TY - JOUR
T1 - Predicting proteome dynamics using gene expression data
AU - Kuchta, Krzysztof
AU - Towpik, Joanna
AU - Biernacka, Anna
AU - Kutner, Jan
AU - Kudlicki, Andrzej
AU - Ginalski, Krzysztof
AU - Rowicka, Maga
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - While protein concentrations are physiologically most relevant, measuring them globally is challenging. mRNA levels are easier to measure genome-wide and hence are typically used to infer the corresponding protein abundances. The steady-state condition (assumption that protein levels remain constant) has typically been used to calculate protein concentrations, as it is mathematically convenient, even though it is often not satisfied. Here, we propose a method to estimate genome-wide protein abundances without this assumption. Instead, we assume that the system returns to its baseline at the end of the experiment, which is true for cyclic phenomena (e.g. cell cycle) and many time-course experiments. Our approach only requires availability of gene expression and protein half-life data. As proof-of-concept, we predicted proteome dynamics associated with the budding yeast cell cycle, the results are available for browsing online at http://dynprot.cent.uw.edu.pl/. The approach was validated experimentally by verifying that the predicted protein concentration changes were consistent with measurements for all proteins tested. Additionally, if proteomic data are available as well, we can also infer changes in protein half-lives in response to posttranslational regulation, as we did for Clb2, a post-translationally regulated protein. The predicted changes in Clb2 abundance are consistent with earlier observations.
AB - While protein concentrations are physiologically most relevant, measuring them globally is challenging. mRNA levels are easier to measure genome-wide and hence are typically used to infer the corresponding protein abundances. The steady-state condition (assumption that protein levels remain constant) has typically been used to calculate protein concentrations, as it is mathematically convenient, even though it is often not satisfied. Here, we propose a method to estimate genome-wide protein abundances without this assumption. Instead, we assume that the system returns to its baseline at the end of the experiment, which is true for cyclic phenomena (e.g. cell cycle) and many time-course experiments. Our approach only requires availability of gene expression and protein half-life data. As proof-of-concept, we predicted proteome dynamics associated with the budding yeast cell cycle, the results are available for browsing online at http://dynprot.cent.uw.edu.pl/. The approach was validated experimentally by verifying that the predicted protein concentration changes were consistent with measurements for all proteins tested. Additionally, if proteomic data are available as well, we can also infer changes in protein half-lives in response to posttranslational regulation, as we did for Clb2, a post-translationally regulated protein. The predicted changes in Clb2 abundance are consistent with earlier observations.
UR - http://www.scopus.com/inward/record.url?scp=85053349900&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053349900&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-31752-4
DO - 10.1038/s41598-018-31752-4
M3 - Article
C2 - 30217992
AN - SCOPUS:85053349900
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 13866
ER -