Abstract
The regulation of gene expression is a key factor in the development and maintenance of life in all organisms. Even so, little is known at whole genome scale for most genes and contexts. We propose a method, Tool for Weighted Epigenomic Networks in Drosophila melanogaster (Fly T-WEoN), to generate context-specific gene regulatory networks starting from a reference network that contains all known gene regulations in the fly. Unlikely regulations are removed by applying a series of knowledge-based filters. Each of these filters is implemented as an independent module that considers a type of experimental evidence, including DNA methylation, chromatin accessibility, histone modifications and gene expression. Fly T-WEoN is based on heuristic rules that reflect current knowledge on gene regulation in D. melanogaster obtained from the literature. Experimental data files can be generated with several standard procedures and used solely when and if available. Fly T-WEoN is available as a Cytoscape application that permits integration with other tools and facilitates downstream network analysis. In this work, we first demonstrate the reliability of our method to then provide a relevant application case of our tool: early development of D. melanogaster. Fly T-WEoN together with its step-by-step guide is available at https://weon.readthedocs.io.
Highlights
The regulation of gene expression is indispensable for adaptation to ever changing contexts and every aspect involved in sustaining life
Our method considers experimental information following this order for each TF binding sites (TFBSs): chromatin accessibility (DNase-seq), methylation of the DNA, histone modifications around the TFBS, the expression of each transcription factors (TFs) with known TFBSs in the reference network and miRNA quantification
As expected, increasing the cut-off employed to assign TFs based on the distance TFBS–transcription start site (TSS), the number of genes and edges in each reference gene regulatory networks (GRNs) increases
Summary
The regulation of gene expression is indispensable for adaptation to ever changing contexts and every aspect involved in sustaining life. Speaking, the regulation of gene expression works through the binding of TFs to certain sites in the chromatin, TF binding sites (TFBSs), and TFs recognize specific DNA patterns called TF binding motifs. These sites are usually specific for each TF, and they are commonly located around the promoter of TF-target genes upstream of their transcription start site. Gene expression can be defined as the process by which the final products encoded by genes are generated, and their regulation can include control of translation and RNA degradation. MiRNAs and other ncRNAs are known to act during translation by binding to other RNAs [7,8], while histone modifiers attach or remove post-translational modifications to control the positions of the chromatin that are available to be occupied by TFs
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