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Plasma Proteomics Platform Comparison

Replication notebook — Kirsher et al. (2025)

"Current landscape of plasma proteomics from technical innovations to biological insights and biomarker discovery"
Kirsher DY, Chand S, Phong A, Nguyen B, Szoke BG, Ahadi S — Communications Chemistry (2025)
PMC12462477


What this is

A self-contained Jupyter notebook that replicates all major figures and analyses from a landmark benchmarking study comparing 8 plasma proteomics platforms on 78 individuals covering 13,011 unique proteins.

Platforms covered

Platform Type Proteins Median CV
SomaScan 11K Affinity / aptamer 9,852 5.3%
SomaScan 7K Affinity / aptamer 6,467 5.8%
Olink 5K Affinity / PEA 5,416 26.8%
Olink 3K Affinity / PEA 2,925 11.4%
NULISA Affinity / antibody 377 ~8%
MS-Nanoparticle MS / Seer Proteograph 5,943 26.4%
MS-HAP Depletion MS / Biognosys 3,575 29.8%
MS-IS Targeted MS / SureQuant 551 8.3%

Quick start

# 1. Clone / enter the repo
cd plasma-proteomics-analysis

# 2. Install dependencies
pip install -r requirements.txt

# 3. Launch Jupyter
jupyter lab plasma_proteomics_analysis.ipynb

Notebook sections

Section Figures replicated Description
1 Setup, imports, CheckpointManager
2 Fig 1 78-person cohort demographics
3 Simulate platform data (realistic CVs, missingness)
4 Fig 2 A–D CV, completeness, linearity, FDA biomarker coverage
5 Fig 3 A Protein coverage, pairwise Jaccard overlap
6 Fig 3 B Cross-platform Spearman correlation heatmap
7 Fig 4 ApoE isoform analysis
8 Fig 6 Age biomarker discovery — linear models, volcano plots
9 Fig 5 Variance decomposition
10 Fig 6 Pathway enrichment (GO / Reactome)
11 Templates to load real data from PRIDE / supplementary

Checkpointing

Every section ends with ckpt.save("section_name", data). After a kernel restart:

data = ckpt.load("section_name")   # instant restore from checkpoints/*.pkl
ckpt.list_checkpoints()            # see all saved state

Checkpoints are stored in checkpoints/ and persisted across sessions. All figures are saved to figures/ automatically.


Using real data

MS data (public — PRIDE)

Platform PRIDE accession
MS-Nanoparticle PXD067119
MS-HAP Depletion PXD067064
MS-IS Targeted PXD067061

Affinity data (SomaScan, Olink, NULISA)

Available upon request from the corresponding author: sahadi@alkahest.com

Supplementary Excel (35.8 MB)

Download from the PMC article page; contains all protein lists, UniProt IDs, and cross-platform correlation matrices. Load with:

supp = pd.read_excel("supplementary_data.xlsx", sheet_name=None)

Once you have real data, replace the platform_data dict entries in Section 3 and re-run Sections 4–10 — all code is data-agnostic.


Pushing to GitHub

# Create a new repo at github.com then:
git remote add origin https://github.com/<your-username>/plasma-proteomics-analysis.git
git push -u origin main

Citation

Kirsher DY, Chand S, Phong A, Nguyen B, Szoke BG, Ahadi S.
Current landscape of plasma proteomics from technical innovations
to biological insights and biomarker discovery.
Commun Chem. 2025. PMC12462477. DOI:10.1038/s42004-025-01456-5

About

Replication notebook for Kirsher et al. 2025 — benchmarking 8 plasma proteomics platforms using real MS data from PRIDE

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