DOCSLIB.ORG

Supplementary Tables

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Supplementary Tables Supplementary Tables Supplementary Table S1: Preselected miRNAs used in feature selection Univariate Cox proportional hazards regression analysis of the endpoint freedom from recurrence in the training set (DKTK-ROG sample) allowed the pre-selection of 524 miRNAs (P< 0.5), which were used in the feature selection. P-value was derived from log-rank test. miRNA p-value miRNA p-value miRNA p-value miRNA p-value hsa-let-7g-3p 0.0001520 hsa-miR-1304-3p 0.0490161 hsa-miR-7108-5p 0.1263245 hsa-miR-6865-5p 0.2073121 hsa-miR-6825-3p 0.0004257 hsa-miR-4298 0.0506194 hsa-miR-4453 0.1270967 hsa-miR-6893-5p 0.2120664 hsa-miR-668-3p 0.0005188 hsa-miR-484 0.0518625 hsa-miR-200a-5p 0.1276345 hsa-miR-25-3p 0.2123829 hsa-miR-3622b-3p 0.0005885 hsa-miR-6851-3p 0.0531446 hsa-miR-6090 0.1278692 hsa-miR-3189-5p 0.2136060 hsa-miR-6885-3p 0.0006452 hsa-miR-1276 0.0557418 hsa-miR-148b-3p 0.1279811 hsa-miR-6073 0.2139702 hsa-miR-6875-3p 0.0008188 hsa-miR-3173-3p 0.0559962 hsa-miR-4425 0.1288330 hsa-miR-765 0.2141536 hsa-miR-487b-5p 0.0011381 hsa-miR-650 0.0564616 hsa-miR-6798-3p 0.1293342 hsa-miR-338-5p 0.2153079 hsa-miR-210-5p 0.0012316 hsa-miR-6133 0.0571407 hsa-miR-4472 0.1300006 hsa-miR-6806-5p 0.2173515 hsa-miR-1470 0.0012822 hsa-miR-4701-5p 0.0571720 hsa-miR-4465 0.1304841 hsa-miR-98-5p 0.2184947 hsa-miR-6890-3p 0.0016539 hsa-miR-202-3p 0.0575741 hsa-miR-514b-5p 0.1308790 hsa-miR-500a-3p 0.2185577 hsa-miR-6511b-3p 0.0017165 hsa-miR-4733-5p 0.0616138 hsa-miR-378c 0.1317442 hsa-miR-4515 0.2187539 hsa-miR-7109-3p 0.0021381 hsa-miR-595 0.0629350 hsa-miR-3121-3p 0.1319386 hsa-miR-4510 0.2194305 hsa-miR-640 0.0033118 hsa-miR-4462 0.0633754 hsa-miR-6743-3p 0.1332837 hsa-miR-146a-5p 0.2220503 hsa-miR-6820-3p 0.0036195 hsa-miR-6763-5p 0.0636346 hsa-miR-1296-5p 0.1352142 hsa-miR-200b-3p 0.2245329 hsa-miR-3617-3p 0.0040518 hsa-miR-1238-3p 0.0638492 hsa-miR-1229-5p 0.1354426 hsa-miR-1273e 0.2247443 hsa-let-7d-3p 0.0040669 hsa-miR-200b-5p 0.0643827 hsa-miR-3607-5p 0.1358297 hsa-miR-181d-5p 0.2254029 hsa-miR-7152-5p 0.0041095 hsa-miR-3609 0.0669743 hsa-miR-3607-3p 0.1365370 hsa-miR-5572 0.2256737 hsa-miR-449b-3p 0.0044936 hsa-miR-2277-3p 0.0687210 hsa-miR-887-3p 0.1366652 hsa-miR-378g 0.2276769 hsa-miR-1227-3p 0.0047357 hsa-miR-4763-5p 0.0720451 hsa-miR-452-5p 0.1440784 hsa-miR-3189-3p 0.2301775 hsa-miR-1273d 0.0060961 hsa-miR-7111-5p 0.0730786 hsa-miR-4478 0.1463108 hsa-miR-758-5p 0.2320042 hsa-miR-3940-3p 0.0071343 hsa-miR-4428 0.0740150 hsa-miR-770-5p 0.1485178 hsa-miR-6730-5p 0.2331420 hsa-miR-6792-3p 0.0078134 hsa-miR-6840-3p 0.0759541 hsa-miR-140-3p 0.1500966 hsa-miR-1-3p 0.2372861 hsa-miR-7161-3p 0.0078813 hsa-miR-4455 0.0775395 hsa-miR-6812-3p 0.1518200 hsa-miR-605-5p 0.2396612 hsa-miR-6722-5p 0.0079627 hsa-miR-2117 0.0776026 hsa-miR-664a-3p 