Predicting new uses of drugs / small molecules using LINCS database.

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

2. Drug repositioning
•Drug repositioning is the application of
known drugs and compounds to new
indications.

3. Method
1-Getting the expression levels of a Drug / small molecule effect “e.g. :
Salbutamol” on a specific cell line “e.g. : A495”.
2-Using the down expression levels for Enrichment for diseases.

4. So What is Enrichment ?
& How we will get the expression level of a
drug / small molecule??

5. LINCS database

6. LINCs L1000 database
• Provide gene expression profiles induced by over 10 000 compounds,
shRNAs, and kinase inhibitors using the L1000 platform.
• aka The Connectivity Map

7. Enrichment Analysis
• Searching a list of genes to label
• To classify them by Pathways, Diseases, Transcription factor.
• Here we will use Enrichr.

8. • web-based software application that facilitates querying,
• browsing and interrogating many of the currently available LINCS
L1000 data
•
•
LINCS Canvas Browser

9. How to predict a new use of a drug “e.g. :
salbutamol” ??
Steps :
1- Get the LINCS L1000 gene list of the drug using LINCS Canvas Browser
2-Search for Enrichment for diseases using Enrichr with the Down
regulated genes.

10. 1-Getting the LINCS L1000 gene list of the
drug using LINCS Canvas Browser
Steps :
• 1- Open LINCs Canvas browser.
• 2- In the search menu, Type * to indicate whatever you type.
• 3-continue after * by typing the drug name, the autocomplete feature
will show a list of candidate experiment.
• 4-select your desired related cell line from the list “ you can search
L1000CDS2 cell line to see related tissues: L1000CDS2 CCLE signature
• http://amp.pharm.mssm.edu/L1000CDS2/#/index”

11. 1-Getting the LINCS L1000 gene list of the
drug using LINCS Canvas Browser
Continue
Steps :
• 5-Wait until the downloading is finished.
• 6-On the down right, You will see “Down regulated genes”, right click
on it then select “Inspect”
• 7-Click CTRL+ F then search “dnGenes”, You will find a list that
resembles down regulated genes. Copy this list to a notepad then
rename it “Down genes”
• 8-repeat 6&7 to the up regulated genes.

12. Demo 1

16. Then save the gene list as down genes.txt

17. LINCS Canvas Browser Continue :
If your desired drug doesn’t appear in LINCs Canvas
Browser:
1- open m.ncbi.nlm.nih.gov/compound/ .
2- Search the PubChems for your drug / small molecule.
3- Copy the CID number.
4- Edit this API with your PubChem ID.
api.lincscloud.org/a2/pertinfo?q={"pubchem_cid":"45375808"}&user_
key=lincsdemo
5-copy and paste it in your browser then search for “alt_iname” by
CTRL+F, then use this name in the LINCS canvas browser.

18. If your desired drug doesn’t appear in LINCs
Canvas Browser:
NB :
If Step 5 return wit no result on your
browser, Then there is any pertubagen is
done yet by your drug / small molecule.
Try many CID in the API if your search on
PubChem ID return with many result “eg:
many salt or ester forms of the drug”

19. 2-
Enrichment Analysis for diseases
using Enrichr with the Down
regulated genes.

20. Goal :
2- What are the top diseases
Enriched ? And what genes are
involved ?
Enrichr:
An integrative web-based and mobile software
application that includes new gene-set libraries,
an alternative approach to rank enriched terms,
and various interactive visualization approaches
to display enrichment results

21. Enrichr Steps for diseases :
• 1- Open Enrichr site : amp.pharm.mssm.edu/Enrichr/
• 2- enter the gene list “down-regulated”
• 3- Click Disease/Pheotype tab
• 4- Choose dbgap.

22. Enrichr output
• The top results is list of diseases has the most enriched gene list with
our gene list.
• Bar Graph : can be changed by clicking to any bar due to changing the
statistical test.
• Table : can be exported to excel file

23. Try it out with our gene list

30. Open the exported file as an Excel sheet
The shared
genes
between your
gene-list &
each disease.

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