To examine whether the chemical space differs obviously between the bitterants and non-bitterants, the histograms of the molecular weight (MW), logP, the number of hydrogen-bond donor (NHBD) and acceptor (NHBA) for this dataset are shown in Figures S1–S4 and analyzed as follows. For logP and MW (Figures S1, S2), the overall distributions for the bitterants and non-bitterants are very similar, except the height of peak. In the histogram of logP, the peak for the bitterants is a bit sharper, which indicates that more bitterants tends to be hydrophobic, while in the histogram of MW, the peak for bitterants is a little flat. Moreover, the scatter plot of logP vs. MW (Figure 1A) also illustrate that there is no apparent separation between the bitterants and non-bitterants from this perspective. For the bitterants, the scatter plot of logP vs. MW is also very close to the counterpart in the work of Wiener et al., where they proposed the bitter domain defined by the relations as follows: −3 = < logP ≤ 7 and MW ≤ 700 (Dagan-Wiener et al., 2017).