**4. Development of advanced bioinformatical platforms for complicated kinase‐substrate interaction networks**

**Author details**

Minato‐ku, Tokyo, Japan

nature12625

**References**

Hiroko Kozuka‐Hata and Masaaki Oyama\*

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\*Address all correspondence to: moyama@ims.u‐tokyo.ac.jp

Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo,

Comprehensive Network Analysis of Cancer Stem Cell Signalling through Systematic...

http://dx.doi.org/10.5772/intechopen.69647

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Although shotgun proteomics strategy based on advanced nanoLC‐MS/MS system can provide us with large‐scale information on various kinds of PTMs, there are only a few PTM‐ based network analysis tools available compared to conventional protein‐protein interaction (PPI). Recently, CEASAR: connecting enzymes and substrates at amino acid resolution [39] and PhosphoPath [40] were developed to visualize kinase‐substrate interactions in a phosphorylation site‐oriented manner. CEASAR was designed to provide a high‐resolution map of kinase‐phosphorylation networks based on functional protein microarrays and bioinformatics analysis. On the other hand, PhosphoPath was developed as a Cytoscape app [41] to visualize both quantitative proteome and phosphoproteome data using PPI information extracted from BioGRID [42] and PhosphoSitePlus [17]. Recently, we also have developed a Cytoscape‐based bioinformatical platform named 'post‐translational modification mapper (PTMapper)' to visualize kinase‐substrate interactions regarding multiple phosphorylation sites on signalling molecules (**Figure 6**) [12]. The kinase‐phosphorylation site interaction dataset for this platform was integratively generated from PhosphoSitePlus [17], Phospho.ELM [43], PhosphoNetworks [44] and Uniprot KB [45], leading to construction of phosphorylation site‐oriented PPI networks using Pathway Commons [46]. We applied this platform to extract crucial kinase‐substrate interactions from the quantitative phosphoproteome data on EGF‐stimulated GSCs [29]. As a result, p70S6K and Lyn were significantly extracted as key regulators (**Figure 7**).
