PDF Output of CLIC (Clustering by Inferred Co-Expression)

Total Page:16

File Type:pdf, Size:1020Kb

PDF Output of CLIC (Clustering by Inferred Co-Expression) PDF Output of CLIC (clustering by inferred co-expression) Dataset: Num of genes in input gene set: 13 Total number of genes: 16493 CLIC PDF output has three sections: 1) Overview of Co-Expression Modules (CEMs) Heatmap shows pairwise correlations between all genes in the input query gene set. Red lines shows the partition of input genes into CEMs, ordered by CEM strength. Each row shows one gene, and the brightness of squares indicates its correlations with other genes. Gene symbols are shown at left side and on the top of the heatmap. 2) Details of each CEM and its expansion CEM+ Top panel shows the posterior selection probability (dataset weights) for top GEO series datasets. Bottom panel shows the CEM genes (blue rows) as well as expanded CEM+ genes (green rows). Each column is one GEO series dataset, sorted by their posterior probability of being selected. The brightness of squares indicates the gene's correlations with CEM genes in the corresponding dataset. CEM+ includes genes that co-express with CEM genes in high-weight datasets, measured by LLR score. 3) Details of each GEO series dataset and its expression profile: Top panel shows the detailed information (e.g. title, summary) for the GEO series dataset. Bottom panel shows the background distribution and the expression profile for CEM genes in this dataset. Overview of Co-Expression Modules (CEMs) with Dataset Weighting Scale of average Pearson correlations Num of Genes in Query Geneset: 13. Num of CEMs: 1. 0.0 0.2 0.4 0.6 0.8 1.0 Rps29 Rps28 Fau Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 Rps29 Rps28 CEM 1 (813 datasets) Fau Rps6 Mrps2 Rps18 Mrps6 Rps25 Singletons Gnb2l1 Mrps12 Dap3 Rps24 Rps16 Symbol Num ofCEMGenes:3.Predicted33.SelectedDatasets:813.Strength:4.4 CEM 1,Geneset"[G]smallribosomalsubunit",Page1 Tmsb4x Cox6a1 Rps3a1 Atp5g3 Cox4i1 Eef1b2 Rpl10a Rpl13a Rpl37a Rpl18a Rps19 Rps11 Rps4x Uba52 Rps28 Rps29 Actg1 Rplp0 Rplp2 Nme2 Rpl27 Rpl7a Rpl26 Rpl38 Rps2 Rps7 Rps5 Naca Eif3f Rpl7 Rpl8 Rpl6 Rpl4 Eif3i Eef2 Fau 0.0 1.0 GSE46871 [6] GSE15610 [12] GSE7219 [12] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE32615 [10] GSE6785 [9] GSE4749 [6] GSE33471 [12] GSE22903 [24] GSE36530 [6] GSE14308 [12] GSE20727 [15] GSE23833 [12] GSE21944 [6] GSE2019 [12] GSE19286 [6] GSE39621 [51] GSE39897 [36] GSE2527 [6] GSE4288 [36] GSE47065 [8] GSE21143 [6] GSE24465 [6] GSE35844 [9] GSE10071 [10] GSE39592 [8] GSE6676 [8] GSE5497 [6] GSE8555 [8] GSE15458 [8] GSE36384 [12] GSE26745 [24] GSE13874 [14] GSE39082 [6] GSE5921 [6] GSE36618 [6] GSE32529 [224] GSE54581 [21] GSE41942 [6] GSE42061 [12] GSE16364 [6] GSE49346 [6] GSE14478 [7] GSE10552 [6] GSE33121 [10] GSE43620 [8] GSE58262 [18] GSE8503 [6] GSE10871 [32] GSE19687 [9] GSE34761 [8] GSE35825 [9] GSE17728 [12] GSE23178 [6] GSE35734 [6] GSE18010 [29] GSE3861 [6] GSE53299 [6] GSE19181 [6] GSE35318 [12] GSE42008 [6] GSE24726 [8] GSE13547 [12] GSE24437 [6] GSE6030 [6] GSE11358 [8] GSE12467 [6] GSE6084 [12] GSE38304 [8] GSE9978 [8] GSE58484 [15] GSE24695 [9] GSE31776 [10] GSE11149 [8] GSE6134 [7] GSE52474 [154] GSE58296 [9] GSE28093 [6] GSE42135 [42] GSE21900 [12] GSE11420 [15] GSE11044 [6] GSE11148 [6] GSE34206 [8] GSE6674 [15] GSE18115 [8] GSE34618 [7] GSE27717 [11] GSE2161 [8] GSE31086 [6] GSE19793 [32] GSE47421 [24] GSE18281 [33] GSE24789 [9] GSE19076 [12] GSE32903 [12] GSE37029 [15] GSE56755 [13] GSE10210 [16] GSE13805 [7] GSE11628 [12] GSE16210 [14] GSE51365 [28] GSE14672 [12] GSE32199 [6] GSE17097 [20] GSE36569 [6] GSE11766 [48] GSE27302 [16] GSE48811 [20] GSE7781 [12] GSE24873 [48] GSE7705 [10] GSE36414 [8] GSE6675 [8] GSE7605 [18] GSE12430 [21] GSE10216 [6] GSE31359 [8] GSE46094 [10] GSE8683 [11] GSE14698 [12] GSE23398 [7] GSE46242 [12] GSE30767 [8] GSE7810 [9] GSE11120 [10] GSE39375 [10] GSE6998 [32] GSE27378 [8] GSE38283 [7] GSE7111 [6] GSE47798 [30] GSE1999 [15] GSE21841 [18] GSE31598 [12] GSE11918 [9] GSE32102 [49] GSE13963 [15] GSE6259 [21] GSE14929 [38] GSE13690 [38] GSE20726 [9] GSE34423 [40] GSE43242 [10] GSE27675 [14] GSE6065 [100] GSE7683 [12] GSE49351 [6] GSE25140 [16] GSE26695 [20] GSE50439 [15] GSE48935 [12] GSE7657 [12] GSE40296 [6] CEM+ CEM GSE4656 [7] GSE9760 [12] GSE56492 [12] GSE12993 [6] GSE8836 [56] GSE21606 [6] 0.0 GSE15794 [6] GSE10954 [8] GSE54656 [27] Scale ofaveragePearsoncorrelations GSE42688 [8] GSE4043 [6] GSE18460 [16] GSE40412 [14] GSE34324 [12] GSE19272 [30] 0.2 GSE5035 [12] GSE26076 [12] GSE8682 [8] GSE51686 [9] GSE46185 [6] GSE56482 [8] GSE6591 [15] GSE35106 [9] GSE3822 [16] 0.4 GSE18587 [9] GSE6526 [16] GSE7487 [24] GSE35077 [26] GSE21033 [12] GSE13799 [18] GSE17553 [16] GSE10556 [6] GSE31646 [11] 0.6 GSE13259 [10] GSE9316 [12] GSE17102 [9] GSE11496 [16] GSE25828 [8] GSE6482 [9] GSE59319 [6] GSE35998 [20] GSE21711 [6] 0.8 GSE41895 [12] GSE26025 [12] GSE21272 [44] GSE4734 [61] Score 5.39 13.81 15.97 18.66 22.80 44.13 47.84 97.20 167.17 212.21 245.03 327.57 389.57 414.31 439.83 457.74 472.00 497.93 506.94 512.94 551.86 605.21 619.89 624.52 627.69 655.55 692.60 694.20 716.72 763.57 784.08 802.10 943.77 1.0 Notes GEO Series "GSE46871" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46871 Status: Public on May 14 2013 Title: Hippocampal gene expression profiling of a model of Alzheimer`s Disease upon treatment with the ACE inhibitor captopril Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23959119 Summary & Design: Summary: Extracellular senile plaques of amyloid beta (Abeta) are a pathological hallmark in brain of patients with Alzheimer`s Disease (AD). Abeta is generated by the amyloidogenic processing of the amyloid precursor protein (APP). Concomitant to Abeta load, AD brain is characterized by an increase in protein level and activity of the angiotensin-converting enzyme (ACE). ACE inhibitors are a widely used class of drugs with established benefits for patients with cardiovascular disease. However, the role of ACE and ACE inhibition in the development of Abeta plaques and the process of AD-related neurodegeneration is not clear since ACE was reported to degrade Abeta. To investigate the effect of ACE inhibition on AD-related pathomechanisms, we used Tg2576 mice with neuron-specific expression of APPSwe as AD model. From 12 months of age, substantial Abeta plaque load accumulates in the hippocampus of Tg2576 mice as a brain region, which is highly vulnerable to AD-related neurodegeneration. The effect of central ACE inhibition was studied by treatment of 12 month-old Tg2576 mice for six