0.1521388 hsa-miR-4655-3p 0.2407594 hsa-miR-1910-5p 0.0086288 hsa-miR-494-3p 0.0786895 hsa-miR-1181 0.1533878 hsa-miR-6800-5p 0.2414789 hsa-miR-6509-5p 0.0087440 hsa-miR-18a-5p 0.0797662 hsa-miR-4746-3p 0.1547788 hsa-miR-6088 0.2420315 hsa-miR-204-5p 0.0096105 hsa-miR-5708 0.0799330 hsa-miR-1224-5p 0.1553392 hsa-miR-4685-5p 0.2422472 hsa-miR-6804-3p 0.0096618 hsa-miR-6752-3p 0.0805763 hsa-miR-128-1-5p 0.1556776 hsa-miR-6748-5p 0.2423384 hsa-miR-939-3p 0.0109262 hsa-miR-10a-5p 0.0814598 hsa-miR-616-3p 0.1565544 hsa-miR-4731-3p 0.2427330 hsa-miR-4306 0.0117792 hsa-miR-328-3p 0.0817575 hsa-miR-1908-3p 0.1581024 hsa-miR-3935 0.2429832 hsa-miR-3174 0.0141084 hsa-miR-92b-3p 0.0822815 hsa-miR-142-5p 0.1582806 hsa-miR-2467-3p 0.2441518 hsa-miR-4732-5p 0.0147261 hsa-miR-3162-5p 0.0839691 hsa-miR-4632-5p 0.1588593 hsa-miR-513c-5p 0.2444128 hsa-miR-33b-3p 0.0156521 hsa-miR-4280 0.0841550 hsa-miR-4449 0.1597510 hsa-miR-623 0.2445756 hsa-miR-6508-5p 0.0158996 hsa-miR-1539 0.0867762 hsa-miR-1183 0.1605472 hsa-miR-4767 0.2445884 hsa-miR-4324 0.0165290 hsa-miR-186-5p 0.0872225 hsa-miR-1291 0.1621822 hsa-miR-574-5p 0.2448785 hsa-miR-590-5p 0.0165776 hsa-miR-4642 0.0876855 hsa-miR-6500-5p 0.1635955 hsa-miR-4322 0.2453192 hsa-miR-6784-3p 0.0166261 hsa-miR-615-3p 0.0879593 hsa-miR-4648 0.1638468 hsa-miR-3202 0.2458438 hsa-miR-885-5p 0.0176496 hsa-miR-6876-5p 0.0891828 hsa-miR-6872-5p 0.1646751 hsa-miR-4257 0.2466355 hsa-miR-6821-5p 0.0184064 hsa-miR-708-5p 0.0897671 hsa-miR-762 0.1652679 hsa-miR-6851-5p 0.2479639 hsa-miR-7155-3p 0.0200061 hsa-miR-711 0.0898413 hsa-miR-5088-5p 0.1652707 hsa-miR-532-5p 0.2487441 hsa-miR-195-3p 0.0203311 hsa-miR-3137 0.0926017 hsa-miR-6753-3p 0.1657836 hsa-miR-6722-3p 0.2494773 hsa-miR-185-5p 0.0227247 hsa-miR-6865-3p 0.0963720 hsa-miR-6801-3p 0.1674969 hsa-miR-6165 0.2501110 hsa-miR-6787-3p 0.0227996 hsa-miR-6775-3p 0.0968004 hsa-miR-184 0.1679089 hsa-miR-6882-5p 0.2503938 hsa-miR-6747-5p 0.0237232 hsa-miR-4530 0.0981749 hsa-miR-23a-5p 0.1679222 hsa-miR-6886-5p 0.2513879 hsa-miR-6511a-3p 0.0238634 hsa-miR-663b 0.0995187 hsa-miR-101-3p 0.1680510 hsa-miR-492 0.2518110 hsa-miR-4506 0.0250136 hsa-miR-6837-5p 0.0997487 hsa-miR-5580-3p 0.1709154 hsa-miR-148a-3p 0.2534658 hsa-miR-191-3p 0.0252090 hsa-miR-4657 0.1002823 hsa-miR-6126 0.1714707 hsa-miR-1913 0.2545273 hsa-miR-4644 0.0254266 hsa-miR-429 0.1019673 hsa-miR-181b-5p 0.1716146 hsa-miR-550a-3-5p 0.2554465 hsa-miR-6730-3p 0.0286103 hsa-miR-301a-3p 0.1028710 hsa-miR-6858-3p 0.1729173 hsa-miR-6862-5p 0.2563177 hsa-miR-7108-3p 0.0286443 hsa-miR-1273h-5p 0.1041604 hsa-miR-874-3p 0.1735055 hsa-miR-4655-5p 0.2572530 hsa-miR-3660 0.0292502 hsa-miR-30c-1-3p 0.1054130 hsa-miR-1233-5p 0.1736421 hsa-miR-4725-3p 0.2582799 hsa-miR-4323 0.0292906 hsa-miR-4753-5p 0.1067460 hsa-miR-6778-5p 0.1745063 hsa-miR-422a 0.2597447 hsa-miR-3976 0.0293703 hsa-miR-1909-5p 0.1078986 