The BioInvestigationIndex (BII)

Title:

Transcriptional profiling of rat liver after exposure to drugs or chemicals (expanded dataset). [original title: Liver Pharmacology and Xenobiotic Response Repertoire]

Organism(s):

Rattus norvegicus

Description:

5312 samples. 344 compounds in triplicate. Note: This file contains data from many of the sample in E-GEOD-8251, but also contains data from samples treated with other NSAIDs and related compounds, including acemetacin, aminosalicylic acid, balsalazide, benoxaprofen, benzocaine, bromfenac, capsaicin, dipyrone (metamizole), ibufenac, mefenamic acid, methyl salicylate, naproxen, nimesulide, salicylamide, salicylic acid, sulindac, and zomepirac. The original GEO curation contains detailed descriptions of which samples were used for statistical matching in the authors' analysis, but this has been removed here due to space considerations. [original description: A definition of RNA expression changes that correlate with liver response programs and an understanding of the similarities and differences in responses to different classes of chemicals would aid in new chemical or drug characterization and add to our understanding of liver biology. We have used a supervised classification approach to systematically mine a large microarray database derived from livers of compound-treated rats. Thirty-four distinct signatures (classifiers) for pharmacological and toxicological endpoints resolvable by gene expression can be identified. The contribution of genes to signatures is not correlated to average expression or amplitude of regulation, and pre-selection of genes can significantly reduce signature performance. Just 200 genes are sufficient to classify all endpoints and can form the basis of a small diagnostic array useful in toxicogenomics. Signature genes were enriched in xenobiotic and acute phase response genes as well as un-annotated genes, suggesting that not all key genes in liver xenobiotic responses have been identified. Individual signatures can be re-derived up to 25 times from a gene set cyclically .stripped. of the signature genes. The union of these non-overlapping sets was used to describe the biological mechanisms of liver fibrosis. Guidelines for commercial use: http://www.iconixbiosciences.com/guidelineCommUse.pdf Keywords: dose response, time course, compound treatment. Overall Design: Treatment of male Sprague-Dawley rats with 344 compounds at various doses and durations, in biological triplicate, along with vehicle-matched control animals. Liver samples were assayed for gene expression. A total of 1695 samples were hybridized to single-channel CodeLink RU1 arrays. Biological triplicates were combined with matched control samples to calculate log ratios. Classifiers were generated and evaluated for 2112 biological questions, resulting in 34 distinct, high-performance 'signatures.']

Design(s):

transcription profiling by array

Experimental factor(s):

