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<h1>ProcessDSL + FlowCell-10 Proposal</h1>
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<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>
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<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>
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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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<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>
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<img src="YeastFlowchart1.drawio.png" alt="Glycolysis Pathway in Yeast" style="max-width: 100%; height: auto;">
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<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>
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<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>
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<p><strong>This proposal demonstrates how computational biology and artificial intelligence can converge to create interpretable, executable models of biological systems.</strong></p>
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