| # ProcessDSL + FlowCell-10 Proposal | |
| This proposal outlines a pilot initiative to integrate the **"genome as program"** concept and **cellular process flowcharting** into the Virtual Cell project. | |
| The goal is to formalize biological processes as executable, interpretable programs that can be learned, simulated, and manipulated by AI. | |
| --- | |
| ## 1. ProcessDSL Specification | |
| **ProcessDSL** is a domain-specific language for representing cellular processes. | |
| It compiles human-readable flowcharts into machine-executable forms such as stochastic rule systems, Petri nets, or hybrid ODE/event simulators. | |
| **Key features:** | |
| - Reactions as rules with explicit guards and rate constants. | |
| - Conditional logic (`IF/ELSE`) for regulation. | |
| - Iterative loops (`WHILE`) for cyclic processes. | |
| - Event triggers for environmental or signaling changes. | |
| - Support for compartments (nucleus, cytosol, organelles). | |
| --- | |
| ## 2. FlowCell-10 Pilot Dataset | |
| **FlowCell-10** is a curated set of ten well-characterized yeast pathways, each represented as: | |
| 1. A canonical flowchart | |
| 2. A ProcessDSL file | |
| 3. Reference simulation outputs from literature data | |
| **Example pathways:** | |
| 1. Glycolysis | |
| 2. TOR nutrient sensing pathway | |
| 3. Heat shock response | |
| 4. Autophagy initiation | |
| 5. Unfolded protein response (UPR) | |
| 6. Cell cycle G1/S transition | |
| 7. Mitochondrial respiration control | |
| 8. Amino acid biosynthesis regulation | |
| 9. Gluconeogenesis | |
| 10. Alcoholic fermentation | |
| --- | |
| ## 3. Example ProcessDSL (Glycolysis) | |
| ```text | |
| process Glycolysis in Cytosol: | |
| state: [Glucose, G6P, F6P, F16BP, G3P, DHAP, PEP, Pyruvate, ATP, ADP, NAD+, NADH] | |
| rule Hexokinase: Glucose + ATP -> G6P + ADP [guard: ATP>θ1] | |
| rule PFK: F6P + ATP -> F16BP + ADP [guard: ATP<θ2 & AMP>θ3] | |
| rule Aldolase: F16BP -> G3P + DHAP | |
| rule TPI: DHAP <-> G3P | |
| rule PyruvateKinase: PEP + ADP -> Pyruvate + ATP [allosteric: F16BP activates] | |
| event GlucosePulse(t=0..T): inflow rate r_in | |
| ``` | |
| --- | |
| ## 4. Expanded Glycolysis Flowchart (Mermaid) | |
| Below is an example from FlowCell-10 showing **Glycolysis in Yeast** with branch and loop structure, rendered with Mermaid: | |
| ```mermaid | |
| flowchart TD | |
| A[Glucose Uptake<br/>(Transport into cell)] | |
| --> B[Hexokinase<br/>Glucose → G6P] | |
| B --> C[Isomerase<br/>G6P → F6P] | |
| C --> D[Phosphofructokinase (PFK)<br/>F6P → F1,6BP] | |
| %% Branch | |
| D --> E1[DHAP<br/>(Dihydroxyacetone phosphate)] | |
| D --> E2[G3P<br/>(Glyceraldehyde‑3‑phosphate)] | |
| E1 -- TPI forward --> E2 | |
| E2 -- TPI reverse --> E1 | |
| %% Payoff phase | |
| E2 --> F[G3P Oxidation & Phosphorylation<br/>(NADH + ATP yield)] | |
| F --> G[Phosphoglycerate Mutase & Enolase<br/>→ PEP] | |
| G --> H[Pyruvate Kinase<br/>PEP → Pyruvate + ATP] | |
| H --> I[End Product:<br/>2 Pyruvate Molecules] | |
| ``` | |
| --- | |
| ## 5. Deliverables | |
| - ProcessDSL specification and parser. | |
| - FlowCell-10 diagrams, DSL files, and simulation benchmarks. | |
| - Jupyter notebook demo: diagram → ProcessDSL → simulation → data comparison. | |
| - Documentation for extending the dataset. | |
| --- | |
| ## 6. Benefits to the Virtual Cell Project | |
| - Provides an interpretable, executable representation of cellular processes. | |
| - Bridges molecular prediction tools (e.g., AlphaFold 3) to systems-level dynamics. | |
| - Enables counterfactual simulations and intervention planning. | |
| - Creates training data for AI models to learn biological program induction. | |
| --- | |
| ## 7. Suggested DeepMind Contacts | |
| 1. **Demis Hassabis** – CEO, DeepMind (vision for Virtual Cell) | |
| 2. **Pushmeet Kohli** – Head of AI for Science, DeepMind | |
| 3. **John Jumper** – Lead researcher on AlphaFold | |
| 4. **Kathryn Tunyasuvunakool** – Research scientist, AlphaFold/biology modeling | |
| 5. **Alexander Zisserman** – Research scientist, graph and vision integration | |