ArticleBioinformatics (Oxford, England)2008
Novel pathway compendium analysis elucidates mechanism of pro-angiogenic synthetic small molecule.
Article in Bioinformatics (Oxford, England), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Evaluating Angiogenic Potential of Small Molecules Using Genetic Network Approaches.Regenerative engineering and translational medicine · 2019Article
- Harnessing systems biology approaches to engineer functional microvascular networks.Tissue engineering. Part B, Reviews · 2010Review
- Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.Biotechnology and bioengineering · 2009Article
- Expansion of microvascular networks in vivo by phthalimide neovascular factor 1 (PNF1).Biomaterials · 2008Article
- Engineering vascularized tissues using natural and synthetic small molecules.Organogenesis · 2008Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
motivationComputational techniques have been applied to experimental datasets to identify drug mode-of-action. A shortcoming of existing approaches is the requirement of large reference databases of compound expression profiles. Here, we developed a new pathway-based compendium analysis that couples multi-timepoint, controlled microarray data for a single compound with systems-based network analysis to elucidate drug mechanism more efficiently.
resultsWe applied this approach to a transcriptional regulatory footprint of phthalimide neovascular factor 1 (PNF1)-a novel synthetic small molecule that exhibits significant in vitro endothelial potency-spanning 1-48 h post-supplementation in human micro-vascular endothelial cells (HMVEC) to comprehensively interrogate PNF1 effects. We concluded that PNF1 first induces tumor necrosis factor-alpha (TNF-alpha) signaling pathway function which in turn affects transforming growth factor-beta (TGF-beta) signaling. These results are consistent with our previous observations of PNF1-directed TGF-beta signaling at 24 h, including differential regulation of TGF-beta-induced matrix metalloproteinase 14 (MMP14/MT1-MMP) which is implicated in angiogenesis. Ultimately, we illustrate how our pathway-based compendium analysis more efficiently generates hypotheses for compound mechanism than existing techniques.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.