A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles.
Aravind Subramanian,Rajiv Narayan,Steven M. Corsello,Steven M. Corsello,David Peck,Ted Natoli,Xiaodong Lu,Joshua Gould,John F. Davis,Andrew A. Tubelli,Jacob K. Asiedu,David L. Lahr,Jodi E. Hirschman,Zihan Liu,Melanie Donahue,Bina Julian,Mariya Khan,David Wadden,Ian Smith,Daniel D. Lam,Arthur Liberzon,Courtney Toder,Mukta Bagul,Marek Orzechowski,Oana M. Enache,Federica Piccioni,Sarah A. Johnson,Nicholas J. Lyons,Alice H. Berger,Alice H. Berger,Alykhan F. Shamji,Angela N. Brooks,Angela N. Brooks,Anita Vrcic,Corey Flynn,Jacqueline Rosains,David Y. Takeda,David Y. Takeda,Roger Hu,Desiree Davison,Justin Lamb,Kristin Ardlie,Larson Hogstrom,Peyton Greenside,Nathanael S. Gray,Nathanael S. Gray,Paul A. Clemons,Serena J. Silver,Xiaoyun Wu,Wen-Ning Zhao,Wen-Ning Zhao,Willis Read-Button,Xiaohua Wu,Stephen J. Haggarty,Stephen J. Haggarty,Lucienne Ronco,Jesse S. Boehm,Stuart L. Schreiber,Stuart L. Schreiber,Stuart L. Schreiber,John G. Doench,Joshua A. Bittker,David E. Root,Bang Wong,Todd R. Golub +64 more
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TLDR
The expanded CMap is reported, made possible by a new, low-cost, high-throughput reduced representation expression profiling method that is shown to be highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts.About:
This article is published in Cell.The article was published on 2017-11-30 and is currently open access. It has received 1943 citations till now.read more
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Transcriptome analysis and connectivity mapping of Cissampelos pareira L. provides molecular links of ESR1 modulation to viral inhibition
Madiha Haider,Madiha Haider,Dhwani Dholakia,Dhwani Dholakia,Aleksha Panwar,Parth Garg,Atish Gheware,Atish Gheware,Dayanidhi Singh,Dayanidhi Singh,Khushboo Singhal,Khushboo Singhal,Shaunak A Burse,Shaunak A Burse,Surekha Kumari,Surekha Kumari,Anmol,Anmol,Arjun Ray,Guruprasad R. Medigeshi,Upendra Sharma,Upendra Sharma,Bhavana Prasher,Bhavana Prasher,Bhavana Prasher,Mitali Mukerji,Mitali Mukerji,Mitali Mukerji +27 more
TL;DR: In this paper, the molecular basis of action of one such herbal formulation Cissampelos pareira, used for the treatment of female hormone disorders and fever, was explored, which revealed a downregulation of signatures of estrogen response governed by estrogen receptor α (ERα).
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Signatures of cell death and proliferation in perturbation transcriptomics data - from confounding factor to effective prediction
TL;DR: It is shown here that a cell death signature is a major factor behind perturbation signatures and this relationship is used to effectively predict cell viability from transcriptomics signatures, and identify compounds that induce either cell death or proliferation.
Journal ArticleDOI
Identification of PIK3CA multigene mutation patterns associated with superior prognosis in stomach cancer.
TL;DR: In this article, the authors explored crucial factors interacting with PIK3CA mutations to facilitate a significant marginal survival effect at the higher-order level and identified therapeutic strategies based on these marginal factors.
Journal ArticleDOI
CLIP-170S is a microtubule +TIP variant that confers resistance to taxanes by impairing drug-target engagement.
Prashant V. Thakkar,Katsuhiro Kita,Urko del Castillo,Giuseppe Galletti,Neel Madhukar,Elena Vila Navarro,Isabel Barasoain,Holly V. Goodson,Dan L. Sackett,José Fernando Díaz,Yao Lu,Arindam RoyChoudhury,Henrik Molina,Olivier Elemento,Manish A. Shah,Paraskevi Giannakakou +15 more
TL;DR: In this article, a microtubule (MT) plus-end-binding CLIP-170 protein variant was found enriched in taxane-resistant cell lines and patient samples, and Imatinib treatment selectively depleted CLIP170S, thus completely reversing taxane resistance.
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Improving cell-specific drug connectivity mapping with collaborative filtering
Rebecca Newman,Christopher Michael Pietras,Fangfang Qu,Diana Sapashnik,Lior Kofman,Sean Butze,Faith Ocitti,Inbar Fried,Donna K. Slonim +8 more
TL;DR: It is concluded that even for cells in which drug responses have not been fully characterized, it is possible to identify unassayed drugs that reverse in those cells the expression signatures observed in disease.
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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Visualizing Data using t-SNE
TL;DR: A new technique called t-SNE that visualizes high-dimensional data by giving each datapoint a location in a two or three-dimensional map, a variation of Stochastic Neighbor Embedding that is much easier to optimize, and produces significantly better visualizations by reducing the tendency to crowd points together in the center of the map.
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
BLAT—The BLAST-Like Alignment Tool
TL;DR: How BLAT was optimized is described, which is more accurate and 500 times faster than popular existing tools for mRNA/DNA alignments and 50 times faster for protein alignments at sensitivity settings typically used when comparing vertebrate sequences.
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Adjusting batch effects in microarray expression data using empirical Bayes methods
TL;DR: This paper proposed parametric and non-parametric empirical Bayes frameworks for adjusting data for batch effects that is robust to outliers in small sample sizes and performs comparable to existing methods for large samples.
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