ArticleBioinformatics (Oxford, England)2020
Predicting mechanism of action of cellular perturbations with pathway activity signatures.
Article in Bioinformatics (Oxford, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Guiding Drug Repositioning for Cancers Based on Drug Similarity Networks.International journal of molecular sciences · 2023Article
- Connecting omics signatures and revealing biological mechanisms with iLINCS.Nature communications · 2022Article
- Chemical-induced gene expression ranking and its application to pancreatic cancer drug repurposing.Patterns (New York, N.Y.) · 2022Article
- Predicting mechanism of action of novel compounds using compound structure and transcriptomic signature coembedding.Bioinformatics (Oxford, England) · 2021Article
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Authors and funding
8 authors.
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Abstract
motivationMisregulation of signaling pathway activity is etiologic for many human diseases, and modulating activity of signaling pathways is often the preferred therapeutic strategy. Understanding the mechanism of action (MOA) of bioactive chemicals in terms of targeted signaling pathways is the essential first step in evaluating their therapeutic potential. Changes in signaling pathway activity are often not reflected in changes in expression of pathway genes which makes MOA inferences from transcriptional signatures (TSeses) a difficult problem.
resultsWe developed a new computational method for implicating pathway targets of bioactive chemicals and other cellular perturbations by integrated analysis of pathway network topology, the Library of Integrated Network-based Cellular Signature TSes of genetic perturbations of pathway genes and the TS of the perturbation. Our methodology accurately predicts signaling pathways targeted by the perturbation when current pathway analysis approaches utilizing only the TS of the perturbation fail. AVAILABILITY AND IMPLEMENTATION: Open source R package paslincs is available at https://github.com/uc-bd2k/paslincs. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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