This project contains all information pertaining to the replication of key experiments from this paper. It includes the detailed protocols, including reagents and author clarifications. We also include any comments from other contributors, researchers from the Science Exchange network, and further information with the original authors that we have learned since the beginning of the project. When experimental studies begin all data collected will also be deposited here, including data analysis and eventually the final written report. <br> **Original citation:** Sirota M., Dudley J.T., Kim J., Chiang A.P., Morgan A.A., Sweet-Cordero A., Sage J., Butte A.J. Discovery and preclinical validation of drug indications using compendia of public gene expression data. Sci Transl Med. 2011 Aug 17;3(96):96ra77. doi: 10.1126/scitranslmed.3001318. <br> **Original paper abstract:** The application of established drug compounds to new therapeutic indications, known as drug repositioning, offers several advantages over traditional drug development, including reduced development costs and shorter paths to approval. Recent approaches to drug repositioning use high-throughput experimental approaches to assess a compound's potential therapeutic qualities. Here, we present a systematic computational approach to predict novel therapeutic indications on the basis of comprehensive testing of molecular signatures in drug-disease pairs. We integrated gene expression measurements from 100 diseases and gene expression measurements on 164 drug compounds, yielding predicted therapeutic potentials for these drugs. We recovered many known drug and disease relationships using computationally derived therapeutic potentials and also predict many new indications for these 164 drugs. We experimentally validated a prediction for the antiulcer drug cimetidine as a candidate therapeutic in the treatment of lung adenocarcinoma, and demonstrate its efficacy both in vitro and in vivo using mouse xenograft models. This computational method provides a systematic approach for repositioning established drugs to treat a wide range of human diseases.