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- Warsow, Gregor, et al.
(författare)
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ExprEssence : revealing the essence of differential experimental data in the context of an interaction/regulation net-work
- 2010
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Ingår i: BMC Systems Biology. - London, UK : BioMed Central (BMC). - 1752-0509. ; 4, s. 164-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Experimentalists are overwhelmed by high-throughput data and there is an urgent need to condense information into simple hypotheses. For example, large amounts of microarray and deep sequencing data are becoming available, describing a variety of experimental conditions such as gene knockout and knockdown, the effect of interventions, and the differences between tissues and cell lines.Results: To address this challenge, we developed a method, implemented as a Cytoscape plugin called ExprEssence. As input we take a network of interaction, stimulation and/or inhibition links between genes/proteins, and differential data, such as gene expression data, tracking an intervention or development in time. We condense the network, highlighting those links across which the largest changes can be observed. Highlighting is based on a simple formula inspired by the law of mass action. We can interactively modify the threshold for highlighting and instantaneously visualize results. We applied ExprEssence to three scenarios describing kidney podocyte biology, pluripotency and ageing: 1) We identify putative processes involved in podocyte (de-)differentiation and validate one prediction experimentally. 2) We predict and validate the expression level of a transcription factor involved in pluripotency. 3) Finally, we generate plausible hypotheses on the role of apoptosis, cell cycle deregulation and DNA repair in ageing data obtained from the hippocampus.Conclusion: Reducing the size of gene/protein networks to the few links affected by large changes allows to screen for putative mechanistic relationships among the genes/proteins that are involved in adaptation to different experimental conditions, yielding important hypotheses, insights and suggestions for new experiments. We note that we do not focus on the identification of 'active subnetworks'. Instead we focus on the identification of single links (which may or may not form subnetworks), and these single links are much easier to validate experimentally than submodules. ExprEssence is available at http://sourceforge.net/projects/expressence/.
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| 2. |
- Zhang, Wensheng, et al.
(författare)
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The BAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 to Control ESC Differentiation
- 2019
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Ingår i: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 24:1, s. 138-
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Tidskriftsartikel (refereegranskat)abstract
- BAF complexes are composed of different subunits with varying functional and developmental roles, although many subunits have not been examined in depth. Here we show that the Baf45 subunit Dpf2 maintains pluripotency and ESC differentiation potential. Dpf2 co-occupies enhancers with Oct4, Sox2, p300, and the BAF subunit Brg1, and deleting Dpf2 perturbs ESC self-renewal, induces repression of Tbx3, and impairs mesendodermal differentiation without dramatically altering Brg1 localization. Mesendodermal differentiation can be rescued by restoring Tbx3 expression, whose distal enhancer is positively regulated by Dpf2-dependent H3K27ac maintenance and recruitment of pluripotency TFs and Brg1. In contrast, the PRC2 subunit Eed binds an intragenic Tbx3 enhancer to oppose Dpf2-dependent Tbx3 expression and mesendodermal differentiation. The PRC2 subunit Ezh2 likewise opposes Dpf2-dependent differentiation through a distinct mechanism involving Nanog repression. Together, these findings delineate distinct mechanistic roles for specific BAF and PRC2 subunits during ESC differentiation.
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