RNAi

Gene Info

  • Species:Human (Homo sapiens)
  • GeneID:54554
  • Symbol:WDR5B
  • Description:WD repeat domain 5B
DataSource: http://genomernai.dkfz.de/v16/genedetails/54554

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Stable_ID Entrez_ID Gene_ID Gene_Symbol Reagent_ID Score Phenotype Conditions Follow_Up Comment Screen_Title Publication_Title Authors Publication_Year Pubmed_ID Biosource Biomodel Assay Method Library Scope Reagent_Type Score_Type Cutoff Notes
GR00053-A 54554 NM_019069 WDR5B np sp none no Genome stability A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Paulsen et al. 2009 19647519 Cell line HeLa gamma-H2AX phosphorylation and DNA content Fluorescence siARRAY human genome siRNA library Genome-wide siRNA p-value Complex criteria Confidence groupings from 4 to 1 (highest level of confidence in group 4)
GR00054-A 54554 NM_019069 WDR5B np 0.82 none no Combinatorial effect with paclitaxel Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Whitehurst et al. 2007 17429401 Cell line NCI-H1155 Viability (synthetic lethal) ATP level # G-005000-01 Genome-wide siRNA Paclitaxel/control ratio Complex criteria Additional information about 87 high-confidence hits
GR00056-A 54554 NM_019069 WDR5B np 1.004 none no Melanogenesis Genome-wide siRNA-based functional genomics of pigmentation identifies novel genes and pathways that impact melanogenesis in human cells. Ganesan et al. 2008 19057677 Cell line MNT-1 Melanin protein expression and viability Absorbance and luminescence rp Genome-wide siRNA Normalized absorbance ratio > 2 standard deviations below mean Additional information about a secondary screen (retest to determine false-positive rate)
GR00057-A-1 54554 NM_019069 WDR5B M-013375-00 -0.74 none no Wnt/beta-catenin pathway regulation (1) A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer. Tang et al. 2008 18621708 Cell line HeLa Wnt pathway reporter Luminescence Human siArray siRNA library Genome-wide siRNA Z-score > 4 Screen without Wnt3A stimulation. Additional information about secondary screens (Dharmacon and Qiagen libraries).
GR00057-A-2 54554 NM_019069 WDR5B M-013375-00 sp none no Wnt/beta-catenin pathway regulation (2) A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer. Tang et al. 2008 18621708 Cell line HeLa Wnt pathway reporter Luminescence Human siArray siRNA library Genome-wide siRNA Complex, SP Complex criteria Screen with Wnt3A stimulation. Additional information about secondary screens (Dharmacon and Qiagen libraries).
GR00098-A-1 54554 ENSG00000196981 WDR5B ENSG00000196981 sp none no Cell division (1) Genome-scale RNAi profiling of cell division in human tissue culture cells. Kittler et al. 2007 17994010 Cell line HeLa Cell number and DNA content Laser scanning cytometry rp Genome-wide esiRNA Complex, sp Complex criteria
GR00133-A-1 54554 54554 WDR5B np -0.023762 none no Salmonella enterica subspecies 1 serovar Typhimurium invasion (1) RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42. Misselwitz et al. 2011 21407211 Cell line HeLa Gentamycin protection invasion assay Fluorescence Druggable genome library V2.0 Druggable genes siRNA log2 median Complex criteria
GR00151-A-1 54554 ENSG00000196981 WDR5B np -0.975 none no Homologous recombination DNA double-strand break repair (HR-DSBR) (1) A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. Słabicki et al. 2010 20613862 Cell line HeLa (HR-DSBR) DR-GFP reporter Flow cytometry Custom-made Genome-wide esiRNA Z-score < -2 OR > 2
GR00180-A-1 54554 54554 WDR5B PL-50005 0.909 none no Hepatitis C virus replication (1) A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Tai et al. 2009 19286138 Cell line Huh7/Rep-Feo HCV replicon RNA copy number Luminescence siARRAY Human Genome siRNA Library Genome-wide siRNA q-value Complex criteria
GR00184-A-1 54554 NM_019069 WDR5B M-013375-00 -2.26958226817271 Decreased POU5F1-GFP protein expression no Self-renewal and pluripotency in human embryonic stem cells (1) A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. Chia et al. 2010 20953172 Cell line hESC H1 POU5F1 protein expression Fluorescence SMARTpool siRNA library Genome-wide siRNA Z-score < -2
GR00196-A-1 54554 ENSG00000196981 np sp none no TP53 interactions (1) A systematic RNAi synthetic interaction screen reveals a link between p53 and snoRNP assembly. Krastev et al. 2011 21642980 Cell line HCT116 ( wildtype and TP53 knockout) TP53 protein expression and viability Fluorescence rp Genome-wide esiRNA Complex, sp Complex criteria
