Gene Symbol Matched Annotations with Genecards Including 628
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BIOINFORMATICS DOI: 10.1093/Bioinformatics/Btg1030
Vol. 19 Suppl. 1 2003, pages i222–i224 BIOINFORMATICS DOI: 10.1093/bioinformatics/btg1030 GeneLoc: exon-based integration of human genome maps Naomi Rosen, Vered Chalifa-Caspi, Orit Shmueli, Avital Adato, Michal Lapidot, Julie Stampnitzky, Marilyn Safran ∗ and Doron Lancet Weizmann Institute of Science, Rehovot, Israel Received on January 6, 2003; accepted on February 20, 2003 ABSTRACT to provide a comprehensive gene list, NCBI’s LocusLink Motivation: Despite the numerous available whole- contains thousands of model genes, categorized by level genome mapping resources, no comprehensive, inte- and type of support. Even known genes appearing in every grated map of the human genome yet exists. database may have different names in each database. The Results: GeneLoc, software adjunct to GeneCards and biologist must move among databases to figure out which UDB, integrates gene lists by comparing genomic coordi- genes are the same, and which could be a novel gene nates at the exon level and assigns unique and meaningful sought. UCSC’s Genome Browser website maps genes identifiers to each gene. from several sources on the same scale, but the maps are Availability: http://bioinfo.weizmann.ac.il/genecards and not integrated, making it difficult to relate genes from http://genecards.weizmann.ac.il/udb different sources. As stated (Jongeneel, 2000),‘there is an Supplementary information: http://bioinfo.weizmann.ac. urgent need for a human gene index that can be used to il/cards-bin/AboutGCids.cgi, http://genecards.weizmann. identify transcripts unambiguously.’ The author contends ac.il/GeneLocAlg.html that this index should have, among others, the following Contact: [email protected] qualities: comprehensiveness, uniqueness, and stability. -
ORAI1 and ORAI2 Modulate Murine Neutrophil Calcium Signaling, Cellular Activation, and Host Defense
ORAI1 and ORAI2 modulate murine neutrophil calcium signaling, cellular activation, and host defense Derayvia Grimesa,1, Ryan Johnsona,1, Madeline Pashosa, Celeste Cummingsa, Chen Kangb, Georgia R. Sampedroa, Eric Tycksenc, Helen J. McBrided, Rajan Sahb, Clifford A. Lowelle, and Regina A. Clemensa,2 aDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110; bDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110; cMcDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63110; dInflammation Research, Amgen, Thousand Oaks, CA 91320; and eDepartment of Laboratory Medicine, University of California, San Francisco, CA 94143 Edited by Michael D. Cahalan, University of California, Irvine, CA, and approved August 11, 2020 (received for review May 5, 2020) Calcium signals are initiated in immune cells by the process of in isoform features, such as activation or inactivation kinetics and store-operated calcium entry (SOCE), where receptor activation sensitivity to modulatory factors, also influence CRAC-channel triggers transient calcium release from the endoplasmic reticulum, function (2–10). ORAI1 and ORAI2 are broadly expressed in im- followed by opening of plasma-membrane calcium-release acti- mune cells, and humans with ORAI1 mutations develop a severe vated calcium (CRAC) channels. ORAI1, ORAI2, and ORAI3 are known combined immunodeficiency-like immunodeficiency, highlighting to comprise the CRAC channel; however, the contributions of indi- the importance of this isoform in immune function (11, 12). In mice, vidual isoforms to neutrophil function are not well understood. ORAI1 also appears to be the dominant functional isoform in im- Here, we show that loss of ORAI1 partially decreases calcium influx, mune cells, with substantial deficits in ORAI1-deficient T cells, while loss of both ORAI1 and ORAI2 completely abolishes SOCE. -
PARSANA-DISSERTATION-2020.Pdf
