PrecigeneticsExplore Cell Cinema ↗

Start here · Parmita Mishra

Virtual cells,
explained.

What they are. How they work. Why they matter.

Add a drug. Switch off a gene. Take away oxygen. What will the cell do next?

A virtual cell is a computer model built to predict an answer. The ambition is to test more ideas, understand why they work, and choose better experiments.

The idea is easy to grasp. The hard part is learning enough about a living cell to make a prediction worth trusting.

01

First, what is a cell?

A cell is the basic unit of life. Inside a tiny boundary, it uses energy, builds and repairs itself, processes information, and responds to its surroundings. It is doing the work of staying alive.

Detailed animal-cell cutaway connecting four activities to cellular structures: maintain a boundary, use energy, build and repair, sense and respond.
A cell maintains itself while responding to the world around it.

Some cells live as whole organisms. In your body, cells work together as tissues and organs. A liver cell behaves differently from a nerve cell—and the same liver cell can behave differently when it is fed, stressed, or exposed to a drug.

That changing behavior is what we want to understand and predict.

How cells sense, maintain, and repair

A cell senses changes and actively keeps its internal conditions within workable ranges. Biologists call this homeostasis. Michael Levin places this capacity at the beginning of a broader framework for biological intelligence:

homeostasis is the first rung on the ladder of intelligence

Michael Levin · Biophysical Intelligence Between Genotype and Phenotype, 2026

He also writes: Single cells are composite agents that exhibit extremely rich patterning and behaviors. Read the 2019 paper.

Consider a gap in a sheet of epithelial cells—the cells that line surfaces. Cells at the edge spread and move. Forces and signals coordinate their neighbors. Together, they can close the gap. The behavior belongs to an organized, interacting system.

Three illustrated views of an epithelial sheet: an open gap, neighboring cells extending into the gap, and a continuous sheet after closure.
A sheet of cells closes a gap.
Liver cells, T cells, and the environments they live in

A liver cell, or hepatocyte, processes nutrients and many drugs. A neuron carries signals. A fibroblast helps build connective tissue. A T cell participates in immune responses. “Cell” names a whole world of different jobs.

Detailed illustrations of a polygonal hepatocyte, branching neuron, spindle-shaped fibroblast and round T lymphocyte.
Different cell identities. Different forms and functions. Sizes are illustrative.

Cell type is its biological identity. Cell state is its condition now. A resting T cell and an activated T cell can share a type while behaving differently.

How we grow cells matters too. In an adherent culture, they attach to a surface. In a suspension culture, they remain in the medium. Plated hepatocytes and suspended T cells are two examples.

Hepatocytes attached in a sheet on a culture surface and T cells suspended in medium in a separate well.
Culture formats describe how we keep cells for an experiment. Hepatocytes can also be studied in suspension.

Sometimes we need both. A mixed culture brings tissue cells and immune cells into a shared environment, letting us study how they affect one another.

Conceptual mixed culture with a hepatocyte layer and T cells above and contacting it.
A mixed-culture concept.
02

What is a virtual cell?

A virtual cell is a model you can ask “what if?” You describe a cell and a change. The model predicts a particular response.

Imagine giving a drug to liver cells. You want to know whether they keep functioning, become stressed, or recover after the drug is removed. A model might tackle one part of that question: how RNA—the messages and working molecules copied from DNA—changes after a specified dose and time.

Predicting RNA is useful. Predicting recovery is a further task, with a different test. The phrase “virtual cell” covers models with very different abilities.

The useful question is: what can this model predict, for which cells, under which conditions?

If the prediction is reliable, it can help choose which compound, dose, or experiment to try next. The point is to make experiments more informative.

Is a virtual cell a complete digital copy?

Usually, a model represents selected features and behaviors. Its scope tells you which cells it describes, which changes it accepts, what it predicts, and over what time span.

The larger ambition is an integrated model of cellular behavior. A model that predicts one measurement well has established that capability; a complete working replica is a much broader goal.

The liver-cell example in this guide is a hypothetical question, not a validated drug-safety prediction. Predicting a response in cultured cells also leaves further work to connect it to an organ or a person.

03

How does a model learn
what cells do?

For a model that learns from data, the starting point is an experiment: change something, measure what follows, and keep a record of the conditions.

