Figure 6.
Metabolome analysis reveals systemic differences between WT and Pax5+/–mice predisposed to develop pB-ALL. (A) Overview of the experimental design is shown. Serum samples were collected from untreated WT (n = 10) and Pax5+/– (n = 10) mice born and housed in SPF facilities at 4 months of age. Additional samples were collected from 10 Pax5+/– mice kept in SPF facilities at onset of pB-ALL after treatment with antibiotics (at ∼15 months of age). (B) The relative response values for 52 quality-controlled gas chromatography peaks were used to create a feature table. Using Bray-Curtis, a beta-diversity distance matrix was computed via Qiime2 version 2020.2. The EMPeror plot shows the PCoA of the resulting matrix (blue, samples from WT mice; red, samples from Pax5+/– mice). Open circles represent leukemic mice, and filled circles represent healthy mice. Clustering indicated a difference by genotype based on measurements of 52 metabolites in the blood. (C-D) Statistical tests (PERMANOVA) confirmed strong significant differences depending on genotype (C) and health state (D). (C) The upper panel shows statistically significant (2-sided PERMANOVA tests with 999 permutations) differences in beta-diversity distance between blood samples from WT (blue) and Pax5+/– (red) mice. Gray box summarizes intergroup distances (ie, pairs of samples in which 1 partner belongs to WT and the other to Pax5+/–). The lower panel shows that after applying discrete FDR on the metabolite feature table, 6 of 52 compounds were found to be significantly differentially abundant between WT and Pax5+/– serum samples. (D) Upper panel visualizes the differences between serum samples from healthy Pax5+/– (light blue represents red solid spheres in panel B) and pB-ALL diseased (green represents red rings in panel B) individual mice. Lower panel shows the top 6 of 16 compounds found to be significantly differentially abundant among all 52 compounds in healthy and pB-ALL samples. The boxes show the quartiles of the dataset, while the whiskers (error bars) show the rest of the distribution, except for points that are determined to be outliers, using 1.5-fold of the interquartile range (C,D). P values are from the PERMANOVA test.

Metabolome analysis reveals systemic differences between WT and Pax5+/–mice predisposed to develop pB-ALL. (A) Overview of the experimental design is shown. Serum samples were collected from untreated WT (n = 10) and Pax5+/– (n = 10) mice born and housed in SPF facilities at 4 months of age. Additional samples were collected from 10 Pax5+/– mice kept in SPF facilities at onset of pB-ALL after treatment with antibiotics (at ∼15 months of age). (B) The relative response values for 52 quality-controlled gas chromatography peaks were used to create a feature table. Using Bray-Curtis, a beta-diversity distance matrix was computed via Qiime2 version 2020.2. The EMPeror plot shows the PCoA of the resulting matrix (blue, samples from WT mice; red, samples from Pax5+/– mice). Open circles represent leukemic mice, and filled circles represent healthy mice. Clustering indicated a difference by genotype based on measurements of 52 metabolites in the blood. (C-D) Statistical tests (PERMANOVA) confirmed strong significant differences depending on genotype (C) and health state (D). (C) The upper panel shows statistically significant (2-sided PERMANOVA tests with 999 permutations) differences in beta-diversity distance between blood samples from WT (blue) and Pax5+/– (red) mice. Gray box summarizes intergroup distances (ie, pairs of samples in which 1 partner belongs to WT and the other to Pax5+/–). The lower panel shows that after applying discrete FDR on the metabolite feature table, 6 of 52 compounds were found to be significantly differentially abundant between WT and Pax5+/– serum samples. (D) Upper panel visualizes the differences between serum samples from healthy Pax5+/– (light blue represents red solid spheres in panel B) and pB-ALL diseased (green represents red rings in panel B) individual mice. Lower panel shows the top 6 of 16 compounds found to be significantly differentially abundant among all 52 compounds in healthy and pB-ALL samples. The boxes show the quartiles of the dataset, while the whiskers (error bars) show the rest of the distribution, except for points that are determined to be outliers, using 1.5-fold of the interquartile range (C,D). P values are from the PERMANOVA test.

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