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| <html lang="en"> | |
| <head> | |
| <meta charset="UTF-8"> | |
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| <title>ProcessDSL + FlowCell-10 Proposal</title> | |
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| <h1>ProcessDSL + FlowCell-10 Proposal</h1> | |
| <div class="highlight"> | |
| <p><strong>This proposal outlines a pilot initiative to integrate the "genome as program" concept and cellular process flowcharting into the Virtual Cell project.</strong> The goal is to formalize biological processes as executable, interpretable programs that can be learned, simulated, and manipulated by AI.</p> | |
| </div> | |
| <h2>1. ProcessDSL Specification</h2> | |
| <p><strong>ProcessDSL</strong> 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.</p> | |
| <h3>Key features:</h3> | |
| <ul> | |
| <li>Reactions as rules with explicit guards and rate constants.</li> | |
| <li>Conditional logic (IF/ELSE) for regulation.</li> | |
| <li>Iterative loops (WHILE) for cyclic processes.</li> | |
| <li>Event triggers for environmental or signaling changes.</li> | |
| <li>Support for compartments (nucleus, cytosol, organelles).</li> | |
| </ul> | |
| <h2>2. FlowCell-10 Pilot Dataset</h2> | |
| <p><strong>FlowCell-10</strong> is a curated set of ten well-characterized yeast pathways, each represented as:</p> | |
| <ul> | |
| <li>A canonical flowchart</li> | |
| <li>A ProcessDSL file</li> | |
| <li>Reference simulation outputs from literature data</li> | |
| </ul> | |
| <h3>Example pathways:</h3> | |
| <ol> | |
| <li>Glycolysis</li> | |
| <li>TOR nutrient sensing pathway</li> | |
| <li>Heat shock response</li> | |
| <li>Autophagy initiation</li> | |
| <li>Unfolded protein response (UPR)</li> | |
| <li>Cell cycle G1/S transition</li> | |
| <li>Mitochondrial respiration control</li> | |
| <li>Amino acid biosynthesis regulation</li> | |
| <li>Gluconeogenesis</li> | |
| <li>Alcoholic fermentation</li> | |
| </ol> | |
| <h2>3. Example ProcessDSL (Glycolysis)</h2> | |
| <div class="code-block"> | |
| 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 | |
| </div> | |
| <h2>4. Expanded Glycolysis Flowchart</h2> | |
| <p>Below is an example from FlowCell-10 showing <strong>Glycolysis in Yeast</strong> with branch and loop structure:</p> | |
| <div class="flowchart-container"> | |
| <img src="YeastFlowchart1.drawio.png" alt="Glycolysis Pathway in Yeast" style="max-width: 100%; height: auto;"> | |
| </div> | |
| <h2>5. Deliverables</h2> | |
| <ul> | |
| <li>ProcessDSL specification and parser.</li> | |
| <li>FlowCell-10 diagrams, DSL files, and simulation benchmarks.</li> | |
| <li>Jupyter notebook demo: diagram → ProcessDSL → simulation → data comparison.</li> | |
| <li>Documentation for extending the dataset.</li> | |
| </ul> | |
| <h2>6. Benefits to the Virtual Cell Project</h2> | |
| <div class="benefit-box"> | |
| <ul> | |
| <li>Provides an interpretable, executable representation of cellular processes.</li> | |
| <li>Bridges molecular prediction tools (e.g., AlphaFold 3) to systems-level dynamics.</li> | |
| <li>Enables counterfactual simulations and intervention planning.</li> | |
| <li>Creates training data for AI models to learn biological program induction.</li> | |
| </ul> | |
| </div> | |
| <div class="highlight"> | |
| <p><strong>This proposal demonstrates how computational biology and artificial intelligence can converge to create interpretable, executable models of biological systems.</strong></p> | |
| </div> | |
| </div> | |
| </body> | |
| </html> |