(12) Patent Application Publication (10) Pub. No.: US 2013/0261006 A1 HAKOZAKI Et Al
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US 20130261 006A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0261006 A1 HAKOZAKI et al. (43) Pub. Date: Oct. 3, 2013 (54) METHOD OF GENERATINGA Publication Classification HYPERPGMENTATION CONDITION GENE EXPRESSION SIGNATURE (51) Int. Cl. CI2O I/68 (2006.01) (71) Applicant: THE PROCTER & GAMBLE (52) U.S. Cl. COMPANY, Cincinnati, OH (US) CPC .................................... CI2O I/6881 (2013.01) USPC ................................................. 506/7:506/16 (72) Inventors: Tomohiro HAKOZAKI, Cincinnati, OH (US); Wenzhu ZHAO, Mason, OH (57) ABSTRACT (US); Robert Lloyd BINDER, A method of generating a hyperpigmentation condition gene Montgomery, OH (US); Jun XU, Mason, expression signature for use in identifying connections OH (US) between perturbagens and genes associated with a skin pig mentation condition. The method includes providing a gene Assignee: The Procter & Gamble Company, expression profile for a reference sample of human skin cells (73) not affected with a pigmentation condition; generating a gene Cincinnati, OH (US) expression profile for a sample of human skin cells from a Subject exhibiting the hyperpigmentation condition; compar (21) Appl. No.: 13/851,873 ing the expression profiles to determine a gene expression signature that includes a set of differentially expressed genes; (22) Filed: Mar. 27, 2013 assigning an identifier to each gene constituting the gene expression signature and ordering the identifiers according to the direction of differential expression to create one or more Related U.S. Application Data gene expression signature lists; and storing the one or more (60) Provisional application No. 61/618,115, filed on Mar. gene expression signature lists on at least one computer read 30, 2012. able medium. Patent Application Publication Oct. 3, 2013 Sheet 1 of 73 US 2013/026100.6 A1 FIG. : Table A Pigmentation control targets and some Benchmark Agents Pigmentation Control Target Effective Agent Examples Examples Tyrosinase inhibition Hydroquinone, resorcinols, koic acid, arbutin, deoxy-arbutin, ascorbic acid (vitamin C) Tyrosinase copper chelation Ellagic acid, kojic acid Inhibition of tyrosinase Glucosamine, N-acetylglucosamine, tunicamycin Melanosome transfer Niacinamide, protease inhibitors Inhibit binding of alpha-MSH to N-undecylenoyl-phenylalanine melanocyte Down regulation of tyrosinase Retinoid (trans-retinoic acid, retino and its esters, retinaldehyde) Antioxidant Vitamin C compounds, vitamin E, sulfhydryl compounds Anti-inflammatory agent Hydrocortisone, phytosterol, glycyrrhetinic acid, tranexamic Increase epidermal turnover acid,Retinoids, chamomile salicylic extract acid, alpha-hydroxy acids, alpha-keto... .............. acids, -- adenosine monophosphate Patent Application Publication Oct. 3, 2013 Sheet 2 of 73 US 2013/026100.6 A1 FIG. 2: TABLES B and C 20745 at 214333 x isocitrate dehydrogenase 3 (NAD+) gamma 207365 x a ubiquitin specific peptidase 34 202396 at TCERC ption elongation regulator 1 20358 at LYST sosomal trafficking regulator ochondrial ribosomal protein L34 / Dutt 7U.4 u.uu J asein kinase I, gamma 2 -AL530441 0. eli division cycle 42 (GTP binding protein, 25kDa) M35543 ansducer of ERBB2, - - - - - - - - - - - - - - - - - v-- . v. - - - - - M. v.- - - - - - - - - - - - - - - - - - - - - - - - - - - W - - - - - -v- W --w---mus ----------v-u------ SRY (sex determining region Y)-box 15 217759 at tripartite motif-containing 44 216859 x 212254s at DST 211464 x at CASP6 206765 at KC 200055 at TAF10 associated factor 30kDa 21 0547 x at ICA .-- -- islet cell autoantigen 1. 69kDa -3- 201471 sat SQSTM1 205555 s at MSX2 212143 NM_002847.0.00396 214715. nc finger protein 160 m---------...-- ------------m-m-r-...- kelch domain containin g 4. 8-M.----- ------------------- testis derived transcript (3 LIM domains) M_015641000474 202720 at 202178 at M_002744 000500 22076 is at TAOK3 NM_016281 000500 : BF439472 000503 Patent Application Publication Oct. 3, 2013 Sheet 3 of 73 US 2013/026100.6 A1 224.54 x Heterogeneous nuclear ribonucleoprotein D-like r protein 24 NM_016623.000539 202468 is - N Ll catenin (cadherin-associated protein), alpha-like 1 ---m 22 1737 at guanine nucleotide binding protein (G protein) alpha 12 '. 0.005 S1 like ( yeast) homeobox D4 mu- -- - - - -m-, -- upstream binding protein (LBP-1a) sulin-like growth factor binding protein 3 M31159 000592 FKIAA 1598 . 'S''' - '''S'm ' protein kinase, AMP-activated, beta 2 non-catalytic subunit eroxisome biogenesis factor l marylacetoacetate hydrolase domain containing 2B enase (lipoamide) alpha 1 integrin, beta (fibronectin receptor, beta polypeptide, antigen CO29 includes MDF2, MSK12) BG500301 O.00649. 