We here apply Saezlab tools on Intestinal organoids treated with Sars-CoV-2 for 60 hours. The original transcriptomic dataset is coming from the following p ublication: Lamers et al. 2020.

To date, this repository contains two scripts:

1.- 01_classical_pipeline: In this script we apply the classical analysis of gene expression data using Saezlab tools. We first compute pathway activity using Progeny. Then, we compute Transcriptio factor activity using Dorothea coupled with Viper. These results along with a prior knowledge network extracted from OmniPath and perturbations (Viral-host protein interactions) are the input for CARNIVAL. CARNIVAL tries to infer the most likely signaling network connecting the upstream perturbations with the downstream transcription factors, given the contrains imposed by the abovementioned inputs.

To check the results visit: https://github.com/saezlab/Covid_IntestinalOrganoids/blob/master/01_classical_pipeline.md

One can click on CARNIVAL output figures (networks) to get a larger image and download it for further exploration.

2.- 02_analysis_carnival_results: This script contains some analysis of different networks generated by CARNIVAL for different situations:

• Considering that the viral proteins inhibitit the human proteins with whom their interact.
• Considering that the viral proteins activates the human proteins with whom their interact.
• Considering that we do not know the effect of the perturbation (inhibition or activation) of the viral proteins on the human proteins. In this situation, CARNIIVAL will infer the most likely effect given the input.

To check the results, we recommend to download the hmtl file because it contains interactive plots with the enrichmets of the different clusters. These plots cannot be visualize in the Github markdown (.md file): https://github.com/saezlab/Covid_IntestinalOrganoids/blob/master/02_analysis_carnival_results.html

In addition, we strongly suggest to check and download the following file: https://github.com/saezlab/Covid_IntestinalOrganoids/blob/master/Carnival_Results/carnival_results_top50tf_pleitropic_minsize15_undefinedEffectNetwork_Clusters.pdf

It contains the networks generated by CARNIVAL when the effect (activation or inhibition) of the viral proteins on their host interactions is unknown. It also groups the proteins by the identified clusters and describes the most significant biological funcitons or pathways associated to each cluster.