From expression footprints to causal pathways: contextualizing large signaling networks with CARNIVAL
Changes in gene expression are generally indirect consequences of upstream dysregulation, and it is often important to understand what caused it. A team of researchers led by Julio Saez-Rodriguez from Heidelberg and Aachen has developed CARNIVAL to infer causal networks of proteins upstream of gene...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
11 November 2019
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| In: |
npj Systems biology and applications
Year: 2019, Volume: 5, Issue: 1 |
| ISSN: | 2056-7189 |
| DOI: | 10.1038/s41540-019-0118-z |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41540-019-0118-z Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41540-019-0118-z 
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| Author Notes: | Anika Liu, Panuwat Trairatphisan, Enio Gjerga, Athanasios Didangelos, Jonathan Barratt and Julio Saez-Rodriguez |
| Summary: | Changes in gene expression are generally indirect consequences of upstream dysregulation, and it is often important to understand what caused it. A team of researchers led by Julio Saez-Rodriguez from Heidelberg and Aachen has developed CARNIVAL to infer causal networks of proteins upstream of gene expression. In the first step, dysregulated transcription factors are inferred from gene expression. Subsequently, an algorithm finds explanations for their up- or down-regulation through known protein-protein interactions using an ILP formulation. Optionally, known targets of perturbation can be provided. This integration of different sources of prior knowledge led to higher performance than alternative methods and was able to identify key pathways and proteins, including TGFβ signaling and β-Catenin, in a case study on IgA nephropathy. Overall, CARNIVAL may provide clues to understand causal mechanisms in diseases and treatments. |
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| Item Description: | Gesehen am 30.03.2020 Anika Liu, Panuwat Trairatphisan and Enio Gjerga contributed equally |
| Physical Description: | Online Resource |
| ISSN: | 2056-7189 |
| DOI: | 10.1038/s41540-019-0118-z |