months with the brain penetrating ACE inhibitor captopril. At an age of 18 months, hippocampal gene expression profiling was performed of captopril-treated Tg2576 mice relative to untreated 18 month-old Tg2576 controls with high Abeta plaque load. As an additional control, we used 12 month-old Tg2576 mice with low Abeta plaque load. Whole genome microarray gene expression profiling revealed gene expression changes induced by the brain-penetrating ACE inhibitor captopril, which could reflect the neuro-regenerative potential of central ACE inhibition. Overall design: Microarray gene expression profiling was performed of hippocampi isolated from aged, 18 month-old Tg2576 (APPSwe-transgenic) AD mice with high Abeta plaque load relative to age-matched Tg2576 mice, which were treated for 6 months with the centrally active ACE inhibitor captopril. Another study group consisted of 12 month-old Tg2576 mice with low Abeta plaque load. In total, three study groups were analyzed, i.e. (i) 18 month-old untreated Tg2576 mice with high Abeta plaque load, (ii) age-matched Tg2576 mice treated for 6 months with the brain-penetrating ACE inhibitor captopril (20 mg/kg body weight/day in drinking water), and (iii) untreated 12 month-old Tg2576 mice with low Abeta plaque load reflecting the time point when captopril treatment was initiated. Two biological replicates were made of each group, and total hippocampal RNA of four mice was pooled for one gene chip. Background corr dist: KL-Divergence = 0.0289, L1-Distance = 0.0256, L2-Distance = 0.0007, Normal std = 0.6941 0.592 Kernel fit Pairwise Correlations Normal fit Density 0.296 0.000 CEM 1 Z-score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Correlation -1.00 -1.00 -1.00 -0.96 -0.76 0.00 0.76 0.96 1.00 1.00 1.00 Pre-normalization Quantiles Hippocampus,Hippocampus, Hippocampus,Tg2576-APPSwe Hippocampus,Tg2576-APPSwe Hippocampus,Tg2576-APPSwe mice, Hippocampus,Tg2576-APPSwe 18 mice, month-old, Tg2576-APPSwe 18 mice, month-old, Tg2576-APPSwe with18 mice, month-old, high with18 mice,Abeta month-old, high [ ACE12 plaque mice,Abetamin month-old, inhibitor-treated-rep1 ACE12 load-rep1plaque month-old,] inhibitor-treated-rep2 with load-rep2 (0.113485) low with Abeta[ (0.195533) (0.0875443)lowmedium plaque Abeta (0.134632) load-rep1plaque load-rep2] (0.218563) (0.250242)[ max ] CEM 1 Rps29 12375.2 14976.7 24076.8 P ( S | Z, I ) = 1.00 Rps28 14336.5 16979.3 26885.3 Mean Corr = 0.99357 Fau 8290.9 9621.0 14102.9 Rpl38 15675.6 19214.5 28807.4 Rpl26 15073.9 17873.6 27509.8 Rpl18a 8685.9 10628.9 16424.2 Rpl37a 9947.9 11659.9 19225.9 Rps5 7671.9 9027.7 12613.7 CEM 1 + Rplp2 12205.7 15310.3 21225.1 Top 10 Genes Uba52 10119.0 11828.0 19404.2 Rpl7a 10525.7 13079.1 17966.5 Rps4x 10410.2 12306.3 18641.7 Rps7 11194.3 12860.6 18807.4 Null module Rps6 Mrps2 Rps18 Mrps6 Rps25 Gnb2l1 Mrps12 Dap3 Rps24 Rps16 GEO Series "GSE15610" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15610 Status: Public on Dec 22 2009 Title: Knockout of the selenocysteine tRNA (Trsp) gene in mouse macrophage Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19863805 Summary & Design: Summary: Comparative analysis of gene expression in bone marrow-derived macrophages (BMDM) from trsp knockout mice (Trspfl/fl-LysM-Cre+/-) and Control (Trspfl/fl-LysM-Cre-/-) mice.
