From 364562b2955d5ba6bc569490088593e6f4ca669b Mon Sep 17 00:00:00 2001 From: Alberto Valdeolivas <alvaldeolivas@gmail.com> Date: Tue, 18 May 2021 11:00:03 +0200 Subject: [PATCH] Update README.md --- README.md | 11 +++++++++++ 1 file changed, 11 insertions(+) diff --git a/README.md b/README.md index fb20d21..a394849 100644 --- a/README.md +++ b/README.md @@ -1,2 +1,13 @@ # Footprint based analysis and causal network contextualisation in SARS-CoV-2 infected A549 cell line +## Introduction + +This repository contains the code to reproduce the analysis presented in section mentioned in the project title contained in the article: *A versatile and interoperable computational framework for the analysis and modelling of COVID-19 disease mechanisms* + +## Procedure Details + +We obtained the transcriptomics dataset from the GEO database with accession number [GSE147507](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE147507) [Blanco-Melo et al., 2020](https://doi.org/10.1016/j.cell.2020.04.026). We extracted the series number 5 from the dataset, consisting of 2 conditions in triplicate, A549 cells treated with a mock and A549 infected with SARS-CoV-2, measured 24 hours after infection. Differential analysis of the transcript abundances was performed using DESeq2 [Love et al., 2014](https://doi.org/10.1186/s13059-014-0550-8). The resulting t-values of the differential analysis were used as input to estimate pathway activity deregulation using Progeny [Schubert et al., 2018](https://doi.org/10.1038/s41467-017-02391-6). The differential analysis t-values were also used to estimate the deregulation of TF activities using Dorothea [Garcia-Alonso et al., 2019](http://www.genome.org/cgi/doi/10.1101/gr.240663.118) as a source of TF-target regulon and the Viper algorithm [Alvarez et al., 2016](https://doi.org/10.1038/ng.3593) to estimate the TF activity score. + +Phosphoproteomic data of mock-treated and SARS-CoV.2 infected cells were extracted from [Stukalov et al., 2021](https://doi.org/10.1038/s41586-021-03493-4). Phosphosite differential analysis log2FC was used to estimate the deregulation of kinase activities using [https://doi.org/10.1101/822668] as a source of kinase-substrate interactions and a z-test to estimate kinase activity score [PMID: 32645325; PMID: 28200105]. + +Finally, we used Carnival [PMID: 31728204] with the COSMOS approach [PMID: 33502086] to connect the top 10 deregulated kinases with the top 30 deregulated TFs with a Prior Knowledge Network assembled from OmniPath resources [PMID: 33749993]. Progeny pathway activity scores were used to weigh the PKN and facilitate the optimal network search to connect kinases and TFs. \ No newline at end of file -- GitLab