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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Histone Signatures Predict Therapeutic Efficacy in Breast Cancer
S. Mollah,Shankar Subramaniam +1 more
TL;DR: A regulatory network of breast cancer response to treatment is constructed and it is shown that histone H3K27me3K36me3 status changes, driven by the BRD4/MYC pathway, upon treatment with drugs are hallmarks of response toreatment.
Journal ArticleDOI
A Graph Feature Auto-Encoder for the prediction of unobserved node features on biological networks.
Ramin Hasibi,Tom Michoel +1 more
Abstract: Molecular interaction networks summarize complex biological processes as graphs, whose structure is informative of biological function at multiple scales. Simultaneously, omics technologies measure the variation or activity of genes, proteins, or metabolites across individuals or experimental conditions. Integrating the complementary viewpoints of biological networks and omics data is an important task in bioinformatics, but existing methods treat networks as discrete structures, which are intrinsically difficult to integrate with continuous node features or activity measures. Graph neural networks map graph nodes into a low-dimensional vector space representation, and can be trained to preserve both the local graph structure and the similarity between node features. We studied the representation of transcriptional, protein–protein and genetic interaction networks in E. coli and mouse using graph neural networks. We found that such representations explain a large proportion of variation in gene expression data, and that using gene expression data as node features improves the reconstruction of the graph from the embedding. We further proposed a new end-to-end Graph Feature Auto-Encoder framework for the prediction of node features utilizing the structure of the gene networks, which is trained on the feature prediction task, and showed that it performs better at predicting unobserved node features than regular MultiLayer Perceptrons. When applied to the problem of imputing missing data in single-cell RNAseq data, the Graph Feature Auto-Encoder utilizing our new graph convolution layer called FeatGraphConv outperformed a state-of-the-art imputation method that does not use protein interaction information, showing the benefit of integrating biological networks and omics data with our proposed approach. Our proposed Graph Feature Auto-Encoder framework is a powerful approach for integrating and exploiting the close relation between molecular interaction networks and functional genomics data.
Journal ArticleDOI
High-Throughput Strategies for the Discovery of Anticancer Drugs by Targeting Transcriptional Reprogramming.
Li-Jun Huang,Xiaohong Yi,Xiankuo Yu,Yumei Wang,Chen Zhang,Lixia Qin,Dale Guo,Shiyi Zhou,Guanbin Zhang,Yun Deng,Xilinqiqige Bao,Dong Wang +11 more
TL;DR: In this paper, two gene expression signature-based high-throughput drug discovery approaches are presented: L1000, which measures the mRNA transcript abundance of 978 "landmark" genes, and HTS2, which takes advantage of RNA-mediated oligonucleotide annealing, selection, and ligation, high throughput sequencing, to quantify gene expression changes by directly measuring gene sequences.
Journal ArticleDOI
Comparison of tumor related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma
Song Xu,Renwang Liu,Yurong Da +2 more
TL;DR: This study compared tumor‐related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma (LUAD) treatment.
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Target identification and drug discovery by data-driven hypothesis and experimental validation in ovarian endometriosis.
TL;DR: In this article, ITPR1-knockeddowned ectopic human endometrial stromal cells (HESCs) were subjected to ribonucleic acid (RNA) sequencing, cell-counting kit-8 (CCK-8) assay, 5-ethynyl-2′-deoxyuridine (EdU) staining, and flow cytometry.
References
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Journal ArticleDOI
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.
Journal Article
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.
Journal ArticleDOI
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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