberg4, JS Wainscoat1 and J Boultwood1 1LRF Molecular Haematology Unit, NDCLS, John Radcliffe Hospital, Oxford, UK; 2Department of Hematology Oncology, University of Pavia Medical School, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 3Medizinische Klinik II, St Johannes Hospital, Duisburg, Germany; 4Division of Hematology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 5Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK; 6Albert Einstein College of Medicine, Bronx, NY, USA and 7Sir William Dunn School of Pathology, University of Oxford, Oxford, UK To gain insight into the molecular pathogenesis of the the World Health Organization.6,7 Patients with refractory myelodysplastic syndromes (MDS), we performed global gene anemia (RA) with or without ringed sideroblasts, according to expression profiling and pathway analysis on the hemato- poietic stem cells (HSC) of 183 MDS patients as compared with the the French–American–British classification, were subdivided HSC of 17 healthy controls. The most significantly deregulated based on the presence or absence of multilineage dysplasia. In pathways in MDS include interferon signaling, thrombopoietin addition, patients with RA with excess blasts (RAEB) were signaling and the Wnt pathways. Among the most signifi- subdivided into two categories, RAEB1 and RAEB2, based on the cantly deregulated gene pathways in early MDS are immuno- percentage of bone marrow blasts.
  • Analysis of Trans Esnps Infers Regulatory Network Architecture

    Analysis of Trans Esnps Infers Regulatory Network Architecture

    Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 © 2014 Anat Kreimer All rights reserved ABSTRACT Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer eSNPs are genetic variants associated with transcript expression levels. The characteristics of such variants highlight their importance and present a unique opportunity for studying gene regulation. eSNPs affect most genes and their cell type specificity can shed light on different processes that are activated in each cell. They can identify functional variants by connecting SNPs that are implicated in disease to a molecular mechanism. Examining eSNPs that are associated with distal genes can provide insights regarding the inference of regulatory networks but also presents challenges due to the high statistical burden of multiple testing. Such association studies allow: simultaneous investigation of many gene expression phenotypes without assuming any prior knowledge and identification of unknown regulators of gene expression while uncovering directionality. This thesis will focus on such distal eSNPs to map regulatory interactions between different loci and expose the architecture of the regulatory network defined by such interactions. We develop novel computational approaches and apply them to genetics-genomics data in human. We go beyond pairwise interactions to define network motifs, including regulatory modules and bi-fan structures, showing them to be prevalent in real data and exposing distinct attributes of such arrangements. We project eSNP associations onto a protein-protein interaction network to expose topological properties of eSNPs and their targets and highlight different modes of distal regulation.
  • Identification of the Binding Partners for Hspb2 and Cryab Reveals

    Identification of the Binding Partners for Hspb2 and Cryab Reveals

    Brigham Young University BYU ScholarsArchive Theses and Dissertations 2013-12-12 Identification of the Binding arP tners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non- Redundant Roles for Small Heat Shock Proteins Kelsey Murphey Langston Brigham Young University - Provo Follow this and additional works at: https://scholarsarchive.byu.edu/etd Part of the Microbiology Commons BYU ScholarsArchive Citation Langston, Kelsey Murphey, "Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins" (2013). Theses and Dissertations. 3822. https://scholarsarchive.byu.edu/etd/3822 This Thesis is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of BYU ScholarsArchive. For more information, please contact [email protected], [email protected]. Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins Kelsey Langston A thesis submitted to the faculty of Brigham Young University in partial fulfillment of the requirements for the degree of Master of Science Julianne H. Grose, Chair William R. McCleary Brian Poole Department of Microbiology and Molecular Biology Brigham Young University December 2013 Copyright © 2013 Kelsey Langston All Rights Reserved ABSTRACT Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactors and Non-Redundant Roles for Small Heat Shock Proteins Kelsey Langston Department of Microbiology and Molecular Biology, BYU Master of Science Small Heat Shock Proteins (sHSP) are molecular chaperones that play protective roles in cell survival and have been shown to possess chaperone activity.
  • In Vivo Genome-Wide Binding Interactions of Mouse and Human Constitutive Androstane Receptors Reveal Novel Gene Targets Ben Niu1, Denise M

    In Vivo Genome-Wide Binding Interactions of Mouse and Human Constitutive Androstane Receptors Reveal Novel Gene Targets Ben Niu1, Denise M

