Predicting the protein half-life in tissue from its cellular properties.

Protein half-life is an important feature of protein homeostasis (proteostasis). The increasing number of in vivo and in vitro studies using high throughput proteomics provide estimates of the protein half-lives in tissues and cells. However, protein half-lives in cells and tissues are different. Du...

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Main Authors: Mahbubur Rahman, Rovshan G Sadygov
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5515413?pdf=render
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author Mahbubur Rahman
Rovshan G Sadygov
author_facet Mahbubur Rahman
Rovshan G Sadygov
author_sort Mahbubur Rahman
collection DOAJ
description Protein half-life is an important feature of protein homeostasis (proteostasis). The increasing number of in vivo and in vitro studies using high throughput proteomics provide estimates of the protein half-lives in tissues and cells. However, protein half-lives in cells and tissues are different. Due to the resource requirements for researching tissues, more data is available from cellular studies than tissues. We have designed a multivariate linear model for predicting protein half-life in tissue from its cellular properties. Inputs to the model are cellular half-life, abundance, intrinsically disordered sequences, and transcriptional and translational rates. Before the modeling, we determined substructures in the data using the relative distance from the regression line of the protein half-lives in tissues and cells, identifying three separate clusters. The model was trained on and applied to predict protein half-lives from murine liver, brain and heart tissues. In each tissue type we observed similar prediction patterns of protein half-lives. We found that the model provides the best results when there is a strong correlation between tissue and cell culture protein half-lives. Additionally, we clustered the protein half-lives to determine variations in correlation coefficients between the protein half-lives in the tissue versus in cell culture. The clusters identify strongly and weakly correlated protein half-lives, further improves the overall prediction and identifies sub groupings which exhibit specific characteristics. The model described herein, is generalizable to other data sets and has been implemented in a freely available R code.
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spelling doaj.art-cb912d71235f46b98c4e31c6beb137962022-12-21T19:46:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e018042810.1371/journal.pone.0180428Predicting the protein half-life in tissue from its cellular properties.Mahbubur RahmanRovshan G SadygovProtein half-life is an important feature of protein homeostasis (proteostasis). The increasing number of in vivo and in vitro studies using high throughput proteomics provide estimates of the protein half-lives in tissues and cells. However, protein half-lives in cells and tissues are different. Due to the resource requirements for researching tissues, more data is available from cellular studies than tissues. We have designed a multivariate linear model for predicting protein half-life in tissue from its cellular properties. Inputs to the model are cellular half-life, abundance, intrinsically disordered sequences, and transcriptional and translational rates. Before the modeling, we determined substructures in the data using the relative distance from the regression line of the protein half-lives in tissues and cells, identifying three separate clusters. The model was trained on and applied to predict protein half-lives from murine liver, brain and heart tissues. In each tissue type we observed similar prediction patterns of protein half-lives. We found that the model provides the best results when there is a strong correlation between tissue and cell culture protein half-lives. Additionally, we clustered the protein half-lives to determine variations in correlation coefficients between the protein half-lives in the tissue versus in cell culture. The clusters identify strongly and weakly correlated protein half-lives, further improves the overall prediction and identifies sub groupings which exhibit specific characteristics. The model described herein, is generalizable to other data sets and has been implemented in a freely available R code.http://europepmc.org/articles/PMC5515413?pdf=render
spellingShingle Mahbubur Rahman
Rovshan G Sadygov
Predicting the protein half-life in tissue from its cellular properties.
PLoS ONE
title Predicting the protein half-life in tissue from its cellular properties.
title_full Predicting the protein half-life in tissue from its cellular properties.
title_fullStr Predicting the protein half-life in tissue from its cellular properties.
title_full_unstemmed Predicting the protein half-life in tissue from its cellular properties.
title_short Predicting the protein half-life in tissue from its cellular properties.
title_sort predicting the protein half life in tissue from its cellular properties
url http://europepmc.org/articles/PMC5515413?pdf=render
work_keys_str_mv AT mahbuburrahman predictingtheproteinhalflifeintissuefromitscellularproperties
AT rovshangsadygov predictingtheproteinhalflifeintissuefromitscellularproperties