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Supplemental Table 1: Results of primary druggable genome v2 (DG2) Achilles heel siRNA screen in KMS11 multiple myeloma cells. Results are provided per siRNA as a B-score centered on the median and normalized to the standard deviation. All statistically validated vulnerable genes are listed in Table 1 in the paper; siRNA against other genes are unverified for sensitivity/specificity (individual siRNA results may be inaccurate and should be examined within a robust statistical framework). Entrez siRNA Gene SYMBOL Description B_Score Target Sequence Vendor target annotation Top refseq hit 1 A1BG alpha-1-B glycoprotein 0.02 CAGAAGATGCGTATCAGTATT NM_130786: NM_130786: 1 A1BG alpha-1-B glycoprotein -1.38 CTGCGTCTACGTGGACCTGAA NM_130786: NM_130786: 2 A2M alpha-2-macroglobulin -4.22 ACGGATGAGCATGGCCTTGTA NM_000014: NM_000014: 2 A2M alpha-2-macroglobulin 0.20 CACCAACTCAAAGATTCGTAA NM_000014: NM_000014: 53947 A4GALT alpha 1,4-galactosyltransferase (globotriaosylceramide synthase) 0.85 AGGAGAATAATCAATAGAATA NM_017436: NM_017436: 53947 A4GALT alpha 1,4-galactosyltransferase (globotriaosylceramide synthase) 1.32 CACGTGCTGGTCCTGATGAAA NM_017436: NM_017436: 13 AADAC arylacetamide deacetylase (esterase) 0.67 TTGGCTGATGACAACAAATTA NM_001086: NM_001086: 13 AADAC arylacetamide deacetylase (esterase) 1.06 CAGCCTCTTGATGTAGATTTA NM_001086: NM_001086: 22848 AAK1 AP2 associated kinase 1 -1.50 AACGTGAGTAGCGGTGATGTA NM_014911: NM_014911: 22848 AAK1 AP2 associated kinase 1 0.53 CCAGGTGGTAAACCTGATGAA NM_014911: NM_014911: 10157 AASS aminoadipate-semialdehyde synthase 0.51 AACGATTGATCTTGTGGCTTA NM_005763: NM_005763: 10157 AASS aminoadipate-semialdehyde synthase 0.50 AACGGTACATTACCTGATAAA NM_005763: NM_005763: 26574 AATF apoptosis antagonizing transcription factor 0.07 TCGAGAACTCATAGAACGGAA NM_012138: NM_012138: 26574 AATF apoptosis antagonizing transcription factor -0.58 TTGGAAGGAAGGATCAAACTA NM_012138: NM_012138: AB095936 1.11 TCCGGGTGATTCACTATAGAA AB095936 No hits found till 3 mismatches 18 ABAT 4-aminobutyrate aminotransferase 0.59 TCCCGATGATTCCATACGGAA NM_000663: NM_020686:NM_000663: 18 ABAT 4-aminobutyrate aminotransferase -1.10 CACGCACTCTAAAGCCATTCA NM_000663: NM_020686:NM_000663: 19 ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1 -2.65 CCGGAACATGCTACAATACCA NM_005502: NM_005502: 19 ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1 0.29 CACCGACAATAAGCTGAATAA NM_005502: NM_005502: 10349 ABCA10 ATP-binding cassette, sub-family A (ABC1), member 10 0.63 AAAGAGATAAGCGTGCGTCAA NM_080282: NM_080282: 10349 ABCA10 ATP-binding cassette, sub-family A (ABC1), member 10 0.61 CAGCCTGTTAATCGTTAATAA NM_080282: NM_080282: 26154 ABCA12 ATP-binding cassette, sub-family A (ABC1), member 12 -2.28 CAGGTGACTCCGATAATATAA NM_015657: NM_015657: 26154 ABCA12 ATP-binding cassette, sub-family A (ABC1), member 12 -0.97 AAGCCTAATGATCCGACTTTA NM_015657: NM_015657:NM_173076: 20 ABCA2 ATP-binding cassette, sub-family A (ABC1), member 2 -3.23 CTGGAAGAACGTGACGCTCAA NM_001606: NM_001606: 20 ABCA2 ATP-binding cassette, sub-family A (ABC1), member 2 1.06 CTGGGTCAGTCCCGTATTTAT NM_001606: NM_001606:NM_212533: 21 ABCA3 ATP-binding cassette, sub-family A (ABC1), member 3 0.09 CCGCTTGAAGATTCAGTCGGA NM_001089: NM_001089: 21 ABCA3 ATP-binding cassette, sub-family A (ABC1), member 3 2.25 CCAAGTTTATCTCATCCTTTA NM_001089: NM_001089: 24 ABCA4 ATP-binding cassette, sub-family A (ABC1), member 4 -1.42 AAGGAGCCCATTGTTGATGAA