A New Genetic Method for Isolating Functionally Interacting Genes
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Analysis of Gene Expression Data for Gene Ontology
ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Robert Daniel Macholan May 2011 ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION Robert Daniel Macholan Thesis Approved: Accepted: _______________________________ _______________________________ Advisor Department Chair Dr. Zhong-Hui Duan Dr. Chien-Chung Chan _______________________________ _______________________________ Committee Member Dean of the College Dr. Chien-Chung Chan Dr. Chand K. Midha _______________________________ _______________________________ Committee Member Dean of the Graduate School Dr. Yingcai Xiao Dr. George R. Newkome _______________________________ Date ii ABSTRACT A tremendous increase in genomic data has encouraged biologists to turn to bioinformatics in order to assist in its interpretation and processing. One of the present challenges that need to be overcome in order to understand this data more completely is the development of a reliable method to accurately predict the function of a protein from its genomic information. This study focuses on developing an effective algorithm for protein function prediction. The algorithm is based on proteins that have similar expression patterns. The similarity of the expression data is determined using a novel measure, the slope matrix. The slope matrix introduces a normalized method for the comparison of expression levels throughout a proteome. The algorithm is tested using real microarray gene expression data. Their functions are characterized using gene ontology annotations. The results of the case study indicate the protein function prediction algorithm developed is comparable to the prediction algorithms that are based on the annotations of homologous proteins. -
New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology
Cancer Research and Treatment 2003;35(4):304-313 New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology Yong-Wan Kim, Ph.D.1, Min-Je Suh, M.S.1, Jin-Sik Bae, M.S.1, Su Mi Bae, M.S.1, Joo Hee Yoon, M.D.2, Soo Young Hur, M.D.2, Jae Hoon Kim, M.D.2, Duck Young Ro, M.D.2, Joon Mo Lee, M.D.2, Sung Eun Namkoong, M.D.2, Chong Kook Kim, Ph.D.3 and Woong Shick Ahn, M.D.2 1Catholic Research Institutes of Medical Science, 2Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul; 3College of Pharmacy, Seoul National University, Seoul, Korea Purpose: This study utilized both mRNA differential significant genes of unknown function affected by the display and the Gene Ontology (GO) analysis to char- HPV-16-derived pathway. The GO analysis suggested that acterize the multiple interactions of a number of genes the cervical cancer cells underwent repression of the with gene expression profiles involved in the HPV-16- cancer-specific cell adhesive properties. Also, genes induced cervical carcinogenesis. belonging to DNA metabolism, such as DNA repair and Materials and Methods: mRNA differential displays, replication, were strongly down-regulated, whereas sig- with HPV-16 positive cervical cancer cell line (SiHa), and nificant increases were shown in the protein degradation normal human keratinocyte cell line (HaCaT) as a con- and synthesis. trol, were used. Each human gene has several biological Conclusion: The GO analysis can overcome the com- functions in the Gene Ontology; therefore, several func- plexity of the gene expression profile of the HPV-16- tions of each gene were chosen to establish a powerful associated pathway, identify several cancer-specific cel- cervical carcinogenesis pathway. -
HERV-K(HML7) Integrations in the Human Genome: Comprehensive Characterization and Comparative Analysis in Non-Human Primates
biology Article HERV-K(HML7) Integrations in the Human Genome: Comprehensive Characterization and Comparative Analysis in Non-Human Primates Nicole Grandi 1,* , Maria Paola Pisano 1 , Eleonora Pessiu 1, Sante Scognamiglio 1 and Enzo Tramontano 1,2 1 Laboratory of Molecular Virology, Department of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, Cagliari, Italy; [email protected] (M.P.P.); [email protected] (E.P.); [email protected] (S.S.); [email protected] (E.T.) 2 Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), 09042 Monserrato, Cagliari, Italy * Correspondence: [email protected] Simple Summary: The human genome is not human at all, but it includes a multitude of sequences