Novel Mutation Hotspots Within Non-Coding Regulatory Regions Of
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
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. -
Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-Like Mouse Models: Tracking the Role of the Hairless Gene
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2006 Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene Yutao Liu University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Life Sciences Commons Recommended Citation Liu, Yutao, "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino- like Mouse Models: Tracking the Role of the Hairless Gene. " PhD diss., University of Tennessee, 2006. https://trace.tennessee.edu/utk_graddiss/1824 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Yutao Liu entitled "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Life Sciences. Brynn H. Voy, Major Professor We have read this dissertation and recommend its acceptance: Naima Moustaid-Moussa, Yisong Wang, Rogert Hettich Accepted for the Council: Carolyn R. -
PHF2 Histone Demethylase Prevents DNA Damage and Genome Instability by Controlling Cell Cycle Progression of Neural Progenitors
PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors Stella Pappaa, Natalia Padillab,c,1, Simona Iacobuccia,1, Marta Viciosoa, Elena Álvarez de la Campab,c, Claudia Navarroa, Elia Marcosa, Xavier de la Cruzb,c,2, and Marian A. Martínez-Balbása,2 aDepartment of Molecular Genomics, Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, 08028 Barcelona, Spain; bClinical and Translational Bioinformatics, Vall d’Hebron Institute of Research, E-08035 Barcelona, Spain; and cInstitut Català per la Recerca i Estudis Avançats, 08018 Barcelona, Spain Edited by Robert E. Kingston, Massachusetts General Hospital/Harvard Medical School, Boston, MA, and approved August 6, 2019 (received for review February 25, 2019) Histone H3 lysine 9 methylation (H3K9me) is essential for cellular terestingly, PHF2 mutations have been found in patients with homeostasis; however, its contribution to development is not well autism spectrum disorder (ASD) (22–24). Despite PHF2 high established. Here, we demonstrate that the H3K9me2 demethy- expression in the neural tube and its implication on mental dis- lase PHF2 is essential for neural progenitor proliferation in vitro eases, PHF2 involvement in neural development has not yet and for early neurogenesis in the chicken spinal cord. Using genome- been explored. wide analyses and biochemical assays we show that PHF2 controls In this study, we analyzed the role of PHF2 in neural stem cell the expression of critical cell cycle progression genes, particularly (NSC) biology. We found that PHF2 is essential for progenitor those related to DNA replication, by keeping low levels of H3K9me3 proliferation in vitro and in vivo, in the chicken spinal cord. -
Seq2pathway Vignette
seq2pathway Vignette Bin Wang, Xinan Holly Yang, Arjun Kinstlick May 19, 2021 Contents 1 Abstract 1 2 Package Installation 2 3 runseq2pathway 2 4 Two main functions 3 4.1 seq2gene . .3 4.1.1 seq2gene flowchart . .3 4.1.2 runseq2gene inputs/parameters . .5 4.1.3 runseq2gene outputs . .8 4.2 gene2pathway . 10 4.2.1 gene2pathway flowchart . 11 4.2.2 gene2pathway test inputs/parameters . 11 4.2.3 gene2pathway test outputs . 12 5 Examples 13 5.1 ChIP-seq data analysis . 13 5.1.1 Map ChIP-seq enriched peaks to genes using runseq2gene .................... 13 5.1.2 Discover enriched GO terms using gene2pathway_test with gene scores . 15 5.1.3 Discover enriched GO terms using Fisher's Exact test without gene scores . 17 5.1.4 Add description for genes . 20 5.2 RNA-seq data analysis . 20 6 R environment session 23 1 Abstract Seq2pathway is a novel computational tool to analyze functional gene-sets (including signaling pathways) using variable next-generation sequencing data[1]. Integral to this tool are the \seq2gene" and \gene2pathway" components in series that infer a quantitative pathway-level profile for each sample. The seq2gene function assigns phenotype-associated significance of genomic regions to gene-level scores, where the significance could be p-values of SNPs or point mutations, protein-binding affinity, or transcriptional expression level. The seq2gene function has the feasibility to assign non-exon regions to a range of neighboring genes besides the nearest one, thus facilitating the study of functional non-coding elements[2]. Then the gene2pathway summarizes gene-level measurements to pathway-level scores, comparing the quantity of significance for gene members within a pathway with those outside a pathway. -
