The present invention provides methods for rapidly and efficiently searching biologically-related data space. More specifically, the present invention provides methods for identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The present invention also provides methods for modeling sequence-activity relationships, including but not limited to stepwise addition or subtraction techniques, Bayesian regression, ensemble regression and other methods. The present invention further provides digital systems and software for performing the methods provided herein.