NM_000350: NM_000350: 24 ABCA4 ATP-binding cassette, sub-family A (ABC1), member 4 -0.71 CCGTCTGAACATCACCTTCTA NM_000350: NM_000350: 23461 ABCA5 ATP-binding cassette, sub-family A (ABC1), member 5 1.71 GTACGTAATGTTCCAATCTAA NM_018672: NM_018672:NM_172232: 23461 ABCA5 ATP-binding cassette, sub-family A (ABC1), member 5 0.61 TGGCGAGCAATTCGAACTGCA NM_018672: NM_018672:NM_172232: 23460 ABCA6 ATP-binding cassette, sub-family A (ABC1), member 6 1.68 ACGCGAGGCTCGCCATCGCAA NM_080284: NM_080284:NM_172346: 23460 ABCA6 ATP-binding cassette, sub-family A (ABC1), member 6 1.80 AAGGATTACATTCTAGAGCTA NM_080284: NM_080284:NM_172346: 10347 ABCA7 ATP-binding cassette, sub-family A (ABC1), member 7 -0.59 CCCGGCCACGTGCGCATCAAA NM_019112: NM_019112:NM_033308: 10347 ABCA7 ATP-binding cassette, sub-family A (ABC1), member 7 0.80 GACGAGGATGTAGCCCGTGAA NM_019112: NM_019112:NM_033308: 10351 ABCA8 ATP-binding cassette, sub-family A (ABC1), member 8 -0.03 TTCGTTAGCATGCAATGCCAA NM_007168: NM_007168: 10351 ABCA8 ATP-binding cassette, sub-family A (ABC1), member 8 0.91 CTATCTGGCATTGGCGATTTA NM_007168: NM_007168: 10350 ABCA9 ATP-binding cassette, sub-family A (ABC1), member 9 -0.06 TCGATAGTTGCTACTGATCTA NM_080283: NM_080283:NM_172386: 10350 ABCA9 ATP-binding cassette, sub-family A (ABC1), member 9 -2.64 GAGGGCGATCATAGGGCATAA NM_080283: NM_080283:NM_172386: 5243 ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), member 1 -0.60 ATCGAGTCACTGCCTAATAAA NM_000927: NM_000927: 5243 ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), member 1 0.00 CACGGAAGGCCTAATGCCGAA NM_000927: NM_000927: 23456 ABCB10 ATP-binding cassette, sub-family B (MDR/TAP), member 10 -3.24 TAGACCCTAAGAAGTAATTAA NM_012089: NM_012089: 23456 ABCB10 ATP-binding cassette, sub-family B (MDR/TAP), member 10 -3.19 CTAGGTATTATTAAGAATGAA NM_012089: NM_012089: 8647 ABCB11 ATP-binding cassette, sub-family B (MDR/TAP), member 11 0.84 CGGGATGATAGTCAATTCCTT NM_003742: NM_003742: 8647 ABCB11 ATP-binding cassette, sub-family B (MDR/TAP), member 11 0.02 TCAGATCGGGATGATAGTCAA NM_003742: NM_003742: 5244 ABCB4 ATP-binding cassette, sub-family B (MDR/TAP), member 4 0.59 CCGACTGTCTACGGTCCGAAA NM_000443: NM_000443:NM_018849:NM_018850: 5244 ABCB4 ATP-binding cassette, sub-family B (MDR/TAP), member 4 -0.93 TCGGCATTTAGTGACAAAGAA NM_000443: NM_000443:NM_018849:NM_018850: 340273 ABCB5 ATPATP-binding-binding cassette,cassette, subsub-family-family B (MDR/TAP),(MDR/TAP), member 5 1.951.95 TTGGAGAATATACGTACTATA NM_ 178559: NM_ 178559: 340273 ABCB5 ATP-binding cassette, sub-family B (MDR/TAP), member 5 -0.58 TACGTACTATAGTGTCATTAA NM_178559: NM_178559: 10058 ABCB6 ATP-binding cassette, sub-family B (MDR/TAP), member 6 0.06 CAGGCTCTCAACTGTGGTCAA NM_005689: NM_005689: 10058 ABCB6 ATP-binding cassette, sub-family B (MDR/TAP), member 6 -2.04 CACCTACATTATCCAGCTGTA NM_005689: NM_005689: 22 ABCB7 ATP-binding cassette, sub-family B (MDR/TAP), member 7 -2.24 AACCCTCATAGTATCTATTCA NM_004299: NM_004299: 22 ABCB7 ATP-binding cassette, sub-family B (MDR/TAP), member 7 -0.48 AGCATTTATCTTGCTGGTCAA NM_004299: NM_004299: 11194 ABCB8 ATP-binding cassette, sub-family B (MDR/TAP), member 8 -3.83 AAGCTGGAAGCTTCCGATGAA NM_007188: NM_007188: 11194 ABCB8 ATP-binding cassette, sub-family B (MDR/TAP), member 8 0.90 AGGAATTTAAGTCATCCTTCA NM_007188: NM_007188: 23457 ABCB9 ATP-binding cassette, sub-family B (MDR/TAP), member 9 2.53 CCCGGTCAATAAAGTGTACTA NM_019624: NM_019624:NM_203445:NM_203444:NM_019625: 23457 ABCB9 