Identification of the Promoter and a Transcriptional Enhancer of The
Proc. Natl. Acad. Sci. USA Vol. 90, pp. 11356-11360, December 1993 Developmental Biology Identification of the promoter and a transcriptional enhancer of the gene encoding L-CAM, a calcium-dependent cell adhesion molecule (gene expression/regulatory sequences/morphogenesis/cadherins) BARBARA C. SORKIN, FREDERICK S. JONES, BRUCE A. CUNNINGHAM, AND GERALD M. EDELMAN The Department of Neurobiology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037 Contributed by Gerald M. Edelman, August 20, 1993 ABSTRACT L-CAM is a calcium-dependent cell adhesion expressed in the dermis, but rather in the adjacent epidermis molecule that is expressed in a characteristic place-dependent (6). pattern during development. Previous studies of ectopic ex- L-CAM mediates calcium-dependent cell-cell adhesion (7) pression of the chicken L-CAM gene under the control of via a homophilic mechanism; i.e., L-CAM on one cell binds heterologous promoters in transgenic mice suggested that directly to L-CAM on apposing cells (8). In all tissues where cis-acting sequences controlling the spatiotemporal expression the molecule is expressed, L-CAM is detected as a trans- patterns ofL-CAM were present within the gene itself. We have membrane protein of 124 kDa (7). Mammalian proteins now examined the L-CAM gene for sequences that control its uvomorulin (9), E-cadherin (10), cell-CAM 120/80 (11), and expression and have found an enhancer within the second Arcl (12) are similar to L-CAM in their biochemical and intron of the gene. A 2.5-kb Kpn I-EcoRI fragment from the functional properties and tissue distributions. -
BCL7A As a Novel Prognostic Biomarker for Glioma Patients
BCL7A as a novel prognostic biomarker for glioma patients Junhui Liu ( [email protected] ) Renmin Hospital of Wuhan University: Wuhan University Renmin Hospital Lun Gao Renmin Hospital of Wuhan University: Wuhan University Renmin Hospital Baowei Ji Renmin Hospital of Wuhan University: Wuhan University Renmin Hospital Rongxin Geng Renmin Hospital of Wuhan University: Wuhan University Renmin Hospital Jing Chen Renmin Hospital of Wuhan University: Wuhan University Renmin Hospital Xiang Tao Renmin Hospital of Wuhan University: Wuhan University Renmin Hospital Qiang Cai Renmin Hospital of Wuhan University: Wuhan University Renmin Hospital Zhibiao Chen Renmin Hospital of Wuhan University: Wuhan University Renmin Hospital Research Article Keywords: BCL7 family, glioma, prognosis, immune, Temozolomide Posted Date: April 21st, 2021 DOI: https://doi.org/10.21203/rs.3.rs-390165/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Version of Record: A version of this preprint was published at Journal of Translational Medicine on August 6th, 2021. See the published version at https://doi.org/10.1186/s12967-021-03003-0. Page 1/24 Abstract Background: Glioma is the most common primary brain tumor and represents one of the most aggressive and lethal types of human cancer. BCL7 family has been found in several cancer types and could be involved in tumor progression. While the role of BCL7 family in human glioma has remained to be elucidated. Methods: Paran-embedded tumor samples were obtained to detect BCL7 expression by performing in glioma. Data (including normalized gene expression and corresponding clinical data) were obtained from Gliovis, CGGA, GEO, cBioportal and Oncomine and were used to investigate BCL7 genes expression in glioma. -
Dual Proteome-Scale Networks Reveal Cell-Specific Remodeling of the Human Interactome