Recommended publications
  • Role of Mitochondrial Ribosomal Protein S18-2 in Cancerogenesis and in Regulation of Stemness and Differentiation
    From THE DEPARTMENT OF MICROBIOLOGY TUMOR AND CELL BIOLOGY (MTC) Karolinska Institutet, Stockholm, Sweden ROLE OF MITOCHONDRIAL RIBOSOMAL PROTEIN S18-2 IN CANCEROGENESIS AND IN REGULATION OF STEMNESS AND DIFFERENTIATION Muhammad Mushtaq Stockholm 2017 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by E-Print AB 2017 © Muhammad Mushtaq, 2017 ISBN 978-91-7676-697-2 Role of Mitochondrial Ribosomal Protein S18-2 in Cancerogenesis and in Regulation of Stemness and Differentiation THESIS FOR DOCTORAL DEGREE (Ph.D.) By Muhammad Mushtaq Principal Supervisor: Faculty Opponent: Associate Professor Elena Kashuba Professor Pramod Kumar Srivastava Karolinska Institutet University of Connecticut Department of Microbiology Tumor and Cell Center for Immunotherapy of Cancer and Biology (MTC) Infectious Diseases Co-supervisor(s): Examination Board: Professor Sonia Lain Professor Ola Söderberg Karolinska Institutet Uppsala University Department of Microbiology Tumor and Cell Department of Immunology, Genetics and Biology (MTC) Pathology (IGP) Professor George Klein Professor Boris Zhivotovsky Karolinska Institutet Karolinska Institutet Department of Microbiology Tumor and Cell Institute of Environmental Medicine (IMM) Biology (MTC) Professor Lars-Gunnar Larsson Karolinska Institutet Department of Microbiology Tumor and Cell Biology (MTC) Dedicated to my parents ABSTRACT Mitochondria carry their own ribosomes (mitoribosomes) for the translation of mRNA encoded by mitochondrial DNA. The architecture of mitoribosomes is mainly composed of mitochondrial ribosomal proteins (MRPs), which are encoded by nuclear genomic DNA. Emerging experimental evidences reveal that several MRPs are multifunctional and they exhibit important extra-mitochondrial functions, such as involvement in apoptosis, protein biosynthesis and signal transduction. Dysregulations of the MRPs are associated with severe pathological conditions, including cancer.
    [Show full text]
  • 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.
    [Show full text]
  • WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT (51) International Patent Classification: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, C12Q 1/68 (2018.01) A61P 31/18 (2006.01) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, C12Q 1/70 (2006.01) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (21) International Application Number: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, PCT/US2018/056167 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (22) International Filing Date: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 16 October 2018 (16. 10.2018) TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (30) Priority Data: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 62/573,025 16 October 2017 (16. 10.2017) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, ΓΕ , IS, IT, LT, LU, LV, (71) Applicant: MASSACHUSETTS INSTITUTE OF MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TECHNOLOGY [US/US]; 77 Massachusetts Avenue, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Cambridge, Massachusetts 02139 (US).
