Nucleic acid-tagged compositions and methods for multiplexed protein-protein interaction profiling

A method for antigen immunoprofiling a biological sample, comprising:

• providing the biological sample, the biological sample comprising a plurality of antibodies with diverse antigen specificities;
• contacting the biological sample with a population of prey polypeptide targets (PPTs), wherein each PPT in the population is chemically linked to a prey nucleic acid, and wherein the contacting conditions permit binding of one or more of the antibodies in the plurality of antibodies in the biological sample to one or more of the PPTs in the population of PPTs to obtain one or more antibody-PPT complexes;
• contacting the biological sample to a population of bait polypeptides comprising diverse amino acid sequences from at least one of transcription factors, G-proteins, receptors, protein kinases, protein phosphatases, proteases, or a combination thereof, wherein at least one of the bait polypeptides binds to at least one of the PPTs;
• immunoprecipitating the one or more antibody-PPT complexes;
• amplifying prey nucleic acid sequences associated with the one or more immunoprecipitated antibody-PPT complexes to obtain a plurality of cDNAs comprising nucleic acid sequences corresponding to the amplified prey nucleic acid sequences;
• and
• sequencing the plurality of cDNAs to obtain an antigen immunoprofile of the biological sample.