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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: 88 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: 88. Num of CEMs: 1. 0.0 0.2 0.4 0.6 0.8 1.0 Cldn7 Epcam Marveld2 Cldn3 Cldn4 Pard6b Ocln Tjp3 Tjp2 F11r Inadl Cldn23 Prkcz Shroom2 Cldn8 Igsf5 Cldn6 Magi3 Tjp1 Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam Cldn7 Epcam Marveld2 Cldn3 Cldn4 Pard6b Ocln Tjp3 Tjp2 F11r CEM 1 (137 datasets) Inadl Cldn23 Prkcz Shroom2 Cldn8 Igsf5 Cldn6 Magi3 Tjp1 Dlg1 Cldn11 Vapa Traf4 Pmp22 Cldn2 Cldn5 Mpdz Lin7b Lin7c Cldn15 Bves Jam2 Ect2 Cldn14 Pard3 Cldn16 Magi2 Pard6g Tgfbr1 Apc Ash1l Arhgef2 Mpp5 Mtdh Cgnl1 Strn Cdh5 Jam3 Aoc1 Rab13 Plxdc1 Cldn19 Cldn10 Tjap1 Singletons Synpo Pard3b Wnk4 Magi1 Amot Sympk Amotl1 Adcyap1r1 Cldn22 Cgn Nphp4 Ubn1 Cldn12 Frmd4a Micall2 Lin7a Ddx58 Cldn1 Cldn9 Arhgap17 Wnk3 Marveld3 Ank3 Cyth1 Clmp Nphp1 Pard6a Cldn18 Cxadr Tbcd Amotl2 Mpp7 Gm626 Esam 2610528J11Rik Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page1 Tmem30b Marveld2 Arhgef16 Shroom2 Tmprss2 Sowahb Mapk13 Pard6b Ap1m2 Cldn23 Epcam Galnt3 Spint2 Spint1 Cdcp1 Kcnk1 Rab25 Erbb3 Magi3 Esrp2 Esrp1 Cldn6 Cldn8 Cldn4 Cldn3 Cldn7 Prss8 Ripk4 Prkcz Grhl2 Tmc4 Krt18 Cdh1 Dsg2 Lad1 Tnk1 Igsf5 Inadl Grb7 Mal2 Ocln St14 F11r Tjp1 Tjp2 Tjp3 Krt7 Krt8 Irf6 0.0 1.0 GSE13259 [10] GSE21761 [43] GSE6837 [8] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE31313 [22] GSE35247 [15] GSE12618 [6] GSE12881 [6] GSE27675 [14] GSE17797 [19] GSE1983 [6] GSE34206 [8] GSE10659 [6] GSE20577 [12] GSE16380 [8] GSE10589 [6] GSE3501 [6] GSE31106 [18] GSE15794 [6] GSE51628 [15] GSE7069 [8] GSE3822 [16] GSE8024 [8] GSE26290 [12] GSE17263 [6] GSE29798 [6] GSE48884 [12] GSE22040 [9] GSE54349 [6] GSE34839 [6] GSE28593 [9] GSE11221 [9] GSE11382 [10] GSE6383 [6] GSE19979 [6] GSE51213 [16] GSE24295 [7] GSE9977 [24] GSE5309 [7] GSE16110 [16] GSE50813 [24] GSE15326 [10] GSE17796 [39] GSE23502 [8] GSE7810 [9] GSE34729 [6] GSE17096 [20] GSE17097 [20] GSE52474 [154] GSE31004 [8] GSE30684 [6] GSE15808 [29] GSE42565 [6] GSE8828 [6] GSE37658 [6] GSE14753 [6] GSE51080 [18] GSE25828 [8] GSE56755 [13] GSE55028 [6] GSE5671 [18] GSE11628 [12] GSE10290 [24] GSE27455 [12] GSE4189 [14] GSE18586 [9] GSE28664 [17] GSE41925 [8] GSE15069 [15] GSE2019 [12] GSE51483 [45] GSE50439 [15] GSE4816 [12] GSE12499 [10] GSE50603 [12] GSE16925 [15] GSE30488 [52] GSE24291 [6] GSE48790 [8] GSE56482 [8] GSE31940 [8] GSE12986 [10] GSE19616 [16] GSE31561 [36] GSE45143 [6] GSE27429 [8] GSE54774 [12] GSE7309 [12] GSE26771 [12] GSE17102 [9] GSE46211 [18] GSE40609 [28] GSE46209 [21] GSE15267 [8] GSE8488 [15] GSE17513 [12] GSE21247 [60] GSE26446 [8] GSE6290 [37] GSE18281 [33] GSE29632 [42] GSE26076 [12] GSE16364 [6] GSE38754 [40] GSE5976 [12] GSE13044 [59] GSE6933 [15] GSE13302 [30] GSE38831 [7] GSE55622 [22] GSE47872 [6] GSE30247 [16] GSE32095 [24] GSE42601 [6] GSE59437 [30] GSE14458 [12] GSE11259 [9] GSE35961 [12] GSE11186 [33] GSE45968 [6] GSE31359 [8] GSE23845 [15] GSE23408 [39] GSE9725 [16] GSE4002 [13] GSE39583 [21] GSE46169 [30] GSE13963 [15] GSE4734 [61] GSE16496 [102] GSE12078 [8] GSE18135 [18] GSE11274 [20] GSE19925 [6] GSE25737 [6] GSE22506 [12] GSE17266 [59] GSE27717 [11] GSE31598 [12] GSE24207 [73] GSE32223 [12] GSE37431 [6] GSE48382 [10] GSE49346 [6] GSE10776 [15] GSE38048 [20] GSE13235 [9] GSE13408 [14] GSE17297 [32] GSE30561 [6] GSE34351 [12] GSE35226 [12] GSE19091 [6] GSE39233 [40] GSE6589 [11] CEM+ CEM GSE20372 [6] GSE23200 [6] GSE10806 [11] GSE19076 [12] GSE6210 [12] GSE27848 [16] 0.0 GSE10989 [6] GSE13032 [18] GSE38693 [8] Scale ofaveragePearsoncorrelations GSE46970 [15] GSE18771 [6] GSE8726 [7] GSE20954 [14] GSE31244 [6] GSE31570 [6] 0.2 GSE9954 [70] GSE44923 [16] GSE32966 [24] GSE21054 [8] GSE29072 [18] GSE5241 [9] GSE15452 [26] GSE6196 [9] GSE9760 [12] 0.4 GSE10246 [182] GSE17794 [44] GSE21755 [25] GSE8249 [46] GSE28389 [20] GSE22989 [10] GSE17840 [9] GSE32199 [6] GSE22307 [23] 0.6 GSE36618 [6] GSE8863 [18] GSE15268 [16] GSE22034 [8] GSE27811 [9] GSE37221 [6] GSE36229 [14] GSE4230 [8] GSE47196 [6] 0.8 GSE6540 [12] GSE7381 [6] GSE42049 [8] GSE28559 [30] Score 22.58 22.71 23.16 23.36 23.94 24.95 25.45 25.66 25.67 25.79 25.90 26.28 26.46 26.51 26.76 27.59 27.75 28.80 28.91 28.96 29.39 29.83 29.90 30.74 31.38 32.12 33.06 33.40 33.55 34.60 36.94 1.0 Notes 2310030G06Rik 0610040J01Rik 1810019J16Rik Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page2 Tmem184a Cdc42bpg Epb4.1l4b Tmem125 Camsap3 AI661453 Ccdc120 Tmem54 Arhgap8 Plekha7 Tacstd2 Arhgef5 Krtcap3 Stard10 Lrrc16a Cyb561 C77080 Tfcp2l1 Cnksr1 Rassf7 Sh3yl1 Eps8l2 Lamc2 Rhpn2 Macc1 Hook1 Eppk1 Epha1 Nipal2 Elmo3 Wfdc2 Fxyd3 Ptpn3 Rasef Stap2 Krt19 Pkp3 Dsc2 Llgl2 Crb3 Perp Cblc Klc3 Stx3 Ildr1 Elf3 Ehf 0.0 1.0 GSE13259 [10] GSE21761 [43] GSE6837 [8] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE31313 [22] GSE35247 [15] GSE12618 [6] GSE12881 [6] GSE27675 [14] GSE17797 [19] GSE1983 [6] GSE34206 [8] GSE10659 [6] GSE20577 [12] GSE16380 [8] GSE10589 [6] GSE3501 [6] GSE31106 [18] GSE15794 [6] GSE51628 [15] GSE7069 [8] GSE3822 [16] GSE8024 [8] GSE26290 [12] GSE17263 [6] GSE29798 [6] GSE48884 [12] GSE22040 [9] GSE54349 [6] GSE34839 [6] GSE28593 [9] GSE11221 [9] GSE11382 [10] GSE6383 [6] GSE19979 [6] GSE51213 [16] GSE24295 [7] GSE9977 [24] GSE5309 [7] GSE16110 [16] GSE50813 [24] GSE15326 [10] GSE17796 [39] GSE23502 [8] GSE7810 [9] GSE34729 [6] GSE17096 [20] GSE17097 [20] GSE52474 [154] GSE31004 [8] GSE30684 [6] GSE15808 [29] GSE42565 [6] GSE8828 [6] GSE37658 [6] GSE14753 [6] GSE51080 [18] GSE25828 [8] GSE56755 [13] GSE55028 [6] GSE5671 [18] GSE11628 [12] GSE10290 [24] GSE27455 [12] GSE4189 [14] GSE18586 [9] GSE28664 [17] GSE41925 [8] GSE15069 [15] GSE2019 [12] GSE51483 [45] GSE50439 [15] GSE4816 [12] GSE12499 [10] GSE50603 [12] GSE16925 [15] GSE30488 [52] GSE24291 [6] GSE48790 [8] GSE56482 [8] GSE31940 [8] GSE12986 [10] GSE19616 [16] GSE31561 [36] GSE45143 [6] GSE27429 [8] GSE54774 [12] GSE7309 [12] GSE26771 [12] GSE17102 [9] GSE46211 [18] GSE40609 [28] GSE46209 [21] GSE15267 [8] GSE8488 [15] GSE17513 [12] GSE21247 [60] GSE26446 [8] GSE6290 [37] GSE18281 [33] GSE29632 [42] GSE26076 [12] GSE16364 [6] GSE38754 [40] GSE5976 [12] GSE13044 [59] GSE6933 [15] GSE13302 [30] GSE38831 [7] GSE55622 [22] GSE47872 [6] GSE30247 [16] GSE32095 [24] GSE42601 [6] GSE59437 [30] GSE14458 [12] GSE11259 [9] GSE35961 [12] GSE11186 [33] GSE45968 [6] GSE31359 [8] GSE23845 [15] GSE23408 [39] GSE9725 [16] GSE4002 [13] GSE39583 [21] GSE46169 [30] GSE13963 [15] GSE4734 [61] GSE16496 [102] GSE12078 [8] GSE18135 [18] GSE11274 [20] GSE19925 [6] GSE25737 [6] GSE22506 [12] GSE17266 [59] GSE27717 [11] GSE31598 [12] GSE24207 [73] GSE32223 [12] GSE37431 [6] GSE48382 [10] GSE49346 [6] GSE10776 [15] GSE38048 [20] GSE13235 [9] GSE13408 [14] GSE17297 [32] GSE30561 [6] GSE34351 [12] GSE35226 [12] GSE19091 [6] GSE39233 [40] GSE6589 [11] CEM+ CEM GSE20372 [6] GSE23200 [6] GSE10806 [11] GSE19076 [12] GSE6210 [12] GSE27848 [16] 0.0 GSE10989 [6] GSE13032 [18] GSE38693 [8] Scale ofaveragePearsoncorrelations GSE46970 [15] GSE18771 [6] GSE8726 [7] GSE20954 [14] GSE31244 [6] GSE31570 [6] 0.2 GSE9954 [70] GSE44923 [16] GSE32966 [24] GSE21054 [8] GSE29072 [18] GSE5241 [9] GSE15452 [26] GSE6196 [9] GSE9760 [12] 0.4 GSE10246 [182] GSE17794 [44] GSE21755 [25] GSE8249 [46] GSE28389 [20] GSE22989 [10] GSE17840 [9] GSE32199 [6] GSE22307 [23] 0.6 GSE36618 [6] GSE8863 [18] GSE15268 [16] GSE22034 [8] GSE27811 [9] GSE37221 [6] GSE36229 [14] GSE4230 [8] GSE47196 [6] 0.8 GSE6540 [12] GSE7381 [6] GSE42049 [8] GSE28559 [30] Score 13.94 14.40 14.42 14.66 14.76 14.82 14.83 15.05 15.15 15.28 15.28 15.32 15.45 15.48 15.55 15.60 15.66 15.89 15.97 16.12 16.17 16.39 16.43 16.63 16.85 17.16 17.18 17.37 18.06 18.12 18.75 18.94 19.14 19.17 19.35 19.39 20.09 20.16 20.21 20.34 20.56 20.75 20.80 21.17 21.30 21.50 21.58 21.81 22.06 22.57 1.0 Notes 4930506M07Rik 2010107G23Rik 5730559C18Rik 2010300C02Rik Symbol Num ofCEMGenes:19.Predicted291.SelectedDatasets:137.Strength:12.1 CEM 1,Geneset"[G]tightjunction",Page3 AA986860 Tmem139 Sh3bgrl2 Cep170b Baiap2l1 Plekhh1 Fam84b Slc44a4 Mansc1 Serinc2 Gyltl1b Cmtm8 Smagp Rnf128 Fgfbp1 Vsig10 Lamb3 Myo5b Myh14 Hook2 Ckmt1 Ap1s3 Nfe2l3 Rab15 Usp43 Elovl7 Foxa1 Prr15l Gipc2 Mpzl3 Mpzl2 Pof1b Grhl1 Map7 Pvrl2 Tuft1 Pawr F2rl1 Agrn Evpl Tgfa Pls1 Etl4 Mal Ppl Ezr 0.0 1.0 GSE13259 [10] GSE21761 [43] GSE6837 [8] Only showingfirst200datasets-Seetxtoutputforfulldetails.
