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Fig 1.

Graphical representation of the experimental designs used.

A) experiment 1, a single 18mg brain section was homogenised then 7 parallel extractions were performed on 50μl aliquots of homogenate. B) Experiment 2, brain sections ranging from 3–17mg were homogenised and extracted parallel.

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Fig 1 Expand

Fig 2.

Applied analytical pipeline.

Shows the seven steps from tissue sectioning to IVDE and onto data processing and multivariate analysis of variation.

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Fig 2 Expand

Fig 3.

Recoveries of HILIC and reversed phase internal standards in experiment 1.

A) plot of intensity of reversed phase internal standards Heptadecanoic acid (negative) and Tripentadecanoin (positive), B) plot of intensity of HILIC internal standards in positive ionisation mode, C) plot of intensity of HILIC internal standards in negative ionisation mode, D) average intensity and coefficient of variance of all internal standards.

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Fig 3 Expand

Table 1.

Measured metabolite features in the HILIC method in experiment 1.

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Table 1 Expand

Table 2.

Measured metabolite features in the reversed phase method in experiment 1.

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Table 2 Expand

Fig 4.

Principal component analysis (components = 2, R2X – 0.439, Q2–0.210) of metabolite features identified in at least 70% of samples in experiment 1.

A) scores plot and B) Hotelling’s T2 and C) DModX plot, showing that sample mass has no effect on overall metabolite composition.

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Fig 4 Expand

Fig 5.

Recoveries of HILIC and reversed phase internal standards in experiment 2.

A) plot of intensity of reversed phase internal standards Heptsdecanoic acid (negative) and Tripentadecanoin (positive), B) plot of intensity of HILIC internal standards in positive ionisation mode, C) plot of intensity of HILIC internal standards in negative ionisation mode, D) average intensity and coefficient of variance of all internal standards.

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Fig 5 Expand

Table 3.

Measured metabolite features in the HILIC method in experiment 2.

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Table 3 Expand

Table 4.

Measured metabolite features in the reversed phase method in experiment 2.

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Table 4 Expand

Fig 6.

Principal component analysis of samples (components = 2, R2X 0.354, Q2 0.049) performed on metabolite features identified in at least 73% of samples in experiment 2.

A) scores plot where point labels represent sample mass B) Hotelling’s T2 and C) DModX plot of analytical samples, showing that sample mass has no effect on overall metabolite composition.

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Fig 6 Expand

Fig 7.

Plots of sample mass in milligrams against intensity for 9 annotated metabolites.

A) taurine B) hypoxanthine C) glutamate D) pantothenate E) aspartate F) glcosylceramide (36:1) G) phosphatidylethanolamine (38:4) H) ceramide (38:1) I) triglyceride (48:3).

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Fig 7 Expand

Table 5.

Metabolites annotated from the HILIC method.

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Table 5 Expand

Table 6.

Metabolites annotated from the reversed phase method.

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Table 6 Expand