Data Fusion Approach for Learning Transcriptional Bayesian Networks

Abstract

The complexity of gene expression regulation relies on the synergic nature underlying the molecular interplay among its principal actors, transcription factors (TFs). Exerting a spatiotemporal control on their target genes, they define transcriptional programs across the genome, which are strongly perturbed in a disease context. In order to gain a more comprehensive picture of these complex dynamics, a data fusion approach, aimed at performing the integration of heterogeneous -omics data is fundamental.

Bayesian Networks provide a natural framework for integrating different sources of data and knowledge through the priors’ use. In this work, we developed an hybrid structure-learning algorithm with the aim of exploiting TF ChIP-seq and gene expression (GE) data to investigate disease-specific transcriptional regulations in a genome-wide perspective. TF ChIP seq profiles were firstly used for structure learning and then integrated in the model as a prior probability. GE panels were employed to learn the model parameters, trying to find the best heuristic transcriptional network. We applied our approach to a specific pathological case, the chronic myeloid leukemia (CML), a myeloproliferative disorder, whose transcriptional mechanisms have not yet been deeply elucidated.

The proposed data-driven method allows to investigate transcriptional signatures, highlighting in the obtained probabilistic network a three-layered hierarchy, as a different TFs influence on gene expression cellular programs.