sex 2 recorded
male female
treatment duration 13 recorded
1 day 5 day 3 day 0.25 day 7 day 28 day 14 day 5 4 day 91 day 30 day 0 day 6 day
treatment compound 346 recorded
dicoumarol choline chloride rolipram acyclovir praziquantel GLIPIZIDE (CHEMBL1073) methotrexate ivermectin gentamycin SCH-351591 (PubChem CID 9802841) fluconazole omeprazole TOSUFLOXACIN (CHEMBL273348) clotrimazole ferulic acid econazole BETA-ESTRADIOL 3-BENZOATE (CHEMBL282575) bisphenol A azathioprine ibuprofen 17alpha-ethynylestradiol hydroxyurea alpha-methyl-L-dopa N,N-dimethylformamide doxycycline erythromycin chloroform control condition rofecoxib nimesulide cyclosporin A neomycin tamoxifen OXYMETHOLONE (CHEMBL1200585) pramocaine sotalol indomethacin promazine pantoprazole melatonin norethisterone diclofenac 3-ACETAMIDOPHENOL (PubChem CID 12124) ethanol amitraz Chlortetracycline primaquine leflunomide fomepizole TOLAZAMIDE (CHEMBL817) aflatoxin B1 3-methylcholanthrene TNFA_RAT deferiprone chlorpromazine pirinixic acid amoxapine benzocaine sildenafil atropine albendazole NISOLDIPINE (CHEMBL1726) fenofibrate cholic acid itraconazole balsalazide diethylstilbestrol metronidazole imatinib alprazolam hexamethylmelamine simvastatin bromfenac methapyrilene clofibric acid hydrazine vinorelbine azithromycin 1-naphthyl isothiocyanate MEFENAMIC ACID carmustine quinolin-8-ol acetylsalicylic acid mestranol SODIUM ARSENITE allyl alcohol 3,3',4',5-tetrachlorosalicylanilide amlodipine NAFENOPIN (CHEMBL1909070) tioguanine citalopram crotamiton genistein manganese(II) chloride acetazolamide citric acid clomiphene bithionol thalidomide progesterone streptozocin TRIACETIN (CHEMBL1489254) TROVAFLOXACIN (CHEMBL428) geraniol OXICONAZOLE (CHEMBL1262) fluphenazine anastrozole 2-acetamidofluorene naloxone quetiapine pentobarbital 4-nonylphenol isoeugenol sparfloxacin zileuton NATEGLINIDE (CHEMBL783) CETYLPYRIDINIUM BROMIDE (CHEMBL334255) 4'-epidoxorubicin dipyridamole FLUDROCORTISONE ACETATE (CHEMBL1201010) Caloric Restriction ifosfamide 2,3,7,8-tetrachlorodibenzodioxine abamectin chlorambucil calciol NORETHINDRONE ACETATE (CHEMBL1201146) tetrachloromethane trichloroacetic acid BENZOTHIAZYL DISULFIDE (CAS 120-78-5) etoposide amantadine megestrol acetate secobarbital nevirapine sulindac doxorubicin GENTIAN VIOLET (CHEMBL64894) METHOCARBAMOL (CHEMBL1201117) oxytetracycline lomefloxacin promethazine atorvastatin IL1B_RAT rifampicin paracetamol FENBENDAZOLE (CHEMBL37161) cerivastatin BROMISOVALUM (CHEMBL1515611) olanzapine GRANISETRON (CHEMBL289469) CLOSANTEL (CHEMBL12131) digoxin naproxen zidovudine famciclovir ETHYLESTRENOL (CHEMBL1200623) raloxifene rifabutin BETA-NAPHTHOFLAVONE (CHEMBL26260) 17beta-estradiol clarithromycin lovastatin methyl salicylate amiodarone zopiclone estriol daunorubicin cortisone ketoconazole HEXACHLOROPHENE (CHEMBL496) cytarabine hydralazine venlafaxine perhexiline 1,1-dichloroethene sertraline N,N'-DIPHENYL-P-PHENYLENEDIAMINE (CHEMBL1333512) methimazole LOMUSTINE (CHEMBL514) pioglitazone enoxacin cetraxate tocainide PROGLUMIDE lead diacetate cyproterone acetate phenacetin