## 3 Results
### Computational Analysis of Lycopene Targets  
The protein-protein interaction (PPI) analysis of all lycopene targets indicated 32 high-interaction and 9 significant-interaction targets (Figure 2). Of the 32 high-interaction targets, 5 (_TRIM24_, _GRIN1_, _NTRK1_, _FGFR1_, and _NTRK3_) showed affinity values to lycopene under 10 uM, while among the 9 significant-interaction targets, only two (CHRNB4 and PIK3 CD) showed affinity values to lycopene under 10 uM. The CA ratios of lycopene targets with affinity values <10 uM ranged from 0.01 to 0.03. Most lycopene targets, in addition to showing low affinity values, had negligible PPI (<10 hydrogen bonds), suggesting these targets are not of relevance to the pharmacological effects of lycopene or may be indirectly regulated. Based on the PPI and affinity values, we observe the following three categories of lycopene targets: (1) targets with high affinity values (<10 uM; _MAP2K2_, _SCN2A_, _SLC6A5_, _SCN3A_, _TOP2A_, _TRIM24_, _P2 RY12_, _SLC6A1_, _AURKB_, _SCN4A_, _GRIN1_, _NTRK1_, _PDGFRA_, _RXFP1_, _CHRNB4_, _PIK3 CA_, _FGFR1_, _ABCC1_, _NTRK3_, and _PIK3 CD_), (2) targets with high network interactions (_TRIM24_, _GRIN1_, _NTRK1_, _CHRNB4_, _FGFR1_, _NTRK3_, _PIK3 CD_, _CLK4_, _RXRG_, _CYP2A6_, _GRK5_, _RXRA_, _RXRB_, _CLK1_, _NAPK1_, _PDGFRB_, _PIK3R1_, _CXCR4_, _GLRA1_, _NR1I2_, _NR3C2_, _NFE2L2_, _NAMPT_, _PRMT1_, _METAP2_, _NR4A1_, _ADAM10_, _VDR_, _HSD17B10_, _SPHK1_, and _APEX1_), and (3) targets with both high affinity values and network interactions (_TRIM24_, _GRIN1_, _NTRK1_, _FGFR1_, _NTRK3_, _CHRNB4_, and _PIK3 CD_) (Figure 2).  
Figure 1: **(A)**: The chemical structure of lycopene to outline its linear nature is shown. The target classes of all (**B**) and the top 15 (**C**) lycopene targets are shown as a pie chart along with the relative percentage of each of the target categories. (**D**): The heatmap shows the affinity and concentration-affinity (CA) ratio values (for plasma concentration of lycopene of 75, 170, and 210 nM) for each of the lycopene targets. The lycopene targets are represented by their UniProt ID. The lycopene targets highlighted in green are high-affinity targets (affinity values below 10 uM). The heatmap scale shown is from high (red) to low (green) CA ratio.  
Figure 2: **(A)**: Heatmap of the protein–protein interaction networks of all lycopene targets based on the number of hydrogen bonds formed between a pair of targets at 10 Armstrong distance. The purple horizontal bars below indicate high/significantly interacting networks (**B**): Venn diagram in the middle shows the logical relationships between all, high (at least ten pairs of targets showing >8000 H-bond between them), and significant (a minimum of ten pairs of targets showing >15,000 H-bond between them) network targets of lycopene. The numbers indicate the total number of targets in each category. **(C)**: The Venn diagram below shows the logical relationships between high-affinity and high-network targets of lycopene. The three major categories of lycopene targets are shown, i.e., (1) high-affinity targets (orange, n = 13), (2) high-network targets (green, n = 25), and (3) targets with high affinity and networks (olive, n = 7).