hsa-miR-328-5p 0.1755199 hsa-miR-4421 0.2598836 hsa-let-7b-3p 0.0299364 hsa-miR-133b 0.1083123 hsa-miR-365b-5p 0.1800151 hsa-miR-3155b 0.2600660 hsa-miR-3972 0.0313027 hsa-miR-6848-3p 0.1100985 hsa-miR-4259 0.1818164 hsa-miR-6125 0.2610979 hsa-miR-4468 0.0324435 hsa-miR-548q 0.1103041 hsa-miR-130b-3p 0.1823601 hsa-miR-6847-5p 0.2618588 hsa-miR-4430 0.0339590 hsa-miR-7113-5p 0.1103884 hsa-miR-29c-5p 0.1827272 hsa-miR-6791-5p 0.2618956 hsa-miR-6800-3p 0.0362758 hsa-miR-425-3p 0.1130173 hsa-miR-378d 0.1866668 hsa-miR-4436b-3p 0.2620868 hsa-miR-4451 0.0363388 hsa-miR-6756-3p 0.1133662 hsa-miR-6873-5p 0.1883127 hsa-miR-339-3p 0.2621292 hsa-miR-4312 0.0368500 hsa-miR-6880-3p 0.1134722 hsa-miR-664b-5p 0.1916503 hsa-miR-141-3p 0.2628940 hsa-miR-378f 0.0389967 hsa-miR-3679-5p 0.1136289 hsa-miR-6777-3p 0.1938001 hsa-miR-516b-5p 0.2638307 hsa-miR-1273g-5p 0.0395595 hsa-miR-1237-3p 0.1148857 hsa-miR-1228-5p 0.1950725 hsa-miR-7150 0.2642509 hsa-miR-6877-3p 0.0413089 hsa-miR-3926 0.1155312 hsa-miR-99b-3p 0.1955799 hsa-miR-3151-3p 0.2646335 hsa-miR-6889-3p 0.0417185 hsa-miR-3154 0.1163788 hsa-miR-6781-5p 0.1963350 hsa-miR-4769-5p 0.2648458 hsa-miR-4695-3p 0.0424169 hsa-miR-6809-5p 0.1171788 hsa-miR-4497 0.1977408 hsa-miR-6796-3p 0.2663793 hsa-miR-1910-3p 0.0434879 hsa-miR-206 0.1174973 hsa-miR-30b-3p 0.2005012 hsa-miR-4634 0.2663950 hsa-miR-6515-3p 0.0443939 hsa-miR-1273h-3p 0.1176645 hsa-miR-4728-3p 0.2054719 hsa-miR-6758-5p 0.2722472 hsa-miR-4800-3p 0.0444738 hsa-miR-378e 0.1189653 hsa-miR-4282 0.2057643 hsa-miR-4538 0.2742868 hsa-miR-631 0.0462931 hsa-miR-1287-5p 0.1234996 hsa-miR-200a-3p 0.2069192 hsa-miR-133a-3p 0.2748945 hsa-miR-4441 0.0471482 hsa-miR-6516-3p 0.1254558 hsa-miR-3678-3p 0.2069721 hsa-miR-106b-5p 0.2751335 miRNA p-value miRNA p-value miRNA p-value miRNA p-value hsa-miR-4701-3p 0.2757559 hsa-miR-4800-5p 0.3389165 hsa-miR-483-5p 0.3982010 hsa-miR-769-3p 0.4622322 hsa-miR-4539 0.2772361 hsa-miR-4444 0.3390121 hsa-miR-4458 0.3983281 hsa-miR-26b-5p 0.4657563 hsa-miR-6819-3p 0.2773291 hsa-miR-6825-5p 0.3397772 hsa-miR-659-3p 0.3988127 hsa-miR-489-3p 0.4673496 hsa-miR-610 0.2775115 hsa-miR-135b-5p 0.3431898 hsa-miR-1207-5p 0.3988137 hsa-miR-4633-5p 0.4680045 hsa-miR-5006-5p 0.2776556 hsa-miR-423-5p 0.3433266 hsa-miR-4311 0.4000437 hsa-miR-8485 0.4684670 hsa-miR-330-3p 0.2787079 hsa-miR-144-3p 0.3437170 hsa-miR-6829-5p 0.4009580 hsa-miR-6861-5p 0.4689076 hsa-miR-1299 0.2787134 hsa-miR-6850-5p 0.3437688 hsa-miR-3663-3p 0.4058370 hsa-miR-7846-3p 0.4697262 hsa-miR-6766-3p 0.2788320 hsa-miR-1285-3p 0.3437961 hsa-miR-6788-5p 0.4065287 hsa-miR-4792 0.4722690 hsa-miR-4750-3p 0.2795178 hsa-miR-345-5p 0.3447189 hsa-miR-5195-5p 0.4068506 hsa-miR-664b-3p 0.4726302 hsa-miR-3620-3p 0.2803378 hsa-miR-3180-5p 0.3450154 hsa-miR-4743-5p 0.4071310 hsa-miR-3141 0.4738397 hsa-miR-4715-5p 0.2819552 hsa-miR-6762-5p 0.3461694 hsa-miR-933 0.4077111 