Cis-GS  ·  Cis-regulatory Element Genome Scanner

A whole-genome pipeline for discovering cis-regulatory elements, coupling them to expression, and finishing with KEGG enrichment — in one PyQt5 desktop app and one interactive CLI.

---

Table of Contents

• What Cis-GS Does
• Highlights of v1.1
• Installation
• Quick Start
• The 7-Step Workflow
• Supported Motif Databases
• CLI Reference
• Programmatic API
• Screenshots
• Troubleshooting
• Contributing
• Citation
• License
• Contact

---

What Cis-GS Does

Cis-GS automates the full promoter → motif → expression → function journey that plant- and animal-genomics labs run by hand today:

1. Fetch a reference genome + annotation directly from NCBI (live Assembly search).
2. Extract promoter sequences (configurable length, strand-aware, intergenic-clipped) from any GFF3.
3. Scan those promoters for transcription-factor binding motifs imported from PlantTFDB, AnimalTFDB, JASPAR 2024, or HOCOMOCO v11 — or any user-supplied IUPAC consensus.
4. Render publication-ready sequence logos and per-gene hit tables with hypergeometric p-values and BH-FDR.
5. Couple the hits to your expression table (RNA-seq, microarray, qPCR) to flag motifs whose presence tracks expression direction.
6. Build a co-expression network (Pearson / Spearman / WGCNA-style soft-thresholding), detect modules via Louvain or hierarchical clustering, and visualise eigengenes.
7. Enrich the top module / cluster against KEGG (live REST queries, 11 700+ organisms) with one-sided hypergeometric ORA + Benjamini-Hochberg FDR.

Everything runs locally, offline-friendly after the first network fetch, and exports CSV / SVG / PDF at every step.

---

Highlights of v1.1

• Live KEGG dropdown — every one of the 11 700+ organisms KEGG knows about, fetched on demand. No more stale species tables.
• Live NCBI Taxonomy search — type any common or Latin name; results stream back as you type.
• 60× faster ID conversion — MyGene.info batched POST + progress bar (previously 60+ minutes for 10 k genes; now ~60 s).
• Interactive CLI wizards — cis-gs wizard walks you through every step with arrow-key menus. Every subcommand also accepts -i / --interactive.
• Fuzzy "did you mean...?" for CLI typos.
• Brand-icon Contact tab with real-website logos (LinkedIn, GitHub, KEGG, NCBI, PlantTFDB, AnimalTFDB, MyGene).
• Modern single-color theme (teal #16A085) with instant light / dark toggle — no more 1-2 s freeze.
• First-run NCBI email prompt — required by the Entrez API, stored only on your machine.
• Three Gene-ID-Mapping methods for the annoying NCBI-LOC vs species-database mismatch (column swap, mapping CSV, GFF3 Dbxref expansion).

See the full release notes for the v1.0 → v1.1 diff.

---

Installation

Option 1 — PyPI (Linux / macOS / Windows)

pip install cis-gs
cis-gs --help          # CLI
cis-gs-gui             # GUI

Python 3.9+ required. The first GUI launch will pop up a one-time NCBI email prompt.

Option 2 — Standalone Windows executable

Download Cis-GS.exe from the latest release page. Double-click. No Python install needed. Roughly 120 MB.

Option 3 — From source

git clone https://github.com/Ayushmania2002/Cis-GS.git
cd Cis-GS
pip install -e ".[dev,docs]"
python app_v4_open.py        # GUI
python -m cis_gs --help      # CLI

Full build details (PyInstaller spec, build scripts for all 3 OSes, PyPI release workflow): see BUILD.md.

---

Quick Start

GUI (one minute)

cis-gs-gui

1. Step 1 — Promoters: drop a FASTA + GFF3, set promoter length (default 2 kb), click Extract.
2. Step 2 — Motif Search: click Import from PlantTFDB (or AnimalTFDB), pick your species, tick the motifs you want, Import Selected.
3. Step 7 — KEGG Enrichment: pick a KEGG organism from the live dropdown, paste your gene list, run.

Done. CSVs and SVGs land in ~/CisGS-Workspace/.

CLI (interactive wizard)

cis-gs wizard

The wizard auto-detects what you've already produced and offers the next sensible step.

CLI (one-liners)

# Extract 2 kb promoters from a GFF3 + FASTA
cis-gs extract --fasta genome.fa --gff annot.gff3 --upstream 2000 --out promoters.fa

# Scan promoters with a MEME motif file
cis-gs search --promoters promoters.fa --motifs motifs.meme --out hits.csv

# KEGG enrichment
cis-gs enrich-kegg --organism ath --genes top_module.txt --out kegg.csv

Every command supports -i / --interactive if you want to be walked through it.

