A metabolism-centric proteomic map on the genomic scale: enabling functional annotation of the unknown genome

Lead Research Organisation: University of Cambridge
Department Name: Biochemistry


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Technical Summary

We will create a genome-spanning functional proteomic map of the model eukaryote Saccharomyces cerevisiae, and use it to dissect the compendium of metabolism-regulating genes, and to annotate yet unknown genes on the basis of their proteomic footprint. This map will be created by systematically recording SWATH-MS based proteome profiles from 4800 yeast single gene knock-out strains, representing the fraction of gene deletions viable in the absence of rich nutrient supplementation, chosen to enable growth that is informative about biosynthetic metabolism. This unique large-scale project will be facilitated by an academia/industry partnership to establish a high-throughput variant of SWATH-MS technology invented by the collaborating laboratory of Ruedi Aebersold, and be capable to process thousands of samples in a proteomic experiment by combining microflow-chromatography, advanced ionisation techniques, and data independent acquisition.

Planned Impact

This is an academia-industry collaboration with direct impact. The biotechnological industry will obtain the information about which gene has to be manipulated in the genome to affect 80% of enzymes and can use this information to develop new production strains, save money by improving existing production cycles for instance to reduce greenhouse gas emissions. The mass spectrometry manufacturing industry will get access to a workflow that allows implementing proteomics technology in industrial scale projects, including diagnostics and environmental analytics, and improve access to a new market for proteomics. Enabling proteomics for the large scale will directly benefit society, that depends on diagnostics in medicine and environmental analytics for food production and marketing. Finally, the results clearly impact basic science, as we will substantially improve the annotation of ~2000 budding yeast genes that are functionally yet uncharacterized.


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Messner CB (2021) Ultra-fast proteomics with Scanning SWATH. in Nature biotechnology

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Kustatscher G (2022) An open invitation to the Understudied Proteins Initiative. in Nature biotechnology

Description We have developed a piece of open source software, DIA-NN which will allow mass spectrometrists using Sciex mass spectrometers to more accurately quantify their data
Exploitation Route The software we have developed will be used by many researchers world wide
Sectors Agriculture, Food and Drink,Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

Description A piece of software - DIA-NN has been published in Nature Methods in January 2020. Bruker, an mass spectrometer instrument manufacturer have been interested in incorporating the software into their analysis pipelines
First Year Of Impact 2019
Sector Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

Title DIA-NN 
Description a computation approach to interrogate data independent acquisition mass spectrometry data 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact The tool is described in a manuscript that is currently under review in Nature Methods 
Description Collabaration with Sciex 
Organisation AB SCIEX
Country United States 
Sector Private 
PI Contribution This project is funded by a BBSRC LINK grant where Sciex is the industrial partner. MY group and that of Markus Ralser, provide experimental data and it interpretation
Collaborator Contribution Sciex assist with setting up of the mass spectrometers, one of which was donated by them to this project.
Impact A tool, DIA-NN has been developed by the Lilley/Ralser labs to enable robust quantitation of data produced from the Sciex 6600 mass spectrometers
Start Year 2017
Title DIA-NN 
Description DIA-NN is a tool that enables robust quantitation of SWATH mass spectrometry data generated by Sciex mass spectrometers with SWATh capabilities 
Type Of Technology Software 
Year Produced 2018 
Impact The tool has just been developed hence its impact is too early to measure