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EstimAte Systems ImmunE Response (EaSIeR)


How to install EaSIeR

Because of the current repository containing large files (i.e. using git-lfs), we first need to clone the repository using git and install git-lfs (instructions below are specific for macOS, please visit the main git-lfs page here to install git-lfs accordingly depending on your OS. Finally, within the repository directory we need to run git lfs pull to replace the text pointers with the actual data files.

Open Terminal and run this command:

git clone https://github.com/olapuentesantana/easier_manuscript.git
brew install git-lfs
cd easier_manuscript/
git lfs pull

Then, in R:

library(devtools)
devtools::install("path/to/easier_manuscript/")
library(easier)

Basic info on EaSIeR

For the essentials on how EaSIeR was developed, we recommend reading the reference paper article.

Features of EaSIeR

Computation of quantitative descriptors of the tumor microenvironment

Quantitative Descriptors Descriptor conception Prior knowledge
Pathway activity Holland et al., BBAGRM, 2019; Schubert et al., Nat Commun, 2018 Holland et al., BBAGRM, 2019; Schubert et al., Nat Commun, 2018
Immune cell quantification Finotello et al., Genome Med, 2019 Finotello et al., Genome Med, 2019
Transcription factor activity Garcia-Alonso et al., Genome Res, 2019 Garcia-Alonso et al., Genome Res, 2019
Ligand-Receptor pairs Lapuente-Santana et al., Patterns, 2021 Ramilowski et al., Nat Commun, 2015
Cell-cell interaction Lapuente-Santana et al., Patterns, 2021 Ramilowski et al., Nat Commun, 2015
# Computation of cell fractions
cell_fractions <- compute_cell_fractions(RNA.tpm=tpm)
# Computation of pathway activity
pathways_activity <- compute_pathways_scores(RNA.counts=counts, remove.genes.ICB_proxies=TRUE)
# Computation of TF activity
tf_activity <- compute_TF_activity(RNA.tpm=tpm, remove.genes.ICB_proxies=FALSE)
# Computation of LR pairs weights
lrpairs_weights <- compute_LR_pairs(RNA.tpm=tpm, remove.genes.ICB_proxies=FALSE, compute.cytokines.pairs=FALSE, cancertype="pancan")
# Computation of Cell-Cell scores
ccpairs_scores <- compute_CC_pairs_grouped(lrpairs=lrpairs_weights$LRpairs, cancertype="pancan")

Computation of different hallmarks of the immune response

Hallmark of the immune response Original study
Cytolytic activity (CYT) Rooney et al, Cell, 2015
Roh immune score (Roh_IS) Roh et al., Sci. Transl. Med., 2017
Chemokine signature (chemokines) Messina et al., Nat. Sci. Rep., 2012
Davoli immune signature (Davoli_IS) Davoli et al., Science 2017
IFNy signature (IFNy) Ayers et al., JCI, 2017
Expanded immune signature (Ayers_expIS) Ayers et al., JCI, 2017
T-cell inflamed signature (Tcell_inflamed) Ayers et al., JCI, 2017
Repressed immune resistance (RIR) Jerby-Arnon et al., Cell, 2018
Tertiary lymphoid structures signature (TLS) Cabrita et al., Nature, 2020
tasks <- c("CYT", "Roh_IS", "chemokines", "Davoli_IS", "IFNy", "Ayers_expIS", "Tcell_inflamed", "RIR", "TLS")
immune_response <- compute_gold_standards(RNA.tpm=tpm, list_gold_standards=tasks, cancertype=cancer_type, output_file_path=tmp_file_path)

Predictions of patients' immune response

predictions_immune_response <- predict_immune_response(pathways = pathways_activity$scores,
                                                       immunecells = cell_fractions,
                                                       lrpairs = lrpairs_weights$LRpairs,
                                                       tfs = tf_activity$scores,
                                                       ccpairs = ccpairs_scores$score,
                                                       cancertype = cancertype)

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