Building block level analysis predicts the activity of trisynthons containing untested building blocks. To mimic an experimental setting in which we would like to propose new building blocks to add after performing a DEL screen, we randomly select 5% of the building blocks at each position and remove all trisynthons containing those building blocks and place them into a holdout set. The training set, now composed of the remaining compounds, represents the information we might have after an initial experimental screen. The holdout set represents a set of proposed follow-up candidates that all contain at least one untested building block.