Bioinformatics

The UCSC and Ensembl Genome Browsers are sophisticated tools that provide free, web-based access to genome assemblies and annotations. This chapter has focused on examples from the human genome and a subset of the annotation tracks available for it. By adding tracks to the default view, users are able to view annotated genes, sequence variants, gene regulatory regions, gene expression data, and much more. The displays are highly customizable, and users can choose which data to view, the display style, and, in some cases, even change the colors of the annotated features. Both browsers can be accessed not only by text-based queries, such as gene symbol or chromosomal position, but also by searches with either nucleotide or protein sequences. The UCSC Genome Browser supports the BLAT search engine, while Ensembl supports both BLAT and BLAST, depending on the analysis type. Furthermore, the UCSC Table Browser and Ensembl's BioMart provide alternate entry points into the underlying data at each site, in which queries can be constructed using a web-based interface and data returned as text that can be downloaded and further manipulated. Although the examples illustrated in this chapter all derive from the GRCh38 assembly of the human genome, both UCSC and Ensembl host assemblies from many other organisms. The genomes may be assembled in shorter scaffolds, rather than chromosomes, and the variety of annotation types may be much smaller, but the basic look and feel of the genome browser will remain the same across different species.

With new developments in sequencing technology, even smaller laboratories are now able to generate whole genome sequencing data, including ChIP-Seq and RNA-seq, exome and genome sequencing, and even novel genome assemblies. Starting in 2015, genomic data sharing policies now require that all NIH-funded research that generates large-scale genomic data be submitted to a public database in a timely manner. While human data must be submitted to an NIH-designated data repository, as of this writing, non-human data may be made available through any widely used data repository. Viewing and sharing these data with the larger community of biologists may best be done with a genome browser. Both the UCSC and Ensembl Genome Browsers provide the option for users to upload their own annotations and view them in the context of the public genome data. Using Sessions or Track Hubs , users can share these data with colleagues. The Assembly Hubs feature at UCSC now allows users to share novel genomes using the Genome Browser framework. Furthermore, the source code for the UCSC Genome Browser is publicly available, so others are free to set up their own browsers to host their own annotations, or even their own genomes. Alternatively, researchers who want to host their own genome browser should consider JBrowse. This freely available software tool can be easily installed on a web server and used to host custom genomes and annotations.

The UCSC and Ensembl teams start with the same source of data, a genome assembly, often provided by the GRC. Each team then layers on its own annotations from different sources, including the location of genes, from GENCODE, RefSeq, and other gene prediction pipelines, and variants, from NCBI's dbSNP. Both browsers also include the location of experimentally determined epigenetic marks, including histone modifications, as well as DNaseI hypersensitive sites, both of which can inform predictions of gene regulatory regions. The regulatory tracks at UCSC come from the ENCODE project, while Ensembl provides a Regulatory Build , which includes data from ENCODE as well as other sources. Although individual researchers may have personal preferences about which interface is easier to use, or which site provides information that is more relevant to the biological question they are studying, most members of the bioinformatics community will undoubtedly use a genome browser at some point in their research career.

The best way to learn about the data and tools available in the UCSC and Ensembl Genome Browsers is to read the relevant sections of the online documentation that accompanies each browser. The documentation on both sites is extensive and up to date, and will likely answer the user's questions. Alternatively, specialized questions can be addressed by contacting the web site development teams. URLs are listed in the Internet Resources section of this chapter.

The Database issue of Nucleic Acids Research , published in January of each year, usually includes articles that provide a broad overview of each Genome Browser as well as a description of new data and resources. The references for 2019 are listed below, and additional information can be found in Chapter 1.

1 Aken, B.L., Ayling, S., Barrell, D. et al. (2016). The Ensembl gene annotation system. Database (Oxford) 2016, pii: baw093.

2 Benson, D.A., Boguski, M.S., Lipman, D.J., and Ostell, J. (1997). GenBank. Nucleic Acids Res. 25 (1): 1–6.