inherited from ancient viral infections that affected primates’ germ line. These elements can be seen as the fossils of now-extinct retroviruses, and are called Human Endogenous Retroviruses (HERVs). View as “junk DNA” for a long time, HERVs constitute 4 times the amount of DNA needed to produce all cellular proteins, and growing evidence indicates their crucial role in primate brain evolution, placenta development, and innate immunity shaping. HERVs are also intensively studied for a pathological role, even if the incomplete knowledge about their exact number and genomic position has thus far prevented any causal association. Among possible relevant HERVs, the HERV-K Citation: Grandi, N.; Pisano, M.P.; supergroup is of particular interest, including some of the oldest (HML5) as well as youngest (HML2) Pessiu, E.; Scognamiglio, S.; integrations. Among HERV-Ks, the HML7 group still lack a detailed description, and the present Tramontano, E. -
Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights Into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle
animals Article Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle Masoumeh Naserkheil 1 , Abolfazl Bahrami 1 , Deukhwan Lee 2,* and Hossein Mehrban 3 1 Department of Animal Science, University College of Agriculture and Natural Resources, University of Tehran, Karaj 77871-31587, Iran; [email protected] (M.N.); [email protected] (A.B.) 2 Department of Animal Life and Environment Sciences, Hankyong National University, Jungang-ro 327, Anseong-si, Gyeonggi-do 17579, Korea 3 Department of Animal Science, Shahrekord University, Shahrekord 88186-34141, Iran; [email protected] * Correspondence: [email protected]; Tel.: +82-31-670-5091 Received: 25 August 2020; Accepted: 6 October 2020; Published: 9 October 2020 Simple Summary: Hanwoo is an indigenous cattle breed in Korea and popular for meat production owing to its rapid growth and high-quality meat. Its yearling weight and carcass traits (backfat thickness, carcass weight, eye muscle area, and marbling score) are economically important for the selection of young and proven bulls. In recent decades, the advent of high throughput genotyping technologies has made it possible to perform genome-wide association studies (GWAS) for the detection of genomic regions associated with traits of economic interest in different species. In this study, we conducted a weighted single-step genome-wide association study which combines all genotypes, phenotypes and pedigree data in one step (ssGBLUP). It allows for the use of all SNPs simultaneously along with all phenotypes from genotyped and ungenotyped animals. Our results revealed 33 relevant genomic regions related to the traits of interest. -
Multiple Hits for the Association of Uterine Fibroids on Human Chromosome 1Q43
Multiple Hits for the Association of Uterine Fibroids on Human Chromosome 1q43 Brahim Aissani1*, Howard Wiener1, Kui Zhang2 1 Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America Abstract Uterine leiomyomas (or fibroids) are the most common tumors in women of reproductive age. Early studies of two familial cancer syndromes, the multiple cutaneous and uterine leiomyomatosis (MCUL1), and the hereditary leiomyomatosis and renal cell cancer (HLRCC), implicated FH, a gene on chromosome 1q43 encoding the tricarboxylic acid cycle fumarate hydratase enzyme. The role of this metabolic housekeeping gene in tumorigenesis is still a matter of debate and pseudo- hypoxia has been suggested as a pathological mechanism. Inactivating FH mutations have rarely been observed in the nonsyndromic and common form of fibroids; however, loss of heterozygosity across FH appeared as a significant event in the pathogenesis of a subset of these tumors. To assess the role of FH and the linked genes in nonsyndromic uterine fibroids, we explored a two-megabase interval spanning FH in the NIEHS Uterine fibroid study, a cross-sectional study of fibroids in 1152 premenopausal women. Association mapping with a dense set of single nucleotide polymorphisms revealed several peaks of association (p = 1022–8.1025) with the risk and/or growth of fibroids. In particular, genes encoding factors suspected (cytosolic FH) or known (EXO1 - exonuclease 1) to be involved in DNA mismatch repair emerged as candidate susceptibility genes whereas those acting in the autophagy/apoptosis (MAP1LC3C - microtubule-associated protein) or signal transduction (RGS7 - Regulator of G-protein and PLD5– Phospoholipase D) appeared to affect tumor growth. -
