The two major caveats to the algorithm functioning as described above are greater noise membership than the overall target value of downsampling and cluster targets being greater than their overall membership. For the former case, where the number of chemical singletons is initially greater than the desired number of molecules to be retained, Dedenser applies Poisson disk downsampling to the noise before downsampling clusters. In this case, the target for noise downsampling is defined as 80% of its equivalent, volume based target, effectively treating it as a cluster in eq. 2. For the latter case, where clusters may have membership lower than their respective target for downsampling, an iterative loop is executed that retains all the molecules in these below target clusters, and subsequently recalculates the remaining targets. This iterative process of checking and managing the cluster targets is executed until all remaining clusters have initial memberships greater than their respective target membership for downsampling. Further details regarding the two-stage downsampling algorithm and some implementation details defining Dedenser are outlined in pseudocode (Algorithm S1.) for Dedenser using volume based cluster downsampling.