The Nucleome Data Bank: web-based resources to simulate and analyze the three-dimensional genome.

Vinícius G Contessoto,Ryan R Cheng,Michele Di Pierro,Arya Hajitaheri,Erez Lieberman-Aiden,Matheus F Mello,José N Onuchic,Esteban Dodero-Rojas,Peter G Wolynes

doi:10.1093/nar/gkaa818

Abstract

We introduce the Nucleome Data Bank (NDB), a web-based platform to simulate and analyze the three-dimensional (3D) organization of genomes. The NDB enables physics-based simulation of chromosomal structural dynamics through the MEGABASE + MiChroM computational pipeline. The input of the pipeline consists of epigenetic information sourced from the Encode database; the output consists of the trajectories of chromosomal motions that accurately predict Hi-C and fluorescence insitu hybridization data, as well as multiple observations of chromosomal dynamics in vivo. As an intermediate step, users can also generate chromosomal sub-compartment annotations directly from the same epigenetic input, without the use of any DNA–DNA proximity ligation data. Additionally, the NDB freely hosts both experimental and computational structural genomics data. Besides being able to perform their own genome simulations and download the hosted data, users can also analyze and visualize the same data through custom-designed web-based tools. In particular, the one-dimensional genetic and epigenetic data can be overlaid onto accurate 3D structures of chromosomes, to study the spatial distribution of genetic and epigenetic features. The NDB aims to be a shared resource to biologists, biophysicists and all genome scientists. The NDB is available at https://ndb.rice.edu.

Highlights

The genome, the human genome, is the object of investigation of an incredibly large and diverse community of scientists
The input of the pipeline consists of epigenetic information sourced from the Encode database; the output consists of trajectories of chromosomal dynamics
The distribution of CCCTCbinding factors (CTCF) along DNA is specific to distinct chromosomes, and so are the resulting looping patterns, observed in Hi-C maps.[4,33]

Summary

Introduction

The genome, the human genome, is the object of investigation of an incredibly large and diverse community of scientists. MiChroM introduced the idea that the compartmentalization seen in Hi-C maps arises from microphase separation of chromatin segments having different biochemical properties; using this idea, the compartmentalization patterns found in Hi-C maps can be transformed into ensembles of 3D models of genome structure at 50-kb resolution These patterns are not universal, as every chromosome and every tissue or cell line from the same organism exhibits its own compartmentalization pattern.[32] the distribution of CCCTCbinding factors (CTCF) along DNA is specific to distinct chromosomes, and so are the resulting looping patterns, observed in Hi-C maps.[4,33]. In the paragraphs we will discuss details of the implementation and a test case in which we illustrate all the steps to be followed in order to generate the structural ensembles of a human cell line directly

Design and Implementation

A Case Study