Journal ArticleDOI
The Connectivity Map: a new tool for biomedical research
TLDR
The Connectivity Map project set out to answer the questions of how the screening process for biomedical research could be systematized and centralized, and hits found and hypotheses generated with something resembling an internet search engine.Abstract:
The ultimate objective of biomedical research is to connect human diseases with the genes that underlie them and drugs that treat them. But this remains a daunting task, and even the most inspired researchers still have to resort to laborious screens of genetic or chemical libraries. What if at least some parts of this screening process could be systematized and centralized? And hits found and hypotheses generated with something resembling an internet search engine? These are the questions the Connectivity Map project set out to answer.read more
Citations
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Journal ArticleDOI
Survivin, cancer networks and pathway-directed drug discovery.
TL;DR: Pursuing the nodal functions of survivin in cancer might lead to the development of global pathway inhibitors with unique therapeutic potential.
Journal ArticleDOI
ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments
TL;DR: The ChEA database allowed us to reconstruct an initial network of transcription factors connected based on shared overlapping targets and binding site proximity, and it is shown how by combining the Connectivity Map with ChEA, it can rank pairs of compounds to be used to target specific transcription factor activity in cancer cells.
Journal ArticleDOI
Discovery of drug mode of action and drug repositioning from transcriptional responses
Francesco Iorio,Roberta Bosotti,Emanuela Scacheri,Vincenzo Belcastro,Pratibha Mithbaokar,Rosa Ferriero,Loredana Murino,Roberto Tagliaferri,Nicola Brunetti-Pierri,Antonella Isacchi,Diego di Bernardo +10 more
TL;DR: This work developed an automatic and robust approach that exploits similarity in gene expression profiles following drug treatment, across multiple cell lines and dosages, to predict similarities in drug effect and MoA, and correctly predicted the MoA for nine anticancer compounds and was able to discover an unreported effect for a well-known drug.
Journal ArticleDOI
PREDICT: a method for inferring novel drug indications with application to personalized medicine.
TL;DR: A novel method for the large‐scale prediction of drug indications (PREDICT) that can handle both approved drugs and novel molecules and lays the computational foundation for future personalized drug treatments, where gene expression signatures from individual patients would replace the disease‐specific signatures.
Journal ArticleDOI
Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.
Nicholas Ekow Thomford,Dimakatso Alice Senthebane,Arielle Rowe,Daniella Munro,Palesa Seele,Alfred Maroyi,Kevin Dzobo,Kevin Dzobo +7 more
TL;DR: This review discusses plant-based natural product drug discovery and how innovative technologies play a role in next-generation drug discovery.
References
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Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Aravind Subramanian,Pablo Tamayo,Vamsi K. Mootha,Sayan Mukherjee,Benjamin L. Ebert,Michael A. Gillette,Amanda G. Paulovich,Scott L. Pomeroy,Todd R. Golub,Eric S. Lander,Jill P. Mesirov +10 more
TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
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Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.
Todd R. Golub,Todd R. Golub,Donna K. Slonim,Pablo Tamayo,Christine Huard,Michelle Gaasenbeek,Jill P. Mesirov,Hilary A. Coller,Mignon L. Loh,James R. Downing,Michael A. Caligiuri,Clara D. Bloomfield,Eric S. Lander +12 more
TL;DR: A generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case and suggests a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
Journal ArticleDOI
Gene Expression Omnibus: NCBI gene expression and hybridization array data repository
TL;DR: The Gene Expression Omnibus (GEO) project was initiated in response to the growing demand for a public repository for high-throughput gene expression data and provides a flexible and open design that facilitates submission, storage and retrieval of heterogeneous data sets from high-power gene expression and genomic hybridization experiments.
Journal ArticleDOI
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
TL;DR: 21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics.
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The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease
Justin Lamb,Emily D. Crawford,David Peck,Joshua W. Modell,Irene C. Blat,Matthew J. Wrobel,Jim Lerner,Jean Philippe Brunet,Aravind Subramanian,Kenneth N. Ross,Michael Reich,Haley Hieronymus,Haley Hieronymus,Guo Wei,Guo Wei,Scott A. Armstrong,Scott A. Armstrong,Stephen J. Haggarty,Stephen J. Haggarty,Paul A. Clemons,Ru Wei,Steven A. Carr,Eric S. Lander,Eric S. Lander,Todd R. Golub +24 more