Chimeric Transcript Discovery by Paired-End Transcriptome Sequencing
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Supplementary Methods
SUPPLEMENTARY METHODS Epilepsy cohorts Epilepsy cohorts contributing to the meta-analysis are detailed below. EPIGEN (Reported by – Chantal Depondt, Sanjay Sisodiya, Norman Delanty, Gianpiero Cavalleri, Erin Heinzen and David Goldstein) The EPIGEN study consisted of epilepsy cohorts from Beaumont Hospital Dublin (Ireland), Université Libre de Bruxelles (ULB, Belgium), Duke University Medical Centre (North Carolina, USA) and University College Hospital London (UK). Inclusion Criteria: Except for Duke, only adult (>16 years) patients with epilepsy were recruited. Exclusion Criteria: No specific exclusion criteria. Quality assurance: At all sites, subjects were recruited and phenotyped by experienced epilepsy specialists. At Duke, all cases underwent independent case-record review by an epilepsy nurse specialist, and ambiguous diagnoses were re-evaluated by a second epileptologist. If the diagnosis remained unclear, then the patient was excluded from the study. For London, all cases underwent review by independent epileptologists. For Brussels, study PI (Chantal Depondt) reviewed the classification of all cases by case-note review. For Dublin, no systematic quality assurance was undertaken. Site-specific details for each EPIGEN cohort as organized for the analysis are as follows: – EPIGEN-Dublin Patients were recruited from a specialized epilepsy clinic at Beaumont Hospital, Dublin, Ireland. Patients were mostly of Irish ethnicity. Patients were genotyped on the Illumina platform using a combination of chips (610-Quad+550+300v1/Omni1-Quad). – EPIGEN-Brussels Patients were recruited from epilepsy clinics at UZ Gasthuisberg, Katholieke Universiteit Leuven, and Hôpital Erasme, Université Libre de Bruxelles. Patients were largely of Belgian ethnicity. Patients were genotyped on the Illumina platform using a combination of chips (610-Quad/300 V1 & V2). -
Multiple Activities of Arl1 Gtpase in the Trans-Golgi Network Chia-Jung Yu1,2 and Fang-Jen S
© 2017. Published by The Company of Biologists Ltd | Journal of Cell Science (2017) 130, 1691-1699 doi:10.1242/jcs.201319 COMMENTARY Multiple activities of Arl1 GTPase in the trans-Golgi network Chia-Jung Yu1,2 and Fang-Jen S. Lee3,4,* ABSTRACT typical features of an Arf-family GTPase, including an amphipathic ADP-ribosylation factors (Arfs) and ADP-ribosylation factor-like N-terminal helix and a consensus site for N-myristoylation (Lu et al., proteins (Arls) are highly conserved small GTPases that function 2001; Price et al., 2005). In yeast, recruitment of Arl1 to the Golgi as main regulators of vesicular trafficking and cytoskeletal complex requires a second Arf-like GTPase, Arl3 (Behnia et al., reorganization. Arl1, the first identified member of the large Arl family, 2004; Setty et al., 2003). Yeast Arl3 lacks a myristoylation site and is an important regulator of Golgi complex structure and function in is, instead, N-terminally acetylated; this modification is required for organisms ranging from yeast to mammals. Together with its effectors, its recruitment to the Golgi complex by Sys1. In mammalian cells, Arl1 has been shown to be involved in several cellular processes, ADP-ribosylation-factor-related protein 1 (Arfrp1), a mammalian including endosomal trans-Golgi network and secretory trafficking, lipid ortholog of yeast Arl3, plays a pivotal role in the recruitment of Arl1 droplet and salivary granule formation, innate immunity and neuronal to the trans-Golgi network (TGN) (Behnia et al., 2004; Panic et al., development, stress tolerance, as well as the response of the unfolded 2003b; Setty et al., 2003; Zahn et al., 2006). -
Supplementary Online Material Promoter-Anchored Chromatin
Supplementary Online Material Promoter-anchored chromatin interactions predicted from genetic analysis of epigenomic data Wu et al. Contents Figure S1 to S8 Supplementary Note 1-2 References Figure S1 Schematic overview of this study. a b mean=3.7 mean=79 Kb median=2 median=23 Kb Count Count 0 1000 3000 5000 0 5000 10000 15000 0 5 10 15 20 25 >30 0 500 1000 1500 2000 No. interacting pairs Distance between interacting DNAm (Kb) Figure S2 Summary of the predicted PAIs. Panel a): distribution of the number of PIDSs (promoter interacting DNAm sites) for each bait probe (located in the promoter of a gene). Panel b): distribution of physical distances between pairwise interacting DNAm sites of the