Retinoblastoma (RB) is a childhood eye cancer. Currently, chemotherapy, local therapy, and enucleation are the main ways in which these tumors are managed. The present work is the first study that uses constraint‐based reconstruction and analysis approaches to identify and explain RB‐specific survival strategies, which are RB tumor specific. Importantly, our model‐specific secretion profile is also found in RB1‐depleted human retinal cells in vitro and suggests that novel biomarkers involved in lipid metabolism may be important. Finally, RB‐specific synthetic lethals have been predicted as lipid and nucleoside transport proteins that can aid in novel drug target development.
Metaproteomic approach is an attractive way to describe a microbiome at the functional level, allowing the identification and quantification of proteins across a broad dynamic range as well as detection of post-translational modifications. However, it remains relatively underutilized, mainly due to technical challenges that should be addressed, including the complexity in extracting proteins from heterogenous microbial communities. Here, we show that a ChipFilter microfluidic device coupled to LC-MS/MS can successfully be used for identification of microbial proteins. Using cultures of E. coli, B. subtilis and S. cerevisiae, we have shown that it is possible to directly lyse the cells and digest the proteins in the ChipFilter to allow higher number of proteins and peptides identification than standard protocols, even at low cell density. The peptides produced are overall longer after ChipFilter digestion but show no change in their degree of hydrophobicity. Analysis of a more complex mixture of 17 species from the gut microbiome showed that the ChipFilter preparation was able to identify and estimate the amount of 16 of these species. These results show that ChipFilter can be used for the proteomic study of microbiomes, in particular in the case of low volume or low cell density.
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