    Published online 8 August 2018 Nucleic Acids Research, 2018, Vol. 46, No. 16 8385–8403 doi: 10.1093/nar/gky692 In vivo genome-wide binding interactions of mouse and human constitutive androstane receptors reveal novel gene targets Ben Niu1, Denise M. Coslo1, Alain R. Bataille2, Istvan Albert2, B. Franklin Pugh2 and Curtis J. Omiecinski1,* 1Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA and 2Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA Received May 04, 2018; Revised July 17, 2018; Editorial Decision July 19, 2018; Accepted July 20, 2018 ABSTRACT tion factors that are activated by direct ligands (1) and gen- erally share a common structure, an N-terminal A/B do- The constitutive androstane receptor (CAR; NR1I3) main, a DNA binding domain (DBD), a hinge domain, a is a nuclear receptor orchestrating complex roles ligand binding/ heterodimerization domain (LBD) and an in cell and systems biology. Species differences in F domain at the C-terminal (2). Upon ligand activation, CAR’s effector pathways remain poorly understood, the LBD would utilize activation function-2 (AF-2) to me- including its role in regulating liver tumor promotion. diate co-regulator interactions (3). However, CAR is dis- We developed transgenic mouse models to assess tinguished from other nuclear receptors in that it lacks an genome-wide binding of mouse and human CAR, A/B domain and is constitutively active in the absence of following receptor activation in liver with direct lig- ligand due to a charge-charge interaction between LBD he- ands and with phenobarbital, an indirect CAR acti- lixes that mimic an active AF-2 conformation, and therefore vator.
  • Tepzz¥ 6Z54za T

    Tepzz¥ 6Z54za T

    (19) TZZ¥ ZZ_T (11) EP 3 260 540 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 27.12.2017 Bulletin 2017/52 C12N 15/113 (2010.01) A61K 9/127 (2006.01) A61K 31/713 (2006.01) C12Q 1/68 (2006.01) (21) Application number: 17000579.7 (22) Date of filing: 12.11.2011 (84) Designated Contracting States: • Sarma, Kavitha AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Philadelphia, PA 19146 (US) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • Borowsky, Mark PL PT RO RS SE SI SK SM TR Needham, MA 02494 (US) • Ohsumi, Toshiro Kendrick (30) Priority: 12.11.2010 US 412862 P Cambridge, MA 02141 (US) 20.12.2010 US 201061425174 P 28.07.2011 US 201161512754 P (74) Representative: Clegg, Richard Ian et al Mewburn Ellis LLP (62) Document number(s) of the earlier application(s) in City Tower accordance with Art. 76 EPC: 40 Basinghall Street 11840099.3 / 2 638 163 London EC2V 5DE (GB) (71) Applicant: The General Hospital Corporation Remarks: Boston, MA 02114 (US) •Thecomplete document including Reference Tables and the Sequence Listing can be downloaded from (72) Inventors: the EPO website • Lee, Jeannie T •This application was filed on 05-04-2017 as a Boston, MA 02114 (US) divisional application to the application mentioned • Zhao, Jing under INID code 62. San Diego, CA 92122 (US) •Claims filed after the date of receipt of the divisional application (Rule 68(4) EPC). (54) POLYCOMB-ASSOCIATED NON-CODING RNAS (57) This invention relates to long non-coding RNAs (IncRNAs), libraries of those ncRNAs that bind chromatin modifiers, such as Polycomb Repressive Complex 2, inhibitory nucleic acids and methods and compositions for targeting IncRNAs.
  • Characterization of a 7.6-Mb Germline Deletion Encompassing the NF1 Locus and About a Hundred Genes in an NF1 Contiguous Gene Syndrome Patient

    Characterization of a 7.6-Mb Germline Deletion Encompassing the NF1 Locus and About a Hundred Genes in an NF1 Contiguous Gene Syndrome Patient

    European Journal of Human Genetics (2008) 16, 1459–1466 & 2008 Macmillan Publishers Limited All rights reserved 1018-4813/08 $32.00 www.nature.com/ejhg ARTICLE Characterization of a 7.6-Mb germline deletion encompassing the NF1 locus and about a hundred genes in an NF1 contiguous gene syndrome patient Eric Pasmant*,1,2, Aure´lie de Saint-Trivier2, Ingrid Laurendeau1, Anne Dieux-Coeslier3, Be´atrice Parfait1,2, Michel Vidaud1,2, Dominique Vidaud1,2 and Ivan Bie`che1,2 1UMR745 INSERM, Universite´ Paris Descartes, Faculte´ des Sciences Pharmaceutiques et Biologiques, Paris, France; 2Service de Biochimie et de Ge´ne´tique Mole´culaire, Hoˆpital Beaujon AP-HP, Clichy, France; 3Service de Ge´ne´tique Clinique, Hoˆpital Jeanne de Flandre, Lille, France We describe a large germline deletion removing the NF1 locus, identified by heterozygosity mapping based on microsatellite markers, in an 8-year-old French girl with a particularly severe NF1 contiguous gene syndrome. We used gene-dose mapping with sequence-tagged site real-time PCR to locate the deletion end points, which were precisely characterized by means of long-range PCR and nucleotide sequencing. The deletion is located on chromosome arm 17q and is exactly 7 586 986 bp long. It encompasses the entire NF1 locus and about 100 other genes, including numerous chemokine genes, an attractive in silico-selected cerebrally expressed candidate gene (designated NUFIP2, for nuclear fragile X mental retardation protein interacting protein 2; NM_020772) and four microRNA genes. Interestingly, the centromeric breakpoint is located in intron 4 of the PIPOX gene (pipecolic acid oxidase; NM_016518) and the telomeric breakpoint in intron 5 of the GGNBP2 gene (gametogenetin binding protein 2; NM_024835) coding a transcription factor.
  • Noelia Díaz Blanco

