# Welcome to the GLMP Validation Project
## Genome Logic Modeling Project — Student Collaboration Package
### Prepared by Gary Welz · CUNY Graduate Center / New Media Lab
### Version: July 2026

---

## What is GLMP?

The Genome Logic Modeling Project proposes that the DNA controlling
when genes turn on and off can be read like a computer program.
Specifically, the spatial arrangement of protein binding sites in
regulatory DNA encodes logical operations — AND gates, OR gates,
NOT gates — the same building blocks used in electronic circuits.

Your contribution is to test that idea against independently curated biological
databases — to find out where our computational predictions match what biologists
have experimentally verified, and where they don't. Disagreements are the valuable
result, not a failure.

This is real science, not a classroom exercise. Your findings will
directly influence a methods paper currently in preparation and will
be cited by name in the acknowledgments or authorship — depending on
the significance of your contribution.

---

## The three circuits you will work with

We have computationally decoded three E. coli regulatory circuits:

**1. The lac operon** — controls lactose metabolism.
When lactose is present and glucose is absent, E. coli switches on
genes to digest lactose. The circuit involves a repressor (LacI)
and an activator (CRP). Our decoder reads the repression side
reliably (a NOT gate); cooperative activation (an AND gate) is
**not** confirmable from sequence alone for a single-activator
promoter like this one, so the honest computational read is
Class I/II. The decoder currently makes zero AND calls across
the whole circuit suite — it says so plainly rather than
inventing one. Class II (dual control) remains the curated
biological understanding, and is the open question we are
asking you to help weigh in on.

**2. The ara operon** — controls arabinose metabolism.
A single protein (AraC) is understood from the literature to act
as both repressor and activator depending on whether arabinose is
present — a bistable switch, biologically. Computationally, our
decoder currently reports **insufficient evidence** for this
circuit: AraC is a prokaryote-specific factor absent from JASPAR,
so there is no validated motif to score yet. A RegulonDB-trained
AraC matrix is in development.

**3. The trp operon** — controls tryptophan biosynthesis.
When tryptophan levels are high, a repressor (TrpR) shuts off
the biosynthesis genes. End-product feedback, a NOT gate.

All three are among the most studied regulatory circuits in all
of molecular biology. They are the ideal starting point for
validating a new computational approach.

---

## Your task

You have been assigned one of two validation tracks based on your
background (see your task brief document for details):

**Computation track:** Cross-reference our computationally predicted
binding sites against RegulonDB — the gold-standard curated database
of E. coli regulatory interactions maintained by UNAM. Write a
Python analysis and produce a structured validation report.

**Biology track:** Review our logic-gate annotations for each of
the three circuits against your knowledge of the primary literature.
Confirm or flag each annotation, and produce a structured report.

Both tracks use the same report template (included in this package).

---

## What is in this package

Everything you need is here — no additional credentials or database
access required:

```
validation/
  README.md                        ← this file
  annotation-review/
    lac-operon-annotation-review.html  ← interactive flowcharts + annotations
  decode-results/
    ecoli_lac_operon_logic.json    ← computational decode output
    ecoli_ara_operon_logic.json
    ecoli_trp_operon_logic.json
  regulondb-v14/
    TF-RISet.tsv                   ← validated TF regulatory interactions
    PromoterSet.tsv                ← promoter annotations
    NetworkRegulatorGene.tsv       ← regulon definitions
    TFSet.tsv                      ← transcription factor list
    README-regulondb.txt           ← what each file contains
  task-brief-computation.md        ← detailed instructions (computation track)
  task-brief-biology.md            ← detailed instructions (biology track)
  report-template.md               ← structure for your validation report
```

**Start here:** open `annotation-review/lac-operon-annotation-review.html`
in any web browser. It renders interactive flowcharts for all three
circuits and explains the GLMP logic gate framework visually.

---

## How to submit your report

When your analysis is complete, submit your report as a Google Doc
or PDF to Gary Welz at gwelz@gc.cuny.edu.

Questions at any time: gwelz@gc.cuny.edu

---

## A note on the bigger picture

GLMP is building a knowledge engine where a researcher can query
any biological process and receive: a logic-gate flowchart, the
source papers behind it, the decoded DNA regulatory sequence, and
eventually a podcast and knowledge graph — all in one query.

Your validation work is the quality control layer that makes the
decoded circuits trustworthy enough to publish and build on.
The E. coli circuits you are validating are the first entries in
a corpus we aim to grow to 1,000+ decoded circuits over the
coming year.

Thank you for contributing.

**Gary Welz**
CUNY Graduate Center / New Media Lab
gwelz@gc.cuny.edu · ORCID: 0009-0005-7806-0892
github.com/garywelz/glmp · doi.org/10.5281/zenodo.20831780