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Primate Specific Retrotransposons, Svas, in the Evolution of Networks That Alter Brain Function
Title: Primate specific retrotransposons, SVAs, in the evolution of networks that alter brain function. Olga Vasieva1*, Sultan Cetiner1, Abigail Savage2, Gerald G. Schumann3, Vivien J Bubb2, John P Quinn2*, 1 Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, U.K 2 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK 3 Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, D-63225 Germany *. Corresponding author Olga Vasieva: Institute of Integrative Biology, Department of Comparative genomics, University of Liverpool, Liverpool, L69 7ZB, [email protected] ; Tel: (+44) 151 795 4456; FAX:(+44) 151 795 4406 John Quinn: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK, [email protected]; Tel: (+44) 151 794 5498. Key words: SVA, trans-mobilisation, behaviour, brain, evolution, psychiatric disorders 1 Abstract The hominid-specific non-LTR retrotransposon termed SINE–VNTR–Alu (SVA) is the youngest of the transposable elements in the human genome. The propagation of the most ancient SVA type A took place about 13.5 Myrs ago, and the youngest SVA types appeared in the human genome after the chimpanzee divergence. Functional enrichment analysis of genes associated with SVA insertions demonstrated their strong link to multiple ontological categories attributed to brain function and the disorders. SVA types that expanded their presence in the human genome at different stages of hominoid life history were also associated with progressively evolving behavioural features that indicated a potential impact of SVA propagation on a cognitive ability of a modern human. -
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Patterns of DNA methylation on the human X chromosome and use in analyzing X-chromosome inactivation by Allison Marie Cotton B.Sc., The University of Guelph, 2005 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate Studies (Medical Genetics) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) January 2012 © Allison Marie Cotton, 2012 Abstract The process of X-chromosome inactivation achieves dosage compensation between mammalian males and females. In females one X chromosome is transcriptionally silenced through a variety of epigenetic modifications including DNA methylation. Most X-linked genes are subject to X-chromosome inactivation and only expressed from the active X chromosome. On the inactive X chromosome, the CpG island promoters of genes subject to X-chromosome inactivation are methylated in their promoter regions, while genes which escape from X- chromosome inactivation have unmethylated CpG island promoters on both the active and inactive X chromosomes. The first objective of this thesis was to determine if the DNA methylation of CpG island promoters could be used to accurately predict X chromosome inactivation status. The second objective was to use DNA methylation to predict X-chromosome inactivation status in a variety of tissues. A comparison of blood, muscle, kidney and neural tissues revealed tissue-specific X-chromosome inactivation, in which 12% of genes escaped from X-chromosome inactivation in some, but not all, tissues. X-linked DNA methylation analysis of placental tissues predicted four times higher escape from X-chromosome inactivation than in any other tissue. Despite the hypomethylation of repetitive elements on both the X chromosome and the autosomes, no changes were detected in the frequency or intensity of placental Cot-1 holes. -
A Master Autoantigen-Ome Links Alternative Splicing, Female Predilection, and COVID-19 to Autoimmune Diseases
bioRxiv preprint doi: https://doi.org/10.1101/2021.07.30.454526; this version posted August 4, 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 4.0 International license. A Master Autoantigen-ome Links Alternative Splicing, Female Predilection, and COVID-19 to Autoimmune Diseases Julia Y. Wang1*, Michael W. Roehrl1, Victor B. Roehrl1, and Michael H. Roehrl2* 1 Curandis, New York, USA 2 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA * Correspondence: [email protected] or [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.07.30.454526; this version posted August 4, 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 4.0 International