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DNA methylation analysis from high-throughput bisulfite sequencing results were performed using Bioconductor R packages "MethylSeekR" and "methylKit" according to software documentation32,35.
Rigorous simulations embedding experimental results were performed using computer aided process engineering tools, such as AspenTech Aspen Plus and Aspen Dynamics.
Descriptive and inferential statistical analyses of survey results were performed using IBM SPSS predictive analytics software.
All analyses of the CLI results were performed using Living Image 4.3.1 software.
Statistical analyses of the results were performed using two-way analysis of variance and one-way ANOVA in SPSS software (version 17.0, SPSS Inc., IL, USA).
Analysis and documentation of results were performed using a Leica FW 4500 B microscope.
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Validation of the results was performed using qRT-PCR using specific primers (Supplementary Table 3).
All modelling results are performed using the commercially available finite-element software (COMSOL Multiphysics, version 4.3b).
Simulation results are performed using Simulink/Matlab and PSB tool.
Validation of the simulation results was performed using experimental measurements.
A summary of the results was performed using a best-evidence synthesis.
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