Mass spectrometry-based draft of the mouse proteome

Abstract

The laboratory mouse ranks among the most important experimental systems for biomedical research and molecular reference maps of such models are essential informational tools. Here, we present a quantitative draft of the mouse proteome and phosphoproteome constructed from 41 healthy tissues and several lines of analyses exemplify which insights can be gleaned from the data. For instance, tissue- and cell-type resolved profiles provide protein evidence for the expression of 17,000 genes, thousands of isoforms and 50,000 phosphorylation sites in-vivo . Proteogenomic comparison of mouse, human and Arabidopsis reveal common and distinct mechanisms of gene expression regulation and, despite many similarities, numerous differentially abundant orthologs that likely serve species-specific functions. We leverage the mouse proteome by integrating phenotypic drug (n>400) and radiation response data with the proteomes of 66 pancreatic ductal adenocarcinoma (PDAC) cell lines to reveal molecular markers for sensitivity and resistance. This unique atlas complements other molecular resources for the mouse and can be explored online via ProteomicsDB and PACiFIC.

Tissue-Characteristic Expression of Mouse Proteome

“…4 A ). This finding is a good complement to a recent study stating that 90% of the total protein abundance is made up by a relatively small fraction of proteins ( 10 ). While in the olfactory bulb (n = 6565), adrenal gland (n = 6570), and cecum (n = 6614), in which highest protein numbers were identified, the percentage of HAPs counts for about 50% of their protein intensity ( Fig.…”

“…All the DIA spectral libraries mentioned above are built against curated protein sequence FASTA file containing about 17,000 entries. This is different from several DDA-based proteomics studies which used much larger protein sequence FASTA files containing over 50,000 curated and predicted protein sequences ( 9 , 10 ). All the proteins we reported here are curated proteins characterized with at least two peptides.…”

“…The Geiger et al paper [9] investigated 28 organs, with samples from three animals pooled to one for data acquisition. The Giansanti et al paper [10] included 15 mice, each contributing one to nine organs, making up a total of 41 organs, seven of which had one biological replicate. We collected 41 mouse organs, each with three to four biological replicates from four mice.…”

“…During the review of this paper, the Kuster group published a data-dependent acquisition (DDA) MS based proteomic investigation of 41 mouse tissues, covering J o u r n a l P r e -p r o o f 17,883 proteins, thousands of isoforms, and 50,000 phosphorylation sites based on a fasta database containing 61,307 curated and predicted mouse protein sequences [10].…”

“…( 9 ) reported a SILAC-based quantitative landscape of 7349 proteins in 28 mouse tissues based on a FASTA database containing 59,345 curated and predicted mouse protein sequences. During the review of this paper, the Kuster group published a DDA-MS–based proteomic investigation of 41 mouse tissues, covering 17,883 proteins, thousands of isoforms, and 50,000 phosphorylation sites based on a FASTA database containing 61,307 curated and predicted mouse protein sequences ( 10 ).…”