Sequence covariance networks, methods and uses therefor

摘要

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.

主权项

1. A method of establishing a plurality of sequence covariance networks useful to determine whether to treat a patient with an antiviral therapy, comprising:
(i) obtaining a plurality of hepatitis C isolates, grouped by response to an antiviral therapy; (ii) determining the amino acid sequence of a plurality of hepatitis C polypeptides from each isolate; (iii) identifying covariance pairs of residues in the amino acid sequences of each group; and (iv) identifying a plurality of sequence covariance networks among the covariance pairs in each group, thereby establishing a plurality of sequence covariance networks in which each network comprises a unique rank order of hubs; (v) using the plurality of sequence covariance networks to determine whether to treat a specific hepatitis C-infected patient with the antiviral therapy.