Figure 2.
Correlations between basal gene expression or DNA methylation and LASP sensitivity. (A) Gene expression heatmap of genes (n = 535) discriminate LASP LC50. Patients are denoted at the top of the heatmap as sensitive (green), intermediate (gray), or resistant (red). Expression is denoted as log10(FPKM+1). (B) Basal gene expression [as log10(FPKM+1)] correlation with ex vivo LASP sensitivity by group (S, sensitive; I, intermediate; R, resistant). Box and whisker plots depict the interquartile ranges (IQRs) and tenth to ninetieth percentiles. The linear regression P value for discovery and validations cohorts is shown for each gene (D, FDR <0.05; V, P < .05). (C) DNA methylation heatmap of CpG sites (n = 246) associated with LASP LC50. For each heatmap, the significance of clustering patients by LASP sensitivity was determined by Fisher’s Exact test (P < .05). (D) Basal DNA methylation (β value) correlated with ex vivo LASP sensitivity by group (S, sensitive; I, intermediate; R, resistant). The Kruskal-Wallis test P value for discovery and validation cohorts is shown for each probe (D, FDR <0.1; V, P < .1). Box and whisker plots depict the IQRs and tenth to ninetieth percentiles. (E) Correlation between basal gene expression and DNA methylation. DNA methylation is depicted as hypo-, hemi-, and hyper-methylation (Kruskal-Wallis test; P < .05; n = 136). Box and whisker plots depict the IQRs and tenth to ninetieth percentiles. (F) DNA methylation pattern of the ASNS promoter across 7 probes by drug sensitivity group. Each CpG displayed a significant difference between S, I, and R groups (Kruskal-Wallis test; P < .05).

Correlations between basal gene expression or DNA methylation and LASP sensitivity. (A) Gene expression heatmap of genes (n = 535) discriminate LASP LC50. Patients are denoted at the top of the heatmap as sensitive (green), intermediate (gray), or resistant (red). Expression is denoted as log10(FPKM+1). (B) Basal gene expression [as log10(FPKM+1)] correlation with ex vivo LASP sensitivity by group (S, sensitive; I, intermediate; R, resistant). Box and whisker plots depict the interquartile ranges (IQRs) and tenth to ninetieth percentiles. The linear regression P value for discovery and validations cohorts is shown for each gene (D, FDR <0.05; V, P < .05). (C) DNA methylation heatmap of CpG sites (n = 246) associated with LASP LC50. For each heatmap, the significance of clustering patients by LASP sensitivity was determined by Fisher’s Exact test (P < .05). (D) Basal DNA methylation (β value) correlated with ex vivo LASP sensitivity by group (S, sensitive; I, intermediate; R, resistant). The Kruskal-Wallis test P value for discovery and validation cohorts is shown for each probe (D, FDR <0.1; V, P < .1). Box and whisker plots depict the IQRs and tenth to ninetieth percentiles. (E) Correlation between basal gene expression and DNA methylation. DNA methylation is depicted as hypo-, hemi-, and hyper-methylation (Kruskal-Wallis test; P < .05; n = 136). Box and whisker plots depict the IQRs and tenth to ninetieth percentiles. (F) DNA methylation pattern of the ASNS promoter across 7 probes by drug sensitivity group. Each CpG displayed a significant difference between S, I, and R groups (Kruskal-Wallis test; P < .05).

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