Mouse Organ-Specific Proteins and Functions

Abstract

Organ-specific proteins (OSPs) possess great medical potential both in clinics and in biomedical research. Applications of them-such as alanine transaminase, aspartate transaminase, and troponins-in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human populations are well known, yet their effects on OSPs are less addressed. Here, we used mice as a model and implemented a breadth study to examine the panorgan proteome for potential variations in organ specificity in different genetic backgrounds. Using reasonable resources, we generated panorgan proteomes of four in-bred mouse strains. The results revealed a large diversity that was more profound among OSPs than among proteomes overall. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ-specific and are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.

Keywords: biomarkers; bone proteome; brain proteome; eye proteome; fat proteome; heart proteome; intestine proteome; kidney proteome; liver proteome; lung proteome; mouse proteome; organ proteome; organ-specific proteins; pancreas proteome; proteome diversity; proteome dynamics; skeletal muscle proteome; spleen proteome; testis proteome.

Figure 1

Overall results of mouse panorgan proteome. (A) Illustrations and histology of the organs and tissues were analyzed. (B) The distribution of detected proteins as a function of detection breadth, i.e., the number of organs/tissues in which a protein was detected. The insert shows the percentage of common proteins (DB = 13), shared proteins (DB = 2~12), and organ-specific proteins (DB = 1) in the total proteome. (C) The number of proteins detected per organ/tissue. (D) The averaged and normalized detection quantity of the three groups of proteins. The error bar is the standard deviation. The insert is the protein detection quantity in the eye, in which NP is normalized quantity, CP is common proteins, SP is shared proteins, and OSP is organ-specific proteins.

Figure 2

Gene ontology enrichment analysis of biological processes in the obtained protein lists. (A) Top10 enriched biological processes of filtered and partially verified organ-specific proteins (vOSPs) of each organ against four genetic backgrounds. (B) Top10 enriched biological processes of complete OSPs of each organ across four genetic backgrounds. (C) Top10 enriched biological processes of each organ proteome of BL6.

Figure 2

Gene ontology enrichment analysis of biological processes in the obtained protein lists. (A) Top10 enriched biological processes of filtered and partially verified organ-specific proteins (vOSPs) of each organ against four genetic backgrounds. (B) Top10 enriched biological processes of complete OSPs of each organ across four genetic backgrounds. (C) Top10 enriched biological processes of each organ proteome of BL6.

Figure 2

Gene ontology enrichment analysis of biological processes in the obtained protein lists. (A) Top10 enriched biological processes of filtered and partially verified organ-specific proteins (vOSPs) of each organ against four genetic backgrounds. (B) Top10 enriched biological processes of complete OSPs of each organ across four genetic backgrounds. (C) Top10 enriched biological processes of each organ proteome of BL6.

Figure 3

Protein distribution as a function of detection breadth in the organ proteomes, in which the Index-Overall represents the frequency a protein was detected in the overall panorgan proteome, and Index-Top100 represents the frequency a protein was in the panorgan proteomes of top100 proteins.

Figure 4

Gene ontology enrichment analysis of biological processes in the panorgan proteome of BL6. (A) Enrichment analysis of the pan-organ proteomes of top100 proteins. (B) Enrichment analysis of the organ-specific proteins.

Figure 4

Gene ontology enrichment analysis of biological processes in the panorgan proteome of BL6. (A) Enrichment analysis of the pan-organ proteomes of top100 proteins. (B) Enrichment analysis of the organ-specific proteins.