Genome Logic Modeling Project · Gary Welz · CUNY Graduate Center

Decoding the logic of gene regulation

80,138
Biology papers in corpus

GLMP's current methodological contribution is layered hybridization: reconciling literature-derived regulatory logic with database-grounded entity completeness, instead of treating them as competing choices. A literature-first flowchart makes a circuit's Boolean logic legible — AND/OR/NOT gates, explicit branch conditions — but tends to leave real biosynthesis steps implicit (a repressor "appears" without a drawn path from gene to protein). A RegulonDB-style wiring diagram has the opposite strength: complete regulatory entities, but no explicit gate logic. The hybrid keeps both — worked out in detail for the E. coli lac operon as a case study, comparing three deliberately different encodings side by side and recommending a four-step workflow (regulatory backbone → interpretive overlay → parts audit → identifier layer) for building one without collapsing distinct abstraction levels into an unreadable graph.

Read the full methods paper: Mermaid Flowcharts for Smarter Perturbation Design.

The flowchart that started it

graph TD lacI_tx["lacI gene → LacI repressor"] lacI_tx --> LacI[LacI repressor protein] Lact[Lactose / allolactose] Lact --> IndR{Repressor released?} LacI --> IndR IndR -->|No| Blocked[Operon blocked] IndR -->|Yes| OpOK[Operator accessible] Glc[Glucose / cAMP state] Glc --> CAPs{CAP-cAMP assists?} CAPs --> AND{Operator free AND CAP assist?} OpOK --> AND AND -->|Yes| Strong[lacZYA transcription ON] AND -->|No| Weak[Basal transcription only] style lacI_tx fill:#ffb74d,stroke:#e65100,color:#000 style LacI fill:#ffb74d,stroke:#e65100,color:#000 style IndR fill:#e1bee7,stroke:#4a148c,color:#000 style CAPs fill:#e1bee7,stroke:#4a148c,color:#000 style AND fill:#e1bee7,stroke:#4a148c,color:#000 style Strong fill:#c8e6c9,stroke:#1b5e20,color:#000 style Weak fill:#e8f5e9,stroke:#33691e,color:#000 style Blocked fill:#ffccbc,stroke:#bf360c,color:#000 style Lact fill:#fff9c4,stroke:#f9a825,color:#000 style Glc fill:#b3e5fc,stroke:#01579b,color:#000 style OpOK fill:#fff9c4,stroke:#f57f17,color:#000
Orange = gene source Purple = logic gate Green = active transcription Red = repression Blue = environmental input

How this works

  1. 1

    LLMs generate logic-gate flowcharts for regulatory circuits across organisms.

  2. 2

    A qualified molecular biologist validates that the flowcharts accurately reflect observed molecular behavior. This is the pivotal open step. Neither PI is a molecular biologist, so the judgment has to come from outside; a student can attempt a first-pass review, but a biologist's sign-off is what this step requires.

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  3. 3

    Computational methods extract and verify the logic directly from DNA sequences using motif scanning and a custom parser.

  4. 4

    Validated results are written up and scaled to advanced methods including Evo 2 and single-cell regulatory inference.

  5. 5

    At scale, the theory is either confirmed or refined — and the knowledge engine is built on solid ground.

The research arc

Theory → framework → empirical test → synthesis → methods.

Papers and links

Circuit diagrams for review

Resources

  • GitHub
  • Annotation Review
  • Validation Package
  • Full catalog — 217 processes

    The Circuit Class (I–V) labels in this catalog are a first-pass stratification, and parts of it are already known to be wrong. Ongoing expert review is finding these errors case by case; once that review completes, the classification will be rebuilt from what it teaches us, not patched piecemeal. A marked limit is a finding, not a failure — this is exactly the kind of check the project is built to survive.

GLMP in the suite

GLMP is a working engine of the CopernicusAI Knowledge Engine — it consumes the shared Knowledge Base (corpus, embeddings, search) and contributes its decoded circuits back into it.