Biologists call the deliberate change a perturbation. It can take several forms.

Three examples of interventions: adding a compound to cells, reducing a gene’s activity with CRISPR interference, and lowering oxygen supply.
Different interventions. Their effects must be measured.
Chemical
Add a drug or another compound.
Genetic
Change a gene or how active it is.
Environmental
Change oxygen, nutrients, temperature, or the surroundings.

First, collect examples. Give cells different treatments and record their responses. The dose, timing, cell type, and comparison condition belong with the data.

Then, train the model. It learns relationships between what changed and what happened. The output could be RNA levels, cell shape, growth, or another measured feature.

Finally, ask a new question. Hold an experiment out of training. Ask the model to predict it, then compare the prediction with the actual result. This is validation.

A model can fit familiar examples and still fail on a new drug or cell type. The test is what it gets right beyond the examples it learned from.

How virtual cells are built
ApproachHow it worksExample
MechanisticRepresents biological processes with explicit rules and equations.Reaction rates predict changes in molecule concentrations.
Data-drivenLearns relationships from experimental observations.A model learns how gene activity changes after treatment.
HybridCombines biological structure with learned relationships.CellBox combines cellular dynamics with machine learning.

Training fits a model using observations. A simulation runs that model under chosen conditions. A prediction is an output that can be compared with an observation. Neither is an experimental measurement. See the AI virtual-cell perspective and the 2012 whole-cell model.

Validation asks whether predictions agree with experiments the model was not fitted to. A useful test specifies the cell type, intervention, time point, readout, and comparison baseline. Success on one task does not establish accuracy across all cell behaviors.

What makes the comparison fair?

A baseline is a measurement before the intervention. A control is a comparison condition. For our drug example, we might compare cells given the dissolved drug with cells given the same solvent alone.

Genetic experiments may use a guide designed not to target a gene. An oxygen experiment needs otherwise matched culture conditions. Controls help distinguish the intended change from other differences in the experiment.

The intervention and the measurement are separate choices. A chemical treatment can be studied through RNA; a genetic change can be studied through shape or survival. Experiments can also apply mechanical forces, change neighboring cells, or combine interventions.

In the illustration, CRISPR interference reduces a gene’s activity without cutting its DNA. Changing a DNA sequence is another kind of genetic perturbation.

04

Why is this so hard?

A cell is one connected system. Our instruments give us different views of it.

One method reads DNA. Another counts RNA. Another measures proteins. These large-scale studies are called omics: measurements of whole classes of biological components.

Four isolated molecular silos—genome, transcriptome, proteome and metabolome—beside one richly organized cell contacting a neighboring cell.
Separate measurements. One connected living system.
Genomics
DNA: genetic information.
Transcriptomics
RNA: messages and other working transcripts.
Proteomics
Proteins: machinery, signals, and structure.
Metabolomics
Small molecules involved in metabolism.

A parts list is not a cell state. The amounts matter, but so do the locations, interactions, surroundings, and activity of those parts.

Think of chess. Knowing which pieces exist does not tell you the position or what happens next. For a cell, we need to understand how its components are organized and working together.

Our data often leave us with a sharded representation—pieces of information about the same living system, collected through different methods and sometimes from different cells.

Multiomics combines several molecular views. Combining molecular measurements with a cell’s shape and behavior gives us a fuller view. The aim is to connect what a cell contains with what it does.

For our liver-cell example, a change in RNA is one clue. To understand recovery, we also need evidence about how the cells function afterward.

What does “holistic” mean here?

Phenotype means observable properties. A holistic view connects molecular makeup, spatial organization, function, and environment instead of treating each measurement as the complete cell.

Rafelski and Theriot’s framework for holistic cell states develops this idea. Multiomics can measure several features in one cell or align measurements from different cells. That distinction matters when interpreting what has actually been observed together.

Parts and their interactions remain essential to explanation. The limitation is a parts list that leaves out organization and dynamics—not a proof that cells cannot be computed.

05

The cell has a history.

Return to our drug-treated liver cell. Four hours later, it is alive. Is it recovering? Adapting? Becoming injured? What happens when the drug is removed?

A final reading can miss the route the cell took to get there.

