Dataset Information

Integration of protein phosphorylation, acetylation, and methylation data sets to outline lung cancer signaling networks.

ABSTRACT: Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs. We used the t-distributed stochastic neighbor embedding (t-SNE) method to identify PTM clusters and then integrated each with known protein-protein interactions (PPIs) to elucidate functional cell signaling pathways. The CFN identified known and previously unknown cell signaling pathways in lung cancer cells that were not present in normal lung epithelial tissue. In various proteins modified by more than one type of PTM, the incidence of those PTMs exhibited inverse relationships, suggesting that molecular exclusive "OR" gates determine a large number of signal transduction events. We also showed that the acetyltransferase EP300 appears to be a hub in the network of pathways involving different PTMs. In addition, the data shed light on the mechanism of action of geldanamycin, an HSP90 inhibitor. Together, the findings reveal that cell signaling pathways mediated by acetylation, methylation, and phosphorylation regulate the cytoskeleton, membrane traffic, and RNA binding protein-mediated control of gene expression.

SUBMITTER: Grimes M

PROVIDER: S-EPMC6822907 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Integration of protein phosphorylation, acetylation, and methylation data sets to outline lung cancer signaling networks.

Grimes Mark M Hall Benjamin B Foltz Lauren L Levy Tyler T Rikova Klarisa K Gaiser Jeremiah J Cook William W Smirnova Ekaterina E Wheeler Travis T Clark Neil R NR Lachmann Alexander A Zhang Bin B Hornbeck Peter P Ma'ayan Avi A Comb Michael M

Science signaling 20180522 531

Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. T ...[more]

PMID: 29789295

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Project description:The management of food fermentation is still largely based on empirical knowledge, as the dynamics of microbial communities and the underlying metabolic networks that produce safe and nutritious products remain beyond our understanding. Although these closed ecosystems contain relatively few taxa, they have not yet been thoroughly characterized with respect to how their microbial communities interact and dynamically evolve. However, with the increased availability of metataxonomic data sets on different fermented vegetables, it is now possible to gain a comprehensive understanding of the microbial relationships that structure plant fermentation. In this study, we applied a network-based approach to the integration of public metataxonomic 16S data sets targeting different fermented vegetables throughout time. Specifically, we aimed to explore, compare, and combine public 16S data sets to identify shared associations between amplicon sequence variants (ASVs) obtained from independent studies. The workflow includes steps for searching and selecting public time-series data sets and constructing association networks of ASVs based on co-abundance metrics. Networks for individual data sets are then integrated into a core network, highlighting significant associations. Microbial communities are identified based on the comparison and clustering of ASV networks using the "stochastic block model" method. When we applied this method to 10 public data sets (including a total of 931 samples) targeting five varieties of vegetables with different sampling times, we found that it was able to shed light on the dynamics of vegetable fermentation by characterizing the processes of community succession among different bacterial assemblages.ImportanceWithin the growing body of research on the bacterial communities involved in the fermentation of vegetables, there is particular interest in discovering the species or consortia that drive different fermentation steps. This integrative analysis demonstrates that the reuse and integration of public microbiome data sets can provide new insights into a little-known biotope. Our most important finding is the recurrent but transient appearance, at the beginning of vegetable fermentation, of amplicon sequence variants (ASVs) belonging to Enterobacterales and their associations with ASVs belonging to Lactobacillales. These findings could be applied to the design of new fermented products.

Dataset Information

Integration of protein phosphorylation, acetylation, and methylation data sets to outline lung cancer signaling networks.

Publications

Integration of protein phosphorylation, acetylation, and methylation data sets to outline lung cancer signaling networks.

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