license. Abstract Chronic and debilitating autoimmune sequelae pose a grave concern for the post-COVID-19 pandemic era. Based on our discovery that the glycosaminoglycan dermatan sulfate (DS) displays peculiar affinity to apoptotic cells and autoantigens (autoAgs) and that DS-autoAg complexes cooperatively stimulate autoreactive B1 cell responses, we compiled a database of 751 candidate autoAgs from six human cell types. At least 657 of these have been found to be affected by SARS-CoV-2 infection based on currently available multi-omic COVID data, and at least 400 are confirmed targets of autoantibodies in a wide array of autoimmune diseases and cancer. -
Cross-Link Guided Molecular Modeling with ROSETTA
Cross-Link Guided Molecular Modeling with ROSETTA Abdullah Kahraman1., Franz Herzog2., Alexander Leitner1, George Rosenberger1, Ruedi Aebersold1,3, Lars Malmstro¨ m1* 1 Department of Biology, Institute of Molecular Systems Biology, Eidgeno¨ssische Technische Hochschule Zu¨rich, Zurich, Switzerland, 2 Gene Center, Ludwig-Maximilians- Universita¨tMu¨nchen, Munich, Germany, 3 Faculty of Science, University of Zurich, Zurich, Switzerland Abstract Chemical cross-links identified by mass spectrometry generate distance restraints that reveal low-resolution structural information on proteins and protein complexes. The technology to reliably generate such data has become mature and robust enough to shift the focus to the question of how these distance restraints can be best integrated into molecular modeling calculations. Here, we introduce three workflows for incorporating distance restraints generated by chemical cross-linking and mass spectrometry into ROSETTA protocols for comparative and de novo modeling and protein-protein docking. We demonstrate that the cross-link validation and visualization software Xwalk facilitates successful cross-link data integration. Besides the protocols we introduce XLdb, a database of chemical cross-links from 14 different publications with 506 intra-protein and 62 inter-protein cross-links, where each cross-link can be mapped on an experimental structure from the Protein Data Bank. Finally, we demonstrate on a protein-protein docking reference data set the impact of virtual cross- links on protein docking calculations and show that an inter-protein cross-link can reduce on average the RMSD of a docking prediction by 5.0 A˚. The methods and results presented here provide guidelines for the effective integration of chemical cross-link data in molecular modeling calculations and should advance the structural analysis of particularly large and transient protein complexes via hybrid structural biology methods. -
Downloaded, Each with Over 20 Samples for AD-Specific Pathways, Biological Processes, and Driver Each Specific Brain Region in Each Condition
Xiang et al. BMC Medical Genomics 2018, 11(Suppl 6):115 https://doi.org/10.1186/s12920-018-0431-1 RESEARCH Open Access Condition-specific gene co-expression network mining identifies key pathways and regulators in the brain tissue of Alzheimer’s disease patients Shunian Xiang1,2, Zhi Huang4, Wang Tianfu1, Zhi Han3, Christina Y. Yu3,5, Dong Ni1*, Kun Huang3* and Jie Zhang2* From 29th International Conference on Genome Informatics Yunnan, China. 3-5 December 2018 Abstract Background: Gene co-expression network (GCN) mining is a systematic approach to efficiently identify novel disease pathways, predict novel gene functions and search for potential disease biomarkers. However, few studies have systematically identified GCNs in multiple brain transcriptomic data of Alzheimer’s disease (AD) patients and looked for their specific functions. Methods: In this study, we first mined GCN modules from AD and normal brain samples in multiple datasets respectively; then identified gene modules that are specific to AD or normal samples; lastly, condition-specific modules with similar functional enrichments were merged and enriched differentially expressed upstream transcription factors were further examined for the AD/normal-specific modules. Results: We obtained 30 AD-specific modules which showed gain of correlation in AD samples and 31 normal- specific modules with loss of correlation in AD samples compared to normal ones, using the network mining tool lmQCM. Functional and pathway enrichment analysis not only confirmed known gene functional categories related to AD, but also identified novel regulatory factors and pathways. Remarkably, pathway analysis suggested that a variety of viral, bacteria, and parasitic infection pathways are activated in AD samples. -