significant PAIs. Figure S3 Overlap of the predicted PAIs with TADs annotated from the Rao et al. 1 Hi-C data. Panel a): a heatmap of the predicted PAIs (red asterisks) and chromatin interactions with correlation score > 0.4 (blue dots) identified by Hi-C in a 1.38 Mb region on chromosome 6. Only 41.5% of the predicted PAIs in this region showed overlap with the TADs. This region harbours the RPS6KA2 locus as shown in Fig. 5. Panel b): a heatmap of the predicted PAIs (red asterisks) and chromatin interactions with correlation score > 0.4 (blue dots) identified by Hi-C in a 0.81 Mb region on chromosome 12. The predicted PAIs were highly consistent with the chromatin interactions identified by Hi-C. This region harbours the ABCB9 locus as shown in Fig. S4. The heatmap is asymmetric for the PAIs with the x- and y-axes representing the physical positions of “outcome” and “exposure” probes respectively. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Identification of Potential Markers for Type 2 Diabetes Mellitus Via Bioinformatics Analysis
1868 MOLECULAR MEDICINE REPORTS 22: 1868-1882, 2020 Identification of potential markers for type 2 diabetes mellitus via bioinformatics analysis YANA LU1, YIHANG LI1, GUANG LI1* and HAITAO LU2* 1Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Yunnan Branch, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Jinghong, Yunnan 666100; 2Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China Received March 20, 2019; Accepted January 20, 2020 DOI: 10.3892/mmr.2020.11281 Abstract. Type 2 diabetes mellitus (T2DM) is a multifactorial and cell proliferation’. These candidate genes were also involved in multigenetic disease, and its pathogenesis is complex and largely different signaling pathways associated with ‘PI3K/Akt signaling unknown. In the present study, microarray data (GSE201966) of pathway’, ‘Rap1 signaling pathway’, ‘Ras signaling pathway’ β-cell enriched tissue obtained by laser capture microdissection and ‘MAPK signaling pathway’, which are highly associated were downloaded, including 10 control and 10 type 2 diabetic with the development of T2DM. Furthermore, a microRNA subjects. A comprehensive bioinformatics analysis of microarray (miR)-target gene regulatory network and a transcription data in the context of protein-protein interaction (PPI) networks factor-target gene regulatory network were constructed based was employed, combined with subcellular location information on miRNet and NetworkAnalyst databases, respectively. to mine the potential candidate genes for T2DM and provide Notably, hsa-miR‑192-5p, hsa-miR‑124-5p and hsa-miR‑335-5p further insight on the possible mechanisms involved. First, appeared to be involved in T2DM by potentially regulating the differential analysis screened 108 differentially expressed expression of various candidate genes, including procollagen genes. -
Effects of Changes in TIA1 on Stress Granule Formation
Effects of changes in TIA1 on stress granule formation Master’s thesis Lydia Sagath University of Helsinki Faculty of Biological and Environmental Sciences Genetics August 2015 Tiedekunta – Fakultet – Faculty Laitos – Institution– Department Bio- och miljövetenskapliga fakulteten Biovetenskapliga institutionen Tekijä – Författare – Author Lydia Johanna Sagath Työn nimi – Arbetets titel – Title Effects of changes in TIA1 on stress granule formation Oppiaine – Läroämne – Subject Humangenetik Työn laji – Arbetets art – Level Aika – Datum – Month and year Sivumäärä – Sidoantal – Number of pages Pro gradu Augusti 2015 63 Tiivistelmä – Referat – Abstract Welanders distala myopati (WDM) orsakas av mutationen p.E384K i genen TIA1. Mutationen antas vara sjukdomsalstrande på grund av en ökad produktion av protein, som relaterats till formationen av stressgranuler (Hackman et al. 2013). Även omgivningsfaktorer har föreslagits verka i sjukdomens utveckling: en ökad mängd stressgranuler har observerats i celler som behandlats med köldshock jämfört med celler som förvarats i 37°C (Hofmann et al. 2012). I patienter med WDM-liknande symptom som undersökts för förändringar i TIA1 har en p.N357S-förändring noterats förrikad. Denna förändring har tidigare anmälts som en polymorfism. Förändringen i fråga ligger i samma prionliknande domän i exon 5 som WDM-orsakande förändringen p.E384K. Därmed kunde p.N357S-förändringen öka predispositionen till aggregering. Pro gradu –arbetet är uppdelat i två delar: • p.N357S-polymorfismens effekt på stressgranulsbildningen i arsenitbehandle celler • Köldshockens effekt på stressgranulsbildningen Resultaten påvisar, att förändringen p.N357S i TIA1 orsakar en förändring i det translaterade proteinets beteende. I likhet med p.E384K-förändringen orsakar även p.N357S en ökad mängd stressgranuler i arsenitbehandlade celler. Däremot tyder resultaten på att stressgranulerna återbildas snabbare i fluorescence recovery after photobleaching-studier (FRAP) I p.N357S-transfekterade celler än i celler som transfekterats med TIA1 p.E384K och vildtyp. -
