A Pipeline to Repurpose Drugs for Treating Lung Injury in COVID19

Step 1

Download L1000 Connectivity Map perturbational profiles GSE70138 and GSE92742 from GEO

Method 1: click file names below

GSE70138_Broad_LINCS_cell_info_2017-04-28.txt

GSE70138_Broad_LINCS_Level5_COMPZ_n118050x12328_2017-03-06.gctx

GSE70138_Broad_LINCS_sig_info_2017-03-06.txt

GSE70138_Broad_LINCS_gene_info_2017-03-06.txt

GSE92742_Broad_LINCS_cell_info.txt

GSE92742_Broad_LINCS_Level5_COMPZ.MODZ_n473647x12328.gctx

GSE92742_Broad_LINCS_sig_info.txt

GSE92742_Broad_LINCS_gene_info.txt

or Method 2: run following commands in linux

wget https://ftp.ncbi.nlm.nih.gov/geo/series/GSE70nnn/GSE70138/suppl/GSE70138_Broad_LINCS_cell_info_2017-04-28.txt.gz
wget https://ftp.ncbi.nlm.nih.gov/geo/series/GSE70nnn/GSE70138/suppl/GSE70138_Broad_LINCS_Level5_COMPZ_n118050x12328_2017-03-06.gctx.gz
wget https://ftp.ncbi.nlm.nih.gov/geo/series/GSE70nnn/GSE70138/suppl/GSE70138_Broad_LINCS_sig_info_2017-03-06.txt.gz
wget https://ftp.ncbi.nlm.nih.gov/geo/series/GSE70nnn/GSE70138/suppl/GSE70138_Broad_LINCS_gene_info_2017-03-06.txt.gz
wget https://ftp.ncbi.nlm.nih.gov/geo/series/GSE92nnn/GSE92742/suppl/GSE92742_Broad_LINCS_cell_info.txt.gz
wget https://ftp.ncbi.nlm.nih.gov/geo/series/GSE92nnn/GSE92742/suppl/GSE92742_Broad_LINCS_Level5_COMPZ.MODZ_n473647x12328.gctx.gz
wget https://ftp.ncbi.nlm.nih.gov/geo/series/GSE92nnn/GSE92742/suppl/GSE92742_Broad_LINCS_sig_info.txt.gz
wget https://ftp.ncbi.nlm.nih.gov/geo/series/GSE92nnn/GSE92742/suppl/GSE92742_Broad_LINCS_gene_info.txt.gz

Step 2

Generate drug reference panel for lung from GSE70138 and GSE92742

Rscript Preparing_reference_lung.R

Output files:

lung_gene_info.txt #Gene information
lung_drug_info.txt #Drug information
lung_rankMatrix.txt #Gene rank list in lung cells with drug treatment

Step 3

Extract differential expression profiles of genes from lung cells with inhibition of ACE2

Rscript ACE2_inhibition_Data.R

Output files:

HCC515_6_data_for_drug.csv #Differential expression of genes in HCC515 cell at 6 h after treatment of ACE2 inhibitor
HCC515_24_data_for_drug.csv #Differential expression of genes in HCC515 cell at 24 h after treatment of ACE2 inhibitor

Extract differential expression profiles of genes from lung tissues with COVID-19

Rscript COVID19-lung.R

Output files:

COVID19-Lung_data_for_drug.csv #Differential expression of genes in lung tissues from COVID-19 patients

Step 4

Drug reposition analysis

Rscript Drug_reposition.R

Output files:

HCC515_6_drug.csv #Drugs for HCC515 cell at 6 h after treatment of ACE2 inhibitor
HCC515_24_drug.csv #Drugs for HCC515 cell at 24 h after treatment of ACE2 inhibitor
COVID19-Lung_drug.csv #Drugs for lung tissuse from COVID-19 patients

Other

Differential gene expressions in response to treatment of COL-3 or CGP-60474

Rscript COL-3_response_Data.R
Rscript CGP-60474_response_Data.R

Output files:

COL-3_single_treatment_response_data.csv #Differential gene expressions in HCC515 cell at 24h after treatment of COL-3
CGP-60474_single_treatment_response_data.csv #Differential gene expressions in HCC515 cell at 24h after treatment of CGP-60474