A method of generating a gene expression signature for use in identifying connections between perturbagens and genes associated with a skin pigmentation condition, the method comprising: (a) generating a gene expression profile for a human skin cell sample treated with at least one benchmark skin pigmentation modifying agent that comprises a skin lightening agent, wherein the benchmark skin pigmentation modifying agent is suspended in a vehicle composition; (b) generating a gene expression profile for a human skin cell sample treated with the vehicle composition, wherein the human skin cell sample treated with the vehicle composition and the human skin cell sample treated with at least one benchmark skin pigmentation modifying agent, are from the same cell line; (c) comparing the expression profiles of (a) and (b) to determine a gene expression signature comprising a set of genes differentially expressed in (a) and (b); (d) 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 gene expression signature lists; (e) storing the one or more gene expression signature lists on at least one computer readable medium; and (f) additionally carrying out steps (a) through (e) as for steps (a) to (e) except that the benchmark skin modifying agent comprises a skin darkening agent; and (g) comparing the gene expression signature list from (e) to the gene expression signature list from (e) and eliminating from the gene expression signature list from (e) any identifier corresponding to a gene appearing on the (e) list and having the same direction of differential expression as the gene on the (e) list. (a) generating a gene expression profile for a human skin cell sample treated with at least one benchmark skin pigmentation modifying agent that comprises a skin lightening agent, wherein the benchmark skin pigmentation modifying agent is suspended in a vehicle composition; (b) generating a gene expression profile for a human skin cell sample treated with the vehicle composition, wherein the human skin cell sample treated with the vehicle composition and the human skin cell sample treated with at least one benchmark skin pigmentation modifying agent, are from the same cell line; (c) comparing the expression profiles of (a) and (b) to determine a gene expression signature comprising a set of genes differentially expressed in (a) and (b); (d) 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 gene expression signature lists; (e) storing the one or more gene expression signature lists on at least one computer readable medium; and (f) additionally carrying out steps (a) through (e) as for steps (a) to (e) except that the benchmark skin modifying agent comprises a skin darkening agent; and (g) comparing the gene expression signature list from (e) to the gene expression signature list from (e) and eliminating from the gene expression signature list from (e) any identifier corresponding to a gene appearing on the (e) list and having the same direction of differential expression as the gene on the (e) list.