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https://github.com/saezlab/macau_synergy_prediction

Target functional similarity based workflows for drug synergy prediction and stratification
https://github.com/saezlab/macau_synergy_prediction

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Target functional similarity based workflows for drug synergy prediction and stratification

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README

          

## Stratification and prediction of drug synergy based on target functional similarity

The first step is to generate the target-pathway interactions using drug response data on cancer cell lines. Those interaction matrices are generated using codes from this publication:

**Yang et al. Linking drug target and pathway activation for effective therapy using multi-task learning.**

https://www.nature.com/articles/s41598-018-25947-y

https://github.com/saezlab/Macau_project_1

![Alt text](https://github.com/saezlab/Macau_Synergy_Prediction/blob/master/image/Figure_1.png)

## Result analysis

**GDSC_DRUG_COMBO_TOP_HITS.Rmd**:

* Identify key pathways for synergy stratification for breast tissue.

* Identify protein target to combine with BRAF for colorectal cancer validation.

* Save target functional similarity values for breast, colon and lung_NSCLC from GDSC dataset.

**Use the key pathways to compute the Delta Pathway Activity (predicted synergy) and stratify new cell lines.**

**check_synergy_AZ.Rmd**:

* Synergy tratification analysis for breast/colon/lung cancer cell lines on AstraZeneca dataset.

* Synergy prediction on AstraZeneca dataset. We show here that synergy arises in case of strong similarity or anti-similarity for breast and colorectal tissues.

**check_synergy_SANGER.Rmd**:

* Synergy stratification on 48 colorectal cancer cell lines (Sanger validation).

**check_synergy_ALMANAC.Rmd**:

* Synergy enrichment in NCI_ALMANAC dataset.

## Source of the data

GDSC data were downloaded from: http://www.cancerrxgene.org/
* Drug IC50 version 17a
* Basal gene expression 12/06/2013 version 2
* Drug target version March 2017

DREAM drug combination challenge data were acquired through an AstraZeneca Open Innovation Proposal.

NCI-ALMANAC data is downloaded from the publication Holbeck et al.

## Snapshot of all R packages used for data analysis

In case you encounter any issue, all packages used in this project are saved in the folder **packrat/src**

https://rstudio.github.io/packrat/commands.html

## License

Distributed under the GNU GPLv3 License. See accompanying file LICENSE.txt or copy at http://www.gnu.org/licenses/gpl-3.0.html.