phenobarbital N-nitrosodiethylamine troglitazone busulfan metamizole sodium TERBINAFINE (CHEMBL822) cisplatin 4-aminosalicylic acid mitomycin C MODAFINIL (CHEMBL1373) bis(2-ethylhexyl) phthalate TICRYNAFEN (CHEMBL267744) rosiglitazone phenylhydrazine sulfathiazole dimenhydrinate zomepirac spironolactone neostigmine bromide STANOZOLOL (CHEMBL1200324) PICLAMILAST (PubChem CID 154575) thiabendazole valproic acid lansoprazole IDEBENONE (CHEMBL252556) carboplatin MEVASTATIN (CHEMBL54440) bezafibrate ticlopidine isoniazide dexamethasone penicillamine cycloheximide fluvastatin SAFROLE phenothiazine 6-propyl-2-thiouracil BENZETHONIUM CHLORIDE (CHEMBL221753) ETHISTERONE (CHEMBL241694) letrozole SULFAPHENAZOLE (CHEMBL1109) LEAD(IV) ACETATE (CHEMBL1909063) clofibrate miconazole mebendazole 4-OCTYLPHENOL (CHEMBL195437) fluoxetine catechol tetracycline gemfibrozil cyclandelate mercaptopurine griseofulvin FLUOCINOLONE ACETONIDE (CHEMBL989) pyrogallol LEVAMISOLE (CHEMBL1454) TROPISETRON (PubChem CID 72165) BENOXAPROFEN OXYMETAZOLINE (CHEMBL762) vitamin D2 finasteride benzoic acid TORSEMIDE (CHEMBL1148) diazepam oxfendazole clomipramine EPALRESTAT (CHEMBL56337) isotretinoin ethylene glycol BROMHEXINE (CHEMBL253376) ACEMETACIN tacrine roxithromycin ciprofloxacin METHYLPARABEN (CHEMBL325372) procarbazine N-nitrosodimethylamine disulfiram mifepristone minoxidil pyrazinecarboxamide nitrofurantoin vecuronium bromide amoxicillin salicylamide isoprenaline KETOROLAC artemether propane-1,2-diol vincaleukoblastine roflumilast carbimazole etodolac primidone carvedilol pergolide nystatin sulfadoxine chlorzoxazone IL6_RAT NITRAZEPAM (CHEMBL13209) LIPOPOLYSACCHARIDE E. COLI O55_B5 testosterone lormetazepam TRICHLOROETHANE (unknown whether alpha or beta) (+)-artemisinin anisindione dichlorvos TRANILAST (CHEMBL415324) clonazepam thioacetamide FLUBENDAZOLE (CHEMBL1454946) SULCONAZOLE (CHEMBL1221) pravastatin prednisolone lamivudine betamethasone salicylic acid colistin ALFACALCIDOL (CHEMBL1601669) insulin aminoglutethimide ALPHA-NAPHTHOFLAVONE (CHEMBL283196) glimepiride MELOXICAM all-trans-retinoic acid sulfadiazine nicotinic acid bupropion cyclopropanecarboxylic acid celecoxib carbamazepine sulfisoxazole EPERISONE (CHEMBL1902981) zalcitabine cortisol PEMOLINE (CHEMBL1177) IPRIFLAVONE (CHEMBL165790) rabeprazole TEMAFLOXACIN (CHEMBL277100) warfarin tinidazole NIMETAZEPAM (CHEMBL13341) 4-chloro-3,5-dimethylphenol danazol diisopropyl fluorophosphate nicotinamide 4,4'-diaminodiphenylmethane zaleplon butenafine pralidoxime chloride IBUFENAC cinnarizine capsaicin doxapram stavudine methyltestosterone ZIRCONIUM(IV) CHLORIDE (CHEMBL1909083)
solvent 12 recorded
CORN OIL water CMC saline RSA/SALINE UNTREATED ACACIA POLYSORBATE 80 CMC/0.25%PS/0.05%A UNKNOWN ACACIA/0.05%A PEG400
dose 246 recorded