GR00197-A-1 54554 54554 WDR5B M-013375-00 -0.442806553 none no Human papillomavirus oncogene expression regulation (1) Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent regulators of human papillomavirus oncogene expression. Smith et al. 2010 20133580 Cell line C33A/BE2/18LCR c4 HPV18 LCR reporter activity Luminescence Human siGENOME SMARTpool library Genome-wide siRNA Z-score > Author-submitted data. Phenotype strength according to Z-scores: weak: 2 - 3; moderate: 3 - 5; strong: > 5
GR00236-A-1 54554 54554 WDR5B M-013375-00 0.50132078581536 none no Homologous recombination DNA double-strand break repair (HR-DSBR) (1) A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response. Adamson et al. 2012 22344029 Cell line DR-U2OS (HR-DSBR) DR-GFP reporter and DNA content Fluorescence Human siGENOME siRNA (G-005000-05) Genome-wide siRNA Relative HR ratio < ~0.4 OR > 1.88 Cutoff values correspond 2 standard deviations from the screen-wide mean
GR00237-A 54554 54554 WDR5B Hs_WDR5B_10 sp none no DNA replication regulation by Cul4-associated genes RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. Piwko et al. 2010 21113133 Cell line HeLa H2B and PCNA protein expression Fluorescence np Cul4-associated genes siRNA Z-score > 5 for > half of siRNAs
GR00237-A 54554 54554 WDR5B Hs_WDR5B_11 sp none no DNA replication regulation by Cul4-associated genes RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. Piwko et al. 2010 21113133 Cell line HeLa H2B and PCNA protein expression Fluorescence np Cul4-associated genes siRNA Z-score > 5 for > half of siRNAs
GR00237-A 54554 54554 WDR5B Hs_WDR5B_8 sp none no DNA replication regulation by Cul4-associated genes RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. Piwko et al. 2010 21113133 Cell line HeLa H2B and PCNA protein expression Fluorescence np Cul4-associated genes siRNA Z-score > 5 for > half of siRNAs
GR00237-A 54554 54554 WDR5B Hs_WDR5B_9 sp Increased S length no DNA replication regulation by Cul4-associated genes RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. Piwko et al. 2010 21113133 Cell line HeLa H2B and PCNA protein expression Fluorescence np Cul4-associated genes siRNA Z-score > 5 for > half of siRNAs
GR00240-S-1 54554 NM_019069 WDR5B M-013375-00 -0.2 none yes TRAIL-induced apoptosis (1) A synthetic lethal screen identifies FAT1 as an antagonist of caspase-8 in extrinsic apoptosis. Kranz and Boutros 2014 24442637 Cell line U251MG Viability Luminescence SMART-pool siRNA Genome-wide siRNA Z-score > 4 Author-submitted data
GR00240-S-2 54554 NM_019069 WDR5B M-013375-00 2.3 none no Z-score 2.3635 TRAIL-induced apoptosis (2) A synthetic lethal screen identifies FAT1 as an antagonist of caspase-8 in extrinsic apoptosis. Kranz and Boutros 2014 24442637 Cell line U251MG Viability (synthetic lethal) Luminescence SMART-pool siRNA Genome-wide siRNA Differential score > 3.6 AND viability Z-score < 4 Author-submitted data. Z-scores from viability screen (1) are considered in score interpretation for this screen.
GR00242-A-1 54554 NM_019069 WDR5B np sp none no Selective autophagy regulation (1) Image-based genome-wide siRNA screen identifies selective autophagy factors. Orvedahl et al. 2011 22020285 Cell line HeLa/GFP-LC3 Sindbis virus (SIN) capsid SIN-mCherry.capsid and autophagosome GFP–LC3 protein expression Fluorescence siGenome Genome-wide siRNA Z-score Complex criteria
GR00247-A-1 54554 WDR5B np sp none rank: 12118 Regulation of FOXO1 nuclear localization (1) Whole genome siRNA cell-based screen links mitochondria to Akt signaling network through uncoupling of electron transport chain. Senapedis et al. 2011 21460183 Cell line U2OS EGFP-FOXO1a protein expression and DNA content Fluorescence Human Genome library Genome-wide siRNA Complex, sp Complex criteria
GR00249-S 54554 54554 WDR5B s29197 -0.89679 none no number of cells compared to control (%): 83.51 Vaccinia virus (VACV) infection Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis. Sivan et al. 2013 23401514 Cell line HeLa Vaccinia virus VACV IHD-J/GFP protein expression and DNA content Fluorescence Silencer Select Version 4, siGENOME SMARTpool and OnTargetPlus Genome-wide siRNA Z-score > Author-submitted data. Primary screen. Decreased viability phenotype if number of cells compared to control < 50 %.