hsa-miR-6834-3p 0.4760892 hsa-miR-93-5p 0.2836876 hsa-miR-6516-5p 0.3468279 hsa-miR-4317 0.4078686 hsa-miR-4429 0.4765072 hsa-miR-146b-5p 0.2853212 hsa-miR-760 0.3487637 hsa-miR-4769-3p 0.4085797 hsa-miR-4717-3p 0.4789832 hsa-miR-1301-5p 0.2857640 hsa-miR-4433a-5p 0.3497714 hsa-miR-3605-5p 0.4094209 hsa-miR-4261 0.4794872 hsa-miR-4676-5p 0.2866471 hsa-miR-151b 0.3498465 hsa-miR-10b-3p 0.4097002 hsa-miR-6739-5p 0.4795600 hsa-miR-3689a-5p 0.2871961 hsa-miR-197-3p 0.3501618 hsa-miR-31-5p 0.4134444 hsa-miR-7515 0.4796186 hsa-miR-200c-3p 0.2877486 hsa-miR-4498 0.3556529 hsa-miR-320c 0.4140729 hsa-miR-6787-5p 0.4806692 hsa-miR-4481 0.2885148 hsa-miR-5196-5p 0.3568088 hsa-miR-3122 0.4145644 hsa-miR-3162-3p 0.4819271 hsa-miR-3667-5p 0.2909124 hsa-miR-601 0.3579403 hsa-miR-6833-5p 0.4146008 hsa-miR-6769a-5p 0.4827356 hsa-miR-4651 0.2909279 hsa-miR-6763-3p 0.3580989 hsa-miR-374a-5p 0.4178368 hsa-miR-6074 0.4840659 hsa-miR-660-5p 0.2910990 hsa-miR-1295a 0.3585605 hsa-miR-5187-5p 0.4186474 hsa-miR-8063 0.4852187 hsa-miR-221-3p 0.2922822 hsa-miR-6132 0.3585949 hsa-miR-526b-5p 0.4197979 hsa-miR-320a
Load more

Recommended publications
  • BLOC-1 and BLOC-3 Regulate VAMP7 Cycling to and From
    BLOC-1 and BLOC-3 regulate VAMP7 cycling to and from melanosomes via distinct tubular transport carriers Megan K. Dennis1,2, Cédric Delevoye3,4, Amanda Acosta-Ruiz1,2, Ilse Hurbain3,4, Maryse Romao3,4, Geoffrey G. Hesketh5, Philip S. Goff6, Elena V. Sviderskaya6, Dorothy C. Bennett6, J. Paul Luzio5, Thierry Galli7, David J. Owen5, Graça Raposo3,4 and Michael S. Marks1,2,8 1Dept. of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute, and 2Dept. of Pathology and Laboratory Medicine and Dept of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 3Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, F-75005, Paris, France; 4 Institut Curie, PSL Research University, CNRS, UMR144, Cell and Tissue Imaging Facility (PICT-IBiSA), F-75005, Paris, France; 5Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; 6Cell Biology & Genetics Research Centre, St. George’s , University of London, London, UK; 7Sorbonne Paris-Cité, Univ. Paris-Diderot, Institut Jacques Monod, CNRS UMR7592, INSERM ERL U950, Membrane Traffic in Health & Disease, Paris, France. 8To whom correspondence should be addressed: Michael S. Marks, Ph.D. Dept. of Pathology & Laboratory Medicine Children's Hospital of Philadelphia Research Institute 816G Abramson Research Center 3615 Civic Center Blvd. Philadelphia, PA 19104 Tel: 215-590-3664 Email: [email protected] Running title: VAMP7 into and out of melanosomes Keywords: SNARE, lysosome-related organelle, melanogenesis, Hermansky-Pudlak syndrome, recycling, endosome, 2 ABSTRACT Endomembrane organelle maturation requires cargo delivery via fusion with membrane transport intermediates and recycling of fusion factors to their sites of origin.