Ocular Coloboma: a Reassessment in the Age of Molecular Neuroscience
881 REVIEW Ocular coloboma: a reassessment in the age of molecular neuroscience C Y Gregory-Evans, M J Williams, S Halford, K Gregory-Evans ............................................................................................................................... J Med Genet 2004;41:881–891. doi: 10.1136/jmg.2004.025494 Congenital colobomata of the eye are important causes of NORMAL EYE DEVELOPMENT The processes that occur during formation of the childhood visual impairment and blindness. Ocular vertebrate eye are well documented and include coloboma can be seen in isolation and in an impressive (i) multiple inductive and morphogenetic events, number of multisystem syndromes, where the eye (ii) proliferation and differentiation of cells into mature tissue, and (iii) establishment of neural phenotype is often seen in association with severe networks connecting the retina to the higher neurological or craniofacial anomalies or other systemic neural centres such as the superior colliculus, the developmental defects. Several studies have shown that, in geniculate nucleus, and the occipital lobes.8–10 At around day 30 of gestation, the ventral surface addition to inheritance, environmental influences may be of the optic vesicle and stalk invaginates leading causative factors. Through work to identify genes to the formation of a double-layered optic cup. underlying inherited coloboma, significant inroads are This invagination gives rise to the optic fissure, allowing blood vessels from the vascular meso- being made into understanding the molecular events derm to enter the developing eye. Fusion of the controlling closure of the optic fissure. In general, severity edges of this fissure starts centrally at about of disease can be linked to the temporal expression of the 5 weeks and proceeds anteriorly towards the rim of the optic cup and posteriorly along the optic gene, but this is modified by factors such as tissue stalk, with completion by 7 weeks.11 Failure of specificity of gene expression and genetic redundancy. -
A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression
Supplementary Materials A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression Table S1. Statistically significant DEGs (Adj. p-value < 0.01) derived from meta-analysis for samples irradiated with high doses of HZE particles, collected 6-24 h post-IR not common with any other meta- analysis group. This meta-analysis group consists of 3 DEG lists obtained from DGEA, using a total of 11 control and 11 irradiated samples [Data Series: E-MTAB-5761 and E-MTAB-5754]. Ensembl ID Gene Symbol Gene Description Up-Regulated Genes ↑ (2425) ENSG00000000938 FGR FGR proto-oncogene, Src family tyrosine kinase ENSG00000001036 FUCA2 alpha-L-fucosidase 2 ENSG00000001084 GCLC glutamate-cysteine ligase catalytic subunit ENSG00000001631 KRIT1 KRIT1 ankyrin repeat containing ENSG00000002079 MYH16 myosin heavy chain 16 pseudogene ENSG00000002587 HS3ST1 heparan sulfate-glucosamine 3-sulfotransferase 1 ENSG00000003056 M6PR mannose-6-phosphate receptor, cation dependent ENSG00000004059 ARF5 ADP ribosylation factor 5 ENSG00000004777 ARHGAP33 Rho GTPase activating protein 33 ENSG00000004799 PDK4 pyruvate dehydrogenase kinase 4 ENSG00000004848 ARX aristaless related homeobox ENSG00000005022 SLC25A5 solute carrier family 25 member 5 ENSG00000005108 THSD7A thrombospondin type 1 domain containing 7A ENSG00000005194 CIAPIN1 cytokine induced apoptosis inhibitor 1 ENSG00000005381 MPO myeloperoxidase ENSG00000005486 RHBDD2 rhomboid domain containing 2 ENSG00000005884 ITGA3 integrin subunit alpha 3 ENSG00000006016 CRLF1 cytokine receptor like -
Robust Sampling of Defective Pathways in Alzheimer's Disease. Implications in Drug Repositioning
