Interact (And Biginteract) Tracks in the UCSC Browser
Total Page：16
File Type：pdf, Size：1020Kb
Load more
Recommended publications
-
Open Data for Differential Network Analysis in Glioma
International Journal of Molecular Sciences Article Open Data for Differential Network Analysis in Glioma , Claire Jean-Quartier * y , Fleur Jeanquartier y and Andreas Holzinger Holzinger Group HCI-KDD, Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Auenbruggerplatz 2/V, 8036 Graz, Austria; [email protected] (F.J.); [email protected] (A.H.) * Correspondence: [email protected] These authors contributed equally to this work. y Received: 27 October 2019; Accepted: 3 January 2020; Published: 15 January 2020 Abstract: The complexity of cancer diseases demands bioinformatic techniques and translational research based on big data and personalized medicine. Open data enables researchers to accelerate cancer studies, save resources and foster collaboration. Several tools and programming approaches are available for analyzing data, including annotation, clustering, comparison and extrapolation, merging, enrichment, functional association and statistics. We exploit openly available data via cancer gene expression analysis, we apply refinement as well as enrichment analysis via gene ontology and conclude with graph-based visualization of involved protein interaction networks as a basis for signaling. The different databases allowed for the construction of huge networks or specified ones consisting of high-confidence interactions only. Several genes associated to glioma were isolated via a network analysis from top hub nodes as well as from an outlier analysis. The latter approach highlights a mitogen-activated protein kinase next to a member of histondeacetylases and a protein phosphatase as genes uncommonly associated with glioma. Cluster analysis from top hub nodes lists several identified glioma-associated gene products to function within protein complexes, including epidermal growth factors as well as cell cycle proteins or RAS proto-oncogenes. -
A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family
Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2018 A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family Linda Molla Follow this and additional works at: https://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Linda Molla June 2018 © Copyright by Linda Molla 2018 A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY Linda Molla, Ph.D. The Rockefeller University 2018 APOBEC2 is a member of the AID/APOBEC cytidine deaminase family of proteins. Unlike most of AID/APOBEC, however, APOBEC2’s function remains elusive. Previous research has implicated APOBEC2 in diverse organisms and cellular processes such as muscle biology (in Mus musculus), regeneration (in Danio rerio), and development (in Xenopus laevis). APOBEC2 has also been implicated in cancer. However the enzymatic activity, substrate or physiological target(s) of APOBEC2 are unknown. For this thesis, I have combined Next Generation Sequencing (NGS) techniques with state-of-the-art molecular biology to determine the physiological targets of APOBEC2. Using a cell culture muscle differentiation system, and RNA sequencing (RNA-Seq) by polyA capture, I demonstrated that unlike the AID/APOBEC family member APOBEC1, APOBEC2 is not an RNA editor. Using the same system combined with enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analyses I showed that, unlike the AID/APOBEC family member AID, APOBEC2 does not act as a 5-methyl-C deaminase. -
A Unified Gene Catalog for the Laboratory Mouse Reference Genome
Mamm Genome (2015) 26:295–304 DOI 10.1007/s00335-015-9571-1 A unified gene catalog for the laboratory mouse reference genome 1 1 1 1 1 Y. Zhu • J. E. Richardson • P. Hale • R. M. Baldarelli • D. J. Reed • 1 1 1,2 1 J. M. Recla • R. Sinclair • T. B. K. Reddy • C. J. Bult Received: 6 March 2015 / Accepted: 3 June 2015 / Published online: 18 June 2015 Ó The Author(s) 2015. This article is published with open access at Springerlink.com Abstract We report here a semi-automated process by fall into categories that require manual inspection to which mouse genome feature predictions and curated resolve structural differences in the gene models from annotations (i.e., genes, pseudogenes, functional RNAs, different annotation sources. Using the MGI unified gene etc.) from Ensembl, NCBI and Vertebrate Genome Anno- catalog, researchers