Using the Wash U Epigenome Browser to Examine Genome‐Wide Sequencing Data
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Abstract
This unit describes the Wash U Epigenome Browser, a next?generation genomic data visualization system. The Browser currently hosts ENCODE and Roadmap Epigenomics data for human and model organisms. The Browser displays many sequencing?based data sets across all or part of the genome, on specific gene sets or pathways, and in the context of their metadata. Investigators can order, filter, aggregate, classify, and display data interactively based on given feature sets including metadata features, annotated biological pathways, and user?defined collections of genes or genomic coordinates. Further, statistical tests can be performed on selected data. Individual labs can upload their sequencing or array?based data as custom tracks and display them in the context of consortium data, allowing for direct comparisons. The Browser is an increasingly important and widely accessible tool for deriving biological insights from unprecedented amounts of high?quality genomic, epigenomic, and expression data. Curr. Protoc. Bioinform. 40:10.10.1?10.10.14. © 2012 by John Wiley & Sons, Inc.
Keywords: genome browser; DNA sequencing data sets; high?throughput genomics epigenomics
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Figure 10.10.1 Annotated screen shot of the Browser panel. In this example, the Browser is displaying default tracks from the human hg19 database, which consists of 36 sequencing experiment tracks in a genome heatmap, one gene track beneath the genome heatmap, and 6 metadata terms in a metadata color map. The genome heatmap shows data in the default genomic location (chr10:20991666‐25987500). These default settings can be changed by supplying parameters through the URL. Please refer to our online manual for information on how to customize the Browser display with URL parameters. Additionally, a short piece of text on top of the genome heatmap provides information on the number of tracks on display in the genome heatmap, the genomic coordinates of the currently displayed region, and display resolution in the form of number of base pairs per pixel. Finally, users can press the cursor on the banner of the floating toolbox and move it around so it will not block the view. View Image -
Figure 10.10.2 Browser showing data over the CHRNA7 gene body. Gene models are visualized as “arrows on a line”. The arrows show the strand of the gene; in this case, the gene is on the forward strand. Thus, by scrolling to right, the gene's upstream region on the left will be exposed. Coding exons are displayed as thick boxes, and untranslated regions (UTRs) are displayed as narrow boxes. Multiple gene models are present, as the CHRNA7 gene has splice variants. Generally, the Browser displays the region spanning the longest gene model. View Image -
Figure 10.10.3 Zooming into the region containing CHRNA7 promoter. The transparent blue box is shown when cursor is pressed on the chromosome ideogram image and dragged. It marks the region to zoom into. View Image -
Figure 10.10.4 In the heatmap track selection function, heatmap tracks are organized as indented text trees for selection. The text tree is composed of metadata vocabulary terms and each line is one term. Terms on top of the tree can be clicked to reveal children terms. Click again to fold. Leaf‐level terms are not clickable. Other contents of the metadata vocabulary can be used to organize the track selection panel, and two categories of metadata terms can even be used to make a two‐dimensional grid. For this purpose, go to the configuration options in the track selection panel and select a category using the second drop‐down menu. Most commonly, the “Sample” and “Assay” are used in combination to generate such a track selection table. View Image -
Figure 10.10.5 Genome browser showing H3K4me3 ChIP‐Seq data over the promoter region of the human gene CHRNA7 . The tracks in genome heatmap are from the Roadmap Epigenomics Project and contain read density count of the sequencing experiments. These tracks are rendered in red with automatic scaling, which is the default setting and can be customized by selecting the “Configure” option in the right‐click menu. Heatmap cells with the most intensive red color indicate read density values close to the maximum read density value over the entire genomic region in the genome heatmap. Experimental samples belonging to categories of “ES/iPS Cells”, “Breast”, and “Blood” are indicated in respective columns in the metadata color map. Users can go to the metadata configuration panel and add more metadata categories to reveal extra attributes of the tracks in the genome heatmap. A gene track is displayed beneath the genome heatmap showing part of the CHRNA7 gene. Multiple gene models are tiled vertically, and they are alternatively spliced variants of the same gene. Clicking on any one of the genes, a tooltip will be displayed showing brief information about that gene. View Image -
