The present invention provides methods for determining the level of
protein activity in a cell by: (i) measuring abundances of cellular
constituents in a cell in which the activity of a specific protein is to
be determined so that a diagnostic profile is thus obtained; (ii)
measuring abundances of cellular constituents that occur in a cell in
response to perturbations in the activity of said protein to obtain
response profiles and interpolating said response profiles to generate
response curves; and (iii) determining a protein activity level at which
the response profile extracted from the response curves best fits the
measured diagnostic profile, according to some objective measure. In
alternative embodiments, the present invention also provides methods for
identifying individuals having genetic mutations or polymorphisms that
disrupt protein activity, and methods for identifying drug activity in
vivo by determining the activity levels of proteins which interact with
said drugs.