    [Show full text]
  • Ubiquitin-Conjugating Enzyme UBE2J1 Negatively Modulates
    Feng et al. Virology Journal (2018) 15:132 https://doi.org/10.1186/s12985-018-1040-5 RESEARCH Open Access Ubiquitin-conjugating enzyme UBE2J1 negatively modulates interferon pathway and promotes RNA virus infection Tingting Feng1, Lei Deng1, Xiaochuan Lu1, Wen Pan1, Qihan Wu2* and Jianfeng Dai1,2* Abstract Background: Viral infection activates innate immune pathways and interferons (IFNs) play a pivotal role in the outcome of a viral infection. Ubiquitin modifications of host and viral proteins significantly influence the progress of virus infection. Ubiquitin-conjugating enzyme E2s (UBE2) have the capacity to determine ubiquitin chain topology and emerge as key mediators of chain assembly. Methods: In this study, we screened the functions of 34 E2 genes using an RNAi library during Dengue virus (DENV) infection. RNAi and gene overexpression approaches were used to study the gene function in viral infection and interferon signaling. Results: We found that silencing UBE2J1 significantly impaired DENV infection, while overexpression of UBE2J1 enhanced DENV infection. Further studies suggested that type I IFN expression was significantly increased in UBE2J1 silenced cells and decreased in UBE2J1 overexpressed cells. Reporter assay suggested that overexpression of UBE2J1 dramatically suppressed RIG-I directed IFNβ promoter activation. Finally, we have confirmed that UBE2J1 can facilitate the ubiquitination and degradation of transcription factor IFN regulatory factor 3 (IRF3). Conclusion: These results suggest that UBE2 family member UBE2J1 can negatively regulate type I IFN expression, thereby promote RNA virus infection. Keywords: UBE2J1, Dengue virus, Interferons, IRF3, K48 ubiquitination Background antiviral responses [3]. IFN-α/β regulates the synthesis Dengue virus (DENV), transmitted by Aedes aegypti and of antiviral proteins and immunoregulatory factors Aedes albopicuts, causes an emerging tropical disease through the JAK/STAT signaling pathway [4, 5].
    [Show full text]
  • Diagnosing Platelet Secretion Disorders: Examples Cases
    Diagnosing platelet secretion disorders: examples cases Martina Daly Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Disclosures for Martina Daly In compliance with COI policy, ISTH requires the following disclosures to the session audience: Research Support/P.I. No relevant conflicts of interest to declare Employee No relevant conflicts of interest to declare Consultant No relevant conflicts of interest to declare Major Stockholder No relevant conflicts of interest to declare Speakers Bureau No relevant conflicts of interest to declare Honoraria No relevant conflicts of interest to declare Scientific Advisory No relevant conflicts of interest to declare Board Platelet granule release Agonists (FIIa, Collagen, ADP) Signals Activation Shape change Membrane fusion Release of granule contents Platelet storage organelles lysosomes a granules Enzymes including cathepsins Adhesive proteins acid hydrolases Clotting factors and their inhibitors Fibrinolytic factors and their inhibitors Proteases and antiproteases Growth and mitogenic factors Chemokines, cytokines Anti-microbial proteins Membrane glycoproteins dense (d) granules ADP/ATP Serotonin histamine inorganic polyphosphate Platelet a-granule contents Type Prominent components Membrane glycoproteins GPIb, aIIbb3, GPVI Clotting factors VWF, FV, FXI, FII, Fibrinogen, HMWK, FXIII? Clotting inhibitors TFPI, protein S, protease nexin-2 Fibrinolysis components PAI-1, TAFI, a2-antiplasmin, plasminogen, uPA Other protease inhibitors a1-antitrypsin, a2-macroglobulin
    [Show full text]
  • A Drosophila Ortholog of the Human Cylindromatosis Tumor Suppressor
    RESEARCH ARTICLE 2605 Development 134, 2605-2614 (2007) doi:10.1242/dev.02859 A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense Theodore Tsichritzis1, Peer C. Gaentzsch3, Stylianos Kosmidis2, Anthony E. Brown3, Efthimios M. Skoulakis2, Petros Ligoxygakis3,* and George Mosialos1,4,* The cylindromatosis (CYLD) gene is mutated in human tumors of skin appendages. It encodes a deubiquitylating enzyme (CYLD) that is a negative regulator of the NF-␬B and JNK signaling pathways, in vitro. However, the tissue-specific function and regulation of CYLD in vivo are poorly understood. We established a genetically tractable animal model to initiate a systematic investigation of these issues by characterizing an ortholog of CYLD in Drosophila. Drosophila CYLD is broadly expressed during development and, in adult animals, is localized in the fat body, ovaries, testes, digestive tract and specific areas of the nervous system. We demonstrate that the protein product of Drosophila CYLD (CYLD), like its mammalian counterpart, is a deubiquitylating enzyme. Impairment of CYLD expression is associated with altered fat body morphology in adult flies, increased triglyceride levels and increased survival under starvation conditions. Furthermore, flies with compromised CYLD expression exhibited reduced resistance to bacterial infections. All mutant phenotypes described were reversible upon conditional expression of CYLD transgenes. Our results implicate CYLD in a broad range of functions associated with fat homeostasis and host defence in Drosophila. KEY WORDS: Cylindromatosis, Drosophila, Fat body, Host defense, NF-kappaB INTRODUCTION disease and it is required for the proper development of T Familial cylindromatosis is an autosomal-dominant predisposition lymphocytes in mice (Costello et al., 2005; Reiley et al., 2006).
