Single-gene knockout analysis in an Escherichia coli whole-cell model reveals medium, temperature, and generational effects on growth
Abstract
Whole-cell models serve as powerful tools to predict cellular phenotype from genotype by integrating genome-scale processes within a single computational framework. Single-gene knockout (KO) growth is a stringent benchmark, but comparisons to experimental resources require close alignment of assay conditions, especially temperature and growth medium. We benchmark an Escherichia coli (E. coli) whole-cell model by simulating multi-generation single-gene KOs in glucose minimal and amino-acid–supplemented media at 37 °C and by analyzing two independent eight-generation KO cohorts. For each KO we estimated generation-specific growth rates and harmonic-mean summaries across early generations. Experimental KO growth rates measured at 30°C were converted to s−1 and scaled to 37°C using an explicit Q10 correction Essential versus nonessential effects were tested using Welch’s t comparisons with 95% confidence intervals based on the Welch–Satterthwaite t approximation, and false discovery rate control across generations. Cross-medium generalization was evaluated using correlations and stratified regression for further prediction. Temperature adjustment shifted the experimental growth-rate distribution toward the simulated distribution. Essential KOs showed lower growth in the earliest generations, while the two eight-generation cohorts exhibited an overall decline in mean growth with substantial heterogeneity. Cross-medium correlations were weak, and in the held-out predictive comparison the global linear model achieved lower RMSE than the stratified SVR.
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BibTeX
@article{wei2026singlegene,
title = {{Single-gene knockout analysis in an Escherichia coli whole-cell model reveals medium, temperature, and generational effects on growth}},
author = {Jiaqi Wei and Weiping Lin},
journal = {Briefings in Bioinformatics},
year = {2026},
month = oct,
doi = {10.1093/bib/bbag344},
url = {https://doi.org/10.1093/bib/bbag344},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Single-gene knockout analysis in an Escherichia coli whole-cell model reveals medium, temperature, and generational effects on growth
AU - Jiaqi Wei
AU - Weiping Lin
PY - 2026
DA - 2026/10/27
JO - Briefings in Bioinformatics
DO - 10.1093/bib/bbag344
UR - https://doi.org/10.1093/bib/bbag344
AB - Whole-cell models serve as powerful tools to predict cellular phenotype from genotype by integrating genome-scale processes within a single computational framework. Single-gene knockout (KO) growth is a stringent benchmark, but comparisons to experimental resources require close alignment of assay conditions, especially temperature and growth medium. We benchmark an Escherichia coli (E. coli) whole-cell model by simulating multi-generation single-gene KOs in glucose minimal and amino-acid–supplemented media at 37 °C and by analyzing two independent eight-generation KO cohorts. For each KO we estimated generation-specific growth rates and harmonic-mean summaries across early generations. Experimental KO growth rates measured at 30°C were converted to s−1 and scaled to 37°C using an explicit Q10 correction Essential versus nonessential effects were tested using Welch’s t comparisons with 95% confidence intervals based on the Welch–Satterthwaite t approximation, and false discovery rate control across generations. Cross-medium generalization was evaluated using correlations and stratified regression for further prediction. Temperature adjustment shifted the experimental growth-rate distribution toward the simulated distribution. Essential KOs showed lower growth in the earliest generations, while the two eight-generation cohorts exhibited an overall decline in mean growth with substantial heterogeneity. Cross-medium correlations were weak, and in the held-out predictive comparison the global linear model achieved lower RMSE than the stratified SVR.
SN - 1467-5463
SN - 1477-4054
ER -