1 Uganda Genome Resource Enables Insights
Uganda Genome Resource enables insights into population history and genomic discovery in Africa Gurdasani D.*1, Carstensen T.2* , Fatumo S.* 3,4,5, Chen G.*6, Franklin CS.*2, Prado-Martinez J.* 2, Bouman H.* 2, Abascal F. 2 , Haber M. 2, Tachmazidou I. 2, Mathieson I.7, Ekoru K.8, DeGorter MK. 9, Nsubuga RN.8, Finan C. 2, Wheeler E. 2, Chen L.2, Cooper DN.10, Schiffels S.11, Chen Y. 2, Ritchie GRS.2, Pollard MO. 2, Fortune MD. 2, Mentzer AJ.12, Garrison E. 2, Bergström A.2, Hatzikotoulas K.2, Adebowale A. 6, Doumatey A. 4, Elding H. 2, Wain LV.13,14, Ehret G.15,16, Auer PL.17, Kooperberg CL.18 , Reiner AP.19,20, Franceschini N.21, Maher DP.6, Montgomery SB.7,22, Kadie C.23, Widmer C.24, Xue Y.2, Seeley J. 6,3 , Asiki G. 8 , Kamali A. 8, Young EH. 25,2, Pomilla C. 25, Soranzo N. 2,26,27, Zeggini E. 28, Pirie F.29, Morris AP.30,12, Heckerman D.24, Tyler-Smith C2‡, Motala A.29‡ , Rotimi C6‡, Kaleebu P. ‡3,4,8, Barroso I.‡31,2, Sandhu MS.23 ‡ *these authors contributed equally ‡ these authors contributed equally Lead Contact: Manjinder Sandhu [email protected] 1 William Harvey Research Institute, Queen Mary’s University of London, London, UK 2 Wellcome Sanger Institute, Hinxton, Cambridge, UK 3 London School of Hygiene and Tropical Medicine, London, UK 4 Uganda Medical Informatics Centre (UMIC), MRC/UVRI and LSHTM (Uganda Research Unit), Entebbe-Uganda 5 H3Africa Bioinformatics Network (H3ABioNet) Node, Center for Genomics Research and Innovation (CGRI)/ National Biotechnology Development Agency CGRI/NABDA, Abuja, Nigeria 6 Center for Research -
T-Scan: a Genome-Wide Method for the Systematic Discovery of T Cell Epitopes
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Cell. Author Manuscript Author manuscript; Manuscript Author available in PMC 2020 January 02. Published in final edited form as: Cell. 2019 August 08; 178(4): 1016–1028.e13. doi:10.1016/j.cell.2019.07.009. T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes Tomasz Kula1,2, Mohammad H. Dezfulian1,2, Charlotte I. Wang1,2,3, Nouran S. Abdelfattah1,2, Zachary C. Hartman4, Kai W. Wucherpfennig5, Herbert Kim Lyerly6, Stephen J. Elledge1,2,7,* 1Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA 2Department of Genetics, Harvard University Medical School, Boston, MA, USA 3Department of Pathology, Massachusetts General Hospital, Boston, MA, USA 4Departments of Surgery and Pathology, Duke University Medical Center, 571 Research Drive, Suite 433, Box 2606, Durham, NC 27710, USA 5Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Department of Immunobiology, Harvard Medical School, Boston, MA 02115, USA 6Departments of Surgery, Immunology, and Pathology, Duke University Medical Center, 571 Research Drive, Suite 433, Box 2606, Durham, NC 27710, USA 7Lead Contact SUMMARY T cell recognition of specific antigens mediates protection from pathogens and controls neoplasias, but can also cause autoimmunity. Our knowledge of T cell antigens and their implications for human health is limited by the technical limitations of T cell profiling technologies. Here, we present T-Scan, a high-throughput platform for identification of antigens productively recognized by T cells. T-Scan uses lentiviral delivery of antigen libraries into cells for endogenous processing and presentation on major histocompatibility complex (MHC) molecules. -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
A 20S Complex Containing CDC27 and CDC16 Catalyzes the Mitosis-Specific Conjugation of Ubiquitin to Cyclin B
Cell, Vol. 81,279-288, April 21, 1995, Copyright© 1995 by Cell Press A 20S Complex Containing CDC27 and CDC16 Catalyzes the Mitosis-Specific Conjugation of Ubiquitin to Cyclin B Randall W. King,*t Jan-Michael Peters,*t cyclin degradation is required to exit mitosis (Surana et Stuart Tugendreich,$ Mark Rolfe,§ Philip Hieter,$ al., 1993; Holloway et al., 1993). Treatments that interfere and Marc W. Kirschnert with the proteolysis of endogenous cyclin B, however, ar- tDepartment of Cell Biology rest cell division earlier, at anaphase (Holloway et al., Harvard Medical School 1993). This discrepancy can be explained by hypothesiz- Boston, Massachusetts 02115 ing that chromosome segregation and cyclin proteolysis $Department of Molecular Biology and Genetics depend upon common components. Support for this idea Johns Hopkins School of Medicine has emerged recently from studies in budding