GR00249-S 54554 54554 WDR5B s29195 -2.10384 Decreased vaccinia virus (VACV) infection no number of cells compared to control (%): 53.51 Vaccinia virus (VACV) infection Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis. Sivan et al. 2013 23401514 Cell line HeLa Vaccinia virus VACV IHD-J/GFP protein expression and DNA content Fluorescence Silencer Select Version 4, siGENOME SMARTpool and OnTargetPlus Genome-wide siRNA Z-score > Author-submitted data. Primary screen. Decreased viability phenotype if number of cells compared to control < 50 %.
GR00249-S 54554 54554 WDR5B J-013375-05 -1.22494 none no number of cells compared to control (%): 81.91 Vaccinia virus (VACV) infection Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis. Sivan et al. 2013 23401514 Cell line HeLa Vaccinia virus VACV IHD-J/GFP protein expression and DNA content Fluorescence Silencer Select Version 4, siGENOME SMARTpool and OnTargetPlus Genome-wide siRNA Z-score > Author-submitted data. Primary screen. Decreased viability phenotype if number of cells compared to control < 50 %.
GR00249-S 54554 54554 WDR5B s29196 -1.48066 none no number of cells compared to control (%): 100.93 Vaccinia virus (VACV) infection Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis. Sivan et al. 2013 23401514 Cell line HeLa Vaccinia virus VACV IHD-J/GFP protein expression and DNA content Fluorescence Silencer Select Version 4, siGENOME SMARTpool and OnTargetPlus Genome-wide siRNA Z-score > Author-submitted data. Primary screen. Decreased viability phenotype if number of cells compared to control < 50 %.
GR00249-S 54554 54554 WDR5B M-013375-00 -1.27068 Decreased viability no number of cells compared to control (%): 45.85 Vaccinia virus (VACV) infection Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis. Sivan et al. 2013 23401514 Cell line HeLa Vaccinia virus VACV IHD-J/GFP protein expression and DNA content Fluorescence Silencer Select Version 4, siGENOME SMARTpool and OnTargetPlus Genome-wide siRNA Z-score > Author-submitted data. Primary screen. Decreased viability phenotype if number of cells compared to control < 50 %.
GR00253-A 54554 NM_019069 WDR5B np -0.631 none hepcidin regulation Unbiased RNAi screen for hepcidin regulators links hepcidin suppression to proliferative Ras/RAF and nutrient-dependent mTOR signaling. Mleczko-Sanecka et al. 2014 24385536 Cell line Huh7 hepcidin::fluc mRNA expression Luminescence siGenome siARRAY SMARTpool Genome-wide siRNA Z-score > Cutoff <
GR00255-A-1 54554 54554 WDR5B TRCN0000117882, TRCN0000117883, TRCN0000117884, TRCN0000117885, TRCN0000117886 -0.76888577 none Negative genetic interactions (1) A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities. Vizeacoumar et al. 2013 24104479 Cell line HCT116 shRNA abundance Microarray np Genome-wide shRNA differential Gene Activity Ranking Profile (dGARP) < -1.0 HCT116 BLM-/- and HCT116 BLM+/+ cells used. Cutoff corresponds to p-value < 0.05. Additional information about a secondary screen (genetic interactions with Cetuximab/Erbitux in LIM1215 cells)
GR00255-A-2 54554 54554 WDR5B TRCN0000117882, TRCN0000117883, TRCN0000117884, TRCN0000117885, TRCN0000117886 0.159878832 none Negative genetic interactions (2) A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities. Vizeacoumar et al. 2013 24104479 Cell line HCT116 shRNA abundance Microarray np Genome-wide shRNA differential Gene Activity Ranking Profile (dGARP) < -1.0 HCT116 MUS81-/- and HCT116 MUS81+/+ cells used. Cutoff corresponds to p-value < 0.05. Additional information about a secondary screen (genetic interactions with Cetuximab/Erbitux in LIM1215 cells)
GR00255-A-3 54554 54554 WDR5B TRCN0000117882, TRCN0000117883, TRCN0000117884, TRCN0000117885, TRCN0000117886 -0.061945189 none Negative genetic interactions (3) A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities. Vizeacoumar et al. 2013 24104479 Cell line HCT116 shRNA abundance Microarray np Genome-wide shRNA differential Gene Activity Ranking Profile (dGARP) < -1.2 HCT116 PTEN-/- and HCT116 PTEN+/+ cells used. Cutoff corresponds to p-value < 0.05. Additional information about a secondary screen (genetic interactions with Cetuximab/Erbitux in LIM1215 cells)