bioRxiv preprint doi: https://doi.org/10.1101/2020.01.19.905109; this version posted January 19, 2020. 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. Dual Proteome-scale Networks Reveal Cell-specific Remodeling of the Human Interactome Edward L. Huttlin1*, Raphael J. Bruckner1,3, Jose Navarrete-Perea1, Joe R. Cannon1,4, Kurt Baltier1,5, Fana Gebreab1, Melanie P. Gygi1, Alexandra Thornock1, Gabriela Zarraga1,6, Stanley Tam1,7, John Szpyt1, Alexandra Panov1, Hannah Parzen1,8, Sipei Fu1, Arvene Golbazi1, Eila Maenpaa1, Keegan Stricker1, Sanjukta Guha Thakurta1, Ramin Rad1, Joshua Pan2, David P. Nusinow1, Joao A. Paulo1, Devin K. Schweppe1, Laura Pontano Vaites1, J. Wade Harper1*, Steven P. Gygi1*# 1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA. 2Broad Institute, Cambridge, MA, 02142, USA. 3Present address: ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA, 02115, USA. 4Present address: Merck, West Point, PA, 19486, USA. 5Present address: IQ Proteomics, Cambridge, MA, 02139, USA. 6Present address: Vor Biopharma, Cambridge, MA, 02142, USA. 7Present address: Rubius Therapeutics, Cambridge, MA, 02139, USA. 8Present address: RPS North America, South Kingstown, RI, 02879, USA. *Correspondence: [email protected] (E.L.H.), [email protected] (J.W.H.), [email protected] (S.P.G.) #Lead Contact: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.01.19.905109; this version posted January 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. -
Leukaemia Section
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST-CNRS Leukaemia Section Short Communication t(7;14)(q35;q32.1) TRB/TCL1A inv(14)(q11q32.1) TRA-TRD/TCL1A t(14;14)(q11;q32.1) TRA-TRD/TCL1A Tatiana Gindina Raisa Gorbacheva Memorial Institute of Children's Oncology, Hematology and Transplantation at First Pavlov St. Petersburg State Medical University, Saint-Petersburg, Russia Published in Atlas Database: June 2018 Online updated version : http://AtlasGeneticsOncology.org/Anomalies/inv14ID2049.html Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/70184/06-2018-inv14ID2049.pdf DOI: 10.4267/2042/70184 This article is an update of : Boyer J. t(7;14)(q35;q32.1) TRB@/TCL1A. Atlas Genet Cytogenet Oncol Haematol 2001;5(3) This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2019 Atlas of Genetics and Cytogenetics in Oncology and Haematology TRD; B lymphoblastic leukaemia/lymphoma; T Abstract lymphoblastic leukaemia/lymphoma; Adult T-cell Review on t(7;14)(q35;q32), inv(14)(q11q32) and leukemia/lymphoma; T-cell prolymphocytic t(14;14)(q11;q32), with data on clinics, and the leukemia; Angioimmunoblastic T-cell lymphoma; genes involved. Chronic lymphocytic leukemia; syndrome; Mycosis Keywords fungoides; Hepatosplenic T-cell lymphoma; Acute Chromosome 7; Chromosome 14; TCL1A; TRA; myeloid leukaemia; Ataxia telangiectasia. Left: inv(14)(q11q32)and i(8q), G- banding - Courtesy Jean Luc Lai; right: inv(14)(q11q32) and t(14)(14) with i(7q), G- banding - Courtesy Tatiana Gindina. Atlas Genet Cytogenet Oncol Haematol. 2019; 23(4) 90 t(7;14)(q35;q32.1) TRB/TCL1A Gindina T inv(14)(q11q32.1) TRA-TRD/TCL1A t(14;14)(q11;q32.1) TRA-TRD/TCL1A Cytogenetics Clinics and pathology Chromosomal abnormalities are detected in most T- Disease PLL after culture with mitogens like PHA. -
Integrating Genomic Alterations in Diffuse Large B-Cell Lymphoma Identifies New Relevant Pathways and Potential Therapeutic Targets
OPEN Leukemia (2018) 32, 675–684 www.nature.com/leu ORIGINAL ARTICLE Integrating genomic alterations in diffuse large B-cell lymphoma identifies new relevant pathways and potential therapeutic targets K Karube1,2, A Enjuanes1,3, I Dlouhy1, P Jares1,3, D Martin-Garcia1,3, F Nadeu1,3, GR Ordóñez4, J Rovira1, G Clot1,3, C Royo1, A Navarro1,3, B Gonzalez-Farre1,3, A Vaghefi1, G Castellano1, C Rubio-Perez5, D Tamborero5, J Briones6, A Salar7, JM Sancho8, S Mercadal9, E Gonzalez-Barca9, L Escoda10, H Miyoshi11, K Ohshima11, K Miyawaki12, K Kato12, K Akashi12, A Mozos13, L Colomo1,7, M Alcoceba3,14, A Valera1, A Carrió1,3, D Costa1,3, N Lopez-Bigas5,15, R Schmitz16, LM Staudt16, I Salaverria1,3, A López-Guillermo1,3 and E Campo1,3 Genome studies of diffuse large B-cell lymphoma (DLBCL) have revealed a large number of somatic mutations and structural alterations. However, the clinical significance of these alterations is still not well defined. In this study, we have integrated the analysis of targeted next-generation sequencing of 106 genes and genomic copy number alterations (CNA) in 150 DLBCL. The clinically significant findings were validated in an independent cohort of 111 patients. Germinal center B-cell and activated B-cell DLBCL had a differential profile of mutations, altered pathogenic pathways and CNA. Mutations in genes of the NOTCH pathway and tumor suppressor genes (TP53/CDKN2A), but not individual genes, conferred an unfavorable prognosis, confirmed in the independent validation cohort. A gene expression profiling analysis showed that tumors with NOTCH pathway mutations had a significant modulation of downstream target genes, emphasizing the relevance of this pathway in DLBCL. -
Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database. -
Role of MALAT1 in Gynecological Cancers: Pathologic and Therapeutic Aspects (Review)
ONCOLOGY LETTERS 21: 333, 2021 Role of MALAT1 in gynecological cancers: Pathologic and therapeutic aspects (Review) FENG‑HUA QIAO1, MIN TU2 and HONG‑YAN LIU3 Departments of 1Gynecology and 2Orthopedics, Second People's Hospital of Jingmen; 3Department of Gynecology, Maternal and Child Health Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China Received June 28, 2020; Accepted February 2, 2021 DOI: 10.3892/ol.2021.12594 Abstract. Gynecological cancers, including breast, ovarian, 5. Targeting MALAT1 in gynecological cancer therapeutics uterine, vaginal, cervical and vulvar cancers are among the 6. Future research major threats to modern life, particularly to female health. 7. Conclusions Long non‑coding RNAs (lncRNAs) play critical roles in normal development of organisms, as well as the tumorigenesis process, and metastasis‑associated lung adenocarcinoma tran‑ 1. Introduction script 1 (MALAT1) is a large infrequently spliced lncRNA, which have been implicated in different gynecological cancers. Gynecologic cancer is any cancer of the female reproduc‑ MALAT1 is overexpressed in breast, ovarian, cervical and tive organs, including ovarian, uterine, vaginal, cervical and endometrial cancers, which initiates cancer progression by vulvar cancers. Generally, all women are at risk of devel‑ inducing changes in the expression of several anti‑apoptotic oping gynecological cancers, and risk increases with age (1). and epithelial‑to‑mesenchymal transition‑related genes. Each gynecologic cancer is unique, with different signs and Targeting MALAT1 is an important strategy to combat symptoms, different risk factors and different therapeutic strat‑ gynecological cancers, and application of RNA‑interference egies (2,3). Gynecological cancers are associated with high technology and chemotherapeutic process are crucial to target mortality rates worldwide as it is difficult to detect the cancers and minimize MALAT1 activity. -
Long Non-Coding RNA MALAT1 Drives Gastric Cancer Progression By
Li et al. Cancer Cell Int (2017) 17:44 DOI 10.1186/s12935-017-0408-8 Cancer Cell International PRIMARY RESEARCH Open Access Long non‑coding RNA MALAT1 drives gastric cancer progression by regulating HMGB2 modulating the miR‑1297 Jijun Li, Jinghua Gao*, Wen Tian, Yongsheng Li and Jinghua Zhang Abstract Background: Emerging evidences have verified that long non-coding RNAs (lncRNAs) play important regulatory roles in the pathogenesis and progression of cancers. lncRNAs metastasis associated lung adenocarcinoma transcript 1 (MALAT1) have been found to be up-regulated in some human cancers. The main objective of this study was to investigate the expression level and biological function of MALAT1 in gastric cancer (GC). Methods: Quantificational real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA levels of MALAT1 in 78 paired gastric carcinoma tissues and adjacent normal tissues, and the associations of MALAT1 expres- sion with the clinicopathological features were analyzed, and the prognosis of gastric carcinoma patients was evalu- ated. The HMGB2 mRNA and protein expressions were detected by qRT-PCR and western-blot analysis. Luciferase reporter assay was used to determine miR-1297 was a target of MALAT1. Results: In this study, we demonstrated MALAT1 was up-regulation in GC tissues compared with adjacent normal tissues and higher MALAT1 expression was correlated with local invasion, lymph node metastasis and TNM stage. Patients with higher MALAT1 expression predicted a shorter survival and poor prognosis. Functionally, we revealed that MALAT1 promoted cells proliferation and invasion in GC. Mechanistically, our results demonstrated that MALAT1 was negatively correlation with miR-1297 and functioned as a molecular sponging miR-1297, antagonizing its ability to suppress HMGB2 expression.