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    www.nature.com/scientificreports OPEN High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma Songwei Li1, Jian Huang2, Fan Yang1, Haiping Zeng3, Yuyun Tong1 & Kejia Li2* Hepatocellular carcinoma (HCC) is one of the most commonly cancers with poor prognosis and drug response. Identifying accurate therapeutic targets would facilitate precision treatment and prolong survival for HCC. In this study, we analyzed liver hepatocellular carcinoma (LIHC) RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), and identifed PARD3 as one of the most signifcantly diferentially expressed genes (DEGs). Then, we investigated the relationship between PARD3 and outcomes of HCC, and assessed predictive capacity. Moreover, we performed functional enrichment and immune infltration analysis to evaluate functional networks related to PARD3 in HCC and explore its role in tumor immunity. PARD3 expression levels in 371 HCC tissues were dramatically higher than those in 50 paired adjacent liver tissues (p < 0.001). High PARD3 expression was associated with poor clinicopathologic feathers, such as advanced pathologic stage (p = 0.002), vascular invasion (p = 0.012) and TP53 mutation (p = 0.009). Elevated PARD3 expression also correlated with lower overall survival (OS, HR = 2.08, 95% CI = 1.45–2.98, p < 0.001) and disease-specifc survival (DSS, HR = 2.00, 95% CI = 1.27–3.16, p = 0.003). 242 up-regulated and 71 down-regulated genes showed signifcant association with PARD3 expression, which were involved in genomic instability, response to metal ions, and metabolisms. PARD3 is involved in diverse immune infltration levels in HCC, especially negatively related to dendritic cells (DCs), cytotoxic cells, and plasmacytoid dendritic cells (pDCs).
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  • Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
    BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in
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  • Effect of Cigarette Smoke on DNA Methylation and Lung Function
    de Vries et al. Respiratory Research (2018) 19:212 https://doi.org/10.1186/s12931-018-0904-y RESEARCH Open Access From blood to lung tissue: effect of cigarette smoke on DNA methylation and lung function Maaike de Vries1,2* , Diana A van der Plaat1,2, Ivana Nedeljkovic3, Rikst Nynke Verkaik-Schakel4, Wierd Kooistra2,5, Najaf Amin3, Cornelia M van Duijn3, Corry-Anke Brandsma2,5, Cleo C van Diemen6, Judith M Vonk1,2 and H Marike Boezen1,2 Abstract Background: Genetic and environmental factors play a role in the development of COPD. The epigenome, and more specifically DNA methylation, is recognized as important link between these factors. We postulate that DNA methylation is one of the routes by which cigarette smoke influences the development of COPD. In this study, we aim to identify CpG-sites that are associated with cigarette smoke exposure and lung function levels in whole blood and validate these CpG-sites in lung tissue. Methods: The association between pack years and DNA methylation was studied genome-wide in 658 current smokers with >5 pack years using robust linear regression analysis. Using mediation analysis, we subsequently selected the CpG-sites that were also associated with lung function levels. Significant CpG-sites were validated in lung tissue with pyrosequencing and expression quantitative trait methylation (eQTM) analysis was performed to investigate the association between DNA methylation and gene expression. Results: 15 CpG-sites were significantly associated with pack years and 10 of these were additionally associated with lung function levels. We validated 5 CpG-sites in lung tissue and found several associations between DNA methylation and gene expression.