GR00255-A-4 54554 54554 WDR5B TRCN0000117882, TRCN0000117883, TRCN0000117884, TRCN0000117885, TRCN0000117886 -0.091048214 none Negative genetic interactions (4) A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities. Vizeacoumar et al. 2013 24104479 Cell line HCT116 shRNA abundance Microarray np Genome-wide shRNA differential Gene Activity Ranking Profile (dGARP) < -1.2 HCT116 PTTG1-/- and HCT116 PTTG1+/+ cells used. Cutoff corresponds to p-value < 0.05. Additional information about a secondary screen (genetic interactions with Cetuximab/Erbitux in LIM1215 cells)
GR00255-A-5 54554 54554 WDR5B TRCN0000117882, TRCN0000117883, TRCN0000117884, TRCN0000117885, TRCN0000117886 -0.040153701 none Negative genetic interactions (5) A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities. Vizeacoumar et al. 2013 24104479 Cell line HCT116 shRNA abundance Microarray np Genome-wide shRNA differential Gene Activity Ranking Profile (dGARP) < -0.8 HCT116 KRASG13D/- and HCT116 KRAS+/- cells used. Cutoff corresponds to p-value < 0.05. Additional information about a secondary screen (genetic interactions with Cetuximab/Erbitux in LIM1215 cells)
GR00257-A-1 54554 wdr5b 132847 sp Effect on mitosis Cell division, migration and survival (1) Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. Neumann et al. 2010 20360735 Cell line HeLa H2B-GFP protein expression Fluorescence Mapped using ENSEMBL genome database version 27 Selected genes siRNA Complex, sp Complex criteria HeLa-H2B-GFP cells used.
GR00257-A-2 54554 wdr5b 132847 sp Effect on mitosis Cell division, migration and survival (2) Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. Neumann et al. 2010 20360735 Cell line HeLa H2B-GFP protein expression Fluorescence np Selected genes siRNA Complex, sp Complex criteria HeLa-H2B-GFP cells used.
GR00293-A 54554 WDR5B np -0.159 none Combinatorial effect with paclitaxel Mechanisms Promoting Escape from Mitotic Stress−Induced Tumor Cell Death Sinnott et al. 2014 24860162 Cell line HCC366 Viability Luminescence Thermo-Fisher Genome-wide siRNA Z-score < -2.5 Final hits according to the author are indicated in the comment.
GR00300-A 54554 WDR5B TRCN0000117882, TRCN0000117883, TRCN0000117884, TRCN0000117885, TRCN0000117886 0 none Combinatorial effect with RAF inhibitor PLX4720 A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition. Whittaker et al. 2013 23288408 Cell line A375 shRNA abundance Sequencing TRC Genome-wide shRNA Number of shRNAs ranked Top1000 > 2 The A375 cell line used here harbours the BRAF V600E mutation and is therefore sensitive to RAF inhibitors.
GR00303-A 54554 NM_019069 WDR5B np -0.29 none Clear cell renal cell carcinoma (ccRCC) survival regulation Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target Gerlinger et al. 2012 22362593 Cell line VHL-deficient RCC4 Proliferation and Viability Fluorescence np Genome-wide siRNA Z-score < In the phenotype data duplicates were in the original document, which have been removed.
GR00310-A-1 54554 54554 WDR5B np 0.78 none Sindbis virus (SINV) infection (1) Genome-Wide RNAi Screen Identifies Novel Host Proteins Required for Alphavirus Entry Ooi et al. 2013 24367265 Cell line U2OS Sindbis virus (SINV) reporter Luminescence Ambion Silencer V3 Genome-wide siRNA Z-score < -3 OR > 2
54554 54554 WDR5B np 19.6 none 81,3% viability
GR00313-A 54554 NM_019069 WDR5B np 0.23 none TNF-alpha pathway regulation A Genome-Wide RNA Interference Screen Identifies Caspase 4 as a Factor Required for Tumor Necrosis Factor Alpha Signaling. Nickles et al. 2012 22733992 Cell line HEK293T NFkappaB pathway reporter Luminescence Qiagen Genome-wide siRNA Z-score < Additional filters were a reduction in firefly luciferase levels by at least 50% compared to the mean of the experiment and a concomitant reduction of renilla luciferase expression of not more than 30%.
