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Drug Repurposing to Treat Glucocorticoid Resistance in Asthma Alberta L

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Drug Repurposing to Treat Glucocorticoid Resistance in Asthma Alberta L Supplementary Materials Drug repurposing to treat glucocorticoid resistance in asthma Alberta L. Wang MD, MS, Ronald Panganiban PhD, Weiliang Qiu PhD, Alvin T. Kho PhD, Geoffrey Chupp MD, Deborah A. Meyers PhD, Eugene R. Bleecker MD, Scott T. Weiss MD, MS, Quan Lu PhD, Kelan G. Tantisira MD, MPH Figure S1. Change in FEV1 percent predicted in CAMP and SARP a) Change in FEV1 % predicted in CAMP from enrollment to month two on inhaled budesonide. Subjects in the first tertile were poor responders and in the third tertile were good responders. Median change in FEV1 % predicted in the lowest tertile was -2.7 (± 6.7), middle tertile was 4.9 (± 3.3), and highest tertile was 15.8 (± 16.7) (P < 0.001). b) Change in FEV1 % predicted in SARP from visit 2 prior to administration of intramuscular triamcinolone to visit 3 eighteen days post-corticosteroid administration. Median change in FEV1 % predicted of -4.0 (± 5.6) in poor responders and 2.6 (± 3.9) in good responders (P < 0.001). J. Pers. Med. 2021, 11, 175. https://doi.org/10.3390/jpm11030175 www.mdpi.com/journal/jpm J. Pers. Med. 2021, 11, 175 2 of 30 Table S1. Genes in CAMP differentially expressed in corticosteroid poor responders compared to corticosteroid good responders Entrez HGNC Chromosome T-statistic P-value gene ID gene symbol band 23090 ZNF423 16q12.1 -4.18 6.17E-05 3763 KCNJ6 21q22.13 -4.16 6.81E-05 168002 DACT2 6q27 -3.86 1.99E-04 8704 B4GALT2 1p34.1 -3.76 2.91E-04 84570 COL25A1 4q25 -3.71 3.42E-04 51166 AADAT 4q33 3.66 4.12E-04 6785 ELOVL4 6q14.1 -3.63 4.57E-04 402317 OR2A42 7q35 -3.62 4.59E-04 9796 PHYHIP 8p21.3 3.57 5.50E-04 10107 TRIM10 6p22.1 -3.50 6.98E-04 54581 SCAND2P 15q25.2 -3.47 7.71E-04 200312 RNF215 22q12.2 3.47 7.74E-04 148170 CDC42EP5 19q13.42 -3.41 9.53E-04 92747 BPIFB1 20q11.21 -3.36 1.09E-03 153579 BTNL9 5q35.3 3.36 1.10E-03 172 AFG3L1P 16q24.3 3.33 1.23E-03 337963 KRTAP23-1 21q22.11 -3.33 1.23E-03 399879 NA NA -3.32 1.28E-03 391114 OR6K3 1q23.1 -3.31 1.31E-03 389337 ARHGEF37 5q32 3.27 1.46E-03 85317 BAGE4 21p11.1 -3.25 1.58E-03 9611 NCOR1 17p12-p11.2 -3.23 1.66E-03 84166 NLRC5 16q13 3.18 1.96E-03 284129 SLC26A11 17q25.3 3.18 1.99E-03 6728 SRP19 5q22.2 -3.17 2.04E-03 6121 RPE65 1p31.3 -3.16 2.07E-03 10347 ABCA7 19p13.3 3.16 2.10E-03 25907 TMEM158 3p21.31 -3.14 2.24E-03 178 AGL 1p21.2 -3.13 2.29E-03 10123 ARL4C 2q37.1 3.13 2.30E-03 341276 OR10A2 11p15.4 -3.12 2.34E-03 84645 C22orf23 22q13.1 -3.10 2.51E-03 5599 MAPK8 10q11.22 3.10 2.55E-03 8601 RGS20 8q11.23 3.08 2.67E-03 57795 BRINP2 1q25.2 -3.07 2.72E-03 149469 NA NA -3.06 2.86E-03 