This document discusses two methods for drug prediction: (1) Using gene expression data from a disease and the LINCS L1000 database to predict drugs that could potentially treat the disease by reversing the gene expression changes. (2) Using the L1000CDS2 tool, which takes a gene list as input and predicts the top single drugs or drug combinations that could treat the disease by reversing the gene expression profile. It provides instructions for using L1000CDS2 to search for potential single drugs or drug combinations to treat a disease of interest.

1. Drug repositioning
& Drug combination
Prediction
Part2
Systems Pharmacology
NGS in Systems Biology workshop
By: Ali Kishk

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

3. Prediction of a list of drugs to treat a
disease
Methods :
•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.

4. 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.

5. Steps:
1-open L1000CDS2 website
http://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.

6. 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.

13. 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

14. Prediction of a list of drug
combinations to treat a disease.

15. 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.

16. Steps :
•1- Click reanalyze on the top left side.
•2- Check “Search for small molecules
combinations”
•3- Click search in the bottom lift.

19. Thank You
 Ph.ali.kishk@gmail.com
 linked-in :
 https://eg.linkedin.com/in/ali-kishk-997423a9