Systems and Methods for Identifying Cosmetic Agents for Skin Care Compositions

Abstract

Provided are methods and systems for determining functional relationships between a cosmetic agent and a skin tissue condition of interest. Also provided are methods and systems for identifying cosmetic agents that affect a skin aging tissue condition, as well as the use of agents identified by such methods and systems for the preparation of cosmetic compositions, personal care products, or both.

1 . A method for constructing a data architecture for use in identifying connections between perturbagens and genes associated with one or more skin aging conditions, comprising:
 (a) providing a gene expression profile for a control human dermal fibroblast cell;   (b) generating a gene expression profile for a human dermal fibroblast cell exposed to at least one perturbagen, wherein at least one perturbagen comprises a cosmetic agent;   (c) identifying genes differentially expressed in response to the at least one perturbagen by comparing the gene expression profiles of (a) and (b);   (d) creating an ordered list comprising identifiers representing the differentially expressed genes, wherein the identifiers are selected from the group consisting of gene names, gene symbols, microarray probe set ID values, and combinations thereof, and the identifiers are ordered according to the differential expression of the genes, and wherein each identifier in the ordered list is in association with a numerical ranking corresponding to its rank in the ordered list;   (e) storing the ordered list as a fibroblast instance on at least one computer readable medium; and   (f) constructing a data architecture of stored fibroblast instances by repeating steps (a) through (e) for between about 50 and about 50,000 instances, wherein the at least one perturbagen of step (a) is different for each fibroblast instance;   wherein a programmable computer performs one or more of steps (c), (d), (e) and (f).   
     
     
         2 . A method according to  claim 1 , wherein the step of generating is performed by extracting a biological sample comprising mRNA from the treated cell and subjecting the biological sample to microarray analysis. 
     
     
         3 . A method according to  claim 1 , wherein the ordered list is arranged so that an identifier associated with a most up-regulated gene is positioned at the top of the ordered list and an identifier associated with a most down-regulated gene is positioned at the bottom of the ordered list. 
     
     
         4 . A method according to  claim 1 , further comprising;
 (g) providing a gene expression profile for a control human keratinocyte cell;   (h) generating a gene expression profile for a human keratinocyte cell exposed to at least one perturbagen;   (i) identifying genes differentially expressed in response to the at least one perturbagen by comparing the gene expression profiles of (g) and (h);   (j) creating an ordered list comprising identifiers representing the differentially expressed genes, wherein the identifiers are ordered according to the differential expression of the genes identified in (i);   (k) storing the ordered list created in step (j) as a keratinocyte instance on the at least one computer readable medium; and   (l) constructing a data base of stored keratinocyte instances by repeating (g) through (k), wherein the at least one perturbagen of step (h) is different for each keratinocyte instance.   
     
     
         5 . A method according to  claim 4 , wherein the at least one perturbagen of step (a) is the same as the at least one perturbagen of step (g). 
     
     
         6 . A method according to  claim 1 , wherein the at least one perturbagen is a botanical derived from one or more of a root, stem, bark, leaf, seed, or fruit of a plant. 
     
     
         7 . A method according to  claim 1 , wherein the at least one perturbagen is selected from the group consisting of a vitamin compound, a sugar amine, a phytosterol, hexamidine, a hydroxy acid, a ceramide, an amino acid, and a polyol. 
     
     
         8 . A method according to  claim 7 , wherein the vitamin compound is selected from the group consisting of a vitamin B3 compound, a vitamin B5 compound, a vitamin B6 compound, a vitamin B9 compound, a vitamin A compound, a vitamin C compound, a vitamin E compound, and derivatives and combinations thereof. 
     
     
         9 . A method according to  claim 7 , wherein the vitamin compound is selected from the group consisting of retinol, retinyl esters, niacinamide, folic acid, panthenol, ascorbic acid, tocopherol, and tocopherol acetate. 
     
