Methods of identifying targets for designing a therapeutic agent are disclosed. These methods comprise: determining an amino acid sequence of one or more polypeptides of each isolate of a plurality of isolates of a biological system； identifying covariance pairs of amino acid residues； establishing a network comprising the covariance pairs； and identifying one or more hub residue positions, wherein a hub residue position comprises a target for designing a therapeutic agent if the hub residue position has a rank order in the 40th percentile or greater. In other aspects, methods are disclosed for selecting a therapy for an infectious disorder. In various configurations, these methods comprise: determining amino acids occupying a plurality of diagnostic amino acid residue positions comprised by one or more polypeptides encoded by an infectious agent infecting a subject； and assigning the infectious agent infecting the subject to one covariance network selected from a plurality of covariance networks, wherein each network comprises a unique rank order of hubs with respect to the other networks, and whereby the therapy is selected on the basis of the covariance network assignment.
