The invention includes a method for determining the differences between the molecular interactions of two different mixtures of molecules and identifying ligands specific for molecules in one mixture. The method utilizes a combinatorial library to compare the molecular interactions of the two mixtures and eliminates those interactions that are common to both mixtures and those that are unique to the first mixture, such that interactions essentially unique to the target mixture are identified. Ligands specific for molecules in the target mixture can then be identified. The invention also includes a method of screening a combinatorial library to distinguish between true positive beads and false positive beads and to provide for the identification of ligands specific for target molecules.