Mouse Organ-Specific Proteins and Functions

Bingyun Sun,Ashley Francke,Robert L Moritz,Gray Li,Cynthia Lorang,Shizhen Qin,Zhiyuan Hu,Yijuan Zhang,Ken Liu,Leroy Hood,Zhi Sun,Angelita G Utleg,Kai Wang

doi:10.3390/cells10123449

Bingyun Sun, Ashley Francke + Show 11 more

Open Access

https://doi.org/10.3390/cells10123449

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Journal: Cells	Publication Date: Dec 8, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: Simon Fraser University, Institute for Systems Biology

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.

Highlights

Multiorgan mammals evolve in such a way that each organ has unique morphology and functions
Many molecular assays have been developed for monitoring organ pathological states and disease progression, such as the cardiac trophonin test for the heart [1], alanine transaminase (ALT) and aspartate transaminase (AST) tests for the liver [2], and prostate-specific membrane antigen (PSMA) for prostate cancer [3]
Dynamics is the change of protein expression across time of the same individual, whereas diversity is the change across different genetic backgrounds in a population

Summary

Introduction

Multiorgan mammals evolve in such a way that each organ has unique morphology and functions. Many molecular assays have been developed for monitoring organ pathological states and disease progression, such as the cardiac trophonin (cTn) test for the heart [1], alanine transaminase (ALT) and aspartate transaminase (AST) tests for the liver [2], and prostate-specific membrane antigen (PSMA) for prostate cancer [3]. Several reasons hinder the research and broad applications of organ-specific proteins (OSPs) The current mapping of the human proteome is approximately 90% [5,6] Due to their detectability, the absolute specificity of OSPs is elusive. In The Cancer Genome Atlas project (TCGA) [11], numerous novel genes were detected in ectopic organs, such as cardiac troponin I in lung cancer tissues [12]

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