Two illustrated cell histories change at different times but reach the same final measured feature.
The same final reading can hide different histories.

A trajectory is a path of change through time. Did a response begin immediately or after a delay? Did it keep growing? Did it reverse after treatment stopped?

Some models infer these paths from snapshots. Repeated measurements can provide direct evidence about how features change. Following the same individual cell also requires tracking it.

This is where trajectomics comes in.

Trajectomics is the name I use for studying cellular response histories: what changes, where, when, and in what order.

The proposal is to give models richer examples of living responses, then test whether those histories improve prediction. In our drug example, the question is whether the early response helps predict later function or recovery.

Waddington’s landscape: a picture of possible paths
Three richly illustrated cells occupy a branching landscape of ridges and valleys, suggesting alternative paths through cell state.
A Waddington-inspired metaphor for paths through cell state.

Picture a ball rolling through branching valleys. Its position represents a state; its route represents change; the valleys suggest alternative outcomes. Waddington described the ball’s path as the developmental history of a particular part of the egg in The Strategy of the Genes (1957, p. 29). His original picture was about development.

Now borrow the metaphor for aging. Imagine following liver cells over time. One path maintains their ability to do their job; another progressively loses function. A hypothetical non-aging reference stays stable. Similar starting points can lead to different histories.

One starting cell branches toward a hypothetical non-aging reference, healthy aging with function maintained, and impaired aging with function reduced.
An aging example of the metaphor. These are illustrative scenarios.

These terrains illustrate an idea. A landscape learned from data is a separate construction whose shape depends on what is measured and how it is modeled.

06

Watch the response
while it happens.

To learn a response history, we need measurements through time. One approach is to keep cells alive in a controlled environment, introduce a treatment, and observe what changes.

Flowing fresh medium through the chamber—perfusion—lets us control the exposure. Replacing drug-containing medium with drug-free medium is washout. The response may continue after the drug supply stops.

Connected inlet, living-cell chamber and outlet with optical sensing at all three locations and measurements during baseline, treatment and washout.
A proposed sensing circuit: observe the cells and their incoming and outgoing medium as exposure changes.

The concept above senses the cells and the medium before and after the chamber. It connects what we deliver with what we observe over time.

This is the measurement direction behind Cell Cinema: living-cell chemical histories that models can learn from. The experiment records the response; a model must still earn its prediction on new data.

How does this compare with destructive sampling?

Conventional destructive single-cell RNA sequencing reads different cells at successive times. A sample leaves the culture vessel. The collected cells are then lysed—broken open—in a separate tube.

Live imaging can return to a retained living field. Both approaches can cover time. One consumes the sampled cells; the other can observe the field again.

Top: separate cultures sampled at three times, cells collected into external tubes and lysed there. Bottom: repeated optical measurements of a retained living field.
Collection and lysis are separate from the culture. Following individual cells additionally requires tracking.

They answer complementary questions and provide different molecular coverage. Specialized methods such as Live-seq can sample RNA while preserving viability. Repeatedly imaging a field is also different from tracking every individual cell within it.

Hyperspectral imaging: chemistry behind each pixel

An ordinary RGB image has three color channels. A hyperspectral image records many spectral channels at each sampled location. Think of an image with a spectrum behind each pixel.

A spectrum records a signal across wavelengths or frequencies. In Raman imaging, its patterns contain chemical information.

Aligned spectral image planes of two cells, with one selected location connected to an illustrative spectrum.
The stacked planes are spectral channels of one observation—not tissue depth or elapsed time.

Repeating that measurement can connect chemistry, location, and time. A spectrum is another view of a cell, with overlapping contributions that require interpretation. It is not automatically a complete molecular inventory or a multiomics experiment.

One measured exampleSeven fields in one pilot

In our exploratory “A cell has more than one clock” observations, heme-associated contrast crossed below half its starting value before broad CH contrast did in seven sampled fields. The timing differed across fields.

Measured sampling intervals for heme-associated and broad CH contrasts crossing below half baseline in seven fixed fields.
Measured RSL3/SK-MEL-2 pilot. Bars preserve the 30-minute sampling brackets.

This is an observation about two processed chemical features. Connecting it to injury or recovery requires independent outcomes. Processing choices and the incomplete raw-source flag are in the figure notes.

