Biological World Models0%
01 · Course Roadmap

Six months. Six themes. One virtual cell.

Each month builds the conceptual and technical scaffolding needed for the next. By month six, you assemble a falsifiable mini world model for a specific disease, pathway, and cell type.

  1. MONTH 01 / 06
    1
    Theme

    Biological Foundations for Technical Thinkers

    Main question

    "What is the biological system, what are its states, and what counts as an intervention?"

    Weekly breakdown
    0/4 weeks · 0%

    Weeks 1–4: Biology → Molecular regulation → Cells & disease → Pharmacology.

    Core concepts
    • ·Genes, transcripts, proteins, metabolites
    • ·Transcription, translation, regulation
    • ·Cell signaling and pathway motifs
    • ·Cell types and cell states
    • ·Disease states
    • ·Pharmacology basics: target, potency, selectivity, PK/PD, ADMET, toxicity
    • ·Single-cell RNA-seq basics
    Deliverable

    A written map of one biological system (e.g. EGFR–RAS–MAPK, PI3K–AKT–mTOR, JAK–STAT, NF-κB, p53, Wnt, TGF-β, insulin signaling).

    CS · AI · Math · Physics → Biology

    Map state variables ↔ molecular species; map control inputs ↔ drugs/CRISPR; map observables ↔ omics readouts.

    What would change my mind?

    Find a single curated case where 'gene X drives phenotype Y' holds across cell types, contexts, and intervention modalities without notable exceptions. If such cases are common, the warning that 'biology is context-dependent' is overstated for this scope.

  2. MONTH 02 / 06
    2
    Theme

    Perturbation Data and Baseline Models

    Main question

    "Can we predict what changes when we perturb a biological system?"

    Weekly breakdown
    0/4 weeks · 0%

    Weeks 5–8: Perturbation biology → single-cell omics → baselines → neural models.

    Core concepts
    • ·Perturb-seq
    • ·CRISPR screens
    • ·LINCS / CMap-style signatures
    • ·DepMap-style gene dependencies
    • ·Drug perturbation signatures
    • ·Train/test leakage
    • ·Linear baselines
    • ·Evaluation metrics
    • ·Uncertainty
    Deliverable

    A perturbation-response benchmark notebook comparing simple baselines against a neural model.

    CS · AI · Math · Physics → Biology

    Benchmarks and leakage are the same problems as in any ML stack — but with biology-specific splits over genes, cell lines, and drugs.

    What would change my mind?

    Show a neural model that beats a strong linear baseline by a meaningful margin on a truly held-out perturbation split, with calibrated uncertainty, on more than one dataset. That would justify the extra complexity.

  3. MONTH 03 / 06
    3
    Theme

    Pathways as Graphs and Dynamical Systems

    Main question

    "Can we turn pathway diagrams into causal, dynamical simulators?"

    Weekly breakdown
    0/4 weeks · 0%

    Weeks 9–12: Graphs → ODE/SDE dynamics → hybrid models → control.

    Core concepts
    • ·Directed signed graphs
    • ·Reactome-style pathway priors
    • ·Gene regulatory networks
    • ·ODEs and SDEs
    • ·Feedback loops
    • ·Bistability
    • ·Attractors
    • ·Network controllability
    • ·Hybrid mechanistic/neural models
    Deliverable

    A pathway graph simulator for one pathway with intervention inputs and predicted downstream state changes.

    CS · AI · Math · Physics → Biology

    Pathways are signed digraphs with dynamics; interventions are control inputs to a partially observed nonlinear system.

    What would change my mind?

    Demonstrate a pure black-box model that, on a held-out intervention, matches a hybrid mechanistic-neural model in both accuracy and calibration. That would weaken the case for mechanistic priors.

  4. MONTH 04 / 06
    4
    Theme

    Causal Inference and Active Experimental Design

    Main question

    "What should we perturb next to learn the most?"

    Weekly breakdown
    0/4 weeks · 0%

    Weeks 13–16: Causality → counterfactuals → experimental design → combinations.

    Core concepts
    • ·Causal graphs
    • ·do-calculus intuition
    • ·Counterfactual prediction
    • ·Invariance
    • ·Confounding
    • ·Optimal experimental design
    • ·Bayesian optimization
    • ·Active learning
    • ·Expected information gain
    Deliverable

    An active-learning loop that proposes the next perturbation experiment.

    CS · AI · Math · Physics → Biology

    Active learning + Bayesian optimization, with biological cost functions and constraints.

    What would change my mind?

    Run a head-to-head where random or uniform sampling matches an active-learning loop in downstream task performance for a fixed budget. That would suggest the acquisition function is not buying us much in this regime.

  5. MONTH 05 / 06
    5
    Theme

    Structure, Binding, and Molecular Intervention

    Main question

    "If a molecule binds a target, what biological state transition follows?"

    Weekly breakdown
    0/4 weeks · 0%

    Weeks 17–20: Structure → docking → allostery → multi-scale linking.

    Core concepts
    • ·Protein structure
    • ·Protein-ligand binding
    • ·Binding free energy
    • ·Docking
    • ·Molecular dynamics intuition
    • ·Allostery
    • ·Selectivity
    • ·Structure-function relationships
    • ·Protein language models
    • ·Generative molecular design
    Deliverable

    A small pipeline connecting one target to molecular structure, candidate intervention ideas, and downstream pathway consequences.

    CS · AI · Math · Physics → Biology

    Energy landscapes, ensembles, and inverse design — physics and ML applied to molecules with biological meaning.

    What would change my mind?

    Show a target where target engagement reliably predicts pathway and cell-state response across cell contexts and dose regimes, without compensation or feedback surprises. That would make multiscale linking simpler than this course implies.

  6. MONTH 06 / 06
    6
    Theme

    Mini Virtual Cell / Biological World Model

    Main question

    "Can we predict cell-state transitions under interventions with uncertainty?"

    Weekly breakdown
    0/4 weeks · 0%

    Weeks 21–24: Architecture → reversal → validation → presentation.

    Core concepts
    • ·State-space modeling
    • ·Multimodal biological state
    • ·Single-cell embeddings
    • ·Pathway priors
    • ·Perturbation prediction
    • ·Disease-state reversal
    • ·Mechanism of action
    • ·Drug combinations
    • ·Model limitations and validation
    Deliverable

    A final capstone: a mini virtual cell for one disease, one pathway, and one cell type.

    CS · AI · Math · Physics → Biology

    Bring it together: a falsifiable, partially-observed dynamical system with interventions, uncertainty, and a next experiment.

    What would change my mind?

    Produce a virtual cell whose top-ranked, novel reversal interventions are validated in a wet-lab experiment with effect sizes and selectivity matching the predictions, on the first attempt and not just post-hoc.

After Month 6
Your mini virtual cell is the deliverable.
Plan the capstone