can easily generate a comprehensive tation database (Vega) are reconciled with the genome report of mouse genome features from a single source and features in the Mouse Genome Informatics (MGI) database compare the details of gene and transcript structure using (http://www.informatics.jax.org) into a comprehensive and MGI’s mouse genome browser. non-redundant catalog. Our gene unification method employs an algorithm (fjoin—feature join) for efficient detection of genome coordinate overlaps among features represented in two annotation data sets. Following the Introduction analysis with fjoin, genome features are binned into six possible categories (1:1, 1:0, 0:1, 1:n, n:1, n:m) based on Generating lists of genes and other genome features in coordinate overlaps. -
Content Based Search in Gene Expression Databases and a Meta-Analysis of Host Responses to Infection
Content Based Search in Gene Expression Databases and a Meta-analysis of Host Responses to Infection A Thesis Submitted to the Faculty of Drexel University by Francis X. Bell in partial fulfillment of the requirements for the degree of Doctor of Philosophy November 2015 c Copyright 2015 Francis X. Bell. All Rights Reserved. ii Acknowledgments I would like to acknowledge and thank my advisor, Dr. Ahmet Sacan. Without his advice, support, and patience I would not have been able to accomplish all that I have. I would also like to thank my committee members and the Biomed Faculty that have guided me. I would like to give a special thanks for the members of the bioinformatics lab, in particular the members of the Sacan lab: Rehman Qureshi, Daisy Heng Yang, April Chunyu Zhao, and Yiqian Zhou. Thank you for creating a pleasant and friendly environment in the lab. I give the members of my family my sincerest gratitude for all that they have done for me. I cannot begin to repay my parents for their sacrifices. I am eternally grateful for everything they have done. The support of my sisters and their encouragement gave me the strength to persevere to the end. iii Table of Contents LIST OF TABLES.......................................................................... vii LIST OF FIGURES ........................................................................ xiv ABSTRACT ................................................................................ xvii 1. A BRIEF INTRODUCTION TO GENE EXPRESSION............................. 1 1.1 Central Dogma of Molecular Biology........................................... 1 1.1.1 Basic Transfers .......................................................... 1 1.1.2 Uncommon Transfers ................................................... 3 1.2 Gene Expression ................................................................. 4 1.2.1 Estimating Gene Expression ............................................ 4 1.2.2 DNA Microarrays ...................................................... -
Identification of Genes Promoting Skin Youthfulness by Genome-Wide Association Study
ORIGINAL ARTICLE Identification of Genes Promoting Skin Youthfulness by Genome-Wide Association Study Anne L.S. Chang1, Gil Atzmon2,AvivBergman2, Samantha Brugmann3, Scott X. Atwood1, Howard Y. Chang1 and Nir Barzilai2 To identify genes that promote facial skin youthfulness (SY), a genome-wide association study on an Ashkenazi Jewish discovery group (n ¼ 428) was performed using Affymetrix 6.0 Single-Nucleotide Polymorphism (SNP) Array. After SNP quality controls, 901,470 SNPs remained for analysis. The eigenstrat method showed no stratification. Cases and controls were identified by global facial skin aging severity including intrinsic and extrinsic parameters. Linear regression adjusted for age and gender, with no significant differences in smoking history, body mass index, menopausal status, or personal or family history of centenarians. Six SNPs met the À 8 À 8 Bonferroni threshold with Palleleo10 ; two of these six had Pgenotypeo10 . Quantitative trait loci mapping confirmed linkage disequilibrium. The six SNPs were interrogated by MassARRAY in a replication group (n ¼ 436) with confirmation of rs6975107, an intronic region of KCND2 (potassium voltage-gated channel, Shal-related family member 2) (Pgenotype ¼ 0.023). A second replication group (n ¼ 371) confirmed rs318125, downstream of DIAPH2 (diaphanous homolog 2 (Drosophila)) (Pallele ¼ 0.010, Pgenotype ¼ 0.002) and rs7616661, downstream of EDEM1 (ER degradation enhancer, mannosidase a-like 1) (Pgenotype ¼ 0.042). DIAPH2 hasbeenassociatedwith premature ovarian insufficiency, an aging phenotype in humans. EDEM1 associates with lifespan in animal models, although not humans. KCND2 is expressed in human skin, but has not been associated with aging. These genes represent new candidate genes to study the molecular basis of healthy skin aging. -