07

What can virtual cells
actually do?

They can already answer some well-defined questions. CellBox predicted responses to drug treatments left out of training in a melanoma cell line. PRESCIENT modeled how cells develop and checked predictions about the kinds of cells they become against records linking cells to their descendants.

These are specific successes. The larger challenge is reliable prediction across new treatments, cell types, and environments.

When you hear a virtual-cell claim, ask three things: what did it predict, what was new to the model, and how was the answer checked? Those questions turn a broad promise into something you can evaluate.

And a virtual organ? A virtual human?

Cells communicate and organize into tissues. Tissues form organs. Connecting models across those scales is the larger ambition.

Anatomical zoom from one cell to organized tissue, a liver and a human body.

Live-cell observations can help describe how cells change and interact. A virtual liver also needs tissue architecture, transport, and organ function. A virtual human adds communication between organs and the rest of the body.

The AI virtual-cell perspective sets out this direction. The path forward is to build capabilities that can be tested, then connect them.

Keep exploring

GlossaryThe core terms
Cell state
The cell’s condition at a particular time: its composition, organization, activities, and relevant surroundings.
Measurement
An observation made with a specified method. It records selected features of a cell, not its entire state.
Representation
The information retained to describe the cell—for example, RNA counts, image features, or spectra.
Model
A mathematical or computational description used to explain observations or predict outcomes.
Perturbation
A deliberate change used to examine how the system responds.
Phenotype
Observable properties, including form, composition, and behavior.
Trajectory
A path of change through time. Its measurement requires repeated observations; its inference depends on a model.
Validation
Testing a model’s predictions against independent experimental observations.
MotivationHMCVelo & the piano

My HMCVelo work uses joint measurements of DNA methylation and hydroxymethylation to infer epigenetic velocity from single-cell snapshots. It motivates a related question: what can be inferred from a snapshot, and what more can be learned by observing change?

A keyboard and a keyboard being played, with small cell illustrations representing coordinated activity over time.

My piano thread offers an analogy. Genes are like keys. Which ones are played, together, and when? The analogy is a starting point for thinking about coordinated activity over time.

What chess makes us askState & computability

My thread on the virtual-cell problem uses chess to ask what a useful state representation must retain. A list of pieces does not describe a game: their positions, whose turn it is, and relevant history matter. A cell’s parts list likewise leaves out organization, interactions, environment, and history.

Computability is not the same as predictability. A computable model may still be costly to simulate, and its starting state may be incompletely measured. Shannon’s 1950 chess paper makes the distinction between a calculable search and a practical one. For cells, we can test whether a limited representation predicts a defined response.

Virtual cells have a history

The ambition predates today’s AI. In 2012, Karr and colleagues integrated 28 process models into a whole-cell model of a small bacterium. Elliot Hershberg’s “What Are Virtual Cells?” tells the longer history.

Newer approaches learn responses from experimental data. Some already study dynamics using population time series. The 2026 State paper evaluates downstream viability predictions, too. RNA-based models can inform functional questions. The test for chemical histories is whether they add predictive value on independently measured outcomes.

Plenty of room at the bottom

In his 1959 lecture, Feynman imagined being able to arrange the atoms one by one the way we want them. “There’s Plenty of Room at the Bottom” asked what becomes possible when we can work at much smaller scales. The related question here is how to observe organized, living matter as it changes.

Sources & figure notes

Illustrations. All biological plates are conceptual illustrations created with AI image generation and checked for the explanatory features described. They are not microscopy, measured trajectories, or model outputs. Molecular components and cell sizes are illustrative. The crossing-time plot is derived from measured data. The cell types shown as examples do not imply that each has been demonstrated on Cell Cinema.

Life at the cell scale. See Alberts and colleagues on cells and genomes, cellular energy use, and membrane structure. The opening describes shared features of cellular life, not a claim that every specialized cell can divide or live independently. The drawing depicts a generalized animal cell; bacteria have different architecture. Its labels identify examples of cellular functions, not exclusive locations for those functions.

