CovidVac - HIM

In this study, we analyze the effect of multiple vaccinations (n>200) on the human immune response repertoire. This repository contains the single-cell analysis of T cell receptor (TCR), Gene expression, Surface Proteins (Antibody Captured), and dextramer staining across 6 donors (1 frequently vaccinated patients, 5 controls).

Data

• The raw sequencing data can be downloaded from GEO GSE249998 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE249998).
• The cellranger output can be downloaded from the same repository and should be stored as ./data/20231017/GEX/gex_mixed_run_{1-3}_feature_bc_matrics.h5 and ./data/20231017/VDJ/vdj_mixed_run_{1-3}_filtered_contigs.csv
• The processed and annotated data can be downloaded from Zenodo (10.5281/zenodo.10301388) and stored as ./data/him/02_him_annotated_cd4.h5ad an ./data/him/02_him_annotated_cd8.h5ad (entry point notebooks 03)

Additionally, we use the following external resources (not provided by us, store in ./data/scores/):

• Genes for various T cell scores by Szabo et al. (Nature Communications, 2019) (https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-019-12464-3/MediaObjects/41467_2019_12464_MOESM7_ESM.xlsx)
• Genes for Cell Scores by Meckiff et al. (Cell, 2020) (https://ars.els-cdn.com/content/image/1-s2.0-S0092867420313076-mmc3.xlsx)

Reproducibility

To recreate the results of the paper:

git clone https://github.com/SchubertLab/CovidVac_HIM.git
cd CovidVac_HIM
conda env create -f requirements.yml

Following, the notebooks must be run (ideally in this order). Note, that there are issues with reproducing UMAPs across different machines, even when the same seeds and package versions are used. Results might therefore look slightly different. To fully reproduce the paper results, use the annotated data.

To separate multiple sequencing runs from the cellranger output in the folder ./analysis/mixed_runs/:

• 01_1_mixed_runs_preprocessing
• 01_2_mixed_runs_preprocessing
• 01_2_mixed_runs_preprocessing

To annotate the data in the folder ./analysis/him/:

• 02_him_annotation

To generate the paper results (if you use the annotated data directly you can start at this point):

• 03A_him_visualization_cd4
• 03B_him_visualization_cd8
• 05_him_tables

Citation

If you refer to this work, please consider citing the following paper:

@article{kocher2024adaptive,
  title={Adaptive immune responses are larger and functionally preserved in a hypervaccinated individual},
  author={Kocher, Katharina and Moosmann, Carolin and Drost, Felix and Sch{\"u}lein, Christine and Irrgang, Pascal and Steininger, Philipp and Zhong, Jahn and Tr{\"a}ger, Johannes and Spriewald, Bernd and Bock, Christoph and others},
  journal={The Lancet. Infectious diseases},
  pages={S1473--3099},
  year={2024}
}