Assessing Compound Interactions and Synergy Analysis
The experimentally measured %Yield data for the entire concentration ranges in Figure 9b, 9c, 9d, and 9e were used to construct the interaction maps shown on the left column in Figure 12. The interaction maps provided an assessment on the %Yield of red spinach when grown with these 2-compound combinations at different concentration ratios. Furthermore, the %Yield data at every compound ratio were subsequently analyzed using the Bliss independence model for synergy analysis, which is conventionally used to assess synergy in drug combinations \cite{Liu_2018,Poon_2021}. The Bliss independence model assumes that two compounds are mutually nonexclusive and compounds affect %Yield via different pathways, and this approach may provide insight into synergies exhibited by compound combinations. The Bliss synergy maps quantified the synergy exhibited by each concentration ratio using the Bliss synergy score, which quantifies the strength of synergy of a given combination with respect to the mono-compounds. Notably, the interaction of 6-BAP/EDTA-Fe at concentrations 1 mg mL-1 and 2 g L-1, respectively, highlighted in the response surface analysis (Figure 9a), was confirmed to be synergistic via Bliss synergy scores. Similarly, Bliss synergy map also suggested that HA/SWE at concentrations 2 g L-1 and 12.5% v/v, respectively, had strong synergy (synergy score of 35.2).