    [Show full text]
  • A Minimum-Labeling Approach for Reconstructing Protein Networks Across Multiple Conditions
    A Minimum-Labeling Approach for Reconstructing Protein Networks across Multiple Conditions Arnon Mazza1, Irit Gat-Viks2, Hesso Farhan3, and Roded Sharan1 1 Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel. Email: [email protected]. 2 Dept. of Cell Research and Immunology, Tel Aviv University, Tel Aviv 69978, Israel. 3 Biotechnology Institute Thurgau, University of Konstanz, Unterseestrasse 47, CH-8280 Kreuzlingen, Switzerland. Abstract. The sheer amounts of biological data that are generated in recent years have driven the development of network analysis tools to fa- cilitate the interpretation and representation of these data. A fundamen- tal challenge in this domain is the reconstruction of a protein-protein sub- network that underlies a process of interest from a genome-wide screen of associated genes. Despite intense work in this area, current algorith- mic approaches are largely limited to analyzing a single screen and are, thus, unable to account for information on condition-specific genes, or reveal the dynamics (over time or condition) of the process in question. Here we propose a novel formulation for network reconstruction from multiple-condition data and devise an efficient integer program solution for it. We apply our algorithm to analyze the response to influenza in- fection in humans over time as well as to analyze a pair of ER export related screens in humans. By comparing to an extant, single-condition tool we demonstrate the power of our new approach in integrating data from multiple conditions in a compact and coherent manner, capturing the dynamics of the underlying processes. 1 Introduction With the increasing availability of high-throughput data, network biol- arXiv:1307.7803v1 [q-bio.QM] 30 Jul 2013 ogy has become the method of choice for filtering, interpreting and rep- resenting these data.
    [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]
  • A Network of Bhlhzip Transcription Factors in Melanoma: Interactions of MITF, TFEB and TFE3
    A network of bHLHZip transcription factors in melanoma: Interactions of MITF, TFEB and TFE3 Josué A. Ballesteros Álvarez Thesis for the degree of Philosophiae Doctor January 2019 Net bHLHZip umritunarþátta í sortuæxlum: Samstarf milli MITF, TFEB og TFE3 Josué A. Ballesteros Álvarez Ritgerð til doktorsgráðu Leiðbeinandi/leiðbeinendur: Eiríkur Steingrímsson Doktorsnefnd: Margrét H. Ögmundsdóttir Þórarinn Guðjónsson Jórunn E. Eyfjörð Lars Rönnstrand Janúar 2019 Thesis for a doctoral degree at tHe University of Iceland. All rigHts reserved. No Part of tHis Publication may be reProduced in any form witHout tHe Prior permission of the copyright holder. © Josue A. Ballesteros Álvarez. 2019 ISBN 978-9935-9421-4-2 Printing by HáskólaPrent Reykjavik, Iceland 2019 Ágrip StjórnPróteinin MITF , TFEB, TFE3 og TFEC (stundum nefnd MiT-TFE þættirnir) tilheyra bHLHZip fjölskyldu umritunarþátta sem bindast DNA og stjórna tjáningu gena. MITF er mikilvægt fyrir myndun og starfsemi litfruma en ættingjar þess, TFEB og TFE3, stjórna myndun og starfsemi lysósóma og sjálfsáti. Sjálfsát er líffræðilegt ferli sem gegnir mikilvægu hlutverki í starfsemi fruma en getur einnig haft áHrif á myndun og meðHöndlun sjúkdóma. Í verkefni þessu var samstarf MITF, TFE3 og TFEB Próteinanna skoðað í sortuæxlisfrumum og hvaða áhrif þau Hafa á tjáningu hvers annars. Eins og MITF eru TFEB og TFE3 genin tjáð í sortuæxlisfrumum og sortuæxlum; TFEC er ekki tjáð í þessum frumum og var því ekki skoðað í þessu verkefni. Með notkun sérvirkra hindra var sýnt að boðleiðir hafa áhrif á staðsetningu próteinanna þriggja í sortuæxlisfrumum. Umritunarþættir þessir geta bundist skyldum DNA-bindisetum og haft áhrif á tjáningu gena sem eru nauðsynleg fyrir myndun bæði lýsósóma og melanósóma.
