docs/paper/ProcessDSL_FlowCell10_Proposal_with_Mermaid.md

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.

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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).

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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

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3. Example ProcessDSL (Glycolysis)

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

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4. Expanded Glycolysis Flowchart (Mermaid)

Below is an example from FlowCell-10 showing Glycolysis in Yeast with branch and loop structure, rendered with 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]

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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.

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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.

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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