yeast, in Baltimore, Maryland 21205 which CDC16 and CDC23, genes required for progression §Mitotix, Incorporated through anaphase, have been shown to be required for One Kendall Square the proteolysis of B-type cyclins (Irniger et al., 1995 [this Cambridge, Massachusetts 02139 issue of Cell]). The proteins encoded by these genes form a complex with the CDC27 protein (Lamb et al., 1994), a homolog of which is also required for anaphase progres- Summary sion in mammalian cells (Tugendreich et al., 1995 [this issue of Cell]). Cyclin B is degraded at the onset of anaphase by a Biochemical evidence suggests that cyclin proteolysis ubiquitin-dependent proteolytic system. We have frac- is mediated by the ubiquitin pathway: cyclin B-ubiquitin tionated mitotic Xenopus egg extracts to identify com- conjugates can be observed in mitotic, but not interphase, ponents required for this process. -
Analysis of the Indacaterol-Regulated Transcriptome in Human Airway
Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol . -
Expression of a Mirna Targeting Mutated SOD1 in Astrocytes Induces Motoneuron Plasticity and Improves Neuromuscular Function in ALS Mice
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.08.425706; this version posted January 9, 2021. 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. Expression of a miRNA targeting mutated SOD1 in astrocytes induces motoneuron plasticity and improves neuromuscular function in ALS mice Rochat C.1, Bernard-Marissal N.1,6, Pradervand S.3, Perrin F.E.4, Raoul C.5, Aebischer P.1, Schneider B.L.1,2* 1 Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland 2 Bertarelli Platform for Gene Therapy, Ecole Polytechnique Fédérale de Lausanne (EPFL), Geneva, Switzerland 3 Genomic Technologies Facility, University of Lausanne, Lausanne, Switzerland. 4 INSERM U1198, University of Montpellier, EPHE, Place Eugène Bataillon CC105, F-34095, Montpellier, France 5 The Neuroscience Institute of Montpellier, Inserm UMR1051, Univ Montpellier, Saint Eloi Hospital, Montpellier, France 6 Aix Marseille Univ, INSERM, MMG, Marseille, France *Correspondence should be addressed to B.L.S. ([email protected]) Short title: miRNA gene therapy targeting astrocytes in ALS Study was performed in Lausanne, Switzerland Current address of corresponding author: Bernard Schneider EPFL SV PTECH PTBTG Ch. des Mines 9 CH-1202 Genève Switzerland Email: [email protected] Tel: +41 21 693 95 05 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.08.425706; this version posted January 9, 2021. 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. -
Follow-Up Examination of Linkage and Association to Chromosome 1Q43 in Multiple Sclerosis
Genes and Immunity (2009) 10, 624–630 & 2009 Macmillan Publishers Limited All rights reserved 1466-4879/09 $32.00 www.nature.com/gene ORIGINAL ARTICLE Follow-up examination of linkage and association to chromosome 1q43 in multiple sclerosis JL McCauley1, RL Zuvich1, Y Bradford1, SJ Kenealy1, N Schnetz-Boutaud1, SG Gregory2, SL Hauser3, JR Oksenberg3, DP Mortlock1, MA Pericak-Vance4 and JL Haines1 1Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA; 2Center for Human Genetics and Department of Medicine, Duke University Medical Center, Durham, NC, USA; 3Department of Neurology, University of California San Francisco, San Francisco, CA, USA and 4Miami Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL, USA Multiple sclerosis (MS) is a debilitating neuroimmunological and neurodegenerative disease affecting 44 00 000 individuals in the United States. Population and family-based studies have suggested that there is a strong genetic component. Numerous genomic linkage screens have identified regions of interest for MS loci. Our own second-generation genome-wide linkage study identified a handful of non-major histocompatibility complex regions with suggestive linkage. Several of these regions were further examined using single-nucleotide polymorphisms (SNPs) with average spacing between SNPs of B1.0 Mb in a dataset of 173 multiplex families. The results of that study provided further evidence for the involvement of the chromosome 1q43 region. This region is of particular interest given linkage evidence in studies of other autoimmune and inflammatory diseases including rheumatoid arthritis and systemic lupus erythematosus. In this follow-up study, we saturated the region with B700 SNPs (average spacing of 10 kb per SNP) in search of disease-associated variation within this region.