G-Dash: A Genome Dashboard Integrating Modeling and Informatics

Abstract

Genomics is a sequence based informatics science and a structure based molecular material science. There are few tools available that unite these approaches in a scientifically robust manner. Here we describe G-Dash, a web based prototype of a genomics dashboard, specifically designed to integrate informatics and 3D material studies of chromatin. G-Dash unites our Interactive Chromatin Modeling(ICM) tools with the Biodalliance genome browser and the JSMol molecular viewer to rapidly fold any DNA sequence into atomic or coarse-grained models of DNA, nucleosomes or chromatin. As a chromatin modeling tool, G-Dash enables users to specify nucleosome positions from various experimental or theoretical sources, interactively manipulate nucleosomes, and assign different conformational states to each nucleosome. As an informatics tool, data associated with 3D structures are displayed as tracks in a genome browser. The exchange of data between informatics and structure is bi-directional so any informatics track can inform a molecular structure (e.g. color by function) and structure features can be displayed as informatics tracks in a genome browser(e.g. Roll, Slide, or Twist). As a sample application, models of the CHA1 promoter based on experimentally determined nucleosome positions are explored with G-Dash. Steric clashes and DNA knotting are observed but can be resolved with G-Dash's minimal coarse-grained model without significant variation in structure. Results raise questions about the interpretation of nucleosome positioning data and promoter structures. In this regard, G-Dash is a novel tool for investigating structure-function relationships for regions of the genome ranging from base pairs to chromosomes and for generating, validating and testing mechanistic hypotheses.

TMB-iBIOMES: An iBIOMES-Lite Database of Nucleosome Trajectories and Meta-Analysis

“…12,45 With advanced sampling protocols, suitable workflows, and access to medium scale supercomputing resources, comparative modeling can be integrated directly into bioinformatics pipelines to directly probe structure-function relationships in atomic detail. Our TMB-iBIOMES dataset serves as a validation suite for the development of more efficient sampling protocols, and our genome dashboard, G-Dash, 46 provides the missing link to bioinformatics workflows.…”

TMB Library of Nucleosome Simulations

“…From this point of view, comparative molecular modeling and dynamics is an ideal complement to Next Generation Sequencing and nucleosome positioning techniques that can rapidly hone in on a limited region of interest of any genome. , Coupled with advanced sampling protocols, simulation, and analysis workflows and access to medium scale supercomputing resources, comparative modeling can be integrated into bioinformatics pipelines to directly probe structure–function relationships in atomic detail. The data in the TMB Library serves as a validation suite for the development of more efficient sampling protocols, and our genome dashboard, G-Dash, provides a missing link to bioinformatics workflows that can be used to inform or to leverage the modeling studies in such workflows.…”