DECIPHERING TRANSCRIPTIONAL PATTERNS OF GENE REGULATION: A COMPUTATIONAL APPROACH by Princy Parsana A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July, 2020 © 2020 Princy Parsana All rights reserved Abstract With rapid advancements in sequencing technology, we now have the ability to sequence the entire human genome, and to quantify expression of tens of thousands of genes from hundreds of individuals. This provides an extraordinary opportunity to learn phenotype relevant genomic patterns that can improve our understanding of molecular and cellular processes underlying a trait. The high dimensional nature of genomic data presents a range of computational and statistical challenges. This dissertation presents a compilation of projects that were driven by the motivation to efficiently capture gene regulatory patterns in the human transcriptome, while addressing statistical and computational challenges that accompany this data. We attempt to address two major difficulties in this domain: a) artifacts and noise in transcriptomic data, andb) limited statistical power. First, we present our work on investigating the effect of artifactual variation in gene expression data and its impact on trans-eQTL discovery. Here we performed an in-depth analysis of diverse pre-recorded covariates and latent confounders to understand their contribution to heterogeneity in gene expression measurements. Next, we discovered 673 trans-eQTLs across 16 human tissues using v6 data from the Genotype Tissue Expression (GTEx) project. Finally, we characterized two trait-associated trans-eQTLs; one in Skeletal Muscle and another in Thyroid. Second, we present a principal component based residualization method to correct gene expression measurements prior to reconstruction of co-expression networks. -
In Silico Prediction of High-Resolution Hi-C Interaction Matrices
ARTICLE https://doi.org/10.1038/s41467-019-13423-8 OPEN In silico prediction of high-resolution Hi-C interaction matrices Shilu Zhang1, Deborah Chasman 1, Sara Knaack1 & Sushmita Roy1,2* The three-dimensional (3D) organization of the genome plays an important role in gene regulation bringing distal sequence elements in 3D proximity to genes hundreds of kilobases away. Hi-C is a powerful genome-wide technique to study 3D genome organization. Owing to 1234567890():,; experimental costs, high resolution Hi-C datasets are limited to a few cell lines. Computa- tional prediction of Hi-C counts can offer a scalable and inexpensive approach to examine 3D genome organization across multiple cellular contexts. Here we present HiC-Reg, an approach to predict contact counts from one-dimensional regulatory signals. HiC-Reg pre- dictions identify topologically associating domains and significant interactions that are enri- ched for CCCTC-binding factor (CTCF) bidirectional motifs and interactions identified from complementary sources. CTCF and chromatin marks, especially repressive and elongation marks, are most important for HiC-Reg’s predictive performance. Taken together, HiC-Reg provides a powerful framework to generate high-resolution profiles of contact counts that can be used to study individual locus level interactions and higher-order organizational units of the genome. 1 Wisconsin Institute for Discovery, 330 North Orchard Street, Madison, WI 53715, USA. 2 Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53715, USA. *email: [email protected] NATURE COMMUNICATIONS | (2019) 10:5449 | https://doi.org/10.1038/s41467-019-13423-8 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-13423-8 he three-dimensional (3D) organization of the genome has Results Temerged as an important component of the gene regulation HiC-Reg for predicting contact count using Random Forests. -
Dietary Supplementation with L-Arginine, Single Nucleotide
The Journal of Nutrition Commentary Dietary Supplementation with L-Arginine, Single Nucleotide Polymorphisms of Arginase Downloaded from https://academic.oup.com/jn/advance-article/doi/10.1093/jn/nxaa431/6131937 by University of Memphis - Library user on 10 February 2021 1 and 2, and Plasma L-Arginine Keith R Martin Center for Nutraceutical and Dietary Supplement Research, College of Health Sciences, University of Memphis, Memphis, TN, USA There are ∼3 million single nucleotide polymorphisms (SNPs) Arginine-dependent NO impacts the immune, neuronal, and between 2 unrelated individuals, with each SNP representing cardiovascular systems and is a potent vasodilator critical for a single modification in the genomic code and cumulatively vascular tone, blood pressure modulation, vascular permeabil- representing 0.1% human genetic diversity. Although many of ity, and angiogenesis (7–9). SNPs in the ARG1 gene are clinically these differences are silent, relatively recent data suggest that associated with cardiovascular diseases such as hypertension, around