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Deriving disease mo...
Deriving disease modules from the compressed transcriptional space embedded in a deep autoencoder
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- Dwivedi, Sanjiv (författare)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten
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- Tjärnberg, Andreas (författare)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten,NYU, NY 10003 USA
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- Tegner, Jesper (författare)
- Karolinska Institutet
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- Gustafsson, Mika (författare)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten
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(creator_code:org_t)
- 2020-02-12
- 2020
- Engelska.
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Disease modules in molecular interaction maps have been useful for characterizing diseases. Yet biological networks, that commonly define such modules are incomplete and biased toward some well-studied disease genes. Here we ask whether disease-relevant modules of genes can be discovered without prior knowledge of a biological network, instead training a deep autoencoder from large transcriptional data. We hypothesize that modules could be discovered within the autoencoder representations. We find a statistically significant enrichment of genome-wide association studies (GWAS) relevant genes in the last layer, and to a successively lesser degree in the middle and first layers respectively. In contrast, we find an opposite gradient where a modular protein-protein interaction signal is strongest in the first layer, but then vanishing smoothly deeper in the network. We conclude that a data-driven discovery approach is sufficient to discover groups of disease-related genes. The study of disease modules facilitates insight into complex diseases, but their identification relies on knowledge of molecular networks. Here, the authors show that disease modules and genes can also be discovered in deep autoencoder representations of large human gene expression datasets.
Ämnesord
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
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