Next, we filtered the set of molecular pairs in the following way: (a) all molecular pairs with SMIRKs occurring less than N1 times were excluded, and (b) for each remaining SMIRK, only N2 randomly chosen pairs of molecules were kept (Fig. ). The first condition eliminated very rare SMIRKs to suppress the noise in the MMPDB output. As a visual inspection of a random subset of rare SMIRKs showed, they correspond to transformations that seem unnatural from the viewpoint of Medicinal Chemistry (e.g., keep a small part of a molecule unchanged, even as small as a methyl group, and replace a much bigger part of a molecule). The second condition was introduced to eliminate an extreme bias of the original set of molecular pairs towards the simplest transformations, such as a replacement of a hydrogen atom by a methyl group or a halogen atom, and thereby to ensure diversity of molecular transformations in the dataset (Fig. ). In general, N1 and N2 may be different, but in this work, we considered only filters with the same values of N1 and N2. For brevity, we use the term "Filter N" in this paper to refer to the above-described dataset filtering procedure with the cutoffs of N = N1 = N2.