Subclassification of an independent PDAC cell line cohort based on tyrosine phosphorylation patterns.
A, Tyrosine phosphorylation sites identified and quantified in the TKCC cell line cohort phosphotyrosine (pTyr) proteomics screen according to localization probability (LP) and valid values, including class 1 (> 0.75 LP), class 2 (>0.5, < 0.75 LP) and class 3 (≥ 0.25, ≤ 0.5 LP). B, The 17 TKCC cell lines reproducibility form 3 subtypes (See colored bars, subtype 1 is purple, 2 is orange and 3 is blue) using stepwise unsupervised hierarchical clustering. The heatmap shows the identified topology using the subtype specific sites identified in a supervised manner using ANOVA. C, A protein-protein interaction network formed by TKCC subtype 3 cell lines (blue bar), with phosphoproteins (purple nodes) connected via protein-protein (blue lines) or by kinase-substrate (green lines) relationships. Phosphoproteins enriched in this subtype for axon guidance pathways and ErbB signaling are highlighted with blue and green shading respectively. D, LC-MS/MS quantified RTK tyrosine phosphorylation across the TKCC cell lines according to the identified subtypes (See colored bars, subtype 1 is purple, 2 is orange and 3 is blue). Activation sites identified are highlighted by red text.