CovidVac - CD8

In this study, we analyze the effect of a three-shot vaccination regime against SARS-CoV-2 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 14 donors and 7 time points.

Data

• The raw sequencing data can be downloaded from GEO GSE261966, GSE261967, and 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, ./data/20231017/VDJ/vdj_mixed_run_{1-3}_filtered_contigs.csv, and ./data/dextramer/gex_{...}_featue_bc_matrix.h5, ./data/dextramer/vdj_{...}_filtered_contig.csv named [first_shot_10, initial, second_shot_10, second_shot_210, third_shot_10].
• The processed and annotated data can be downloaded from Zenodo (10.5281/zenodo.13981508) and stored as ./data/him/02_dex_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_CD8.git
cd CovidVac_CD8
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/dextramer/:

• 01_dextramer_preprocessing
• 02_dextramer_annotation

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

• 03_2_dextramer_visualization_cd8_paper
• 03_2_dextramer_visualization_cd8_avidity
• 04_dextramer_tables_cd8

Citation

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

@article{kocher2024quality,
  title={Quality of vaccination-induced T cell responses is conveyed by polyclonality and high, but not maximum, antigen receptor avidity},
  author={Kocher, Katharina and Drost, Felix and Tesfaye, Abel Mekonnen and Moosmann, Carolin and Sch{\"u}lein, Christine and Grotz, Myriam and D’Ippolito, Elvira and Graw, Frederik and Spriewald, Bernd and Busch, Dirk H and others},
  journal={bioRxiv},
  pages={2024--10},
  year={2024},
  publisher={Cold Spring Harbor Laboratory}
}