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Summary We present a flexible, user-friendly R package called protti for comprehensive quality control, analysis and interpretation of quantitative bottom-up proteomics data. protti supports the analysis of protein-centric data such as those associated with protein expression analyses, as well as peptide-centric data such as those resulting from limited proteolysis-coupled mass spectrometry analysis. Due to its flexible design, it supports analysis of label-free, data-dependent, data-independent and targeted proteomics datasets. protti can be run on the output of any search engine and software package commonly used for bottom-up proteomics experiments such as Spectronaut, Skyline, MaxQuant or Proteome Discoverer, adequately exported to table format. Availability protti is implemented as an open-source R package. Release versions are available via CRAN (https://CRAN.R-project.org/package=protti) and work on all major operating systems. The development version is maintained on GitHub (https://github.com/jpquast/protti). Full documentation including examples is provided in the form of vignettes on our package website (jpquast.github.io/protti/).

Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to appropriately regulate cellular anabolism and catabolism. During nutrient restriction, different organs in an animal do not respond equally, with vital organs being relatively spared. This raises the possibility that mTORC1 is differentially regulated in different cell types, yet little is known about this mechanistically. The Rag GTPases, RagA or RagB bound to RagC or RagD, tether mTORC1 in a nutrient-dependent manner to lysosomes where mTORC1 becomes activated. Although the RagA and B paralogues were assumed to be functionally equivalent, we find here that the RagB isoforms, which are highly expressed in neurons, impart mTORC1 with resistance to nutrient starvation by inhibiting the RagA/B GTPase-activating protein GATOR1. We further show that high expression of RagB isoforms is observed in some tumours, revealing an alternative strategy by which cancer cells can retain elevated mTORC1 upon low nutrient availability.

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