Abstract: A method of selecting sets of short shared nucleotide sequences from amongst members of nucleic acid populations and identifying subsets of those selected short shared nucleotide sequences that differentiate those members from one another. Probes corresponding to the sets of short shared nucleotide sequences can be synthesized and utilized, inter alia, to detect target nucleic acids in a sample population, to provide expression profiles, or to identify polymorphisms of a gene. The invention also includes integrated systems for performing various steps involved in the method and certain probe compositions.