International Journal of Molecular Sciences Article Robust Sampling of Defective Pathways in Alzheimer’s Disease. Implications in Drug Repositioning Juan Luis Fernández-Martínez 1,2,* , Óscar Álvarez-Machancoses 1,2 , Enrique J. deAndrés-Galiana 1,3 , Guillermina Bea 1 and Andrzej Kloczkowski 4,5 1 Group of Inverse Problems, Optimization and Machine Learning, Department of Mathematics, University of Oviedo, C/Federico García Lorca, 18, 33007 Oviedo, Spain; [email protected] (Ó.Á.-M.); [email protected] (E.J.d.-G.); [email protected] (G.B.) 2 DeepBioInsights, C/Federico García Lorca, 18, 33007 Oviedo, Spain 3 Department of Informatics and Computer Science, University of Oviedo, C/Federico García Lorca, 18, 33007 Oviedo, Spain 4 Battelle Center for Mathematical Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA; [email protected] 5 Department of Pediatrics, The Ohio State University, Columbus, OH 43205, USA * Correspondence: [email protected] Received: 27 April 2020; Accepted: 13 May 2020; Published: 19 May 2020 Abstract: We present the analysis of the defective genetic pathways of the Late-Onset Alzheimer’s Disease (LOAD) compared to the Mild Cognitive Impairment (MCI) and Healthy Controls (HC) using different sampling methodologies. These algorithms sample the uncertainty space that is intrinsic to any kind of highly underdetermined phenotype prediction problem, by looking for the minimum-scale signatures (header genes) corresponding to different random holdouts. The biological pathways can be identified performing posterior analysis of these signatures established via cross-validation holdouts and plugging the set of most frequently sampled genes into different ontological platforms. That way, the effect of helper genes, whose presence might be due to the high degree of under determinacy of these experiments and data noise, is reduced. -
AF1Q ALL1-Fused Gene from Chromosome 1Q PPP2CB Protein
AF1Q ALL1-fused gene from chromosome 1q PPP2CB protein phosphatase 2 formerly 2A, catalytic subunit, beta isoform TLK1 tousled-like kinase 1 WFDC2 WAP four-disulfide core domain 2 FVT1 follicular lymphoma variant translocation 1 MYL5 myosin, light polypeptide 5, regulatory FECH ferrochelatase protoporphyria BECN1 beclin 1 coiled-coil, myosin-like BCL2 interacting protein AQP3 aquaporin 3 ATP5G1 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c subunit 9, isoform 1 BMP4 bone morphogenetic protein 4 ANK3 ankyrin 3, node of Ranvier ankyrin G EIF4G3 eukaryotic translation initiation factor 4 gamma, 3 HSF2 heat shock transcription factor 2 FLT1 fms-related tyrosine kinase 1 vascular endothelial growth factor/vascular permeability factor receptor BIRC1 baculoviral IAP repeat-containing 1 BST2 bone marrow stromal cell antigen 2 CEACAM6 carcinoembryonic antigen-related cell adhesion molecule 6 non-specific cross reacting antigen MAP2K4 mitogen-activated protein kinase kinase 4 BLVRA biliverdin reductase A MSX2 msh homeo box homolog 2 Drosophila ACADSB acyl-Coenzyme A dehydrogenase, short/branched chain QDPR quinoid dihydropteridine reductase LRBA LPS-responsive vesicle trafficking, beach and anchor containing BF B-factor, properdin RAB2L RAB2, member RAS oncogene family-like APBB2 amyloid beta A4 precursor protein-binding, family B, member 2 Fe65-like TFF1 trefoil factor 1 breast cancer, estrogen-inducible sequence expressed in TFF3 trefoil factor 3 intestinal FOXA1 forkhead box A1 XBP1 X-box binding protein 1 GATA3 GATA binding -
Supplementary Material Peptide-Conjugated Oligonucleotides Evoke Long-Lasting Myotonic Dystrophy Correction in Patient-Derived C
Supplementary material Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice Arnaud F. Klein1†, Miguel A. Varela2,3,4†, Ludovic Arandel1, Ashling Holland2,3,4, Naira Naouar1, Andrey Arzumanov2,5, David Seoane2,3,4, Lucile Revillod1, Guillaume Bassez1, Arnaud Ferry1,6, Dominic Jauvin7, Genevieve Gourdon1, Jack Puymirat7, Michael J. Gait5, Denis Furling1#* & Matthew J. A. Wood2,3,4#* 1Sorbonne Université, Inserm, Association Institut de Myologie, Centre de Recherche en Myologie, CRM, F-75013 Paris, France 2Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK 3Department of Paediatrics, John Radcliffe Hospital, University of Oxford, Oxford, UK 4MDUK Oxford Neuromuscular Centre, University of Oxford, Oxford, UK 5Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK 6Sorbonne Paris Cité, Université Paris Descartes, F-75005 Paris, France 7Unit of Human Genetics, Hôpital de l'Enfant-Jésus, CHU Research Center, QC, Canada † These authors contributed equally to the work # These authors shared co-last authorship Methods Synthesis of Peptide-PMO