    Noelia Díaz Blanco

    Effects of environmental factors on the gonadal transcriptome of European sea bass (Dicentrarchus labrax), juvenile growth and sex ratios Noelia Díaz Blanco Ph.D. thesis 2014 Submitted in partial fulfillment of the requirements for the Ph.D. degree from the Universitat Pompeu Fabra (UPF). This work has been carried out at the Group of Biology of Reproduction (GBR), at the Department of Renewable Marine Resources of the Institute of Marine Sciences (ICM-CSIC). Thesis supervisor: Dr. Francesc Piferrer Professor d’Investigació Institut de Ciències del Mar (ICM-CSIC) i ii A mis padres A Xavi iii iv Acknowledgements This thesis has been made possible by the support of many people who in one way or another, many times unknowingly, gave me the strength to overcome this "long and winding road". First of all, I would like to thank my supervisor, Dr. Francesc Piferrer, for his patience, guidance and wise advice throughout all this Ph.D. experience. But above all, for the trust he placed on me almost seven years ago when he offered me the opportunity to be part of his team. Thanks also for teaching me how to question always everything, for sharing with me your enthusiasm for science and for giving me the opportunity of learning from you by participating in many projects, collaborations and scientific meetings. I am also thankful to my colleagues (former and present Group of Biology of Reproduction members) for your support and encouragement throughout this journey. To the “exGBRs”, thanks for helping me with my first steps into this world. Working as an undergrad with you Dr.
  • Targeting PH Domain Proteins for Cancer Therapy

    Targeting PH Domain Proteins for Cancer Therapy

    The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 12-2018 Targeting PH domain proteins for cancer therapy Zhi Tan Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Bioinformatics Commons, Medicinal Chemistry and Pharmaceutics Commons, Neoplasms Commons, and the Pharmacology Commons Recommended Citation Tan, Zhi, "Targeting PH domain proteins for cancer therapy" (2018). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 910. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/910 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. TARGETING PH DOMAIN PROTEINS FOR CANCER THERAPY by Zhi Tan Approval page APPROVED: _____________________________________________ Advisory Professor, Shuxing Zhang, Ph.D. _____________________________________________
  • Gene Alterations Identified by Expression Profiling in Tumor-Associated Endothelial Cells from Invasive Ovarian Carcinoma

    Gene Alterations Identified by Expression Profiling in Tumor-Associated Endothelial Cells from Invasive Ovarian Carcinoma

    Research Article Gene Alterations Identified by Expression Profiling in Tumor-Associated Endothelial Cells from Invasive Ovarian Carcinoma Chunhua Lu,1 Tomas Bonome,3 Yang Li,1 Aparna A. Kamat,1 Liz Y. Han,1 Rosemarie Schmandt,1 Robert L. Coleman,1 David M. Gershenson,1 Robert B. Jaffe,4 MichaelJ. Birrer, 3 and AnilK. Sood 1,2 Departments of 1Gynecologic Oncology and 2Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, Texas; 3Cell and Cancer Biology Branch, National Cancer Institute, Bethesda, Maryland; and 4Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California Abstract the promise of such approaches. However, the full spectrum of Therapeutic strategies based on antiangiogenic approaches differences in the tumor vasculature compared with its normal are beginning to show great promise in clinical studies. counterpart is not known. Identification of additional targets on However, full realization of these approaches requires tumor endothelium may allow opportunities for developing new identification of key differences in gene expression between therapeutic approaches to inhibit angiogenesis in a tumor-specific endothelial cells from tumors versus their normal counter- manner. parts. Here, we examined gene expression differences in Higher levels of proangiogenic cytokines and angiogenesis are purified endothelial cells from 10invasive epithelial ovarian associated with an increased risk of metastasis and poor prognosis cancers and 5 normal ovaries using Affymetrix U133 Plus in ovarian cancer (5, 6). To date, a small number of breast, colon, 2.0microarrays. More than 400differentially expressed genes and brain cancers have been analyzed for gene expression changes were identified in tumor-associated endothelial cells.
  • Variation in Protein Coding Genes Identifies Information