Molecular Genetic Characterization of Ataxic Movement Disorders in Mouse and Human
MOLECULAR GENETIC CHARACTERIZATION OF ATAXIC MOVEMENT DISORDERS IN MOUSE AND HUMAN A thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy to the University College London by Joyce Catharina Hendrika van de Leemput Department of Neurodegenerative Disease, Institute of Neurology, University College London (UK) in partnership with Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health (USA) 1 Declaration on origin of work described herein I, Joyce Catharina Hendrika van de Leemput, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, every effort has been made to indicate this clearly in the thesis, with due reference to literature and acknowledgement of collaborative research and discussion. 2 Part of the work described herein has been published in scientific journals van de Leemput J., Chandran J., Knight M. A., Holtzclaw L. A., Scholz S., Cookson M. R., Houlden H., Gwinn-Hardy K., Fung H. C., Lin X., Hernandez D., Simon-Sanchez J., Wood N. W., Giunti P., Rafferty I., Hardy J., Storey E., Gardner R. J., Forrest S. M., Fisher E. M., Russell J. T., Cai H., and Singleton A. B. (2007) Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans. PLoS Genet 3, e108. Knight M. A., Hernandez D., Diede S. J., Dauwerse H. G., Rafferty I., van de Leemput J., Forrest S. M., Gardner R. J., Storey E., van Ommen G. J., Tapscott S. J., Fischbeck K. H., and Singleton A. B. (2008) A duplication at chromosome 11q12.2-11q12.3 is associated with spinocerebellar ataxia type 20. -
Interact (And Biginteract) Tracks in the UCSC Browser
Interact (and bigInteract) tracks in the UCSC browser Kate Rosenbloom October 2018 Motivation • Show long-range pairwise interactions/ relationships • Support cross-chromosome as well as same chromosome interactions • Handle multiple data types: – Regulatory elements (e.g. SNP/gene) – Chromatin interactions (e.g. chiaPet) – Genomic rearrangements Interact track features chr3: 10,000,000 20,000,000 30,000,000 40,000,000 50,000,000 Distant SNP-Gene Interactions (Trans eQTLs) from GTEx Analysis chr7 chr19 chr22 eQTL SNPs where affected gene is on other chromosome, from GTEx rs149829576/F2RL3/adrenalGland eQTL genes where SNP is on other chromosome, from GTEx EDEM1 LSMEM2 • Curved connectors represent interactions with both endpoints on-screen. Curve type is configurable (bezier, ellipse) • Dashed lines represent reverse direction • Mouseover and click-through on endpoints and ‘peaks’ (with glyph) • Vertical in lower band represents off-chromosome interaction. Labeled if space permits • User-colored or grayscale coloring Example: GTEx trans-eQTLs chr3: 10,000,000 20,000,000 30,000,000 40,000,000 50,000,000 Distant SNP-Gene Interactions (Trans eQTLs) from GTEx Analysis chr7 chr19 chr22 eQTL SNPs where affected gene is on other chromosome, from GTEx rs149829576/F2RL3/adrenalGland eQTL genes where SNP is on other chromosome, from GTEx EDEM1 LSMEM2 50 Mbp region of chromosome 3 where GTEx analysis identifies 15 significant long-distance eQTLs spanning the region, one variant affecting expression of a gene on another chromosome (F2RL3 on chromosome 19) and two genes (EDEM1 and LSMEM2) affected by variants on other chromosomes. Interactions are colored to indicate tissue. Example: chiaPET chromatin interactions chr3: 4,700,000 4,800,000 4,900,000 5,000,000 5,100,000 gisChiaPet MCF7 RNAPII saturated rep1 (long200), interact 16 ChiaPet chromatin interactions identified in a 640 Kbp region of chromosome 3 in the MCF7 cell line (courtesy Genome Institute of Singapore). -
Parental Micronutrient Deficiency Distorts Liver DNA Methylation And
