Data and software/code repository for "Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus" (Kotliarov, Y., Sparks, R. et al. Nat. Med. DOI: https://doi.org/10.1038/s41591-020-0769-8(2020))
Posted on 2020-02-23 - 05:23 authored by Yuri Kotliarov
Data and software/code accompanying the publication Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus by Yuri Kotliarov, Rachel Sparks, Andrew J. Martins, Matthew P. Mulè, Yong Lu, Meghali Goswami, Lela Kardava, Romain Banchereau, Virginia Pascual, Angelique Biancotto, Jinguo Chen, Pamela L. Schwartzberg, Neha Bansal, Candace C. Liu, Foo Cheung, Susan Moir and John S. Tsang. Nat. Med. DOI: https://doi.org/10.1038/s41591-020-0769-8 (2020)
Abstract
Responses to vaccination and to diseases vary widely across individuals, which may be partly due to baseline immune variations. Identifying such baseline predictors and their biological basis are of broad interest given their potential importance for cancer immunotherapy, disease outcomes, vaccination and infection responses. Here we uncover baseline blood transcriptional signatures predictive of antibody responses to both influenza and yellow fever vaccinations in healthy subjects. These same signatures evaluated at clinical quiescence are correlated with disease activity in systemic lupus erythematosus patients with plasmablast-associated flares. CITE-seq profiling of 82 surface proteins and transcriptomes of 53,201 single cells from healthy high and low influenza-vaccination responders revealed that our signatures reflect the extent of activation in a plasmacytoid dendritic cell—Type I IFN—T/B lymphocyte network. Our findings raise the prospect that modulating such immune baseline states may improve vaccine responsiveness and mitigate undesirable autoimmune disease activities.
If you use our data (including CITE-seq data) or code for your work please cite:
Kotliarov, Y., Sparks, R. et al. Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus. Nat. Med. DOI: https://doi.org/10.1038/s41591-020-0769-8 (2020)
General contact: John Tsang (john.tsang@nih.gov)
Questions about software/code: Yuri Kotliarov (yuri.kotliarov@nih.gov)
Data
Download the data.zip file
and unpack it into a working directory (see below for directory structure of our code if you want to use it to reproduce our results). You will find all the data needed to reproduce our results, including the 1) data for predictive signature development and testing; and 2) CITE-seq protein-mRNA single cell data from high and low vaccine responders.
RNAseq data from sorted B cell subsets from healthy donors and a file
with random signatures are provided as a separate items in this
collection.
Software/code
Figures 1-3 and Extended Figures 1-7 (development and testing of baseline predictive signatures) can be reproduced using the singularity container we provide with R 3.4.1 and all required packages installed.
Figures 4-6 and Extended Figures 8-10 (analysis of CITE-seq data) can be reproduced using the singularity container we provide with R 3.6.1 and all required packages installed.
The R code/workflow is available on GitHub: https://github.com/kotliary/baseline
- R
- data
- generated_data
- figure_generation
- citeseq
--- data
--- sig
--- results
--- figures
When you unpack the data.zip file, this should add the data
subdirectory. B cell subset RNAseq data and a file
with random signatures are provided as a separate items in this
collection. CITE-seq data should be downloaded into the citeseq/data
directory.
Running the workflow to reproduce our results
Please check Workflow.Rmd and CITE-seq.Rmd from github for instructions on how to run the workflows.
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Kotliarov, Yuri; Sparks, Rachel; Martins, Andrew; Mulé, Matthew P.; Tsang, John (2020). Data and software/code repository for "Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus" (Kotliarov, Y., Sparks, R. et al. Nat. Med. DOI: https://doi.org/10.1038/s41591-020-0769-8(2020)). The NIH Figshare Archive. Collection. https://doi.org/10.35092/yhjc.c.4753772.v1
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FUNDING
Funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and institutes funding the Center for Human Immunology, National Institutes of Health, Bethesda, MD, USA
I confirm there is no human identifiable information in this dataset.
- Yes