ATP-binding cassette, sub-family B (MDR/TAP), member 9 4.45 CTGCGTGACCACGGCCATCTA NM_019624: NM_019624:NM_203445:NM_203444:NM_019625: NM_004996:NM_019902:NM_019901:NM_019900: 4363 ABCC1 ATP-binding cassette, sub-family C (CFTR/MRP), member 1 -1.62 CCGAGTGGAATTCCGGAACTA NM_004996: NM_019899:NM_019862:NM_019898: NM_004996:NM_019902:NM_019901:NM_019900: 4363 ABCC1 ATP-binding cassette, sub-family C (CFTR/MRP), member 1 -0.96 TCGGATGTCATCTGAAATGGA NM_004996: NM_019899:NM_019862:NM_019898: 89845 ABCC10 ATP-binding cassette, sub-family C (CFTR/MRP), member 10 0.01 AGCCCAGATTGTGGTAGATTA NM_033450: NM_033450: 89845 ABCC10 ATP-binding cassette, sub-family C (CFTR/MRP), member 10 0.29 CTGCTGGTACCCGTCAACAAA NM_033450: NM_033450: 85320 ABCC11 ATP-binding cassette, sub-family C (CFTR/MRP), member 11 0.35 AGGCTACTTGATGGCTCTCAA NM_032583: NM_145186:NM_033151:NM_032583: 85320 ABCC11 ATP-binding cassette, sub-family C (CFTR/MRP), member 11 -1.84 CTCCTCCAGTTGGATCATCAA NM_032583: NM_145186:NM_033151:NM_032583: NM_145188:NM_145190:NM_145189:NM_145187: 94160 ABCC12 ATP-binding cassette, sub-family C (CFTR/MRP), member 12 -0.45 CGGTAGGAAATTACCCTGAAA NM_033226: NM_033226: NM_145188:NM_145190:NM_145189:NM_145187: 94160 ABCC12 ATP-binding cassette, sub-family C (CFTR/MRP), member 12 0.39 CCGGAAAGTCATCGTTAGGAA NM_033226: NM_033226: 150000 ABCC13 ATP-binding cassette, sub-family C (CFTR/MRP), member 13 1.08 CTCGCTTGAATGTATGCGATA NM_138726: NM_138726: 150000 ABCC13 ATP-binding cassette, sub-family C (CFTR/MRP), member 13 -0.30 TAGGGTTATCTACAATATAAA NM_138726: NM_138726: 1244 ABCC2 ATP-binding cassette, sub-family C (CFTR/MRP), member 2 -2.38 CCGTATCAGGTTTGCCAGTTA NM_000392: NM_000392: 1244 ABCC2 ATP-binding cassette, sub-family C (CFTR/MRP), member 2 -1.35 CTGGAGTACCTACAAGCAATA NM_000392: NM_000392: 8714 ABCC3 ATP-binding cassette, sub-family C (CFTR/MRP), member 3 -0.43 AAGGGTGAAATCCGCATTGAT NM_003786: NM_020037:NM_020038:NM_003786: 8714 ABCC3 ATP-binding cassette, sub-family C (CFTR/MRP), member 3 0.01 CCGGAATTATTCTGTGCGCTA NM_003786: NM_020037:NM_020038:NM_003786: 10257 ABCC4 ATP-binding cassette, sub-family C (CFTR/MRP), member 4 0.07 GAGGTTAAAGACAGTCATATA NM_005845: NM_005845: 10257 ABCC4 ATP-binding cassette, sub-family C (CFTR/MRP), member 4 -3.17 CTCCTAGTACTTAGAAATACA NM_005845: NM_005845: 10057 ABCC5 ATP-binding cassette, sub-family C (CFTR/MRP), member 5 -1.52 ATAGCCTATATTTACAGTGAA NM_005688: NM_005688: 10057 ABCC5 ATP-binding cassette, sub-family C (CFTR/MRP), member 5 1.00 ATCCTTCACGATCAAACCTAA NM_005688: NM_005688: 368 ABCC6 ATP-binding cassette, sub-family C (CFTR/MRP), member 6 -1.28 CACGTGTGCTGTGCTGAGCAA NM_001171: NM_001171: 368 ABCC6 ATP-binding cassette, sub-family C (CFTR/MRP),
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    Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of
  • 5' Untranslated Region Elements Show High Abundance and Great

    5' Untranslated Region Elements Show High Abundance and Great

