Drug repositioning& Drug combination

PredictionPart2

Systems PharmacologyNGS in Systems Biology workshop

By: Ali Kishk

Index• Prediction of a list of drugs to treat a disease.• Prediction of a list of drug combinations to treat a disease.

Prediction of a list of drugs to treat a diseaseMethods :

• 1- Using the gene list of the disease• 2- using LINCs L1000 to get list of drugs that can

reverse this gene list.• Input : disease name / Disease expression gene list• Output : List of drugs.

L1000CDS2

An ultra-fast LINCS L1000 Characteristic Direction Signature Search Engine

It take a gene list of up and down genes as input and predict using LINCS connectivity map database the top drugs that reverse this gene list.

L1000CDS2 disease signature contain processed genelists of Human diseases microarray experiments.

Steps :

1-open L1000CDS2 websitehttp://amp.pharm.mssm.edu/L1000CDS2/#/index .

2- click on Disease signature.

3- Search for your desired disease, Specify the organ / tissue.The signature of this disease will be uploaded automatically.

L1000CDS2 Output :

• -The predicted drugs that inhibit the disease you choose

are under “Pertubagens”.

• -Click on Overlap to see the overlapped gene set of your

gene-list and the expression of this experiment.

• -You can use the GSE number in the disease signature to

return to the micro array experiment for further analysis.

L1000CDS2 upload your own gene list NB : You can upload your own gene list that represent the disease / phenotype you are working on.

in the configuration :• Select “reverse” if your biological question is about drug target

for the phenotype represented by gene-list

• Or select “mimic” if your biological question is about drug for the phenotype represented by gene-list

Prediction of a list of drug combinations to treat a

disease.

Goal :• Using drug combination can

• 1- Enhance the therapeutic effect by targeting more proteins in the disease pathway.

• 2- Reduce the side effect of a drug by blocking the undesired drug-target interaction.

• 3- Reduce the required dose of a single drug.

Steps :

• 1- Click reanalyze on the top left side.• 2- Check “Search for small molecules

combinations”• 3- Click search in the bottom lift.

Thank You Ph.ali.kishk@gmail.com

linked-in : https://eg.linkedin.com/in/ali-kishk-997423a9