    [Show full text]
  • Whole Exome Sequencing in Families at High Risk for Hodgkin Lymphoma: Identification of a Predisposing Mutation in the KDR Gene
    Hodgkin Lymphoma SUPPLEMENTARY APPENDIX Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene Melissa Rotunno, 1 Mary L. McMaster, 1 Joseph Boland, 2 Sara Bass, 2 Xijun Zhang, 2 Laurie Burdett, 2 Belynda Hicks, 2 Sarangan Ravichandran, 3 Brian T. Luke, 3 Meredith Yeager, 2 Laura Fontaine, 4 Paula L. Hyland, 1 Alisa M. Goldstein, 1 NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, Stephen J. Chanock, 5 Neil E. Caporaso, 1 Margaret A. Tucker, 6 and Lynn R. Goldin 1 1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 2Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 3Ad - vanced Biomedical Computing Center, Leidos Biomedical Research Inc.; Frederick National Laboratory for Cancer Research, Frederick, MD; 4Westat, Inc., Rockville MD; 5Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; and 6Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA ©2016 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2015.135475 Received: August 19, 2015. Accepted: January 7, 2016. Pre-published: June 13, 2016. Correspondence: [email protected] Supplemental Author Information: NCI DCEG Cancer Sequencing Working Group: Mark H. Greene, Allan Hildesheim, Nan Hu, Maria Theresa Landi, Jennifer Loud, Phuong Mai, Lisa Mirabello, Lindsay Morton, Dilys Parry, Anand Pathak, Douglas R. Stewart, Philip R. Taylor, Geoffrey S. Tobias, Xiaohong R. Yang, Guoqin Yu NCI DCEG Cancer Genomics Research Laboratory: Salma Chowdhury, Michael Cullen, Casey Dagnall, Herbert Higson, Amy A.
    [Show full text]
  • Chapter 4.1 a 400 Kb Duplication, 2.4 Mb Triplication and 130 Kb
    High-resolution karyotyping by oligonucleotide microarrays : the next revolution in cytogenetics Gijsbers, A.C.J. Citation Gijsbers, A. C. J. (2010, November 30). High-resolution karyotyping by oligonucleotide microarrays : the next revolution in cytogenetics. Retrieved from https://hdl.handle.net/1887/16187 Version: Corrected Publisher’s Version Licence agreement concerning inclusion of doctoral thesis in the License: Institutional Repository of the University of Leiden Downloaded from: https://hdl.handle.net/1887/16187 Note: To cite this publication please use the final published version (if applicable). Chapter 4.1 A 400 kb duplication, 2.4 Mb triplication and 130 kb duplication of 9q34.3 in a patient with severe mental retardation Antoinet CJ Gijsbers, Emilia K Bijlsma, Marjan M Weiss, Egbert Bakker, Martijn H Breuning, Mariëtte JV Hoffer and Claudia AL Ruivenkamp Center for Human and Clinical Genetics; Leiden University Medical Center (LUMC), Leiden, The Netherlands Eur J Med Genet 2008;51:479-487 Chapter 4 Abstract The presence of a duplication as well as a triplication in one chromosome is a rare rearrangement and not easy to distinguish with routine chromosomal analysis. Recent developments in array technologies, however, not only allow screening of the whole genome at a higher resolution, but also make it possible to characterize complex chromosomal rearrangements in more detail. Here we report a molecular cytogenetic analysis of a 16-year old female with severe mental retardation and an abnormality on the end of the long arm of chromosome 9. Subtelomeric multiplex ligation-dependent probe amplification (MLPA) analysis revealed that the extra material originated from the telomeric end of chromosome 9q.
