Deriving disease modules from the compressed transcriptional space embedded in a deep autoencoder.

Dwivedi SK, Tjärnberg A, Tegnér J, Gustafsson M

Nat Commun 11 (1) 856 [2020-02-12; online 2020-02-12]

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.

PubMed 32051402

DOI 10.1038/s41467-020-14666-6

Crossref 10.1038/s41467-020-14666-6

pmc: PMC7016183
pii: 10.1038/s41467-020-14666-6