## 2 Results and Discussion
### Quantitative Compound \(\times\) Individual Matrix Effects in a Grape Population  
In initial inspection of our HS-SPME-GC-MS dataset, we observed good reproducibility of internal standard peak areas for analytical replicates from the same grape individual (\(\sigma_{x,within}\)); precisions ranged over RSD = 12-20% for all volatiles except for [U\({}^{13}\)C]hexanal = 32% (data not shown). This range for precision is comparable to those in previous literature reports using HS-SPME-GC-MS on grape volatiles [30]. The presence of Compound \(\times\) Individual interactions in the grape population is illustrated by three representative chromatograms, each depicting the behavior of a different compound pair across three individuals (Figure 2). For certain compound pairs, the variation in matrix effects is well correlated, e.g., for [2H3]IBMP and [2H3]IPMP, Figure 2 (top). Although the signal is ~50% higher in Individual C than in Individual A for [2H3]IPMP, a similar change is seen for [2H3]IBMP; thus, the two compounds could serve as surrogate standards. In contrast, the relative responses of other compound pairs ([2H3]eucalypt and [2H3]methyl anthranilate, Figure 2 (middle); and [U\({}^{13}\)C]hexanal and [U\({}^{13}\)C]hexanal, Figure 2 (bottom)) were not consistent. For example, the [2H3]methyl anthranilate signal was 4-fold higher in Individual B, but the [2H3]eucalypt signal was nearly unchanged. In our analyses, samples were prepared and run in batches of up to 30 runs. Since a run length was approximately 60 min, including oven cooling time, some samples would have sat for up to 30 hours before analysis. Although we used brine addition to disrupt enzymatic activity and randomized the order of analyses, we were still concerned that variation in the signal could have arisen from nonenzymatic reactions or residual enzymatic activity. To evaluate this possibility, regression analyses of peak area versus run number were performed for each standard. Representative plots for [U\({}^{13}\)C]hexanal and [U\({}^{13}\)C]hexanal are shown in Supplementary Figure S2; other plots are not shown. With the exception of [U\({}^{13}\)C]hexanal (\(p\) = 0.01, \(r^{2}\) = 0.18), no significant effect of run number  
Figure 2: Chromatograms (left) and corresponding box plots (right) of Compound \(\times\) Individual matrix effects for three pairs of internal standards in three different grape individuals (A, B, C). Internal standards are [2H3]IBMP and [2H3]IPMP (top), [2H3]eucalypt and [2H3]methyl anthranilate (middle), and [U\({}^{13}\)C]hexanal and [U\({}^{13}\)C]hexanal (bottom). was observed for any of the internal standards. The effect of run number on [U\({}^{13}\)C]hexanal was negative (decreasing signal intensity over time), and we observed that eliminating the first five vials of each batch from the ANOVA resulted in no significant correlation between run number and signal (\(p>0.05\), data not shown). The higher [U\({}^{13}\)C]hexanal response in earlier runs was not due to instability of the standard under aqueous conditions--we observed no change in [U\({}^{13}\)C]hexanal in a model juice system over 48 h (data not shown), nor was an increase observed for [U\({}^{13}\)C]hexanol during later runs (Supplementary Figure S2). An alternate explanation for the higher [U\({}^{13}\)C]hexanal in the first few runs of each batch is that the compound reacted with other nucleophilic juice components (e.g., polyphenols) [31]. Regardless of the cause, the effect of pre-analysis time explained only a small portion of the total variation observed in the [U\({}^{13}\)C]hexanal response among individuals. To quantitate Compound \(\times\) Individual matrix effects (\(\sigma_{std\ 1 std\ 2}\)) we used the approach described in the previous subsection and outlined in Figure 1. Summary statistics are shown for each compound pair (Figure 3), where the percent relative standard deviation was calculated from the log-normalized pairwise matrix error.