PATRI, a Genomics Data Integration Tool for Biomarker Discovery
Translational” analysis of lapatinib sensitivity in breast cancer cell lines and clinical samples. Results of PATRI “Translational” analysis workflow performed on a panel of breast cancer cell lines sensitive or resistant to lapatinib treatment and on a panel of 1017 TCGA breast cancer clinical samples. (a) List of treated breast cell lines with respective lapatinib IC50 values. A threshold of 1μM was chosen to define “Sensitive” and “Resistant” cell lines. (b) Heatmap dendrogram of 17 markers differentiating lapatinib sensitive versus resistant breast cell lines, obtained by ANOVA gene expression analysis (p value>10−4, log2 FC>|1.5|). Significantly high or low expressed genes are highlighted in red and green, respectively. (c) Scatter plot visualization of the identified genes in the different cell lines, combining dot size, representing magnitude of copy number values, and dot color shades, ranging from low (green) to high (red) gene expression values. (d) Heatmap representing hierarchical cluster analysis via random forest categorization of the predicted “Sensitive” or “Resistant” 1071 breast cancer samples, based on the selected genes (with the exception of TMEM35B, not represented in the clinical dataset; sample IDs could not be represented on the lower part of the graph). (e-f) Top ranking of significant clinical features (where available) associated with TCGA breast cancer samples, classified as potentially “Sensitive” or “Resistant”. (e) Histogram representing distribution of clinically evaluated Her2 immunohistochemistry levels (0-3+) in the predicted “Sensitive” and “Resistant” clinical sample groups. The displayed data correspond to the column “Her2 IHC score” in the TCGA Breast Invasive Carcinoma “Provisional” Clinical Data annotation file. (f) Box plot representing the clinically assessed average signal value for chromosome 17 amplification in predicted “Sensitive” (4.28) and “Resistant” (1.32) clinical sample groups. The displayed data correspond to the column “Her2 cent 17 ratio” in the TCGA Breast Invasive Carcinoma “Provisional” Clinical Data annotation file.