    [Show full text]
  • Supplementary Dataset S2
    mitochondrial translational termination MRPL28 MRPS26 6 MRPS21 PTCD3 MTRF1L 4 MRPL50 MRPS18A MRPS17 2 MRPL20 MRPL52 0 MRPL17 MRPS33 MRPS15 −2 MRPL45 MRPL30 MRPS27 AURKAIP1 MRPL18 MRPL3 MRPS6 MRPS18B MRPL41 MRPS2 MRPL34 GADD45GIP1 ERAL1 MRPL37 MRPS10 MRPL42 MRPL19 MRPS35 MRPL9 MRPL24 MRPS5 MRPL44 MRPS23 MRPS25 ITB ITB ITB ITB ICa ICr ITL original ICr ICa ITL ICa ITL original ICr ITL ICr ICa mitochondrial translational elongation MRPL28 MRPS26 6 MRPS21 PTCD3 MRPS18A 4 MRPS17 MRPL20 2 MRPS15 MRPL45 MRPL52 0 MRPS33 MRPL30 −2 MRPS27 AURKAIP1 MRPS10 MRPL42 MRPL19 MRPL18 MRPL3 MRPS6 MRPL24 MRPS35 MRPL9 MRPS18B MRPL41 MRPS2 MRPL34 MRPS5 MRPL44 MRPS23 MRPS25 MRPL50 MRPL17 GADD45GIP1 ERAL1 MRPL37 ITB ITB ITB ITB ICa ICr original ICr ITL ICa ITL ICa ITL original ICr ITL ICr ICa translational termination MRPL28 MRPS26 6 MRPS21 PTCD3 C12orf65 4 MTRF1L MRPL50 MRPS18A 2 MRPS17 MRPL20 0 MRPL52 MRPL17 MRPS33 −2 MRPS15 MRPL45 MRPL30 MRPS27 AURKAIP1 MRPL18 MRPL3 MRPS6 MRPS18B MRPL41 MRPS2 MRPL34 GADD45GIP1 ERAL1 MRPL37 MRPS10 MRPL42 MRPL19 MRPS35 MRPL9 MRPL24 MRPS5 MRPL44 MRPS23 MRPS25 ITB ITB ITB ITB ICa ICr original ICr ITL ICa ITL ICa ITL original ICr ITL ICr ICa translational elongation DIO2 MRPS18B MRPL41 6 MRPS2 MRPL34 GADD45GIP1 4 ERAL1 MRPL37 2 MRPS10 MRPL42 MRPL19 0 MRPL30 MRPS27 AURKAIP1 −2 MRPL18 MRPL3 MRPS6 MRPS35 MRPL9 EEF2K MRPL50 MRPS5 MRPL44 MRPS23 MRPS25 MRPL24 MRPS33 MRPL52 EIF5A2 MRPL17 SECISBP2 MRPS15 MRPL45 MRPS18A MRPS17 MRPL20 MRPL28 MRPS26 MRPS21 PTCD3 ITB ITB ITB ITB ICa ICr ICr ITL original ITL ICa ICa ITL ICr ICr ICa original
    [Show full text]
  • Structural Basis of Mitochondrial Translation Shintaro Aibara1†, Vivek Singh1,2, Angelika Modelska3‡, Alexey Amunts1,2*
    RESEARCH ARTICLE Structural basis of mitochondrial translation Shintaro Aibara1†, Vivek Singh1,2, Angelika Modelska3‡, Alexey Amunts1,2* 1Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden; 2Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; 3Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, Trento, Italy Abstract Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report ~3.0 A˚ resolution structure of the human mitoribosome, including the L7/L12 stalk, and eight structures of its functional complexes with mt-mRNA, mt-tRNAs, recycling factor and additional trans factors. The study reveals a transacting protein module LRPPRC-SLIRP that delivers mt-mRNA to the mitoribosomal small subunit through a dedicated platform formed by the mitochondria-specific protein mS39. Mitoribosomal proteins of the large subunit mL40, mL48, and *For correspondence: mL64 coordinate translocation of mt-tRNA. The comparison between those structures shows [email protected] dynamic interactions between the mitoribosome and its ligands, suggesting a sequential Present address: †Department mechanism of conformational changes. of Molecular Biology, Max- Planck-Institute for BiophysicalChemistry, Go¨ ttingen, Germany; ‡Aix Marseille Introduction Universite´, CNRS, INSERM, Translation in humans takes place in the cytosol and mitochondria. Mitochondrial translation is Centre d’Immunologie responsible for the maintenance of the cellular energetic balance through synthesis of proteins deMarseille-Luminy (CIML), Marseille, France involved in oxidative phosphorylation.