ABCG1 (ABC8), the Human Homolog of the Drosophila White Gene, Is a Regulator of Macrophage Cholesterol and Phospholipid Transport
ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport Jochen Klucken*, Christa Bu¨ chler*, Evelyn Orso´ *, Wolfgang E. Kaminski*, Mustafa Porsch-Ozcu¨ ¨ ru¨ mez*, Gerhard Liebisch*, Michael Kapinsky*, Wendy Diederich*, Wolfgang Drobnik*, Michael Dean†, Rando Allikmets‡, and Gerd Schmitz*§ *Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, 93042 Regensburg, Germany; †National Cancer Institute, Laboratory of Genomic Diversity, Frederick, MD 21702-1201; and ‡Departments of Ophthalmology and Pathology, Columbia University, Eye Research Addition, New York, NY 10032 Edited by Jan L. Breslow, The Rockefeller University, New York, NY, and approved November 3, 1999 (received for review June 14, 1999) Excessive uptake of atherogenic lipoproteins such as modified low- lesterol transport. Although several effector molecules have been density lipoprotein complexes by vascular macrophages leads to proposed to participate in macrophage cholesterol efflux (6, 9), foam cell formation, a critical step in atherogenesis. Cholesterol efflux including endogenous apolipoprotein E (10) and the cholesteryl mediated by high-density lipoproteins (HDL) constitutes a protective ester transfer protein (11), the detailed molecular mechanisms mechanism against macrophage lipid overloading. The molecular underlying cholesterol export in these cells have not yet been mechanisms underlying this reverse cholesterol transport process are characterized. currently not fully understood. To identify effector proteins that are Recently, mutations of the ATP-binding cassette (ABC) trans- involved in macrophage lipid uptake and release, we searched for porter ABCA1 gene have been causatively linked to familial HDL genes that are regulated during lipid influx and efflux in human deficiency and Tangier disease (12–14). -
4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4). -
Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes In
ORIGINAL ARTICLE Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort Steven C. Elbein,1,2 Swapan K. Das,1,2 D. Michael Hallman,3 Craig L. Hanis,3 and Sandra J. Hasstedt4 OBJECTIVE—We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes ype 2 diabetes is marked by a clear genetic diagnosis, and BMI. propensity, a high concordance in identical twins, tendencies for both diabetes and age of RESEARCH DESIGN AND METHODS—After removing outli- onset to be familial (1), and marked differences ers and problematic samples, we conducted linkage analysis T in prevalence among ethnic groups (2). Despite consider- using 5,914 SNPs in 1,344 individuals from 530 families. Linkage analysis was conducted using variance components for type 2 able evidence for a genetic predisposition, unraveling the diabetes, age of type 2 diabetes diagnosis, and BMI and nonpara- genetic etiology has been daunting, with few confirmed metric linkage analyses. Ordered subset analyses were con- genes identified from genome-wide linkage scans. Recent ducted ranking on age of type 2 diabetes diagnosis, BMI, waist successes with genome-wide association scans (3) have circumference, waist-to-hip ratio, and amount of European ad- greatly increased the number of confirmed genetic loci, mixture. Admixture mapping was conducted using 4,486 markers but these successes have been limited primarily to Cauca- not in linkage disequilibrium. -
Research Article Deletion of Herpud1 Enhances Heme Oxygenase-1 Expression in a Mouse Model of Parkinson's Disease
