Abstract

Background:Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation.Findings:We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered.Conclusions:Through a combination of streamlined data acquisition, interoperable representation of dataset collections, and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no.

Highlights

  • Recent large-scale undertakings such as Encyclopedia of DNA Elements (ENCODE) and Roadmap Epigenomics have generated experimental data mapped to the human reference genome representing a variety of functional elements across a large number of cell types

  • Most of these datasets are in the form of genomic tracks, i.e., sets of elements anchored to locations in a reference genome, which provide a good foundation for the integration of data representing disparate genomic features

  • The present work is concerned with sets of information elements anchored to specific coordinates in a reference genome, which we refer to as genomic tracks

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Summary

Introduction

Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. The Encyclopedia of DNA Elements (ENCODE) [1] project marked a substantial leap in this respect by making available to the human genomics community a broad collection of cell line–specific data on DNA accessibility and transcription factor binding. Kundaje et al [2] refer to the combined collection of ENCODE and Roadmap data as 127 human reference epigenomes Most of these datasets are in the form of genomic tracks, i.e., sets of elements anchored to locations in a reference genome, which provide a good foundation for the integration of data representing disparate genomic features

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