# gedine-lab/garreau_2026 architecture

> Architecture diagram of the GitHub repository gedine-lab/garreau_2026, generated by GitDiagram from its file tree, README and a sample of source files (last updated 2026-11-14). It is an AI-made overview: check details against the source.

- Interactive diagram: https://gitdiagram.com/gedine-lab/garreau_2026
- Repository: https://github.com/gedine-lab/garreau_2026

## Overview

This repository contains research code and supplementary results for a study that builds a context-specific co-expression network and uses patient-wise network propagation to prioritize candidate genes in holoprosencephaly. The documented workflow covers expression and patient-variant processing, per-patient propagation and signal-gene analysis, then candidate-gene evidence rating and figure/table analyses. Edges reflect only roles and outputs stated in the README; source excerpts were unavailable, so undocumented calls and data transfers are omitted.

Main entry points: [`Suplementary_Tables`](https://github.com/gedine-lab/garreau_2026/tree/main/Suplementary_Tables) (Supplementary tables S1–S13), [`scripts/PUBMED_query.R`](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/PUBMED_query.R) (PubMed evidence queries), [`scripts/rwr.R`](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/rwr.R) (Per-patient RWR), [`scripts/rwr_normalization_fct.R`](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/rwr_normalization_fct.R) (RWR profile normalization)

## Diagram (Mermaid)

```mermaid
flowchart TD

subgraph group_inputs["Data preparation"]
  node_scrna["Forebrain gene selection<br/>[scrna.R]"]
  node_network_build["Co-expression network<br/>[tprimrna.R]"]
  node_patient_variants["Patient variant filtering"]
end

subgraph group_propagation["Network propagation"]
  node_rwr["Per-patient RWR<br/>[rwr.R]"]
  node_rwr_helpers["RWR helpers<br/>[custom_fct.R]"]
  node_weighted_bank["CDS-weighted permutation bank"]
  node_normalization["RWR profile normalization"]
  node_signal_genes["Signal gene analysis<br/>[signal_gene_fct.R]"]
end

subgraph group_evidence["Candidate evidence"]
  node_pubmed["PubMed evidence queries<br/>[PUBMED_query.R]"]
  node_mgi["Mouse phenotype ratings<br/>[MGI_query.R]"]
  node_loeuf["Constraint metrics retrieval<br/>[loeuf_query.R]"]
end

subgraph group_analyses["Analyses and results"]
  node_ora["Over-representation analysis<br/>[ora_fct.R]"]
  node_ethseq["Ancestry analysis<br/>[ethseq_analysis.R]"]
  node_network_analysis["Network topology and enrichment<br/>[network_analysis.R]"]
  node_seeds_analysis["Seed and seed-enrichment analysis<br/>[seeds_analysis.R]"]
  node_rwr_results["RWR results analysis"]
  node_cohort_permutations["Cohort permutation analysis"]
  node_subnetwork["Candidate subnetwork analysis"]
  node_tables["Supplementary tables S1–S13"]
end

node_atlas["Early-forebrain atlas"]
node_ipsc["iPSC RNA-seq"]
node_exome["Patient exome variants"]
node_pubmed_service(("PubMed"))
node_mgi_service(("MGI"))
node_gnomad(("gnomAD constraint metrics"))

node_scrna -->|"selects genes from"| node_atlas
node_network_build -->|"normalizes data"| node_ipsc
node_patient_variants -->|"filters variants"| node_exome
node_rwr -.->|"uses RWR functions"| node_rwr_helpers
node_normalization -.->|"normalizes profiles"| node_rwr
node_signal_genes -.->|"aggregates profiles"| node_normalization
node_pubmed -->|"queries"| node_pubmed_service
node_mgi -->|"retrieves phenotypes"| node_mgi_service
node_loeuf -->|"retrieves metrics"| node_gnomad
node_ethseq -->|"produces S1"| node_tables
node_network_analysis -->|"produces S6–S7"| node_tables
node_seeds_analysis -->|"produces S4, S8–S10"| node_tables
node_rwr_results -->|"produces S11"| node_tables
node_subnetwork -->|"produces S12"| node_tables
node_pubmed -.->|"rates evidence for S13"| node_tables
node_cohort_permutations -.->|"tests signal counts"| node_signal_genes

click node_scrna "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/scrna.R"
click node_network_build "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/tprimrna.R"
click node_patient_variants "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/patient_data_HPE_POI.R"
click node_rwr "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/rwr.R"
click node_rwr_helpers "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/custom_fct.R"
click node_weighted_bank "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/cds_weighted_bank_generation.R"
click node_normalization "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/rwr_normalization_fct.R"
click node_signal_genes "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/signal_gene_fct.R"
click node_ora "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/ora_fct.R"
click node_pubmed "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/PUBMED_query.R"
click node_mgi "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/MGI_query.R"
click node_loeuf "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/loeuf_query.R"
click node_ethseq "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/ethseq_analysis.R"
click node_network_analysis "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/network_analysis.R"
click node_seeds_analysis "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/seeds_analysis.R"
click node_rwr_results "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/rwr_results_analysis.R"
click node_cohort_permutations "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/rwr_cohort_permutations.R"
click node_subnetwork "https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/rwr_subnetwork_analysis.R"
click node_tables "https://github.com/gedine-lab/garreau_2026/tree/main/Suplementary_Tables"

classDef toneNeutral fill:#f8fafc,stroke:#334155,stroke-width:1.5px,color:#0f172a
classDef toneBlue fill:#dbeafe,stroke:#2563eb,stroke-width:1.5px,color:#172554
classDef toneAmber fill:#fef3c7,stroke:#d97706,stroke-width:1.5px,color:#78350f
classDef toneMint fill:#dcfce7,stroke:#16a34a,stroke-width:1.5px,color:#14532d
classDef toneRose fill:#ffe4e6,stroke:#e11d48,stroke-width:1.5px,color:#881337
classDef toneIndigo fill:#e0e7ff,stroke:#4f46e5,stroke-width:1.5px,color:#312e81
classDef toneTeal fill:#ccfbf1,stroke:#0f766e,stroke-width:1.5px,color:#134e4a
class node_scrna,node_network_build,node_patient_variants toneBlue
class node_rwr,node_rwr_helpers,node_weighted_bank,node_normalization,node_signal_genes toneAmber
class node_pubmed,node_mgi,node_loeuf toneMint
class node_ora,node_ethseq,node_network_analysis,node_seeds_analysis,node_rwr_results,node_cohort_permutations,node_subnetwork,node_tables toneRose
class node_atlas,node_ipsc,node_exome,node_pubmed_service,node_mgi_service,node_gnomad toneIndigo
```