27239 GPR162 12p13.31 -3.05 2.92E-03 28981 IFT81 12q24.11 -3.05 2.95E-03 J. Pers. Med. 2021, 11, 175 3 of 30 554226 ANKRD30BL 2q21.2 3.05 2.96E-03 504188 NA NA -3.05 2.96E-03 117144 CATSPER1 11q13.1 -3.04 3.00E-03 899 CCNF 16p13.3 -3.04 3.04E-03 5333 PLCD1 3p22.2 3.03 3.08E-03 56034 PDGFC 4q32.1 3.03 3.16E-03 6442 SGCA 17q21.33 -3.02 3.25E-03 10520 ZNF211 19q13.43 3.02 3.26E-03 56888 KCMF1 2p11.2 -3.00 3.39E-03 6772 STAT1 2q32.2 -2.98 3.58E-03 54819 ZCCHC10 5q31.1 -2.97 3.69E-03 30812 SOX8 16p13.3 -2.97 3.71E-03 11162 NUDT6 4q28.1 -2.96 3.82E-03 8793 TNFRSF10D 8p21.3 2.96 3.84E-03 256933 NPB 17q25.3 2.96 3.84E-03 9424 KCNK6 19q13.2 2.96 3.88E-03 9128 PRPF4 9q32 -2.95 3.99E-03 2115 ETV1 7p21.2 2.94 4.09E-03 51700 CYB5R2 11p15.4 -2.93 4.25E-03 9628 RGS6 14q24.2 -2.92 4.34E-03 84929 FIBCD1 9q34.12 2.91 4.50E-03 51816 ADA2 22q11.1 2.91 4.50E-03 160518 DENND5B 12p11.21 -2.91 4.50E-03 252995 FNDC5 1p35.1 -2.90 4.54E-03 4361 MRE11 11q21 2.89 4.71E-03 2230 FDX1 11q22.3 -2.88 4.80E-03 283685 GOLGA6L2 15q11.2 -2.88 4.81E-03 55867 SLC22A11 11q13.1 2.87 5.08E-03 337976 KRTAP20-2 21q22.11 2.86 5.12E-03 166336 PRICKLE2 3p14.1 2.86 5.14E-03 9609 RAB36 22q11.23 2.86 5.17E-03 23414 ZFPM2 8q23.1 2.86 5.20E-03 387758 FIBIN 11p14.2 2.85 5.26E-03 4916 NTRK3 15q25.3 2.84 5.41E-03 79642 ARSJ 4q26 -2.84 5.41E-03 7399 USH2A 1q41 2.84 5.50E-03 84171 LOXL4 10q24.2 2.83 5.57E-03 127254 ERICH3 1p31.1 -2.83 5.57E-03 2054 STX2 12q24.33 2.83 5.58E-03 80279 CDK5RAP3 17q21.32 2.82 5.80E-03 4192 MDK 11p11.2 2.82 5.86E-03 8706 B3GALNT1 3q26.1 2.80 6.16E-03 J. Pers. Med. 2021, 11, 175 4 of 30 147409 DSG4 18q12.1 2.80 6.18E-03 255352 NA NA 2.80 6.19E-03 3305 HSPA1L 6p21.33 -2.79 6.26E-03 90187 EMILIN3 20q12 2.79 6.37E-03 8484 GALR3 22q13.1 -2.78 6.43E-03 81833 SPACA1 6q15 2.78 6.56E-03 56606 SLC2A9 4p16.1 2.77 6.67E-03 9689 BZW1 2q33.1 -2.77 6.77E-03 441639 OR9K2 12q13.2 -2.77 6.78E-03 66037 BOLL 2q33.1 2.76 6.79E-03 221718 LINC00518 6p24.3 -2.76 6.95E-03 8218 CLTCL1 22q11.21 -2.74 7.24E-03 1761 DMRT1 9p24.3 2.74 7.25E-03 400110 ANKRD20A19P 13q12.12 -2.74 7.32E-03 55281 TMEM140 7q33 -2.73 7.40E-03 25948 KBTBD2 7p14.3 2.73 7.51E-03 54567 DLL4 15q15.1 2.73 7.51E-03 4009 LMX1A 1q23.3 2.72 7.63E-03 339175 METTL2A 17q23.2 -2.72 7.66E-03 2917 GRM7 3p26.1 -2.72 7.76E-03 400823 FAM177B 1q41 -2.72 7.80E-03 27237 ARHGEF16 1p36.32 2.71 7.87E-03 26952 SMR3A 4q13.3 -2.71 7.89E-03 8503 PIK3R3 1p34.1 2.71 8.01E-03 3855 KRT7 12q13.13 2.70 8.19E-03 84106 PRAM1 19p13.2 -2.70 8.20E-03 10413 YAP1 11q22.1 -2.70 8.26E-03 54887 UHRF1BP1 6p21.31 2.69 8.33E-03 440590 ZYG11A 1p32.3 2.69 8.34E-03 127064 OR2T12 1q44 -2.69 8.43E-03 554251 FBXO48 2p13.3 2.69 8.45E-03 27129 HSPB7 1p36.13 -2.69 8.48E-03 283358 B4GALNT3 12p13.33 2.69 8.48E-03 8785 MATN4 20q13.12 -2.68 8.60E-03 84251 SGIP1 1p31.3 2.68 8.60E-03 84220 