    [Show full text]
  • Comparative Host-Coronavirus Protein Interaction Networks Reveal Pan
    Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms David Gordon, Joseph Hiatt, Mehdi Bouhaddou, Veronica Rezelj, Svenja Ulferts, Hannes Braberg, Alexander Jureka, Kirsten Obernier, Jeffrey Guo, Jyoti Batra, et al. To cite this version: David Gordon, Joseph Hiatt, Mehdi Bouhaddou, Veronica Rezelj, Svenja Ulferts, et al.. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science, American Association for the Advancement of Science, 2020, 370 (6521), pp.eabe9403. 10.1126/science.abe9403. hal-03102291 HAL Id: hal-03102291 https://hal.archives-ouvertes.fr/hal-03102291 Submitted on 7 Jan 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Corrected 21 December 2020. See full text. RESEARCH ◥ RESULTS: Quantitative comparison of the 389 RESEARCH ARTICLE SUMMARY interactors of SARS-CoV-2, 366 of SARS-CoV-1, and 296 of MERS-CoV highlighted interactions CORONAVIRUS with host processes that are conserved across all three viruses, including where nonortholo- Comparative host-coronavirus protein interaction gous proteins from different virus strains seem to fill similar roles. We also localized each networks reveal pan-viral disease mechanisms individually-expressed viral protein by micros- copy and then raised and validated antisera David E.
    [Show full text]
  • A Novel 2.3 Mb Microduplication of 9Q34. 3 Inserted Into 19Q13. 4 in A
    Hindawi Publishing Corporation Case Reports in Pediatrics Volume 2012, Article ID 459602, 7 pages doi:10.1155/2012/459602 Case Report A Novel 2.3 Mb Microduplication of 9q34.3 Inserted into 19q13.4 in a Patient with Learning Disabilities Shalinder Singh,1 Fern Ashton,1 Renate Marquis-Nicholson,1 Jennifer M. Love,1 Chuan-Ching Lan,1 Salim Aftimos,2 Alice M. George,1 and Donald R. Love1, 3 1 Diagnostic Genetics, LabPlus, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand 2 Genetic Health Service New Zealand-Northern Hub, Auckland City Hospital, Private Bag 92024, Auckland 1142, New Zealand 3 School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand Correspondence should be addressed to Donald R. Love, [email protected] Received 1 July 2012; Accepted 27 September 2012 Academic Editors: L. Cvitanovic-Sojat, G. Singer, and V. C. Wong Copyright © 2012 Shalinder Singh 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. Insertional translocations in which a duplicated region of one chromosome is inserted into another chromosome are very rare. We report a 16.5-year-old girl with a terminal duplication at 9q34.3 of paternal origin inserted into 19q13.4. Chromosomal analysis revealed the karyotype 46,XX,der(19)ins(19;9)(q13.4;q34.3q34.3)pat. Cytogenetic microarray analysis (CMA) identified a ∼2.3Mb duplication of 9q34.3 → qter, which was confirmed by Fluorescence in situ hybridisation (FISH).
    [Show full text]
  • A SARS-Cov-2 Protein Interaction Map Reveals Targets for Drug Repurposing
    Article A SARS-CoV-2 protein interaction map reveals targets for drug repurposing https://doi.org/10.1038/s41586-020-2286-9 A list of authors and affiliations appears at the end of the paper Received: 23 March 2020 Accepted: 22 April 2020 A newly described coronavirus named severe acute respiratory syndrome Published online: 30 April 2020 coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than Check for updates 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efcacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and eforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identifed the human proteins that physically associated with each of the SARS-CoV-2 proteins using afnity-purifcation mass spectrometry, identifying 332 high-confdence protein–protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors.
