Due to semi-suppressive PCR (click here to see a detailed explanation), only 50% of the tagmented material from the regular Tn5 are amplifiable. The s3-WGS approach introduced uracil bases in the Tn5 adapters and used uracil intolerant and tolerant DNA polymerases for the gap fill-in and PCR amplification, respectively. In this way, every Tn5 cutting event is amplifiable. The procedure is very similar to s3-ATAC, except that s3-WGS is perform on crosslinked and nucleosome-depleted nuclei.
The library structure of s3-WGS is the same as s3-ATAC. Click here to see the detailed library generation steps.