    Variation in Protein Coding Genes Identifies Information

    bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 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-NC-ND 4.0 International license. Animal complexity and information flow 1 1 2 3 4 5 Variation in protein coding genes identifies information flow as a contributor to 6 animal complexity 7 8 Jack Dean, Daniela Lopes Cardoso and Colin Sharpe* 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Institute of Biological and Biomedical Sciences 25 School of Biological Science 26 University of Portsmouth, 27 Portsmouth, UK 28 PO16 7YH 29 30 * Author for correspondence 31 [email protected] 32 33 Orcid numbers: 34 DLC: 0000-0003-2683-1745 35 CS: 0000-0002-5022-0840 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Abstract bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 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-NC-ND 4.0 International license. Animal complexity and information flow 2 1 Across the metazoans there is a trend towards greater organismal complexity. How 2 complexity is generated, however, is uncertain. Since C.elegans and humans have 3 approximately the same number of genes, the explanation will depend on how genes are 4 used, rather than their absolute number.
  • Identification of Promoter Regions in the Human Genome by Using a Retroviral Plasmid Library-Based Functional Reporter Gene Assa

    Identification of Promoter Regions in the Human Genome by Using a Retroviral Plasmid Library-Based Functional Reporter Gene Assa

    Downloaded from genome.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Methods Identification of Promoter Regions in the Human Genome by Using a Retroviral Plasmid Library-Based Functional Reporter Gene Assay Shirin Khambata-Ford,1,5 Yueyi Liu,2 Christopher Gleason,1 Mark Dickson,3 Russ B. Altman,2 Serafim Batzoglou,4 and Richard M. Myers1,3,6 1Department of Genetics, 2Stanford Medical Informatics, 3Stanford Human Genome Center, Stanford University School of Medicine, Stanford, California 94305, USA; 4Department of Computer Science, Stanford University, Stanford, California 94305, USA Attempts to identify regulatory sequences in the human genome have involved experimental and computational methods such as cross-species sequence comparisons and the detection of transcription factor binding-site motifs in coexpressed genes. Although these strategies provide information on which genomic regions are likely to be involved in gene regulation, they do not give information on their functions. We have developed a functional selection for promoter regions in the human genome that uses a retroviral plasmid library-based system. This approach enriches for and detects promoter function of isolated DNA fragments in an in vitro cell culture assay. By using this method, we have discovered likely promoters of known and predicted genes, as well as many other putative promoter regions based on the presence of features such as CpG islands. Comparison of sequences of 858 plasmid clones selected by this assay with the human genome draft sequence indicates that a significantly higher percentage of sequences align to the 500-bp segment upstream of the transcription start sites of known genes than would be expected from random genomic sequences.
  • Literature Mining Sustains and Enhances Knowledge Discovery from Omic Studies

    Literature Mining Sustains and Enhances Knowledge Discovery from Omic Studies

    LITERATURE MINING SUSTAINS AND ENHANCES KNOWLEDGE DISCOVERY FROM OMIC STUDIES by Rick Matthew Jordan B.S. Biology, University of Pittsburgh, 1996 M.S. Molecular Biology/Biotechnology, East Carolina University, 2001 M.S. Biomedical Informatics, University of Pittsburgh, 2005 Submitted to the Graduate Faculty of School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2016 UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE This dissertation was presented by Rick Matthew Jordan It was defended on December 2, 2015 and approved by Shyam Visweswaran, M.D., Ph.D., Associate Professor Rebecca Jacobson, M.D., M.S., Professor Songjian Lu, Ph.D., Assistant Professor Dissertation Advisor: Vanathi Gopalakrishnan, Ph.D., Associate Professor ii Copyright © by Rick Matthew Jordan 2016 iii LITERATURE MINING SUSTAINS AND ENHANCES KNOWLEDGE DISCOVERY FROM OMIC STUDIES Rick Matthew Jordan, M.S. University of Pittsburgh, 2016 Genomic, proteomic and other experimentally generated data from studies of biological systems aiming to discover disease biomarkers are currently analyzed without sufficient supporting evidence from the literature due to complexities associated with automated processing. Extracting prior knowledge about markers associated with biological sample types and disease states from the literature is tedious, and little research has been performed to understand how to use this knowledge to inform the generation of classification models from ‘omic’ data. Using pathway analysis methods to better understand the underlying biology of complex diseases such as breast and lung cancers is state-of-the-art. However, the problem of how to combine literature- mining evidence with pathway analysis evidence is an open problem in biomedical informatics research.