www.nature.com/scientificreports OPEN Parental micronutrient defciency distorts liver DNA methylation and expression of lipid genes associated Received: 24 October 2017 Accepted: 31 January 2018 with a fatty-liver-like phenotype in Published: xx xx xxxx ofspring Kaja H. Skjærven1, Lars Martin Jakt2, Jorge M. O. Fernandes2, John Arne Dahl 3, Anne-Catrin Adam1, Johanna Klughammer4, Christoph Bock 4 & Marit Espe1 Micronutrient status of parents can afect long term health of their progeny. Around 2 billion humans are afected by chronic micronutrient defciency. In this study we use zebrafsh as a model system to examine morphological, molecular and epigenetic changes in mature ofspring of parents that experienced a one-carbon (1-C) micronutrient defciency. Zebrafsh were fed a diet sufcient, or marginally defcient in 1-C nutrients (folate, vitamin B12, vitamin B6, methionine, choline), and then mated. Ofspring livers underwent histological examination, RNA sequencing and genome-wide DNA methylation analysis. Parental 1-C micronutrient defciency resulted in increased lipid inclusion and we identifed 686 diferentially expressed genes in ofspring liver, the majority of which were downregulated. Downregulated genes were enriched for functional categories related to sterol, steroid and lipid biosynthesis, as well as mitochondrial protein synthesis. Diferential DNA methylation was found at 2869 CpG sites, enriched in promoter regions and permutation analyses confrmed the association with parental feed. Our data indicate that parental 1-C nutrient status can persist as locus specifc DNA methylation marks in descendants and suggest an efect on lipid utilization and mitochondrial protein translation in F1 livers. This points toward parental micronutrients status as an important factor for ofspring health and welfare. -
Universal Nomenclature for Oxytocin–Vasotocin Ligand and Receptor
Article Universal nomenclature for oxytocin– vasotocin ligand and receptor families https://doi.org/10.1038/s41586-020-03040-7 Constantina Theofanopoulou1,2,3 ✉, Gregory Gedman1, James A. Cahill1, Cedric Boeckx2,3,4 & Erich D. Jarvis1,5 ✉ Received: 16 October 2019 Accepted: 29 May 2020 Oxytocin (OXT; hereafter OT) and arginine vasopressin or vasotocin (AVP or VT; Published online: 28 April 2021 hereafter VT) are neurotransmitter ligands that function through specifc receptors Open access to control diverse functions1,2. Here we performed genomic analyses on 35 species Check for updates that span all major vertebrate lineages, including newly generated high-contiguity assemblies from the Vertebrate Genomes Project3,4. Our fndings support the claim5 that OT (also known as OXT) and VT (also known as AVP) are adjacent paralogous genes that have resulted from a local duplication, which we infer was through DNA transposable elements near the origin of vertebrates and in which VT retained more of the parental sequence. We identifed six major oxytocin–vasotocin receptors among vertebrates. We propose that all six of these receptors arose from a single receptor that was shared with the common ancestor of invertebrates, through a combination of whole-genome and large segmental duplications. We propose a universal nomenclature based on evolutionary relationships for the genes that encode these receptors, in which the genes are given the same orthologous names across vertebrates and paralogous names relative to each other. This nomenclature avoids confusion due to diferential naming in the pre-genomic era and incomplete genome assemblies, furthers our understanding of the evolution of these genes, aids in the translation of fndings across species and serves as a model for other gene families. -
Mtorc1 Coordinates an Immediate Unfolded Protein Response-Related Transcriptome in Activated B Cells Preceding Antibody Secretion
ARTICLE https://doi.org/10.1038/s41467-019-14032-1 OPEN mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion Brian T. Gaudette 1, Derek D. Jones1, Alexandra Bortnick1, Yair Argon1,2 & David Allman1* How activated B cells build biosynthetic pathways and organelle structures necessary for subsequent robust antibody secretion is still unclear. The dominant model holds that nascent 1234567890():,; plasma cells adapt to increased antibody synthesis by activating the unfolded protein response (UPR) under the control of the transcription factor Xbp1. Here, by analyzing gene expression in activated B cells with or without plasma cell-inductive signals, we find that follicular B cells up-regulate a wide array of UPR-affiliated genes before initiating antibody secretion; furthermore, initial transcription of these loci requires the mTORC1 kinase adaptor, Raptor, but not Xbp1. Transcriptomic analyses of resting marginal zone B cells, which gen- erate plasma cells with exceptionally rapid kinetics, reinforce these results by revealing the basal expression of UPR-affiliated mRNA networks without detectable Xbp1 activity. We thus conclude that B cells utilize mTORC1 to prepare for subsequent plasma cell function, before the onset of antibody synthesis. 1 The Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. 2 The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA. *email: [email protected] NATURE COMMUNICATIONS | (2020) 11:723 | https://doi.org/10.1038/s41467-019-14032-1 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-14032-1 ntibody-secreting plasma cells are essential components Results of humoral immunity. -