GR00318-A 54554 54554 WDR5B np 0.958 none siRNA set: gPCR Huntingtin toxicity A Genome-Scale RNA–Interference Screen Identifies RRAS Signaling as a Pathologic Feature of Huntington’s Disease Miller et al. 2012 23209424 Cell line HEK293T Caspase 3/7 activity Fluorescence Dharmacon Selected genes siRNA Sum of normalized caspase 3/7 activity mean and standard error < 0.683 HEK293T cells were cotransfected with mutant Huntingtin fused to GFP (Htt1-558141Q-GFP).
GR00363-A 54554 54554 WDR5B SI03034857, 132847, SI02643655, SI00124019, 132849, esi16594, SI02779819 sp Increased epidermal growth factor (EGF) endocytosis, increased transferrin (TF) endocytosis weak but specific Endocytosis regulation Systems survey of endocytosis by multiparametric image analysis. Collinet et al. 2010 20190736 Cell line HeLa Transferrin (TF) and epidermal growth factor (EGF) subcellular localisation, DNA content Fluorescence Ambion, Qiagen and esiRNA library (Kittler et al.) Genome-wide siRNA Complex, sp Complex criteria Two hit categories: "strong" (maximum of Prob Chi2, Prob Chi2 EGF, Prob Chi2 Tfn > 0.95) and "weak but specific" (maximum of Prob Chi2, Prob Chi2 EGF, Prob Chi2 Tfn < 0.95 but Phenoscore > 0.95). Additional information about secondary screens with kinase and phospatase libraries.
54554 54554 WDR5B 0.009999999999999995 none
GR00376-A-1 54554 54554 WDR5B 0.189997032 none Mitigators of SS1P-induced immunotoxicity Whole-genome RNAi screen highlights components of the endoplasmic reticulum/Golgi as a source of resistance to immunotoxin-mediated cytotoxicity Pasetto et al. 2015 25713356 Cell line KB cells Viability Luminescence Ambion Silencer Select Version 4 Genome-wide siRNA RSA P-value <0.001 SS1P was applied in a "high dose", ≈EC90, 13 ng/ml. Cutoff was derived from data submitted to Pubchem (ID 1117281). Reagent sequences but no ID
GR00376-A-2 54554 54554 WDR5B 0.169925853 none Sensitizers of SS1P-induced immunotoxicity Whole-genome RNAi screen highlights components of the endoplasmic reticulum/Golgi as a source of resistance to immunotoxin-mediated cytotoxicity Pasetto et al. 2015 25713356 Cell line KB cells Viability Luminescence Ambion Silencer Select Version 4 Genome-wide siRNA RSA P-value <0.001 SS1P was applied in a "low dose", ≈EC30, 3 ng/ml. Cutoff was derived from data submitted to PubChem (ID 1117281). Reagent sequences but no ID
GR00378-A 54554 WDR5B -0.23055905 none Poliovirus vaccine production Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game van der Sanden et al. 2015 26581994 Cell line HEp-2C Infection with Attenuated Poliovirus ELISA Dharmacon Genome-wide siRNA Z-score > For infection, a single lot of the attenuated Sabin type 2 poliovirus was used for the screen. Gene IDs were not provided, only the gene name/symbol
54554 NM_019069 WDR5B 47.262 none
GR00386-A-1 54554 54554 WDR5B 81.9987730567297 none NOD2 stimulation by MDP A genome-wide small interfering RNA (siRNA) screen reveals nuclear factor-κB (NF-κB)-independent regulators of NOD2-induced interleukin-8 (IL-8) secretion. Warner et al. 2014 25170077 Cell line HEK293 stably expressing NOD2 Viability Luminescence Dharmacon Genome-wide siRNA Percentage growth Decreased: <70, increased: >120 Reagent IDs not provided
GR00386-A-2 54554 54554 WDR5B -18 none MDP-induced IL-8 secretion A genome-wide small interfering RNA (siRNA) screen reveals nuclear factor-κB (NF-κB)-independent regulators of NOD2-induced interleukin-8 (IL-8) secretion. Warner et al. 2014 25170077 Cell line HEK293 stably expressing NOD2 IL-8 secretion ELISA Dharmacon Genome-wide siRNA Percent inhibition of IL-8 secretion Increased: <-300, Decreased: >60 Concentration of IL-8 was measured from cell supernatants by sandwich ELISA. IL-8 values (pg/ml) were normalized to IL-8 secreted in cells treated with RIPK2-specific siRNA (100% inhibition) and non-targeting siRNA (0% inhibition). Secondary validating screen assessed 554 genes whose silencing affected MDP-induced IL-8 secretion in the primary screen. Final validated IL-8 regulators (positive or negative) are listed in the comments column. Reagent IDs not provided