    International Journal of Molecular Sciences Article 0 5 Untranslated Region Elements Show High Abundance and Great Variability in Homologous ABCA Subfamily Genes Pavel Dvorak 1,2,* , Viktor Hlavac 2,3 and Pavel Soucek 2,3 1 Department of Biology, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech Republic 2 Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech Republic; [email protected] (V.H.); [email protected] (P.S.) 3 Toxicogenomics Unit, National Institute of Public Health, 100 42 Prague, Czech Republic * Correspondence: [email protected]; Tel.: +420-377593263 Received: 7 October 2020; Accepted: 20 November 2020; Published: 23 November 2020 Abstract: The 12 members of the ABCA subfamily in humans are known for their ability to transport cholesterol and its derivatives, vitamins, and xenobiotics across biomembranes. Several ABCA genes are causatively linked to inborn diseases, and the role in cancer progression and metastasis is studied intensively. The regulation of translation initiation is implicated as the major mechanism in the processes of post-transcriptional modifications determining final protein levels. In the current bioinformatics study, we mapped the features of the 50 untranslated regions (50UTR) known to have the potential to regulate translation, such as the length of 50UTRs, upstream ATG codons, upstream open-reading frames, introns, RNA G-quadruplex-forming sequences, stem loops, and Kozak consensus motifs, in the DNA sequences of all members of the subfamily. Subsequently, the conservation of the features, correlations among them, ribosome profiling data as well as protein levels in normal human tissues were examined. The 50UTRs of ABCA genes contain above-average numbers of upstream ATGs, open-reading frames and introns, as well as conserved ones, and these elements probably play important biological roles in this subfamily, unlike RG4s.
  • Identification of New Substrates and Physiological Relevance

    Identification of New Substrates and Physiological Relevance

    Université de Montréal The Multifaceted Proprotein Convertases PC7 and Furin: Identification of New Substrates and Physiological Relevance Par Stéphanie Duval Biologie Moléculaire, Faculté de médecine Thèse présentée en vue de l’obtention du grade de Philosophiae doctor (Ph.D) en Biologie moléculaire, option médecine cellulaire et moléculaire Avril 2020 © Stéphanie Duval, 2020 Résumé Les proprotéines convertases (PCs) sont responsables de la maturation de plusieurs protéines précurseurs et sont impliquées dans divers processus biologiques importants. Durant les 30 dernières années, plusieurs études sur les PCs se sont traduites en succès cliniques, toutefois les fonctions spécifiques de PC7 demeurent obscures. Afin de comprendre PC7 et d’identifier de nouveaux substrats, nous avons généré une analyse protéomique des protéines sécrétées dans les cellules HuH7. Cette analyse nous a permis d’identifier deux protéines transmembranaires de fonctions inconnues: CASC4 et GPP130/GOLIM4. Au cours de cette thèse, nous nous sommes aussi intéressé au rôle de PC7 dans les troubles comportementaux, grâce à un substrat connu, BDNF. Dans le chapitre premier, je présenterai une revue de la littérature portant entre autres sur les PCs. Dans le chapitre II, l’étude de CASC4 nous a permis de démontrer que cette protéine est clivée au site KR66↓NS par PC7 et Furin dans des compartiments cellulaires acides. Comme CASC4 a été rapporté dans des études de cancer du sein, nous avons généré des cellules MDA- MB-231 exprimant CASC4 de type sauvage et avons démontré une diminution significative de la migration et de l’invasion cellulaire. Ce phénotype est causé notamment par une augmentation du nombre de complexes d’adhésion focale et peut être contrecarré par la surexpression d’une protéine CASC4 mutante ayant un site de clivage optimale par PC7/Furin ou encore en exprimant une protéine contenant uniquement le domaine clivé N-terminal.