Hindawi Publishing Corporation Parkinson’s Disease Volume 2016, Article ID 6163934, 9 pages http://dx.doi.org/10.1155/2016/6163934 Research Article Deletion of Herpud1 Enhances Heme Oxygenase-1 Expression in a Mouse Model of Parkinson’s Disease Thuong Manh Le,1 Koji Hashida,1 Hieu Minh Ta,1 Mika Takarada-Iemata,1,2 Koichi Kokame,3 Yasuko Kitao,1,2 and Osamu Hori1,2 1 Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan 2CREST, JST (Japan Science and Technology), Tokyo 102-8666, Japan 3Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan Correspondence should be addressed to Osamu Hori; [email protected] Received 21 November 2015; Revised 25 January 2016; Accepted 28 January 2016 Academic Editor: Antonio Pisani Copyright © 2016 Thuong Manh Le et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Herp is an endoplasmic reticulum- (ER-) resident membrane protein that plays a role in ER-associated degradation. We studied the expression of Herp and its effect on neurodegeneration in a mouse model of Parkinson’s disease (PD), in which both the oxidative stress and the ER stress are evoked. Eight hours after administering a PD-related neurotoxin, 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), to mice, the expression of Herp increased at both the mRNA and the protein levels. Experiments using +/+ −/− Herpud1 and Herpud1 mice revealed that the status of acute degeneration of nigrostriatal neurons and reactive astrogliosis was comparable between two genotypes after MPTP injection. -
Essential Genes and Their Role in Autism Spectrum Disorder
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2017 Essential Genes And Their Role In Autism Spectrum Disorder Xiao Ji University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Bioinformatics Commons, and the Genetics Commons Recommended Citation Ji, Xiao, "Essential Genes And Their Role In Autism Spectrum Disorder" (2017). Publicly Accessible Penn Dissertations. 2369. https://repository.upenn.edu/edissertations/2369 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2369 For more information, please contact [email protected]. Essential Genes And Their Role In Autism Spectrum Disorder Abstract Essential genes (EGs) play central roles in fundamental cellular processes and are required for the survival of an organism. EGs are enriched for human disease genes and are under strong purifying selection. This intolerance to deleterious mutations, commonly observed haploinsufficiency and the importance of EGs in pre- and postnatal development suggests a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication and repetitive behavior. More and more genetic evidence points to a polygenic model of ASD and it is estimated that hundreds of genes contribute to ASD. The central question addressed in this dissertation is whether genes with a strong effect on survival and fitness (i.e. EGs) play a specific oler in ASD risk. I compiled a comprehensive catalog of 3,915 mammalian EGs by combining human orthologs of lethal genes in knockout mice and genes responsible for cell-based essentiality. -
Supplementary Figures 1-14 and Supplementary References
SUPPORTING INFORMATION Spatial Cross-Talk Between Oxidative Stress and DNA Replication in Human Fibroblasts Marko Radulovic,1,2 Noor O Baqader,1 Kai Stoeber,3† and Jasminka Godovac-Zimmermann1* 1Division of Medicine, University College London, Center for Nephrology, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK. 2Insitute of Oncology and Radiology, Pasterova 14, 11000 Belgrade, Serbia 3Research Department of Pathology and UCL Cancer Institute, Rockefeller Building, University College London, University Street, London WC1E 6JJ, UK †Present Address: Shionogi Europe, 33 Kingsway, Holborn, London WC2B 6UF, UK TABLE OF CONTENTS 1. Supplementary Figures 1-14 and Supplementary References. Figure S-1. Network and joint spatial razor plot for 18 enzymes of glycolysis and the pentose phosphate shunt. Figure S-2. Correlation of SILAC ratios between OXS and OAC for proteins assigned to the SAME class. Figure S-3. Overlap matrix (r = 1) for groups of CORUM complexes containing 19 proteins of the 49-set. Figure S-4. Joint spatial razor plots for the Nop56p complex and FIB-associated complex involved in ribosome biogenesis. Figure S-5. Analysis of the response of emerin nuclear envelope complexes to OXS and OAC. Figure S-6. Joint spatial razor plots for the CCT protein folding complex, ATP synthase and V-Type ATPase. Figure S-7. Joint spatial razor plots showing changes in subcellular abundance and compartmental distribution for proteins annotated by GO to nucleocytoplasmic transport (GO:0006913). Figure S-8. Joint spatial razor plots showing changes in subcellular abundance and compartmental distribution for proteins annotated to endocytosis (GO:0006897). Figure S-9. Joint spatial razor plots for 401-set proteins annotated by GO to small GTPase mediated signal transduction (GO:0007264) and/or GTPase activity (GO:0003924).