Abstract: Methods, systems, and computer readable media perform predictive modeling of gene activity. The methods may comprise obtaining the amino acid and/or nucleic acid sequence of a portion of the at least one gene from a biological sample obtained from a subject; comparing the amino acid and/or nucleic acid sequence of the portion of the at least one gene to a database of sequences for the portion of the at least one gene and for which the biological activity of the at least one gene has been evaluated; and applying a generalization of ridge regression analysis to estimate the effects of individual mutations in the at least one gene. A model is based on generalization of ridge regression (GRR) analysis to estimate the effects of individual mutations in at least one gene for the subject. At least one gene may comprise the reverse transcriptase and protease genes of an HIV vims.