the present invention recognizes that identifying genes expressed during developmental processes , stress responses , and disease states can advance understanding of these biological functions , and can contribute to identifying targets for therapeutic drugs . in addition , the present invention recognizes that rapid and reliable profiling of genetic variations , such as mutations and snps , is of increasing importance to diagnostics , prognostics , forensics , heredity determinations , and pharmacogenetics . one aspect of the present invention provides a method of identifying one or more nucleic acid molecules that are expressed under a given set of conditions based on their complementarity to known sequences , or one or more mutations or snps in a population of nucleic acid molecules . the method includes : contacting at least one probe nucleic acid molecule with a survey population of nucleic acid molecules under conditions that promote nucleic acid hybridization to generate a probe - survey population mixture of nucleic acid molecules , treating the probe - survey population mixture of nucleic acid molecules with a nucleolytic activity , such that nucleolytic activity - sensitive nucleic acid molecules are digested , and contacting the resulting mixture of nucleolytic activity - protected nucleic acid molecules with a solid support comprising one or more attached nucleic acid molecules to generate attached nucleic acid molecule / nucleolytic activity - protected nucleic acid molecule complexes , and identifying one or more of the attached nucleic acid molecules or one or more of the nucleolytic activity - protected nucleic acid molecules in one or more attached nucleic acid molecule / nucleolytic activity - protected nucleic acid molecule complexes .