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DNA Methylation Network Estimation with Sparse Latent Gaussian Graphical Model

By Bernard Ng, Sina Jafarzadeh, Daniel Cole, Anna Goldenberg, Sara Mostafavi

Posted 12 Jul 2018
bioRxiv DOI: 10.1101/367748

Inferring molecular interaction networks from genomics data is important for advancing our understanding of biological processes. Whereas considerable research effort has been placed on inferring such networks from gene expression data, network estimation from DNA methylation data has received very little attention due to the substantially higher dimensionality and complications with result interpretation for non-genic regions. To combat these challenges, we propose here an approach based on sparse latent Gaussian graphical model (SLGGM). The core idea is to perform network estimation on q latent variables as opposed to d CpG sites, with q<d. To impose a correspondence between the latent variables and genes, we use the distance between CpG sites and transcription starting sites of the genes to generate a prior on the CpG sites' latent class membership. We evaluate this approach on synthetic data, and show on real data that the gene network estimated from DNA methylation data significantly explains gene expression patterns in unseen datasets.

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