Next Generation Sequencing of DNA-Encoded Libraries.

DEL technology is dependent on the generation and analysis of large amounts of DNA sequence data. In this chapter, we describe a method to sequence DEL libraries that uses a customized preparative PCR protocol, along with standard steps for purification, analysis, and sequencing of the amplified library DNA on an Illumina sequencing platform. Compared with standard Illumina sequencing library preparation protocols, in which a PCR reaction is followed by end repair, adenylation, ligation of Illumina adapters, and a second preparative PCR reaction, the customized operations described here provide significantly improved process efficiency and sequencing quality.