The Islet Regulome Browser

The Islet Regulome Browser is a visualization tool that provides access to interactive exploration of pancreatic islet genomic data.

A plot can be generated by selecting a valid gene name or an absolute chromosomal location by specifying the genomic coordinates (chromosome, start, and end). The human builds available are: hg18, hg19 (default), and hg38. The plot can be extended on both sides by selecting a 0, 1Kb, 5Kb, 10Kb, 50Kb (default), 100Kb, 500Kb, 1Mb range. Plots can span a maximum of 5Mb genomic space.

From the "Features" panel 4 major track types can be loaded to obtain the desired plot.

  1. tracks called chromatin maps refer to genomic maps of regions that may be involved in gene transcription regulation. Such maps were inferred from experimental data sets such as open chromatin and histone modification profiles obtained from adult human pancreatic islets and pancreatic progenitors cell types.
  2. transcription factors tracks are maps of transcription factors binding sites obtained from Chip-seq experiments performed in human adult pancreatic islets and pancreatic progenitors.
  3. SNPs tracks include GWAS variants datasets associated to type 2 diabetes and fasting glycemia.
  4. an optional chromatin profile track can be loaded to visualize open chromatin profiles obtained from ATAC-Seq experiments performed in FACS purified alpha and beta cells.

The plot illustrates regulatory regions, transcription factors binding sites and GWAS variants in which the sequence of the base genome is represented on the horizontal axis. In the upper part of the plot a red line on the chromosome ideogram reflects the portion of the chromosome displayed. Each dot represents a genomic variant, being the color intensity of the dot proportional to -Log10 p-value of association, as indicated on the side of the plot.

The rs# ID depicts the top associated variant in the locus. The black box in the middle of the plot contains vertical colored bands depicting different chromatin states, open chromatin classes or regulatory elements as described in the legend above the plot. Black lines connecting the circles (each representing a different transcription factor) to the black box, point to the genomic location of each transcription factor binding site. The color intensity of such lines is proportional to the number of co-bound transcription factors. Annotated genes are depicted as horizontal gray lines at the bottom of the plot, with transcriptional orientation indicated by arrows. Boxes along the line correspond to positions of coding exons. Islet-specific genes are shown in dark grey.

It is possible to change the coordinates of the plot by moving left or right (25%, 50% and 75% of the length of the plot) with the buttons above the plot. Zooming in and out is also easily done through the two buttons above the plot, which can provide 1.5x, 3x, and 10x zoom in or zoom out steps.

Variants or regions files can be uploaded by the user for temporary display. The file size of the uploaded file should not exceed 50Mb. If a file contains a header, this should start with the "#" symbol.

A variant file should consist of three or four tab-delimited fields. Mandatory fields are those of chromosome, position, and p-value. The files can also contain an optional fourth field with the names of the variants. Other columns after the fourth, will be ignored. For instance:

  • column 1: Chromosome, a number between 1 and 22 or the letters X, Y, preceded by the prefix 'chr' (eg. chr1, chr2....chrY)
  • column 2: Position, a positive integer (eg. 32541241)
  • column 3: P-value, a numerical value (eg. 0.000005)
  • column 4: Name, any alphanumeric string (eg. rs9581940)

A region file has a typical BED file format and should be composed of at least 3 mandatory tab-delimited fields: chromosome, start, and end. Other columns after the third, will be ignored. For instance:

  • column 1: Chromosome, a number between 1 and 22 or the letters X, Y, preceded by the prefix 'chr' (eg. chr1, chr2....chrY)
  • column 2: Start, a positive integer (eg. 49356749)
  • column 3: End, a positive integer (eg. 51674938)

To avoid errors during the upload remember that the chromosomes should be named as follow: chr1, chr2, chr3, chr4, chr5, chr6, chr7, chr8, chr9, chr10, chr11, chr12, chr13, chr14, chr15, chr16, chr17, chr18, chr19, chr20, chr21, chr22, chrX, chrY.

The fields with positional information should only contain integer values while the p-values should be numerical values.

Upon data upload, a Share uploaded files button may be clicked. This will generate a URL that can be copy-pasted to a browser address bar in order to reproduce the Islet Regulome Browser session in use, including the uploaded data. Such link may be shared with other users in order to share data on the Islet Regulome Browser. Data uploaded by the user will be available for one month.

Graphical representations and text tables are available for download.

The plot can be downloaded as PNG (Portable Network Graphics) or as PDF (Adobe Portable Document) format by clicking on the download icon above the plot. The difference between the two formats is that the latter uses vector graphics.

A button above the plot provides a link to a UCSC browser session containing all the data currently available in the Islet Regulome Browser for classic UCSC visualization. For this purpose bigwig files were generated by aligning unique reads from the raw data using Bowtie2 (default parameters). For transcription factor binding sites and chromatin maps refer to the parameters used in the original publications.

Two tables related to the selected locus can be downloaded from the "Table" panel, selectable from the top left corner of the plot page. One table contains the regulatory regions, open chromatin classes or chromatin states selected for display along with the transcription factors who's bind sites overlap them. The other table contains a list of the variants contained in the selected locus along with their p-value of association.

The Setting panel, selectable from top left corner of the plot page, allows to retrieve all the settings used to make the plot including genomic coordinates genome build, SNPs datasets and feature selected.

If you make use of any result generated by the Islet Regulome Browser, please include the following reference in your scientific publication:
Mularoni L, Ramos M and Pasquali L (2017). The pancreatic islet regulome browser. Front. Genet. 8:13. doi: 10.3389/fgene.2017.00013