---

The 7-Step Workflow

Step	What it does	Output
1. Promoters	Strand-aware promoter extraction from any FASTA + GFF3	promoters.fa
2. Motif Search	IUPAC / MEME / PlantTFDB / AnimalTFDB scanning with hypergeometric p-values + BH-FDR	hits.csv, significance summary
3. Motif Logos	logomaker sequence logos with information-content shading	per-motif SVG / PNG
4. Expression Feeding	Joins hits with an expression CSV via three Gene-ID-Mapping methods (LOC swap, mapping CSV, GFF3 Dbxref expansion)	expression_matched.csv
5. Coexpression	Pearson / Spearman / WGCNA-style soft-thresholding, Louvain / hierarchical module detection	network.gexf, eigengene plot
6. K-means	Elbow + silhouette, deterministic seeding, exportable per-cluster gene lists	clusters/*.txt
7. KEGG Enrichment	Live REST query against any of 11 700+ KEGG organisms, hypergeometric ORA, BH-FDR, fold-enrichment	kegg_enrichment.csv

A full description of each step's algorithm and parameters lives in the online documentation.

---

Supported Motif Databases

Database	Coverage	Access
PlantTFDB v5	157 plant species, ~6 000 motifs	Built-in importer with live species list
AnimalTFDB v4	Human, mouse, zebrafish, insects	Built-in importer
JASPAR 2024 (non-redundant)	575 vertebrate + 99 insect motifs	Direct REST download
HOCOMOCO v11	~700 human + ~400 mouse ChIP-Seq motifs	Direct REST download
Custom IUPAC / MEME	Anything you can write down	Paste into Step 2

---

CLI Reference

cis-gs --help

usage: cis-gs [-h] {wizard,fetch,extract,search,feed,coexpr,kmeans,enrich-kegg,id-convert} ...

  wizard         Step-by-step wizard (recommended for new users)
  fetch          Download a genome + annotation from NCBI
  extract        Extract promoter sequences from FASTA + GFF3
  search         Scan promoters for motif occurrences
  feed           Couple motif hits with an expression table
  coexpr         Build a co-expression network
  kmeans         K-means clustering with elbow / silhouette
  enrich-kegg    KEGG over-representation analysis
  id-convert     Convert gene IDs across namespaces (MyGene.info, batched)

Every subcommand accepts -i / --interactive for a guided run, and --help for full flags.

---

Programmatic API

from cis_gs.enrichment import KEGGEnricher

e = KEGGEnricher(organism="ath")          # Arabidopsis
result = e.enrich(["AT1G01010", "AT2G18790", "AT3G09600"])
print(result.table.head())

from cis_gs.enrichment.idmap import IDConverter

idc = IDConverter(species="human")
mapping = idc.convert(["TP53", "BRCA1", "MYC"], target="entrez")

Full API reference: Ayushmania2002.github.io/Cis-GS/api.

---

Screenshots

Live GUI screenshots of all 7 workflow steps are available in the online documentation.

---

Troubleshooting

Symptom	Likely cause	Fix
cis-gs-gui: command not found after pip install	Scripts dir not on PATH	python -m cis_gs works, or add pip --user bin dir to PATH
First NCBI Fetch returns 0 results	NCBI email not set	Settings → Set NCBI Email, then retry
KEGG REST unreachable	Firewall or VPN	Set HTTPS_PROXY env var, or use the Browse & Import tab with a manually downloaded MEME
Motif hits CSV has empty gene_symbol column	Annotation GFF3 not loaded in Step 2	Re-run with the same GFF3 from Step 1 in Gene ID Resolution
Coexpression freezes on > 30k genes	All-vs-all correlation is O(n²)	Pre-filter to expressed genes (TPM > 1) before Step 5

Open an issue with the log file from ~/CisGS-Workspace/cisgs.log if you hit anything else.

---

Contributing

Bug reports, feature requests, and pull requests are welcome. For substantial contributions please open an issue first to discuss the change.

git clone https://github.com/Ayushmania2002/Cis-GS.git
cd Cis-GS
pip install -e ".[dev]"
pytest                       # run the test suite

---

Citation

If Cis-GS contributes to a publication, please cite:

Mallick A. Cis-GS: a unified pipeline for whole-genome cis-regulatory element discovery, expression coupling, and KEGG enrichment. (manuscript in preparation, Plant Signaling Lab, IISER Tirupati, 2026).

BibTeX:

@software{mallick_cisgs_2026,
  author  = {Mallick, Ayushman},
  title   = {{Cis-GS}: Cis-regulatory Element Genome Scanner},
  year    = {2026},
  url     = {https://github.com/Ayushmania2002/Cis-GS},
  version = {1.1.0}
}

A CITATION.cff is included for GitHub's automatic citation widget.

---

License

Released under the MIT License. Free for academic and commercial use.

---

Contact

Ayushman Mallick · ayushmania2002@gmail.com Plant Signaling Lab, IISER Tirupati

_{© 2026 Ayushman Mallick · Plant Signaling Lab · Cis-GS}