Methods for measuring relative amounts of nucleic acids in a complex mixture and retrieval of specific sequences therefrom

A method of normalizing a genetic library, comprising the steps of:

• (a) attaching unique oligonucleotide identifier tags to nucleic acid sequence inserts derived from a genetic library;
• (b) hybridizing the inserts of step (a) with a nucleic acid sample derived from a source of interest under conditions that promote the formation of perfectly matched duplexes, wherein the nucleic acid sample is labeled with a first label;
• (c) contacting the mixture of step (b) with solid supports having attached thereto the complements of the oligonucleotide identifier tags under conditions that promote the formation of perfectly matched duplexes between the oligonucleotide identifier tags and their respective complements in the presence of free oligonucleotide identifier tags labeled with a second label and corresponding in sequence to the oligonucleotide identifier tags of step (a);
• (d) sorting solid supports according to the relative amount of said first label and said second label;
• and
• (e) amplifying insert sequences present at lower abundance in order to match the abundance of insert sequences such that they are represented at substantially similar levels in the library.

A method for comparing the relative amounts of specific nucleic acid molecules in at least two samples derived from a single nucleic acid source, wherein the relative abundance of one or more of said molecules changes during propagation in a host cell population, comprising the steps of:

• (a) introducing a nucleic acid sample from a starting nucleic acid source into a cell population;
• (b) propagating the cell population;
• (c) re-isolating the nucleic acid sample from the propagated cell population;
• and
• (d) performing quantitative comparison of the relative amounts of at least one specific nucleic acid molecule in the propagated nucleic acid sample and the starting nucleic acid source.