SELPHI: correlation-based identification of kinase-associated networks from global phospho-proteomics data sets.
Bottom Line: We illustrate SELPHI via analysis of phospho-proteomics data acquired in the presence of erlotinib-a tyrosine kinase inhibitor (TKI)-in cancer cells expressing TKI-resistant and -sensitive variants of the Epidermal Growth Factor Receptor.In this data set, SELPHI revealed information overlooked by the reporting study, including the known role of MET and EPHA2 kinases in conferring resistance to erlotinib in TKI sensitive strains.SELPHI can significantly enhance the analysis of phospho-proteomics data contributing to improved understanding of sample-specific signaling networks.
Affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X8, Canada email@example.com.Show MeSH
Related in: MedlinePlus
Mentions: SELPHI's workflow is presented in Figure 1. If the user has provided protein sequences, SELPHI first pre-processes the input data to identify the associated UniprotKB ID (17) and phosphosite positions in the sequence and filters the data according to the fold change cutoff defined (default is 3-fold). Duplicate peptide identifications are merged using either their weighted average (if there is an intensity or score column available) or the value that represents the maximum change, according to the preferred user settings. Combined input data sets with less than two data points, defined as a ratio or intensity value acquired by a single sample, replicate and condition, are not processed by SELPHI, while the user can restrict their data to only peptides that appear in a minimum number of samples/conditions through the submission interface. There is no limit to the number of peptides in a data set. KEGG pathway (18) and GO Term (FuncAssociate 5) enrichment for the changed peptides is then calculated. The results are plotted as a clustered matrix of the over-represented pathways/GO terms against the samples (Figure 2A, B), colored by the additive (pathways) or average additive (GO terms) log-ratio of intensity for peptides belonging to that term for each sample and demonstrating the enrichment's effect size (log odds ratio) via the size of the box.
Affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X8, Canada firstname.lastname@example.org.