Figure 10.10.6 Data is juxtaposed to reveal H3K4me3 patterns on CHRNA7 and its surrounding neighbors. To contrast with neighboring genes, a gray line is drawn vertically between genes in the genome heatmap, and alternating background colors (white and yellow) are used for neighboring genes in the gene track. In the gene track, it is seen that OTUD7A and CHRNA7 have different background colors, indicating that the non‐genic region between them is not shown. But CHRNA7 is sharing the same background color with DKFZp434L187 and some other genes because these genes overlap, sharing the same segment in the view. View Image -
Figure 10.10.7 The Browser is juxtaposing data to reveal H3K4me3 patterns on promoter regions with CHRNA7 and its neighbors. The display style is the same as explained in Figure . View Image -
Figure 10.10.8 Gene Set View of the H3K4me3 signal over the nAChR family genes. In this view, genes are tiled to form the horizontal axis of the genome heatmap. A gray line is plotted between every two genes in the genome heatmap. Under the genome heatmap, the chromosome bar is replaced by a graph of hollow boxes, which serve as a visual indication of the genes. The user can drag this bar to zoom in and get a detailed view over regions of interest, and drag the genome heatmap to scroll. The content of the gene track at the bottom updates accordingly. Genes have been arranged by their order of submission, but can be rearranged or sorted using editing options in the control panel. View Image -
Figure 10.10.9 Gene Set View of the H3K4me3 signal over the 16 genes in the nAChR family. Unlike Fig. , the 5‐kb regions centering over the transcription start sites are displayed for every gene. As a result, 16 equal length regions are present in this view. In in the gene track at the bottom, only partial gene structures are shown instead of complete genes. Beneath the genome heatmap where the chromosome bar used to be, filled rectangles are drawn to indicate each region. The green half of the rectangle indicates the portion of the upstream region relative to the gene's transcription start site, and likewise the red‐filled half indicates the downstream part of the region. Orientation of the red/green filling is determined by the gene's strand. The user can still drag on this graph to zoom in and see detailed data patterns and scroll to explore. View Image -
Figure 10.10.10 Hierarchical clustering of genes reveals how H3K4me3 marks are distributed across the genomic intervals belonging to the nAChR gene family. Move the cursor over the heatmap to view the gene name and data value of the heatmap cell under the cursor. In the heatmap, genes from top to bottom are: CHRNA5, CHRNA7, CHRNB4, CHRNB1, CHRNE, CHRND, CHRNB2, CHRNA4, CHRNA6, CHRNG, CHRNB3, CHRNA1, CHRNA9, CHRNA10, CHRNA3, CHRNA2 . To select genes inside a sub‐cluster, click the splitting point of that sub‐cluster in the dendrogram and the list of genes will be displayed in a table below the graph. View Image
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Literature Cited
| Dreszer, T.R., Karolchik, D., Zweig, A.S., Hinrichs, A.S., Raney, B.J., Kuhn, R.M., Meyer, L.R., Wong, M., Sloan, C.A., Rosenbloom, K.R., Roe, G., Rhead, B., Pohl, A., Malladi, V.S., Li, C.H., Learned, K., Kirkup, V., Hsu, F., Harte, R.A., Guruvadoo, L., Goldman, M., Giardine, B.M., Fujita, P.A., Diekhans, M., Cline, M.S., Clawson, H., Barber, G.P., Haussler, D., and Kent, W.J. 2012. The UCSC Genome Browser Database: Extensions and updates 2011. Nucleic Acids Res. 40:D918‐D923. | |
| Kent, W.J., Zweig, A.S., Barber, G., Hinrichs, A.S., and Karolchik, D., 2010. BigWig and BigBed: Enabling browsing of large distributed datasets. 26:2204‐2207. | |
| Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., and 1000 Genome Project Data Processing Subgroup. 2009. The Sequence Alignment Map (SAM) format and SAMtools. Bioinformatics 25:2078‐2079. | |
| Sanborn, J.Z., Benz, S.C., Craft, B., Szeto, C., Kober, K.M., Meyer, L., Vaske, C.J., Goldman, M., Smith, K.E., Kuhn, R.M., Karolchik, D., Kent, W.J., Stuart, J.M., Haussler, D., and Zhu, J. 2011. The UCSC cancer genomics browser database: Update 2011. Nucleic Acids Res. 39:D951‐D959. | |
| Key Reference | |
| Zhou, X., Maricque, B., Xie, M., Li, D., Sundaram, V., Martin, E.A., Koebbe, B.C., Nielsen, C., Hirst, M., Farnham, P., Kuhn, R.M., Zhu, J., Smirnov, I., Kent, W.J., Haussler, D., Madden, P.A.F., Costello, J.F., and Wang, T. 2011. The human epigenome browser at Washington University. Nat. Methods 8:989‐990. | |
| The original publication describing Wash U Epigenome Browser's innovative designs and critical applications. |
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