    [Show full text]
  • The Schizophrenia Risk Gene Product Mir-137 Alters Presynaptic Plasticity
    The schizophrenia risk gene product miR-137 alters presynaptic plasticity The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Siegert, S., J. Seo, E. J. Kwon, A. Rudenko, S. Cho, W. Wang, Z. Flood, et al. 2015. “The schizophrenia risk gene product miR-137 alters presynaptic plasticity.” Nature neuroscience 18 (7): 1008-1016. doi:10.1038/nn.4023. http://dx.doi.org/10.1038/nn.4023. Published Version doi:10.1038/nn.4023 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:24983896 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA HHS Public Access Author manuscript Author Manuscript Author ManuscriptNat Neurosci Author Manuscript. Author manuscript; Author Manuscript available in PMC 2016 January 01. Published in final edited form as: Nat Neurosci. 2015 July ; 18(7): 1008–1016. doi:10.1038/nn.4023. The schizophrenia risk gene product miR-137 alters presynaptic plasticity Sandra Siegert1,2, Jinsoo Seo1,2,*, Ester J. Kwon1,2,*, Andrii Rudenko1,2,*, Sukhee Cho1,2, Wenyuan Wang1,2, Zachary Flood1,2, Anthony J. Martorell1,2, Maria Ericsson4, Alison E. Mungenast1,2, and Li-Huei Tsai1,2,3,5 1Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA 2Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA 3Broad Institute of MIT and Harvard, Cambridge, MA, USA 4Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA Abstract Non-coding variants in the human MIR137 gene locus increase schizophrenia risk at a genome- wide significance level.
    [Show full text]
  • The Ubiquitination Enzymes of Leishmania Mexicana
    The ubiquitination enzymes of Leishmania mexicana Rebecca Jayne Burge Doctor of Philosophy University of York Biology October 2020 Abstract Post-translational modifications such as ubiquitination are important for orchestrating the cellular transformations that occur as the Leishmania parasite differentiates between its main morphological forms, the promastigote and amastigote. Although 20 deubiquitinating enzymes (DUBs) have been partially characterised in Leishmania mexicana, little is known about the role of E1 ubiquitin-activating (E1), E2 ubiquitin- conjugating (E2) and E3 ubiquitin ligase (E3) enzymes in this parasite. Using bioinformatic methods, 2 E1, 13 E2 and 79 E3 genes were identified in the L. mexicana genome. Subsequently, bar-seq analysis of 23 E1, E2 and HECT/RBR E3 null mutants generated in promastigotes using CRISPR-Cas9 revealed that the E2s UBC1/CDC34, UBC2 and UEV1 and the HECT E3 ligase HECT2 are required for successful promastigote to amastigote differentiation and UBA1b, UBC9, UBC14, HECT7 and HECT11 are required for normal proliferation during mouse infection. Null mutants could not be generated for the E1 UBA1a or the E2s UBC3, UBC7, UBC12 and UBC13, suggesting these genes are essential in promastigotes. X-ray crystal structure analysis of UBC2 and UEV1, orthologues of human UBE2N and UBE2V1/UBE2V2 respectively, revealed a heterodimer with a highly conserved structure and interface. Furthermore, recombinant L. mexicana UBA1a was found to load ubiquitin onto UBC2, allowing UBC2- UEV1 to form K63-linked di-ubiquitin chains in vitro. UBC2 was also shown to cooperate with human E3s RNF8 and BIRC2 in vitro to form non-K63-linked polyubiquitin chains, but association of UBC2 with UEV1 inhibits this ability.
