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. Author manuscript; available in PMC: 2021 Mar 21.
Published in final edited form as: Nat Metab. 2020 Sep 21;2(10):1149–1162. doi: 10.1038/s42255-020-00278-3

Figure 5. Web resource LipidGenie guides exploration of genome-lipid connections.

Figure 5.

a, We quantified 2,558 features in B6 plasma (n=4 for each sex). 254 features were sex-specific (FC > 1.0, p < 0.05, non-paired, two-sided Student’s t-test). Precursor m/z (±10 ppm) matching to our DO database provided genetic information for ⅓ of the otherwise unidentified features. b, Six male-specific unidentified features (red) share a QTL on Chr 6:91 Mbp with a common A/J down effect (Extended Data Figure S5a). c, The features further clustered in m/z-RT space. d-g, Targeted fragmentation spectra (exemplary spectra for two species ([M+H]+ m/z 1156 and 1158) in positive (MS2) and negative (MS2 and MS3) mode) exhibited signals consistent with a lipid class built of a PC headgroup and three FAs. h, The DO database further confirmed LysoPC 14:0 mapping to Abhd160 with j, an enrichment of FA 14:0 containing lipids k, We compare Hepa1-6 overexpressing ABHD1 and ABHD3 versus a control overexpressing GFP (n=12 for each, 4 biological x 3 technical replicates, boxplots are defined with first and third quartiles for lower and upper hinges, 1.5x interquartile range for the length of the whiskers, center line at median). The boxplots show absolute FC of each mutant over GFP by lipid class; the dashed line is at FC=0.4 l, The lowest (negative) FC for both is observed for LysoPC 14:0; isomers are summed. m, All 14:0 containing PCs exhibit a negative FC for ABHD1 and ABHD3 mutants consistently, while 18:0 containing species are showing opposing positive FC. Plotted are sum-normalized, log2-transformed FC means with error bars representing 95% confidence interval, significance indicated by * (p < 0.05), ** (p < 0.01), *** (p < 0.001) of non-paired two-sided Student’s t-test, equal variance, n=12 for each, details in source data. Abbreviations: DO (diversity outbred), FC (fold change), m/z (mass-to-charge), QTL (quantitative trait loci), Chr (chromosome), Mbp (megabase pair), SNP (single nucleotide polymorphism), PC (phosphatidylcholine), F/M (female-to-male), RT (retention time), FA (fatty acid), PE (phosphatidylethanolamine), GFP (green fluorescent protein)