Model that predictsphenotypes byaccounting for each gene Framework for integratingand interpretingexperimental data Tool for assessing ourunderstanding andgenerating hypotheses What is a whole-cell(WC) model?

How will WC models predict phenotype from genotype?

Genome sequence


Genome sequence with single-nucleotide resolution

Molecular structures


Structure of each compound, chromosome, RNA transcript, and protein

Molecular interactions


Participants and sites of each molecular interaction

Subcellular organization

Subcellular organization

Subcellular compartmentalization of each compound

Molecular concentrations

Molecular concentrations

Concentration of compound in each compartment

Thermodynamics and kinetics

Thermodynamics and kinetics

Equilibrium constant and rate law of each reaction

Stochastic variation


Stochastic fluctuations of the concentration of each compound

Temporal dynamics


Temporal dynamics of each compound over the entire cell cycle

Spatial dynamics


Spatial distribution of each compound and reaction throughout cells

Population heterogeneity

Population heterogeneity

Stochastic intrinsic variation in the behavior of individual cells

Complex phenotypes


Complex phenotypes such as the growth rate and self-renewal

Extracellular environment

Extracellular environment

How cells behave in any extracellular environment

WC modeling is a grand challenge

Few scalable methods & tools Multiple scales from genotype to phenotype Incomplete & disparate knowledge Explain each molecule & interaction

Researchers are developing the tools needed for WC modeling

Calibrate model Reduce results WC-Analysis Simulate model WC-SimE-Cell Aggregate data DBS-pipesDatanator Discover cell data WC-KB-Gen Design model WC-Model-GenE-Cell P Experimental data Articles, DBs Experimental DB Datanator Cell knowledge DB WC-KB Validate results WC-Test Interpret results Validated model Visualization WC-Viz Model WC-Lang Simulation results WC-SimDB Discovery & application Model structure WC-Lang
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Researchers are prototyping models for medicine and bioengineering

Basic science signal processing, cell cycle regulation Minimal bacterium Mycoplasma genitalium Whole-cell modeling methods, tools, resources Archetypal cell methods, tools, resources Bioengineering biosensors, bioproduction, bioremediation Model bacterium Escherichia coli Medicine personalized diagnosis, precision therapy Archetypal human cell Homo sapiens H1-hESC
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