    [Show full text]
  • Supporting Information
    Supporting Information Figure S1. The functionality of the tagged Arp6 and Swr1 was confirmed by monitoring cell growth and sensitivity to hydeoxyurea (HU). Five-fold serial dilutions of each strain were plated on YPD with or without 50 mM HU and incubated at 30°C or 37°C for 3 days. Figure S2. Localization of Arp6 and Swr1 on chromosome 3. The binding of Arp6-FLAG (top), Swr1-FLAG (middle), and Arp6-FLAG in swr1 cells (bottom) are compared. The position of Tel 3L, Tel 3R, CEN3, and the RP gene are shown under the panels. Figure S3. Localization of Arp6 and Swr1 on chromosome 4. The binding of Arp6-FLAG (top), Swr1-FLAG (middle), and Arp6-FLAG in swr1 cells (bottom) in the whole chromosome region are compared. The position of Tel 4L, Tel 4R, CEN4, SWR1, and RP genes are shown under the panels. Figure S4. Localization of Arp6 and Swr1 on the region including the SWR1 gene of chromosome 4. The binding of Arp6- FLAG (top), Swr1-FLAG (middle), and Arp6-FLAG in swr1 cells (bottom) are compared. The position and orientation of the SWR1 gene is shown. Figure S5. Localization of Arp6 and Swr1 on chromosome 5. The binding of Arp6-FLAG (top), Swr1-FLAG (middle), and Arp6-FLAG in swr1 cells (bottom) are compared. The position of Tel 5L, Tel 5R, CEN5, and the RP genes are shown under the panels. Figure S6. Preferential localization of Arp6 and Swr1 in the 5′ end of genes. Vertical bars represent the binding ratio of proteins in each locus.
    [Show full text]
  • RNF11 at the Crossroads of Protein Ubiquitination
    biomolecules Review RNF11 at the Crossroads of Protein Ubiquitination Anna Mattioni, Luisa Castagnoli and Elena Santonico * Department of Biology, University of Rome Tor Vergata, Via della ricerca scientifica, 00133 Rome, Italy; [email protected] (A.M.); [email protected] (L.C.) * Correspondence: [email protected] Received: 29 September 2020; Accepted: 8 November 2020; Published: 11 November 2020 Abstract: RNF11 (Ring Finger Protein 11) is a 154 amino-acid long protein that contains a RING-H2 domain, whose sequence has remained substantially unchanged throughout vertebrate evolution. RNF11 has drawn attention as a modulator of protein degradation by HECT E3 ligases. Indeed, the large number of substrates that are regulated by HECT ligases, such as ITCH, SMURF1/2, WWP1/2, and NEDD4, and their role in turning off the signaling by ubiquitin-mediated degradation, candidates RNF11 as the master regulator of a plethora of signaling pathways. Starting from the analysis of the primary sequence motifs and from the list of RNF11 protein partners, we summarize the evidence implicating RNF11 as an important player in modulating ubiquitin-regulated processes that are involved in transforming growth factor beta (TGF-β), nuclear factor-κB (NF-κB), and Epidermal Growth Factor (EGF) signaling pathways. This connection appears to be particularly significant, since RNF11 is overexpressed in several tumors, even though its role as tumor growth inhibitor or promoter is still controversial. The review highlights the different facets and peculiarities of this unconventional small RING-E3 ligase and its implication in tumorigenesis, invasion, neuroinflammation, and cancer metastasis. Keywords: Ring Finger Protein 11; HECT ligases; ubiquitination 1.
    [Show full text]
  • Syntaxin 16'S Newly Deciphered Roles in Autophagy
    cells Perspective Syntaxin 16’s Newly Deciphered Roles in Autophagy Bor Luen Tang 1,2 1 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore; [email protected]; Tel.: +65-6516-1040 2 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 119077, Singapore Received: 19 November 2019; Accepted: 6 December 2019; Published: 17 December 2019 Abstract: Syntaxin 16, a Qa-SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor), is involved in a number of membrane-trafficking activities, particularly transport processes at the trans-Golgi network (TGN). Recent works have now implicated syntaxin 16 in the autophagy process. In fact, syntaxin 16 appears to have dual roles, firstly in facilitating the transport of ATG9a-containing vesicles to growing autophagosomes, and secondly in autolysosome formation. The former involves a putative SNARE complex between syntaxin 16, VAMP7 and SNAP-47. The latter occurs via syntaxin 16’s recruitment by Atg8/LC3/GABARAP family proteins to autophagosomes and endo-lysosomes, where syntaxin 16 may act in a manner that bears functional redundancy with the canonical autophagosome Qa-SNARE syntaxin 17. Here, I discuss these recent findings and speculate on the mechanistic aspects of syntaxin 16’s newly found role in autophagy. Keywords: ATG9; autophagy; autophagosome; SNARE; syntaxin 16; syntaxin 17; VAMP7 1. Introduction Vesicular membrane trafficking [1] and macroautophagy [2] are two highly conserved cellular membrane remodeling processes in eukaryotes. The former mediates the transfer of materials between membrane compartments, while the latter serves to degrade and recycle cytosolic as well as membranous cellular materials.
    [Show full text]