## Components

### Data preparation

- [Forebrain gene selection](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/scrna.R): `scripts/scrna.R`
- [Co-expression network](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/tprimrna.R): `scripts/tprimrna.R`
- [Patient variant filtering](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/patient_data_HPE_POI.R): `scripts/patient_data_HPE_POI.R`

### Network propagation

- [Per-patient RWR](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/rwr.R): `scripts/rwr.R`
- [RWR helpers](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/custom_fct.R): `scripts/custom_fct.R`
- [CDS-weighted permutation bank](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/cds_weighted_bank_generation.R): `scripts/cds_weighted_bank_generation.R`
- [RWR profile normalization](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/rwr_normalization_fct.R): `scripts/rwr_normalization_fct.R`
- [Signal gene analysis](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/signal_gene_fct.R): `scripts/signal_gene_fct.R`

### Candidate evidence

- [PubMed evidence queries](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/PUBMED_query.R): `scripts/PUBMED_query.R`
- [Mouse phenotype ratings](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/MGI_query.R): `scripts/MGI_query.R`
- [Constraint metrics retrieval](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/loeuf_query.R): `scripts/loeuf_query.R`

### Analyses and results

- [Over-representation analysis](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/ora_fct.R): `scripts/ora_fct.R`
- [Ancestry analysis](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/ethseq_analysis.R): `scripts/Figures/ethseq_analysis.R`
- [Network topology and enrichment](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/network_analysis.R): `scripts/Figures/network_analysis.R`
- [Seed and seed-enrichment analysis](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/seeds_analysis.R): `scripts/Figures/seeds_analysis.R`
- [RWR results analysis](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/rwr_results_analysis.R): `scripts/Figures/rwr_results_analysis.R`
- [Cohort permutation analysis](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/rwr_cohort_permutations.R): `scripts/Figures/rwr_cohort_permutations.R`
- [Candidate subnetwork analysis](https://github.com/gedine-lab/garreau_2026/blob/main/scripts/Figures/rwr_subnetwork_analysis.R): `scripts/Figures/rwr_subnetwork_analysis.R`
- [Supplementary tables S1–S13](https://github.com/gedine-lab/garreau_2026/tree/main/Suplementary_Tables): `Suplementary_Tables`

### Other components

- **Early-forebrain atlas**
- **iPSC RNA-seq**
- **Patient exome variants**
- **PubMed**
- **MGI**
- **gnomAD constraint metrics**

## Connections

- Forebrain gene selection → Early-forebrain atlas: selects genes from (evidence: `README.md`)
- Co-expression network → iPSC RNA-seq: normalizes data (evidence: `README.md`)
- Patient variant filtering → Patient exome variants: filters variants (evidence: `README.md`)
- Per-patient RWR → RWR helpers: uses RWR functions
- RWR profile normalization → Per-patient RWR: normalizes profiles
- Signal gene analysis → RWR profile normalization: aggregates profiles
- PubMed evidence queries → PubMed: queries (evidence: `README.md`)
- Mouse phenotype ratings → MGI: retrieves phenotypes (evidence: `README.md`)
- Constraint metrics retrieval → gnomAD constraint metrics: retrieves metrics (evidence: `README.md`)
- Ancestry analysis → Supplementary tables S1–S13: produces S1 (evidence: `README.md`)
- Network topology and enrichment → Supplementary tables S1–S13: produces S6–S7 (evidence: `README.md`)
- Seed and seed-enrichment analysis → Supplementary tables S1–S13: produces S4, S8–S10 (evidence: `README.md`)
- RWR results analysis → Supplementary tables S1–S13: produces S11 (evidence: `README.md`)
- Candidate subnetwork analysis → Supplementary tables S1–S13: produces S12 (evidence: `README.md`)
- PubMed evidence queries → Supplementary tables S1–S13: rates evidence for S13
- Cohort permutation analysis → Signal gene analysis: tests signal counts