Profiling APOL1 Nephropathy Risk Variants in Genome-Edited Kidney Organoids with Single-Cell Transcriptomics
Original Investigation Profiling APOL1 Nephropathy Risk Variants in Genome-Edited Kidney Organoids with Single-Cell Transcriptomics Esther Liu,1 Behram Radmanesh,1 Byungha H. Chung,2 Michael D. Donnan,1 Dan Yi,1 Amal Dadi,1 Kelly D. Smith,3 Jonathan Himmelfarb,2 Mingyao Li,4 Benjamin S. Freedman,2,3 and Jennie Lin 1,5 Abstract Background DNA variants in APOL1 associate with kidney disease, but the pathophysiologic mechanisms remain incompletely understood. Model organisms lack the APOL1 gene, limiting the degree to which disease states can be recapitulated. Here we present single-cell RNA sequencing (scRNA-seq) of genome-edited human kidney organoids as a platform for profiling effects of APOL1 risk variants in diverse nephron cell types. Methods We performed footprint-free CRISPR-Cas9 genome editing of human induced pluripotent stem cells (iPSCs) to knock in APOL1 high-risk G1 variants at the native genomic locus. iPSCs were differentiated into kidney organoids, treated with vehicle, IFN-g, or the combination of IFN-g and tunicamycin, and analyzed with scRNA-seq to profile cell-specific changes in differential gene expression patterns, compared with isogenic G0 controls. Results Both G0 and G1 iPSCs differentiated into kidney organoids containing nephron-like structures with glomerular epithelial cells, proximal tubules, distal tubules, and endothelial cells. Organoids expressed detectable APOL1 only after exposure to IFN-g. scRNA-seq revealed cell type–specific differences in G1 organoid response to APOL1 induction. Additional stress of tunicamycin exposure led to increased glomerular epithelial cell dedifferentiation in G1 organoids. Conclusions Single-cell transcriptomic profiling of human genome-edited kidney organoids expressing APOL1 risk variants provides a novel platform for studying the pathophysiology of APOL1-mediated kidney disease. -
Unraveling the Molecular Mechanism Underlying ALS-Linked Astrocyte
Unraveling the molecular mechanism underlying ALS- linked astrocyte toxicity for motor neurons Burcin Ikiz Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2013 © 2013 Burcin Ikiz All rights reserved Abstract Unraveling the molecular mechanism underlying ALS-linked astrocyte toxicity for motor neurons Burcin Ikiz Mutations in superoxide dismutase-1 (SOD1) cause a familial form of amyotrophic lateral sclerosis (ALS), a fatal paralytic disorder. Transgenic mutant SOD1 rodents capture the hallmarks of this disease, which is characterized by a progressive loss of motor neurons. Studies in chimeric and conditional transgenic mutant SOD1 mice indicate that non-neuronal cells, such as astrocytes, play an important role in motor neuron degeneration. Consistent with this non-cell autonomous scenario are the demonstrations that wild-type primary and embryonic stem cell- derived motor neurons selectively degenerate when cultured in the presence of either mutant SOD1-expressing astrocytes or medium conditioned with such mutant astrocytes. The work in this thesis rests on the use of an unbiased genomic strategy that combines RNA-Seq and “reverse gene engineering” algorithms in an attempt to decipher the molecular underpinnings of motor neuron degeneration caused by mutant astrocytes. To allow such analyses, first, mutant SOD1- induced toxicity on purified embryonic stem cell-derived motor neurons was validated and characterized. This was followed by the validation of signaling pathways identified by bioinformatics in purified embryonic stem cell-derived motor neurons, using both pharmacological and genetic techniques, leading to the discovery that nuclear factor kappa B (NF-κB) is instrumental in the demise of motor neurons exposed to mutant astrocytes in vitro.