tooluniverse-proteomics-analysis - Claude MCP Skill

# Proteomics Analysis

Comprehensive analysis of mass spectrometry-based proteomics data from protein identification through quantification, differential expression, post-translational modifications, and systems-level interpretation.

## When to Use This Skill

**Triggers**: User has proteomics MS output files, asks about protein abundance/expression, differential protein expression, PTM analysis, protein-RNA correlation, multi-omics integration involving proteomics, protein complex/interaction analysis, or proteomics biomarker discovery.

## Core Capabilities

| Capability | Description |
|-----------|-------------|
| **Data Import** | MaxQuant, Spectronaut, DIA-NN, Proteome Discoverer, FragPipe outputs |
| **Quality Control** | Missing value analysis, intensity distributions, sample clustering |
| **Normalization** | Median, quantile, TMM, VSN normalization methods |
| **Imputation** | MinProb, KNN, QRILC for missing values |
| **Differential Expression** | Limma, DEP, MSstats for statistical testing |
| **PTM Analysis** | Phospho-site localization, PTM enrichment, kinase prediction |
| **Protein-RNA Integration** | Correlation analysis, translation efficiency |
| **Pathway Enrichment** | Over-representation and GSEA for protein sets |
| **PPI Analysis** | Protein complex detection, interaction networks via STRING/IntAct |
| **Reporting** | Comprehensive reports with volcano plots, heatmaps, pathway diagrams |

## Workflow Overview

```
Input: MS Proteomics Data
    |
Phase 1: Data Import & QC
Phase 2: Preprocessing (filter, impute, normalize)
Phase 3: Differential Expression Analysis
Phase 4: PTM Analysis (if applicable)
Phase 5: Functional Enrichment (GO, KEGG, Reactome)
Phase 6: Protein-Protein Interactions (STRING networks)
Phase 7: Multi-Omics Integration (optional, protein-RNA correlation)
Phase 8: Generate Report
```

See [PHASE_DETAILS.md](PHASE_DETAILS.md) for detailed procedures per phase.

## Integration with ToolUniverse

| Skill | Used For | Phase |
|-------|----------|-------|
| `tooluniverse-gene-enrichment` | Pathway enrichment | Phase 5 |
| `tooluniverse-protein-interactions` | PPI networks | Phase 6 |
| `tooluniverse-rnaseq-deseq2` | RNA-seq for integration | Phase 7 |
| `tooluniverse-multi-omics-integration` | Cross-omics analysis | Phase 7 |
| `tooluniverse-target-research` | Protein annotation | Phase 8 |

## Quantified Minimums

| Component | Requirement |
|-----------|-------------|
| Proteins quantified | At least 500 proteins |
| Replicates | At least 3 per condition |
| Filtering | 2+ unique peptides per protein |
| Statistical test | limma or t-test with multiple testing correction |
| Pathway enrichment | At least one method (GO, KEGG, or Reactome) |
| Report | Summary, QC, DE results, pathways, visualizations |

## Limitations

- **Platform-specific**: Optimized for MS-based proteomics (not Western blot quantification)
- **Missing values**: High missing rate (>50% per protein) limits statistical power
- **PTM analysis**: Requires enrichment protocols for comprehensive PTM profiling
- **Absolute quantification**: Relative abundance only (unless TMT/SILAC used)
- **Protein isoforms**: Typically collapsed to gene level
- **Dynamic range**: MS has limited dynamic range vs mRNA sequencing

## References

**Methods**: MaxQuant (doi:10.1038/nbt.1511), Limma for proteomics (doi:10.1093/nar/gkv007), DEP workflow (doi:10.1038/nprot.2018.107)

**Databases**: [STRING](https://string-db.org), [PhosphoSitePlus](https://www.phosphosite.org), [CORUM](https://mips.helmholtz-muenchen.de/corum)

## Reference Files

- [PHASE_DETAILS.md](PHASE_DETAILS.md) - Detailed procedures for each analysis phase, including report template