A system for identifying connections between perturbagens and genes associated with a skin hyperpigmentation condition, comprising: (a) at least one computer readable medium having stored thereon a plurality of instances, and a skin hyperpigmentation-relevant gene expression signature, wherein the instances and the gene expression signature are derived from a human keratinocyte cell, wherein each instance comprises an instance list of rank-ordered identifiers of differentially expressed genes in response to at least one perturbagen, and wherein the hyperpigmentation-relevant gene expression signature comprises one or more gene expression signature lists of identifiers representing differentially expressed genes associated with a hyperpigmentation condition or differentially expressed genes associated with a benchmark skin-lightening agent selected from the group consisting of vitamin B3 compound, hexamidine diisothionate, N-acetylglucosamine, an N-acyl amino acid compound, hydroquinone, a retinoid compound, hexyldecanol, and combinations thereof, wherein said retinoid compound is selected from the group consisting of retinol, retinol esters, and/or retinal; (b) a programmable computer comprising computer-readable instructions that cause the programmable computer to execute the following: (i) accessing the plurality of instances and a hyperpigmentation-relevant gene expression signature stored on the computer readable medium; (ii) comparing the hyperpigmentation-relevant 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 based on (ii). (a) at least one computer readable medium having stored thereon a plurality of instances, and a skin hyperpigmentation-relevant gene expression signature, wherein the instances and the gene expression signature are derived from a human keratinocyte cell, wherein each instance comprises an instance list of rank-ordered identifiers of differentially expressed genes in response to at least one perturbagen, and wherein the hyperpigmentation-relevant gene expression signature comprises one or more gene expression signature lists of identifiers representing differentially expressed genes associated with a hyperpigmentation condition or differentially expressed genes associated with a benchmark skin-lightening agent selected from the group consisting of vitamin B3 compound, hexamidine diisothionate, N-acetylglucosamine, an N-acyl amino acid compound, hydroquinone, a retinoid compound, hexyldecanol, and combinations thereof, wherein said retinoid compound is selected from the group consisting of retinol, retinol esters, and/or retinal; (b) a programmable computer comprising computer-readable instructions that cause the programmable computer to execute the following: (i) accessing the plurality of instances and a hyperpigmentation-relevant gene expression signature stored on the computer readable medium; (ii) comparing the hyperpigmentation-relevant 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 based on (ii). (i) accessing the plurality of instances and a hyperpigmentation-relevant gene expression signature stored on the computer readable medium; (ii) comparing the hyperpigmentation-relevant 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 based on (ii).