     
         10 . A method for implementing the data architecture according to  claim 1  to generate connections useful for identifying cosmetic agents effective for treating aged skin, the method comprising querying the data architecture with at least one skin aging gene expression signature, wherein querying comprises comparing the at least one skin aging gene expression signature to each stored fibroblast instance, wherein the skin aging gene expression signature represents genes differentially expressed in association with at least one skin aging condition. 
     
     
         11 . A method according to  claim 10 , wherein the at least one skin aging condition is selected from intrinsic skin aging conditions; photo-aging skin conditions; and combinations thereof. 
     
     
         12 . A method according to  claim 10 , wherein the at least one skin aging gene expression signature is constructed by a method comprising (i) identifying genes having up-regulated expression in the at least one skin aging condition when compared to a control; (ii) identifying genes having down-regulated expression in the at least one skin aging condition when compared to a control; (iii) creating one or more gene expression signature lists associated with the at least one skin aging gene expression signature comprising identifiers corresponding to a plurality of the genes identified in (i) and (ii); and storing the one or more gene expression signature lists on the at least one computer readable medium. 
     
     
         13 . A method according to  claim 12 , wherein the number of genes having up-regulated expression in the at least one skin aging condition is between about 10 and about 400, and the number of genes down-regulated in the at least one skin aging condition is between about 10 and about 400. 
     
     
         14 . A method according to  claim 13  wherein the identifiers for from between about 80% and about 100% of the up-regulated genes are set forth as in Table C and wherein identifiers for from between about 80% and about 100% of the down-regulated genes are set forth in Table D. 
     
     
         15 . A method according to  claim 12 , wherein the one or more gene expression signature lists comprises a first list representing a plurality of the up-regulated genes identified in (i) and a second list representing a plurality of down-regulated genes identified in (ii). 
     
     
         16 . A method according to  claim 12 , wherein at least one skin sample is taken from a human subject exhibiting the at least one skin condition, a biological sample is extracted from the skin sample, and a gene expression profile of the at least one skin sample is generated prior to at least one of the steps (i) and (ii). 
     
     
         17 . A method according to  claim 16 , wherein the skin sample comprises cells from epidermal and dermal layers of the human subject. 
     
     
         18 . A method according to  claim 10 , wherein the comparison further comprises assigning a connectivity score to each of plurality of instances, wherein a plurality of connectivity scores represents a positive correlation and a plurality of the connectivity scores represents a negative correlation, and wherein the connectivity score has a value between +2 and −2. 
     
     
         19 . A system for identifying connections between perturbagens and genes associated with one or more skin aging conditions, comprising:
 (a) at least one computer readable medium having stored thereon a plurality of instances, and at least one skin aging gene expression signature, wherein the instances and the at least one gene expression signature are derived from either a human dermal fibroblast cell or a human keratinocyte cell or both, wherein each instance comprises an instance list of rank-ordered identifiers of differentially expressed genes, and wherein the at least one skin aging gene expression signature comprises one or more gene expression signature lists of identifiers representing differentially expressed genes associated with a skin aging condition;   (b) a programmable computer comprising computer-readable instructions that cause the programmable computer to execute one or more of the following:
 (i) accessing the plurality of instances and the at least one skin aging gene expression signature stored on the computer readable medium; 
 (ii) comparing the at least one skin aging gene expression signature to the plurality of the instances, wherein the comparison comprises comparing each identifier in the gene expression signature list with the position of the same identifier in the instance list for each of the plurality of instances; and 
 (iii) assigning a connectivity score to each of the plurality of instances. 
   
     
     
         20 . A system according to  claim 19 , further comprising: a microarray scanner for receiving a sample comprising human dermal fibroblast cells and/or human keratinocyte cells; and a second programmable computer for transmitting gene expression data from the scanner to the first programmable computer, and an array of perturbagens for application to the human dermal fibroblast cells and/or the keratinocyte cells.