half of the various responses to dietary agents could cardiomyopathy, myocardial infarction, and carotid intima be related to genetic variation, a field coined as nutrigenetics. media thickness, and upregulation of arginase is implicated in These variations are of considerable interest in improving the vascular dysfunction (10, 11). Thus, dietary supplementation health of individuals and collectively mitigating the risk of with l-arginine could be warranted. chronic disease. In this issue of the Journal, Hannemann et The study by Hannemann et al. is the first to describe al. (1) describe a possible functional relation between arginase an association between genotypes of ARG1 and ARG2 with isoforms, important in the urea cycle and nitric oxide (NO) consequent circulating plasma concentrations of l-arginine. -
Loss of NEIL3 DNA Glycosylase Markedly Increases Replication Associated Double Strand Breaks and Enhances Sensitivity to ATR Inhibitor in Glioblastoma Cells
www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 68), pp: 112942-112958 Research Paper Loss of NEIL3 DNA glycosylase markedly increases replication associated double strand breaks and enhances sensitivity to ATR inhibitor in glioblastoma cells Alex W. Klattenhoff1, Megha Thakur1, Christopher S. Chu1, Debolina Ray1, Samy L. Habib2 and Dawit Kidane1 1Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX, United States 2South Texas Veterans Health System and Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX, United States Correspondence to: Dawit Kidane, email: [email protected] Keywords: DNA glycosylase; ATR; replication stress Received: June 19, 2017 Accepted: November 16, 2017 Published: December 04, 2017 Copyright: Klattenhoff et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT DNA endonuclease eight-like glycosylase 3 (NEIL3) is one of the DNA glycosylases that removes oxidized DNA base lesions from single-stranded DNA (ssDNA) and non-B DNA structures. Approximately seven percent of human tumors have an altered NEIL3 gene. However, the role of NEIL3 in replication-associated repair and its impact on modulating treatment response is not known. Here, we report that NEIL3 is localized at the DNA double-strand break (DSB) sites during oxidative DNA damage and replication stress. Loss of NEIL3 significantly increased spontaneous replication-associated DSBs and recruitment of replication protein A (RPA). -
Mesenchymal Stem Cells Prevent the Progression of Diabetic
Lee et al. Experimental & Molecular Medicine (2019) 51:77 https://doi.org/10.1038/s12276-019-0268-5 Experimental & Molecular Medicine ARTICLE Open Access Mesenchymal stem cells prevent the progression of diabetic nephropathy by improving mitochondrial function in tubular epithelial cells Seung Eun Lee1,2,7,JungEunJang1,2,8,HyunSikKim2,MinKyoJung2,MyoungSeokKo2,Mi-OkKim2, Hye Sun Park2, Wonil Oh3, Soo Jin Choi3,HyeJinJin3, Sang-Yeob Kim4,YunJaeKim2,SeongWhoKim5, Min Kyung Kim5, Chang Ohk Sung6, Chan-Gi Pack 2,Ki-UpLee1,2 and Eun Hee Koh1,2 Abstract The administration of mesenchymal stem cells (MSCs) was shown to attenuate overt as well as early diabetic nephropathy in rodents, but the underlying mechanism of this beneficial effect is largely unknown. Inflammation and mitochondrial dysfunction are major pathogenic factors in diabetic nephropathy. In this study, we found that the repeated administration of MSCs prevents albuminuria and injury to tubular epithelial cells (TECs), an important element in the progression of diabetic nephropathy, by improving mitochondrial function. The expression of M1 macrophage markers was significantly increased in diabetic kidneys compared with that in control kidneys. Interestingly, the expression of arginase-1 (Arg1), an important M2 macrophage marker, was reduced in diabetic kidneys and increased by MSC treatment. In cultured TECs, conditioned media from lipopolysaccharide-activated 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; macrophages reduced peroxisomal proliferator-activated receptor gamma coactivator 1α (Pgc1a) expression and impaired mitochondrial function. The coculture of macrophages with MSCs increased and decreased the expression of Arg1 and M1 markers, respectively. Treatment with conditioned media from cocultured macrophages prevented activated macrophage-induced mitochondrial dysfunction in TECs. -
NPRL3 Gene NPR3 Like, GATOR1 Complex Subunit