201227s at NDUFB8 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa NM_005040.00652 220602_s at s solute carrier familymm mm. 2 (facilitated glucose/fructose transporter), NM_0250840.00652. member 5 ' ' ' ' ' ' ' ' ' m arbonyl reductase 3. poly (ADP-ribose) polymerase family, member 2 guanine nucleotide binding protein-like 3 (nucleolar) line 1 (Opitz/BBB syndrome) hromosome 5 open reading frame 13 -u-m-m-m-m-m-m-r ------ golgi associated, gamma adaptin ear containing, ARF binding protein asparaginyl-tRNA synthetase etallothionein pseudogene 3 219231 at methylguanosine synthase homolog (S. cerevisiae) 215228 at scient helix loop helix 2 2 9790s at NPR3 peptide receptor C) NM_0009080.00821 ter-rig-r---210424s at GOLGA8A golgi autoantigen, golgin subfamily a 8A AF163441 000827. 210424s at GOLGA8B golgi autoantigen, golgin subfamily a, 8B AF16344 0.00827. sema domain, immunoglobulin domain (g), transmembrane domain (TM) and short cytoplasmic domain. (semaphorin) 4C M_017789 000835 slocated promoter region (to activated MET oncogene) 'WWW K0231. 209306 s a SWAP70. SWAP-70 protein-------------------------------------------------------------------------------------------------------------------------------------------------------------- A1139569-------------------------------- 000837 Patent Application Publication Oct. 3, 2013 Sheet 4 of 73 US 2013/0261006 A1 ise (STE24 homolog, S. cerevisiae) 857 000853. 0.00858 c fin ger protein 57 pindlin family, member 2B indlin family, member 2A F356353 000886. sprouty homolog4 (Drosophila) WA8843 0.00898 zinc finger and BTB domain containing 1 0.00899 ctin filament) muscle ine, alpha - apoptotic chromatin condensation inducer 1 t CCDC101 coiled-coil domain containing 101 OX4 -- SRY (sex determining region Y)-box 4. BG528420 000 201810 sat SH3BP5 SH3-domain binding protein 5 (BTK associated) AL562152 000931 221 188s at CIDEB cell death-inducing DFFA-like effector b 213140 s at SS18Ll ----- synovial sarcoma translocation gene on chromosome 18-like 1 i 218612 s at TSSC4 - tumor suppressing subtransferable candidate 4 - transcription factor AP-2 gamma (activating enhancer binding i 205286 at protein 2 gamma) U85658 ------------(),00978 let cell autoantigen 1 , 69kDa w- V 004968 0.00978 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase 200639_s_at YWHAZ tactivation protein, Zeta polypeptide 201804 x at TBCB tubulin folding cofactor B actor VIII associated (intronic transcript) 220051 at PRSS21 protease, serine, 21 (testisin) 21.0153 s at ME2 malic enzyme 2, NAD(+)-dependent, mitochondrial 202123 s at bl Abelson murine leukemia viral oncogene homolog 1 20701 lSat PTK7 protein tyrosine kinase 7 r scaffold homolog (S. cerevisiae) NM_015700 001083 polymerase (DNA directed), gamma 2, accessory subunit NM_007215 001108 - - omain containing 4B 01 126 sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F , ticulocalbin 3, EF-hand calcium binding domain ---------------------------- ------------------------- -------------- desmocollin 2 domain family. member 2 protocadherin 7 Patent Application Publication Oct. 3, 2013 Sheet 5 of 73 US 2013/0261006 A1 homeobox D1 ondin 2, extracellular matrix protein dicarbonyl/L-xylulose reductase NM_016286001188. leoporin 43kDa NM_0246470.01 195 222136 x at ZNF43 zinc finge - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ----------------------- 217752 s at CNDP2 CNDP dipeptidase 2 (metallopeptidase M20 family) 204078------------------- at SC65 --------------------------------------------synaptonemal complex - protein------------ SC65 microtubule associated monoxygenase, calponin andLIM domain ----...- ...-- | ------- 218376 sat MICAL1 containing NM_022765 0.01.237 208820207060 at PTK2EN2 engrailedPTK2 protein homeobox2 tyrosine kinase 2 - A057,3900279M001427. ---202265 - - - - - - - - - - - - - - - at BMI1 polycomb ring finger oncogene ... --. zinc finger protein 419 219826-------------------- at M_02469100.335 RRP9, small subunit (SSU) processome component, homolog (yeast) - M-004704001341 rf34 chromosome I open reading frame 34 C004399 001353 221974 at - IIIPW Imprinted in Prader-Willi syndroine w770748 00135 amyloid beta (A4) precursor protein-binding, family A, member 210720s at APBA2BP binding protein AB039947 0.01365; 204525 at PHF14 PHD finger protein 14 NM_014660 001366 rimatogenesis associated g protein 1 (liprin beta1) 200775 s at HNRPK heterogeneous nuclear ribonucleoprotein K i golgi associated, gamma adaptin ear containing, ARF binding GAI :protein RNA, cDNA DKFZp547C126 (from clone DKFZp547C126). AL3595 215828 ---------------------------------- --------------------------------...-as-------------------------------------------------------. 211609 x SMD4 proteasome (prosone, macropain)26S subunit, non-ATPase, 4, U5 1007 0.01444------------- 43977 at