5 mg/kg 2550 mg/kg 75 mg/kg 330 mg/kg 1200 mg/kg 2500 mg/kg 0.3 mg/kg 7.5 mg/kg 267 mg/kg 4.6 mg/kg 10 mg/kg 415 mg/kg 2000 mg/kg 89 mg/kg 1500 mg/kg 334 mg/kg 2 mg/kg 610 mg/kg 160 mg/kg 263 mg/kg 1480 mg/kg 400 mg/kg 325 mg/kg 1400 mg/kg 14 mg/kg 60 mg/kg NA 3 mg/kg 162 mg/kg 350 mg/kg 877 mg/kg 2.5 mg/kg 1170 mg/kg 526 mg/kg 30 mg/kg 12 mg/kg 100 mg/kg 1100 mg/kg 375 mg/kg 700 mg/kg 3000 mg/kg 0.25 mg/kg 45 mg/kg 155 mg/kg 12.5 mg/kg 500 mg/kg 73 mg/kg 364 mg/kg 313 mg/kg 275 mg/kg 2.3 mg/kg 62 mg/kg 15 mg/kg 215 mg/kg 1125 mg/kg 1402 mg/kg 1093 mg/kg 2.8 mg/kg 50 mg/kg 150 mg/kg 115 mg/kg 13 mg/kg 280 mg/kg 9.6 mg/kg 980 mg/kg 448 mg/kg 1.5 mg/kg 93 mg/kg 4 mg/kg 68 mg/kg 43 mg/kg 250 mg/kg 16 mg/kg 0.2 mg/kg 338 mg/kg 24 mg/kg 40 mg/kg 750 mg/kg 47 mg/kg 59 mg/kg 113 mg/kg 11.3 mg/kg 138 mg/kg 20 mg/kg 90 mg/kg 600 mg/kg 22 mg/kg 76 mg/kg 70 mg/kg 200 mg/kg 1560 mg/kg 29 mg/kg 35 mg/kg 450 mg/kg 625 mg/kg 16.5 mg/kg 2.7 mg/kg 1550 mg/kg 125 mg/kg 17 mg/kg 7.0E-4 mg/kg 0.6 mg/kg 8 mg/kg 19 mg/kg 474 mg/kg 2600 mg/kg 188 mg/kg 220 mg/kg 1175 mg/kg 132 mg/kg 4.5 mg/kg 64 mg/kg 0.65 mg/kg 2100 mg/kg 18 mg/kg 0.01 mg/kg 300 mg/kg 99 mg/kg 800 mg/kg 0.05 mg/kg 23 mg/kg 14.6 mg/kg 175 mg/kg 11 mg/kg 134 mg/kg 1540 mg/kg 112 mg/kg 390 mg/kg 650 mg/kg 25 mg/kg 56 mg/kg 444 mg/kg 54 mg/kg 147 mg/kg 414 mg/kg 414 3.25 mg/kg 206 mg/kg 114 mg/kg 487 mg/kg 143 mg/kg 3.5 mg/kg 320 mg/kg 210 mg/kg 1000 mg/kg 4.2 mg/kg 1503 mg/kg 224 mg/kg 619 mg/kg 34 mg/kg 9 mg/kg 1636 mg/kg 1.17 mg/kg 2337 mg/kg 0.5 mg/kg 17.5 mg/kg 570 mg/kg 486 mg/kg 420 mg/kg 78 mg/kg 2629 mg/kg 165 mg/kg 225 mg/kg 92 mg/kg 0.02 mg/kg 235 mg/kg 6000 mg/kg 140 mg/kg 223 mg/kg 1800 mg/kg 79 mg/kg 167 mg/kg 178 mg/kg 94 mg/kg 488 mg/kg 386 mg/kg 1695 mg/kg 476 mg/kg 1.7 mg/kg 333 mg/kg 27 mg/kg 52 mg/kg 120 mg/kg 67 mg/kg 1700 mg/kg 710 mg/kg 352 mg/kg 58 mg/kg 312 mg/kg 0.26 mg/kg 1300 mg/kg 48 mg/kg 74 mg/kg 852 mg/kg 775 mg/kg 3525 mg/kg 1.1 mg/kg 380 mg/kg 195 mg/kg 763 mg/kg 0.125 mg/kg 430 mg/kg 119 mg/kg 310 mg/kg 1.25 mg/kg 920 mg/kg 0.08 mg/kg 972 mg/kg 1.67 mg/kg 850 mg/kg 8.75 mg/kg 184 mg/kg 130 mg/kg 39 mg/kg 121 mg/kg 0.043 mg/kg 0.56 mg/kg 7 mg/kg 3178 mg/kg 80 mg/kg 33 mg/kg 2625 mg/kg 714 mg/kg 895 mg/kg 394 mg/kg 490 mg/kg 36 mg/kg 501 mg/kg 1024 mg/kg 110 mg/kg 1340 mg/kg 122 mg/kg 1915 mg/kg 28 mg/kg 72 mg/kg 164 mg/kg 227 mg/kg 3.75 mg/kg 81 mg/kg 617 mg/kg 32 mg/kg 6 mg/kg 6.5 mg/kg 1 mg/kg 31 mg/kg 633 mg/kg
administration route 5 recorded
gavage subcutaneous injection intravenous injection intraperitoneal injection NONE

Publication(s):

Natsoulis G, Pearson CI, Gollub J, P Eynon B, Ferng J, Nair R, Idury R, Lee MD, Fielden MR, Brennan RJ, Roter AH, Jarnagin K
The liver pharmacological and xenobiotic gene response repertoire. PubMed:18364709

Sample attribute(s):

Material Type 1 recorded
polyA RNA
age 1 recorded
6 to 8 weeks
organism part 1 recorded
liver
Label 1 recorded
biotin
organism 1 recorded
Rattus norvegicus

Contact(s):

Alan Roter

Jeremy Gollub

May Lee

Joe Ferng

Cecelia Pearson

Barray Eynon

Jeremy Gollub

Radha Idury

Kurt Jarnagin

Mark Fielden

Georges Natsoulis

Richard Brennan

Ramesh Nair

Release Date:

3/28/2008

Metadata Downloads

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Assay Downloads

transcription profiling using DNA microarray

5312 assays

Processed Data Processed Data

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