Thread by @carmonation

Projecting single-cell transcriptomics data onto a reference T cell atlas to interpret immune responses biorxiv.org/content/10.110…

Definition of robust, biologically relevant cell clusters or states by scRNA-seq analysis is typically an iterative, time-consuming process that requires advanced bioinformatics and biological domain expertise

Even after successful analyses, clusters are not directly comparable between studies, preventing us from learning general biological rules across cohorts, conditions and models…

Here we present ProjecTILs, a novel computational method to interpret immunological states by projecting scRNA-seq data onto a reference T cell atlas.
github.com/carmonalab/Pro…

ProjecTILs enables the classification of query cells into curated, discrete states, but also over a continuous space of intermediate states, and allows exploring the effect of cellular perturbations in terms of reference gene modules.

To build reference atlases, we used STACAS, a novel tool for data integration based on #Seurat 3 and specifically designed for the challenges of integrating heterogeneous datasets with limited overlap of cell subtypes doi.org/10.1101/2020.0…

We re-analyzed multiple published scRNA-seq datasets using two novel cross-study murine T cell reference atlases: one for tumor-infiltrating T lymphocytes (TILs), another one for acute and chronic viral infection

ProjecTILs accurately predicted the effects of multiple perturbations, including the ablation of genes controlling T cell differentiation, such as Tox, Ptpn2, miR-155 and Regnase-1, and identified novel gene programs that were altered in these cells

ProjecTILs & STACAS are implemented in #RStats stats and are integrated with Seurat 3, which facilitates the construction of complex analytical pipelines.

Check out our reproducible tutorials:
carmonalab.github.io/ProjecTILs/tut…
carmonalab.github.io/STACAS/tutoria…

Or try running a quick ProjecTILs analysis directly on a GEO/ArrayExpress dataset, without any package installation, using our Docker container
hub.docker.com/r/mandrea1/pro…

The TIL reference atlas version 1 can be explored through the #iSEE web app available at TILatlas.unil.ch
and is available as a Seurat object at doi.org/10.6084/m9.fig…

The T cell reference atlas for viral infection version 1 is available at doi.org/10.6084/m9.fig…

Thanks for reaching the end! User’s feedback is highly appreciated