Michael Levin. The homeostasis quotation is an exact fragment from Levin’s own chapter draft, published on his blog on 31 May 2026. The composite-agents quotation is an exact fragment from his 2019 Frontiers in Psychology article. Agency and intelligence describe his framework for studying regulation, adaptation, and coordination; these quotations do not establish subjective consciousness in individual cells. For experimental work on collective epithelial closure, see Brugués and colleagues, Nature Physics (2014): cell crawling and actomyosin contraction contribute to closure in their cultured-sheet system. The repair plate is conceptual, not a depiction of a Levin experiment, a measured time series, or evidence that Cell Cinema measures every underlying signal.

Omics and holistic state. “Sharded representation” is the author’s metaphor. See EMBL-EBI’s omics definitions, CITE-seq for joint RNA and selected surface-protein measurement, and GLUE for integration across different cells. Rafelski & Theriot, Cell (2024) is a conceptual framework, not a demonstration that one instrument measures a complete phenotype.

Hyperspectra. The spectral cube and curve are schematic. See JPL’s imaging-spectroscopy explanation and Ando & Hamaguchi’s living-cell Raman study. Spectra combine overlapping biochemical contributions; interpretation and quantitative concentration estimates require appropriate methods, calibration, and validation. Spectral planes are channels, not tissue sections or successive times.

Cells and cultures. The drawings distinguish cell identity from culture configuration. ATCC’s guide describes adherent and suspension growth; some cultures contain both. Hepatocyte protocols include suspension and plated preparations. The hepatocyte/T-cell coculture is a conceptual example, not a tested experimental result here.

Perturbations and models. Qi and colleagues (2013) introduced CRISPRi using catalytically inactive Cas9 to repress transcription without cutting DNA. Adamson and colleagues’ Perturb-seq study (2016) combines genetic perturbations with RNA readouts and includes chemical stressors. Shen and colleagues (2024) provide a cell-specific example of altered oxygen conditions. The atlas is conceptual: molecule counts, binding geometry, and RNA marks are illustrative. The drawn intervention does not establish its effect, specificity, reversibility, or viability outcome. CellBox (2021) is an example of combining explicit dynamics with learned parameters and evaluating held-out perturbations. “Trajectomics” is the author’s term for the measurement-and-analysis approach described here.

Sensing and acquisition. The inlet, cell-chamber, and outlet sensing positions illustrate a proposed architecture, not a specification of current hardware. Orange marks represent treatment. Washout does not establish intracellular clearance or recovery. Cadence and measurement effects depend on modality. The sampling illustration shows one schematic ex-situ lysis workflow; harvesting, dissociation, and processing vary. A retained field is not automatically a tracked single-cell history. Optical imaging and RNA sequencing do not provide equivalent molecular coverage.

Trajectories and landscapes. The early/late figure varies one hypothetical feature; matching final readings do not establish identical biological states. The Waddington-inspired terrains are metaphors, not fitted energy landscapes, drug-response predictions, or evidence that every trajectory must run downhill. The aging illustration extends Waddington’s developmental metaphor; it is not his original claim. Stable measurements over a finite experiment do not establish absence of aging. The quote is from Figure 4’s caption, p. 29; see the original page.

Parts, state, and computation. Molecular silos illustrate separated measurements, not literal compartments within a cell. A parts list alone is insufficient; this does not establish that cells are mathematically uncomputable. Chess is not solved, and a FEN position alone omits repetition history. Feynman’s quoted words appear on printed p. 34 of the lecture published in Engineering and Science (1960); the connection to observing living matter is the author’s.

Seven-field evidence. RSL3-treated SK-MEL-2; mean 750 cm⁻¹ heme-associated and broad CH contrasts; signed local spectral baseline and spatial-background correction on fixed initial high-CH pixels. Bars preserve adjacent 30-minute brackets for the first below-half observation that remains below half at subsequent sampled times. Seven fields are spatial samples from one pilot, not seven biological replicates or tracked cells. Field 07’s underlying Region 13 is flagged incomplete in raw-source metadata; its feature-summary series is present. Ordering is specific to the declared features and processing. Neither contrast directly measures viability. Inspect the evidence.

Motivation. HMCVelo is a preprint and infers hydroxymethylation velocity from static joint molecular measurements using a biochemical model. It does not directly record cell trajectories. The piano is an analogy.

The idea to take with you

Predict what a cell will do.
Then ask the living cell.

Better models need better experiments.
Better experiments can teach us what to model.

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