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  • Association Study Between Polymorphisms of the PARD3 Gene and Schizophrenia
    EXPERIMENTAL AND THERAPEUTIC MEDICINE 3: 881-885, 2012 Association study between polymorphisms of the PARD3 gene and schizophrenia SU KANG KIM1*, JONG YOON LEE2*, HAE JEONG PARK1, JONG WOO KIM3 and JOO-HO CHUNG1 1Department of Pharmacology and Kohwang Medical Research Institute; 2School of Medicine, Kyung Hee University, Seoul 130-701; 3Department of Neuropsychiatry, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea Received December 13, 2011; Accepted January 20, 2012 DOI: 10.3892/etm.2012.496 Abstract. The aim of this study was to investigate whether Introduction par-3 partitioning defective 3 homolog (C. elegans) (PARD3) single nucleotide polymorphisms (SNPs) are associated with Schizophrenia is a severe, debilitating, psychiatric disorder. schizophrenia. A total of 204 Korean schizophrenic patients Although the exact etiology of schizophrenia is unknown, [117 male, 41.1±9.6 years (mean age ± SD); 87 female, twin, family and adoption studies have provided consistent 42.6±11.5] and 351 control subjects (170 male, 43.8±6.6 years; evidence that genetic factors play a major role in the pathogen- 181 female, 44.2±5.8) were enrolled. We genotyped nine esis of schizophrenia. SNPs of the PARD3 gene [rs7075263 (intron), rs10827392 In a recent study, the data showed that polymorphisms (intron), rs773970 (intron), rs2252655 (intron), rs10763984 of several genes affect gene expression or the function of (intron), rs3781128 (Ser889Ser), rs1936429 (intron), rs671228 the encoded protein in the human brain (1). Clinical, epide- (intron) and rs16935163 (intron)]. Genotypes of PARD3 poly- miological, neuroimaging and postmortem data suggest that morphisms were evaluated by direct sequencing.
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  • ADHD) Gene Networks in Children of Both African American and European American Ancestry
    G C A T T A C G G C A T genes Article Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry Yichuan Liu 1 , Xiao Chang 1, Hui-Qi Qu 1 , Lifeng Tian 1 , Joseph Glessner 1, Jingchun Qu 1, Dong Li 1, Haijun Qiu 1, Patrick Sleiman 1,2 and Hakon Hakonarson 1,2,3,* 1 Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA; [email protected] (Y.L.); [email protected] (X.C.); [email protected] (H.-Q.Q.); [email protected] (L.T.); [email protected] (J.G.); [email protected] (J.Q.); [email protected] (D.L.); [email protected] (H.Q.); [email protected] (P.S.) 2 Division of Human Genetics, Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 3 Department of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA * Correspondence: [email protected]; Tel.: +1-267-426-0088 Abstract: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with poorly understood molecular mechanisms that results in significant impairment in children. In this study, we sought to assess the role of rare recurrent variants in non-European populations and outside of coding regions. We generated whole genome sequence (WGS) data on 875 individuals, Citation: Liu, Y.; Chang, X.; Qu, including 205 ADHD cases and 670 non-ADHD controls. The cases included 116 African Americans H.-Q.; Tian, L.; Glessner, J.; Qu, J.; Li, (AA) and 89 European Americans (EA), and the controls included 408 AA and 262 EA.
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  • Role of PDZ-Binding Motif from West Nile Virus NS5 Protein on Viral
    www.nature.com/scientificreports OPEN Role of PDZ‑binding motif from West Nile virus NS5 protein on viral replication Emilie Giraud1*, Chloé Otero del Val2, Célia Caillet‑Saguy2, Nada Zehrouni2, Cécile Khou5, Joël Caillet4, Yves Jacob3, Nathalie Pardigon5 & Nicolas Wolf2 West Nile virus (WNV) is a Flavivirus, which can cause febrile illness in humans that may progress to encephalitis. Like any other obligate intracellular pathogens, Flaviviruses hijack cellular protein functions as a strategy for sustaining their life cycle. Many cellular proteins display globular domain known as PDZ domain that interacts with PDZ‑Binding Motifs (PBM) identifed in many viral proteins. Thus, cellular PDZ‑containing proteins are common targets during viral infection. The non‑structural protein 5 (NS5) from WNV provides both RNA cap methyltransferase and RNA polymerase activities and is involved in viral replication but its interactions with host proteins remain poorly known. In this study, we demonstrate that the C‑terminal PBM of WNV NS5 recognizes several human PDZ‑ containing proteins using both in vitro and in cellulo high‑throughput methods. Furthermore, we constructed and assayed in cell culture WNV replicons where the PBM within NS5 was mutated. Our results demonstrate that the PBM of WNV NS5 is important in WNV replication. Moreover, we show that knockdown of the PDZ‑containing proteins TJP1, PARD3, ARHGAP21 or SHANK2 results in the decrease of WNV replication in cells. Altogether, our data reveal that interactions between the PBM of NS5 and PDZ‑containing proteins afect West Nile virus replication. Arboviruses include numerous human and animal pathogens that are important global health threats responsible for arboviroses.
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