Methods of nucleic acid sample preparation for immune repertoire sequencing

A method of preparing nucleic acids for analysis, the method comprising:

• (a) contacting a nucleic acid molecule comprising a target nucleotide sequence with a capture moiety modified primer that specifically anneals to the target nucleotide sequence under hybridization conditions;
• (b) conducting a first strand synthesis reaction that is primed by a hybridized capture moiety modified primer and that uses the nucleic acid molecule as a template;
• (c) conducting a second strand synthesis reaction that uses a product of the first strand synthesis reaction as a template to generate a double-stranded nucleic acid comprising a capture moiety;
• (d) ligating an adapter nucleic acid to the double-stranded nucleic acid to produce a ligation product comprising the capture moiety;
• (e) capturing the ligation product by contacting the ligation product with a binding partner of the capture moiety;
• and
• (f) amplifying the captured ligation product by polymerase chain reaction using a target-specific primer that comprises a 3′ portion that specifically anneals to the target nucleotide sequence and a first adapter primer that specifically anneals to a complementary sequence of the adapter nucleic acid, wherein the target-specific primer comprises a 5′ tail portion that does not specifically anneal to the target nucleotide sequence.