PATRI, a Genomics Data Integration Tool for Biomarker Discovery

Figure 5

Translational” analysis of entrectinib sensitivity in lymphoma cell lines and clinical samples. Results of PATRI “Translational” analysis workflow performed on a panel of lymphoma cell lines sensitive or resistant to entrectinib treatment and on two panels of 20 and 130 lymphoma clinical samples (GSE14879 [25] and GSE19069 [26], respectively). (a) List of lymphoma cell lines with respective entrectinib IC50 values. A threshold of 1μM was chosen to define “Sensitive” and “Resistant” cell lines. (b) Heatmap dendrogram of 26 markers differentiating entrectinib sensitive versus resistant lymphoma cell lines, obtained by Limma gene expression analysis (p value<10⁻⁷, logFC>|5|). Significantly high or low expressed genes are highlighted in red and green, respectively. (c) Volcano plot visualizing significance and magnitude of gene expression differences in sensitive versus resistant conditions, with pop-up indicating ALK expression level. Significantly high or low expressed genes (p value<0.05, logFC>|1|) are highlighted in red and green, respectively. (d) Results from STRING analysis [27] showing the protein-protein interaction network connecting the identified genes (STRING interaction score: 0.150). (e) Heatmap representing hierarchical cluster analysis via random forest categorization of the predicted “Sensitive” or “Resistant” GSE14879 lymphoma samples, based on the selected genes (sample IDs are represented on the lower part of the graph). (f-g) Top ranking of significant clinical features associated with GSE14879 lymphoma samples, classified as potentially “Sensitive” or “Resistant”. (f) Histogram representing distribution of clinically assessed ALK immunohistochemistry (IHC) positivity (reported in [25]) in the predicted “Sensitive” and “Resistant” sample groups. (g) Box plot representing the distribution of the reported age [25] in predicted “Sensitive” (avg. 21.6) and “Resistant” (avg. 61.3) lymphoma sample groups.

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