RGPD5 2q13 -2.68 8.62E-03 284296 NA NA 2.68 8.65E-03 53335 BCL11A 2p16.1 -2.68 8.67E-03 3886 KRT35 17q21.2 -2.68 8.71E-03 337880 KRTAP11-1 21q22.11 -2.68 8.73E-03 917 CD3G 11q23.3 -2.67 8.89E-03 947 CD34 1q32.2 -2.67 8.91E-03 J. Pers. Med. 2021, 11, 175 5 of 30 3671 ISLR 15q24.1 -2.66 9.05E-03 163259 DENND2C 1p13.2 2.66 9.10E-03 149233 IL23R 1p31.3 2.66 9.13E-03 22981 NINL 20p11.21 -2.66 9.23E-03 4620 MYH2 17p13.1 2.65 9.40E-03 10575 CCT4 2p15 -2.64 9.56E-03 6183 MRPS12 19q13.2 -2.64 9.57E-03 196527 ANO6 12q12 -2.64 9.63E-03 388646 GBP7 1p22.2 2.63 9.91E-03 777 CACNA1E 1q25.3 2.63 9.94E-03 4197 NA NA 2.63 9.94E-03 5803 PTPRZ1 7q31.32 2.63 9.97E-03 J. Pers. Med. 2021, 11, 175 6 of 30 Table S2. Genes in SARP differentially expressed in corticosteroid poor responders compared to corticosteroid good responders Entrez HGNC Chromosome Ensembl stable ID T-statistic P-value gene ID gene symbol band ENSG00000188242 170622 COMMD6 13q22.2 -4.75 2.19E-04 ENSG00000224936 100302691 LINC00184 1q42.3 -4.68 2.52E-04 ENSG00000172425 221421 RSPH9 6p21.1 -4.67 2.59E-04 ENSG00000196465 90576 ZNF799 19p13.2 -4.65 2.70E-04 ENSG00000260053 352963 HLA-P 6p22.1 -4.61 2.92E-04 ENSG00000162910 574407 OBSCN-AS1 1q42.13 -4.36 4.87E-04 ENSG00000158560 5207 PFKFB1 Xp11.21 -4.32 5.31E-04 ENSG00000213971 --- NA NA -4.24 6.25E-04 ENSG00000272888 --- NA NA 4.21 6.65E-04 ENSG00000236035 100507114 LINC00445 13q13.3 -4.17 7.30E-04 ENSG00000239128 --- NA NA 4.16 7.36E-04 ENSG00000248126 --- NA NA -4.15 7.52E-04 ENSG00000174951 170506 DHX36 3q25.2 -4.09 8.65E-04 ENSG00000213046 163486 DENND1B 1q31.3 4.07 8.88E-04 ENSG00000262516 --- NA NA -4.07 8.89E-04 ENSG00000163202 4184 SMCP 1q21.3 -4.02 9.90E-04 ENSG00000231169 --- NA NA -3.99 1.07E-03 ENSG00000273192 246785 OLA1P1 22q13.2 -3.97 1.11E-03 ENSG00000261519 284215 DLGAP1-AS5 18p11.31 -3.94 1.17E-03 ENSG00000167618 284339 TMEM145 19q13.2 -3.91 1.24E-03 ENSG00000187952 441194 PMS2CL 7p22.1 3.88 1.33E-03 ENSG00000131686 261734 NPHP4 1p36.31 -3.83 1.49E-03 ENSG00000152082 112714 TUBA3E 2q21.1 -3.79 1.60E-03 ENSG00000167311 10449 ACAA2 18q21.1 3.79 1.60E-03 ENSG00000088320 22974 TPX2 20q11.21 3.75 1.75E-03 ENSG00000271525 --- NA NA 3.75 1.75E-03 ENSG00000207926 407028 MIR302A 4q25 -3.73 1.82E-03 ENSG00000105205 79935 CCNP 19q13.2 3.72 1.88E-03 ENSG00000212158 --- NA NA -3.70 1.96E-03 ENSG00000169918 2990 GUSB 7q11.21 3.70 1.97E-03 ENSG00000259208 --- NA NA -3.69 2.00E-03 ENSG00000073536 6389 SDHA 5p15.33 -3.66 2.12E-03 ENSG00000237211 --- NA NA 3.64 2.22E-03 ENSG00000120279 80231 TASL Xp21.2 3.62 2.29E-03 ENSG00000262096 --- NA NA -3.60 2.40E-03 ENSG00000164077 4486 MST1R 3p21.31 -3.60 2.42E-03 ENSG00000257838 --- NA NA -3.59 2.45E-03 ENSG00000140465 170691 ADAMTS17 15q26.3 -3.54 2.72E-03 J.
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