NPRL3 gene NPR3 like, GATOR1 complex subunit Normal Function The NPRL3 gene provides instructions for making a protein that is one piece of a group of proteins (complex) called GATOR1. This complex is found in cells throughout the body, where it regulates a signaling pathway called the mTOR pathway. The mTOR pathway is involved in cell growth and division (proliferation), the survival of cells, and the creation (synthesis) of new proteins. The role of the GATOR1 complex is to block this pathway by inhibiting (stopping) the activity of a complex called mTOR complex 1 ( mTORC1) that is integral to the mTOR pathway. In the brain, the mTOR pathway regulates many processes, including the growth and development of nerve cells and their ability to change and adapt over time (plasticity). Health Conditions Related to Genetic Changes Familial focal epilepsy with variable foci At least ten NPRL3 gene mutations have been found to cause familial focal epilepsy with variable foci (FFEVF), which is an uncommon form of recurrent seizures (epilepsy) that runs in families. Most of these mutations lead to the production of an abnormally short, nonfunctional protein. As a result, formation of normal GATOR1 complex is reduced, leading to overactivity of mTORC1 and excessive signaling of the mTOR pathway. It is not clear how an abnormally active mTOR pathway leads to the seizures of FFEVF. Research suggests that increased mTOR pathway signaling in the brain leads to changes in the connections between nerve cells (synapses) and increased activation (excitation) -
Comprehensive Identification and Characterization of Somatic Copy Number Alterations in Triple‑Negative Breast Cancer
INTERNATIONAL JOURNAL OF ONCOLOGY 56: 522-530, 2020 Comprehensive identification and characterization of somatic copy number alterations in triple‑negative breast cancer ZAIBING LI1,2*, XIAO ZHANG3*, CHENXIN HOU4, YUQING ZHOU4, JUNLI CHEN1, HAOYANG CAI5, YIFENG YE3, JINPING LIU3 and NING HUANG1 1Department of Pathophysiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041; 2Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan 646000; 3Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731; 4West China Medical School, Sichuan University, Chengdu, Sichuan 610041; 5Center of Growth, Metabolism and Aging, Key Laboratory of Bio‑Resources and Eco‑Environment, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, P.R. China Received January 30, 2019; Accepted August 30, 2019 DOI: 10.3892/ijo.2019.4950 Abstract. Triple-negative breast cancer (TNBC) accounts hierarchical clustering of tumors resulted in three main for ~15% of all breast cancer diagnoses each year. Patients subgroups that exhibited distinct CNA profiles, which with TNBC tend to have a higher risk for early relapse and may reveal the heterogeneity of molecular mechanisms in a worse prognosis. TNBC is characterized by extensive TNBC subgroups. These results will extend the molecular somatic copy number alterations (CNAs). However, the DNA understanding of TNBC and will facilitate the discovery of CNA profile of TNBC remains to be extensively investigated. therapeutic and diagnostic target candidates. The present study assessed the genomic profile of CNAs in 201 TNBC samples, aiming to identify recurrent CNAs that Introduction may drive the pathogenesis of TNBC. -
Analysis of Translating Mitoribosome Reveals Functional Characteristics of Translation in Mitochondria of Fungi
ARTICLE https://doi.org/10.1038/s41467-020-18830-w OPEN Analysis of translating mitoribosome reveals functional characteristics of translation in mitochondria of fungi Yuzuru Itoh 1,2,4, Andreas Naschberger1,4, Narges Mortezaei1,4, Johannes M. Herrmann 3 & ✉ Alexey Amunts 1,2 1234567890():,; Mitoribosomes are specialized protein synthesis machineries in mitochondria. However, how mRNA binds to its dedicated channel, and tRNA moves as the mitoribosomal subunit rotate with respect to each other is not understood. We report models of the translating fungal mitoribosome with mRNA, tRNA and nascent polypeptide, as well as an assembly inter- mediate. Nicotinamide adenine dinucleotide (NAD) is found in the central protuberance of the large subunit, and the ATPase inhibitory factor 1 (IF1) in the small subunit. The models of the active mitoribosome explain how mRNA binds through a dedicated protein platform on the small subunit, tRNA is translocated with the help of the protein mL108, bridging it with L1 stalk on the large subunit, and nascent polypeptide paths through a newly shaped exit tunnel involving a series of structural rearrangements. An assembly intermediate is modeled with the maturation factor Atp25, providing insight into the biogenesis of the mitoribosomal large subunit and translation regulation. 1 Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17165 Solna, Sweden. 2 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17165 Solna, Sweden. 3 Cell Biology, University -