    [Show full text]
  • Transcriptomic and Proteomic Landscape of Mitochondrial
    TOOLS AND RESOURCES Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals Inge Ku¨ hl1,2†*, Maria Miranda1†, Ilian Atanassov3, Irina Kuznetsova4,5, Yvonne Hinze3, Arnaud Mourier6, Aleksandra Filipovska4,5, Nils-Go¨ ran Larsson1,7* 1Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany; 2Department of Cell Biology, Institute of Integrative Biology of the Cell (I2BC) UMR9198, CEA, CNRS, Univ. Paris-Sud, Universite´ Paris-Saclay, Gif- sur-Yvette, France; 3Proteomics Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany; 4Harry Perkins Institute of Medical Research, The University of Western Australia, Nedlands, Australia; 5School of Molecular Sciences, The University of Western Australia, Crawley, Australia; 6The Centre National de la Recherche Scientifique, Institut de Biochimie et Ge´ne´tique Cellulaires, Universite´ de Bordeaux, Bordeaux, France; 7Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden Abstract Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative *For correspondence: analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five [email protected] knockout mouse strains deficient in essential factors required for mitochondrial DNA gene (IKu¨ ); expression, leading to OXPHOS dysfunction. Moreover,
    [Show full text]
  • Synthesis of UMI ( 8 Bases )
    TAN TANTA CU O USLA 20180030515A1DA MATA MATA MALTA MARTINI ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2018/ 0030515 A1 Regev et al. (43 ) Pub . Date : Feb . 1 . 2018 ( 54 ) DROPLET -BASED METHOD AND Related U . S . Application Data APPARATUS FOR COMPOSITE (63 ) Continuation - in -part of application No . PCT/ SINGLE - CELL NUCLEIC ACID ANALYSIS US2015 / 049178 , filed on Sep . 9 , 2015 . ( 71) Applicants : The Broad Institute Inc ., Cambridge, (60 ) Provisional application No . 62 /048 ,227 , filed on Sep . MA (US ) ; Massachusetts Institute of 9 , 2014 , provisional application No. 62 / 146 ,642 , filed Technology , Cambridge , MA (US ) ; on Apr. 13 , 2015 . President and Fellows of Harvard College, Cambridge, MA (US ) Publication Classification (51 ) Int . CI. (72 ) Inventors : Aviv Regev , Cambridge, MA (US ) ; C120 1 /68 (2006 .01 ) Evan Zane MACOSKO , Cambridge , GO6K 19 / 06 ( 2006 . 01 ) MA (US ) ; Steven Andrew ( 2006 .01 ) MCCARROLL , Cambridge , MA (US ) ; C12N 15 / 10 Alexander K . SHALEK , Cambridge, (52 ) U . S . CI. MA (US ) ; Anindita BASU , Cambridge , CPC .. .. C12Q 1/ 6809 ( 2013. 01 ) ; C12N 15 / 1096 MA (US ) ; Christopher B . FORD , (2013 . 01 ) ; C12Q 1 /6869 ( 2013 .01 ) ; C12Q Cambridge, MA (US ) ; Hongkun 1 /6834 ( 2013. 01 ) ; G06K 19 / 06 ( 2013. 01 ) PARK , Lexington , MA (US ) ; David A . (57 ) ABSTRACT WEITZ , Bolton , MA (US ) The present invention generally relates to a combination of molecular barcoding and emulsion - based microfluidics to (21 ) Appl. No. : 15 / 453 ,405 isolate , lyse , barcode , and prepare nucleic acids from indi (22 ) Filed : Mar. 8 , 2017 vidual cells in a high - throughput manner . Synthesis of UMI ( 8 bases) 8 rounds of synthesis • Millions of the same cell barcode per bead • 48 differentmolecular barcodes (UMIS ) per bead Patent Application Publication Feb .
    [Show full text]