Deriving Disease Modules from the Compressed Transcriptional Space Embedded in a Deep Auto-encoder

Sanjiv K. Dwivedi, Andreas Tjärnberg, Jesper Tegnér and Mika Gustafsson

Aug 02, 2019
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Received Date: 11th July 19

Disease modules in molecular interaction maps have been useful for characterizing diseases. Yet biological networks, commonly used to 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 assuming the prior knowledge of a biological network. To this end we train a deep auto-encoder on a large transcriptional data-set. Our hypothesis is that such modules could be discovered in the deep representations within the auto-encoder when trained to capture the variance in the input-output map of the transcriptional profiles. Using a three-layer deep auto-encoder we find a statistically significant enrichment of GWAS relevant genes in the third layer, and to a successively lesser degree in the second and first layers respectively. In contrast, we found an opposite gradient where a modular protein-protein interaction signal was strongest in the first layer but then vanishing smoothly deeper in the network. We conclude that a data-driven discovery approach, without assuming a particular biological network, is sufficient to discover groups of disease-related genes.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature