Add DILI Discovery Proteomics vignette

[Copilot]

• Create vignettes/DILI_Hotgenes.Rmd based on data-raw/Build_DILI_Hotgenes.R
• Run parallel validation and address review comments
• Rename vignette 03 title to "Visualization, Exploration, and Enrichment"
• Update cross-reference in vignette 01 to match vignette 04's current title
• Add fgsea_() vs HotgeneSets() distinguishing note in vignette 05 overview

Original prompt

Create a new vignette for the Hotgenes package that documents the DILI (Drug-Induced Liver Injury) Discovery Proteomics analysis workflow based on the existing data-raw/Build_DILI_Hotgenes.R script.

Requirements:

• Convert the Build_DILI_Hotgenes.R script into a comprehensive R Markdown vignette
• Include all 12 analysis steps (data loading, filtering, normalization, modeling, contrasts, Hotgenes object creation)
• Add context from the original publication (Federspiel et al. 2023, J Hepatol)
• Document the MassIVE deposit ID (MSV000089782)
• Include examples of downstream analyses using the resulting Hotgenes object (plots, GSEA, etc.)
• Follow the format and style of the existing vignette (vignettes/Hotgenes.Rmd)
• Include optional code for refreshing data directly from MassIVE
• Add explanatory text about data limitations and methodology choices

The vignette should serve as both a reproducible example and educational material for users working with proteomics data and limma-based differential expression analysis in the Hotgenes framework.

The following is the prior conversation context from the user's chat exploration (may be truncated):

User: Hi I need a new vignette that needs to be part of this repo and package. It should be based on this script: @pfizer-opensource/Open-Hotgenes/files/data-raw/Build_DILI_Hotgenes.R

Assistant: I'll help you create a new vignette based on the Build_DILI_Hotgenes.R script. Let me first examine the repository structure to understand how vignettes are organized and the package structure.

Assistant: Now let me check the existing vignettes structure to understand the format:

Assistant: Now I'll create a comprehensive vignette based on the DILI Hotgenes build script. This vignette will document how to build the DILI (Drug-Induced Liver Injury) Hotgenes object from proteomics data.

Assistant: I've created a new vignette DILI_Hotgenes.Rmd for the Open-Hotgenes package based on the Build_DILI_Hotgenes.R script. Here's what the vignette includes:

Key Features:

1. Clear Workflow Structure - All 12 steps from the script organized as executable sections with explanations

2. Data Context - Detailed information about:

   • Original publication (Federspiel et al. 2023, J Hepatol)
   • MassIVE deposit ID (MSV000089782)
   • Important notes about private metadata limitations

3. Processing Steps Documented:

   • Data loading from pre-parsed RDS
   • Sample column identification
   • Protein filtering (contaminants, UniProt reviews, min peptides)
   • VSN normalization
   • voomaByGroup transformation with Pool batch correction
   • Robust lmFit modeling
   • Contrast definitions (7 comparisons)
   • Hotgenes object creation

4. Downstream Analysis Examples - Demonstrates how to use the resulting DILI Hotgenes object with:

   • Differential expression summaries
   • Volcano plots
   • Venn diagrams
   • Heatmaps
   • Expression plots
   • GSEA analysis
   • Interactive Shiny exploration

5. Best Practices - Includes optional code for refreshing data directly from MassIVE

The vignette follows the same format and style as the existing Hotgenes.Rmd vignette and is ready to build with the package documentation system.

User: This needs to be a PR.

Assistant: I'm waiting for your confirmation on whether to proceed with creating the pull request. The tool is asking to verify the repository details and PR scope.

This pull request was created from Copilot chat.

[Rvirgenslane]

@copilot Please make three final editorial updates to improve vignette consistency:

Rename vignette 03 so its title better reflects the current scope, since it now includes not only visualization but also enrichment and gene-set configuration.
A good option would be:
“Visualization, Exploration, and Enrichment”

Update the reference to vignette 04 inside vignettes/01_Creating_Hotgenes_Objects.Rmd so it matches the current title.
Replace the outdated wording:

04 Interactive Exploration with Shiny
with the current title:

04 Using Shiny to Prioritize Genes of Interest
Clarify vignette 05 relative to fgsea_() with one short explanatory note in the overview or early in the vignette.
The goal is to distinguish:

fgsea_() in vignette 03 as enrichment from ranked DE results per contrast
HotgeneSets() in vignette 05 as sample-wise pathway activity scoring that returns a new Hotgenes object
A suggested sentence would be:

Unlike fgsea_(), which evaluates enrichment from ranked differential expression results for a contrast, HotgeneSets() computes pathway activity scores for each sample and returns a new Hotgenes object for downstream analysis.

Please keep the changes minimal.

[Copilot]

@copilot Please make three final editorial updates to improve vignette consistency:

Rename vignette 03 so its title better reflects the current scope, since it now includes not only visualization b...

Done in commit 48ded85:

1. Vignette 03 — title updated to "Visualization, Exploration, and Enrichment" (both the YAML title: and %\VignetteIndexEntry{}).
2. Vignette 01 — footer cross-reference updated to "04 Using Shiny to Prioritize Genes of Interest".
3. Vignette 05 — added the distinguishing sentence to the Overview, right after the existing description of HotgeneSets().