An error model for protein quantification.
BACKGROUND
Quantitative experimental data is the critical bottleneck in the modeling of dynamic cellular processes in systems biology. Here, we present statistical approaches improving reproducibility of protein quantification by immunoprecipitation and immunoblotting.


RESULTS
Based on a large data set with more than 3600 data points, we unravel that the main sources of biological variability and experimental noise are multiplicative and log-normally distributed. Therefore, we suggest a log-transformation of the data to obtain additive normally distributed noise. After this transformation, common statistical procedures can be applied to analyze the data. An error model is introduced to account for technical as well as biological variability. Elimination of these systematic errors decrease variability of measurements and allow for a more precise estimation of underlying dynamics of protein concentrations in cellular signaling. The proposed error model is relevant for simulation studies, parameter estimation and model selection, basic tools of systems biology.


BACKGROUND
Matlab and R code is available from the authors on request. The data can be downloaded from our website www.fdm.uni-freiburg.de/~ckreutz/data.
Kreutz
C
C
Freiburg Center for Data Analysis and Modeling FDM, Eckerstrasse 1, Freiburg, Germany. ckreutz@fdm.uni-freiburg.de
Bartolome Rodriguez
M M
MM
Maiwald
T
T
Seidl
M
M
Blum
H E
HE
Mohr
L
L
Timmer
J
J
D000465:Algorithms; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D020869:Gene Expression Profiling / Q000379:methods*; D015151:Immunoblotting / Q000379:methods*; D047468:Immunoprecipitation / Q000379:methods*; D008954:Models, Biological; D015233:Models, Statistical; D011506:Proteins / Q000032:analysis* / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D011506:Proteins