Genome Analysis and Knowledge
Dahary et al. BMC Medical Genomics (2019) 12:200 https://doi.org/10.1186/s12920-019-0647-8 SOFTWARE Open Access Genome analysis and knowledge-driven variant interpretation with TGex Dvir Dahary1*, Yaron Golan1, Yaron Mazor1, Ofer Zelig1, Ruth Barshir2, Michal Twik2, Tsippi Iny Stein2, Guy Rosner3,4, Revital Kariv3,4, Fei Chen5, Qiang Zhang5, Yiping Shen5,6,7, Marilyn Safran2, Doron Lancet2* and Simon Fishilevich2* Abstract Background: The clinical genetics revolution ushers in great opportunities, accompanied by significant challenges. The fundamental mission in clinical genetics is to analyze genomes, and to identify the most relevant genetic variations underlying a patient’s phenotypes and symptoms. The adoption of Whole Genome Sequencing requires novel capacities for interpretation of non-coding variants. Results: We present TGex, the Translational Genomics expert, a novel genome variation analysis and interpretation platform, with remarkable exome analysis capacities and a pioneering approach of non-coding variants interpretation. TGex’s main strength is combining state-of-the-art variant filtering with knowledge-driven analysis made possible by VarElect, our highly effective gene-phenotype interpretation tool. VarElect leverages the widely used GeneCards knowledgebase, which integrates information from > 150 automatically-mined data sources. Access to such a comprehensive data compendium also facilitates TGex’s broad variant annotation, supporting evidence exploration, and decision making. TGex has an interactive, user-friendly, and easy adaptive interface, ACMG compliance, and an automated reporting system. Beyond comprehensive whole exome sequence capabilities, TGex encompasses innovative non-coding variants interpretation, towards the goal of maximal exploitation of whole genome sequence analyses in the clinical genetics practice. This is enabled by GeneCards’ recently developed GeneHancer, a novel integrative and fully annotated database of human enhancers and promoters. -
Elements of Immunoglobulin E Network Associate with Aortic Valve Area in Patients with Acquired Aortic Stenosis
biomedicines Communication Elements of Immunoglobulin E Network Associate with Aortic Valve Area in Patients with Acquired Aortic Stenosis Daniel P. Potaczek 1,2,† , Aleksandra Przytulska-Szczerbik 2,†, Stanisława Bazan-Socha 3 , Artur Jurczyszyn 4, Ko Okumura 5, Chiharu Nishiyama 6, Anetta Undas 2,7,‡ and Ewa Wypasek 2,8,*,‡ 1 Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Medical Faculty, Philipps University Marburg, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center, 35043 Marburg, Germany; [email protected] 2 Krakow Center for Medical Research and Technology, John Paul II Hospital, 31-202 Krakow, Poland; [email protected] (A.P.-S.); [email protected] (A.U.) 3 Department of Internal Medicine, Jagiellonian University Medical College, 31-066 Krakow, Poland; [email protected] 4 Department of Hematology, Jagiellonian University Medical College, 31-501 Krakow, Poland; [email protected] 5 Atopy Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan; [email protected] 6 Laboratory of Molecular Biology and Immunology, Department of Biological Science and Technology, Tokyo University of Science, Tokyo 125-8585, Japan; [email protected] 7 Institute of Cardiology, Jagiellonian University Medical College, 31-202 Krakow, Poland 8 Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland * Correspondence: [email protected]; Tel.: +48-12-614-31-35 † These first authors contributed equally to this work. ‡ These last authors contributed equally to this work. Abstract: Allergic mechanisms are likely involved in atherosclerosis and its clinical presentations, Citation: Potaczek, D.P.; Przytulska-Szczerbik, A.; Bazan-Socha, such as coronary artery disease (CAD).