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ProcessDSL_FlowCell10_Proposal_with_TORC1.md

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+# 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. Glycolysis Flowchart (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]
+    D --> E1[DHAP<br/>(Dihydroxyacetone phosphate)]
+    D --> E2[G3P<br/>(Glyceraldehyde‑3‑phosphate)]
+    E1 -- TPI forward --> E2
+    E2 -- TPI reverse --> E1
+    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. TORC1 Nutrient Sensing Pathway
+
+This diagram shows the TORC1 pathway in *Saccharomyces cerevisiae*, including nutrient signal integration, bifurcated signaling, and autophagy suppression vs activation under stress conditions.
+
+![TORC1 Flowchart](torc1.png)
+
+---
+
+## 6. 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.
+
+---
+
+## 7. 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.
+
+---
+
+## 8. 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  

torc1_mermaid.mmd

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+flowchart TD
+  AA[Amino Acid / Nutrient Signals] --> AB[EGO Complex (Ego1-3) + Gtr1/2]
+  AB --> AC[TORC1 Activation]  
+  AC --> AD[Sch9 kinase branch]  
+  AC --> AE[PP2A/Sit4 branch]  
+
+  AD --> AF[Ribosome Biogenesis & Protein Translation ↑]
+  AE -- Tap42/PP2A → downstream --> AG[NPR1 inhibition → Amino Acid Transport ↑]
+
+  AC -. Negative regulation .-> AH[Atg13 phosphorylation → Inhibit Atg1 complex]
+  AH -->|Inhibition| AI[Autophagy suppressed]
+
+  subgraph Stress / Starvation
+    AA2[Low Nutrients] --> AB2[EGO inactive → TORC1 off]
+    AB2 --> AC2[TORC1 Inactive]
+    AC2 --> AH2[Atg13 de-phosphorylated + Atg1 complex formed]
+    AH2 --> AJ[Autophagy induced via Atg1-Atg13-Atg17 complex]
+  end