Conjugates. Pip6a Ac-(RXRRBRRXRYQFLIRXRBRXRB)-CO OH was synthesized and conjugated to PMO as described previously (1). The PMO sequence targeting CUG expanded repeats (5′-CAGCAGCAGCAGCAGCAGCAG-3′) and PMO control reverse (5′-GACGACGACGACGACGACGAC-3′) were purchased from Gene Tools LLC. Animal model and ASO injections. Experiments were carried out in the “Centre d’études fonctionnelles” (Faculté de Médecine Sorbonne University) according to French legislation and Ethics committee approval (#1760-2015091512001083v6). HSA-LR mice are gift from Pr. Thornton. The intravenous injections were performed by single or multiple administrations via the tail vein in mice of 5 to 8 weeks of age. -
Differential Interactome Proposes Subtype-Specific Biomarkers And
Journal of Personalized Medicine Article Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas Aysegul Caliskan 1,2,† , Gizem Gulfidan 1,† , Raghu Sinha 3,* and Kazim Yalcin Arga 1,* 1 Department of Bioengineering, Marmara University, Istanbul 34722, Turkey; [email protected] (A.C.); gizemgulfi[email protected] (G.G.) 2 Faculty of Pharmacy, Istinye University, Istanbul 34010, Turkey 3 Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA 17033, USA * Correspondence: [email protected] (R.S.); [email protected] (K.Y.A.) † These authors contributed equally to this work. Abstract: Although many studies have been conducted on single gene therapies in cancer patients, the reality is that tumor arises from different coordinating protein groups. Unveiling perturbations in protein interactome related to the tumor formation may contribute to the development of effective di- agnosis, treatment strategies, and prognosis. In this study, considering the clinical and transcriptome data of three Renal Cell Carcinoma (RCC) subtypes (ccRCC, pRCC, and chRCC) retrieved from The Cancer Genome Atlas (TCGA) and the human protein interactome, the differential protein–protein interactions were identified in each RCC subtype. The approach enabled the identification of dif- ferentially interacting proteins (DIPs) indicating prominent changes in their interaction patterns during tumor formation. Further, diagnostic and prognostic performances were generated by taking into account DIP clusters which are specific to the relevant subtypes. Furthermore, considering the mesenchymal epithelial transition (MET) receptor tyrosine kinase (PDB ID: 3DKF) as a potential Citation: Caliskan, A.; Gulfidan, G.; drug target specific to pRCC, twenty-one lead compounds were identified through virtual screening Sinha, R.; Arga, K.Y. -
An Integrated Workflow for Charting the Human Interaction Proteome: Insights Into the PP2A System
Research Collection Journal Article An integrated workflow for charting the human interaction proteome: insights into the PP2A system Author(s): Glatter, Timo; Wepf, Alexander; Aebersold, Ruedi; Gstaiger, Matthias Publication Date: 2009-01 Permanent Link: https://doi.org/10.3929/ethz-b-000014116 Originally published in: Molecular Systems Biology 5(1), http://doi.org/10.1038/msb.2008.75 Rights / License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported This page was generated automatically upon download from the ETH Zurich Research Collection. For more information please consult the Terms of use. ETH Library Molecular Systems Biology 5; Article number 237; doi:10.1038/msb.2008.75 Citation: Molecular Systems Biology 5:237 & 2009 EMBO and Macmillan Publishers Limited All rights reserved 1744-4292/09 www.molecularsystemsbiology.com An integrated workflow for charting the human interaction proteome: insights into the PP2A system Timo Glatter1,2,5, Alexander Wepf1,2,5, Ruedi Aebersold1,2,3,4 and Matthias Gstaiger1,2,* 1 Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland, 2 Competence Center for Systems Physiology and Metabolic Diseases, ETH Zurich, Zurich, Switzerland, 3 Faculty of Science, University of Zurich, Zurich, Switzerland and 4 Institute for Systems Biology, Seattle, WA, USA 5 These authors contributed equally to this work * Corresponding author. Institute of Molecular Systems Biology, ETH, Wolfgang Pauli Strasse 16, Zu¨rich 8093, Switzerland. Tel.: þ 41 44 633 71 49; Fax: þ 41 44 633 10 51; E-mail: [email protected] Received 26.6.08; accepted 4.12.08 Protein complexes represent major functional units for the execution of biological processes.