Visualization and Information Graphics
For years, the BCBC has collaborated on various projects that aim to ease the consumption of complex information. This page serves as an index of these tools generated and maintained by the BCBC:
- Gene Network Visualization
- Genome Browser
- Meta Analysis
- Comparison Profiles
- Differentiation Protocol Display
- Experimental Design Graphs
- Gene Expression in Pancreatic Cells
- Genetic Markers and Key Transcriptional Cascades in Pancreatic Development
- TRAFEX - TRAnscription Factor EXpression survey
Gene Network Visualization
Understanding relationships between genes (or gene products) is an ongoing effort to better understand the development and maintenance of the endocrine pancreas.
Using data from published sources and inferred from expression studies, immunoprecipitation and motif similarity, the BCBC has developed a network of data that provide key details on interactions between genes (or their products) in defined contexts. This gene network visualization tool allows you to:
- Visualize the local network surrounding a single gene, or a list of genes,
- Interactively add more genes to expand the network,
- Filter by the type of relationship - activating, binding and/or repressing,
- Filter by curated contexts defined by anatomical entities, biology processes and development stages,
- Filter by the type of evidence,
- Review detailed annotations for genes (nodes) and relationships (edges),
- Follow links to look at gene and study details, and even publications, and
- Export the network graph has an image or as data.
Our Genome Browser enables users to explore genomic regions of interest, viewing gene annotation and results from studies relevant to the BCBC.
On this browser the user can select various types of tracks for viewing. These include:
- Gene models,
- DoTS transcripts,
- Transcription factor binding sites computational predictions, and
- Coverage plots and peak calls from High-Throughput Sequencing studies.
Users select the genome and tracks of interest. They can rearrange the order in which tracks are displayed and mouse-over or click on tracks for additional information. Moreover users can upload their own custom tracks.
The example to the right illustrates tracks corresponding to peak calls from the study Genomewide Analysis of Histone Modifications in Normal Human Islets around the human INS gene.
The Meta-Analysis tool summarizes expression and ChIP comparisons derived from Beta Cell Genomics studies.
This tool can be used to quickly identify where the genes in a specified list have an interesting behavior, such as differential expression in a given pairwise comparison or in a time series or such as being bound by a specific transcription factor. The results are displayed as a heatmap with homologenes as rows and comparisons as columns. Homologenes are used so to encompass in one heatmap results from studies in different species. Cells in the heatmap which are colored indicate gene-comparison pairs of interest. A red cell indicates that the gene is significantly up-regulated/bound in a pairwise comparison. A green cell indicates that the gene is significantly down-regulated/bound in a pairwise comparison. A blue cell indicates that the gene is significantly differentially expressed across time or significantly differentially expressed between two conditions across time in a time series. Mousing over a cell displays the comparison short name and clicking on a cell brings the user to the study page from which that comparison was derived. More details are described here.
The example to the right provides a link to the tool, where mousing over the appropriate cells, one can quickly discover that the homologene corresponding to Nkx6-1 (Human, Mouse and Rat) was identified as upregulated in a microarray comparison of Ngn3 EYFP+ mouse embryonic pancreatic cells as compared to Ngn3 EYFP- ones and was identified as down-regulated in a study comparing human acinar cells to islets.
A comparison profile indicates the behaviour of a gene across a collection of pairwise expression or ChIP comparisons of conditions and 1-condition time series expression comparisons. Comparison Profiles are available on the gene pages. More details are here.
A Comparison Profile conveys a different kind of information than an Expression Profile. A Comparison Profile displays the fold-change for a gene across a list consisting of pairwise expression or ChIP comparisons and 1-condition time series expression comparisons. Each bar represents the fold-change for that gene in the corresponding comparison and is colored according to whether or not there was statistical evidence. Similar to the Meta-Analysis tool, a comparison profile highlights under what conditions the gene has an interesting behavior, but it focuses on one gene only and provides fold-change information.
The example shown is from the Mouse Pdx1 gene page. The yellow bars correspond to comparisons where this gene was differentially expressed/bound with high confidence. Mousing over each bar displays the comparison's short name. There are some green bars which are tall, but their color indicates that even though the fold change was high (or low), the confidence in differential expression was not high, possibly due to high variability of the within-condition gene expression for this gene in this comparison. Bars colored in gray indicate comparisons where statistical analysis was not possible, e.g. due to lack of replicates.
Differentiation Protocol Display
For studies which monitor gene expression across distinct time points in a differentiation protocol application, we can generate displays that allow the user to quickly see the treatments used in the protocol along with the expression data.
Currently we only have one study for which this visualization is available, namely for the H9 hESC directed differentiation following Novocell protocol study. On this study page, click on the microarray icon in the section "Differentiation Protocol Display". You will be presented with a page in which you can choose the genes you want to view and the samples, as well as the data type you want to view. Upon clicking on Get Answer, you will obtain the data visualization across the protocol time points.
Experimental Design Graphs
On each study page we provide a graph illustrating the experimental design of the study. The graph is clickable and provides more detailed biomaterial and protocol information.
These graphs can be opened on the study pages by clicking on the Biomaterials Graph link. Red bordered nodes correspond to treatments and clicking on any such node opens up a window with the protocol information. The other nodes are inputs and outputs of treatments and are also clickable, opening up windows with information about biomaterials and assays.
The example shown illustrates the experimental design for study Suspension Differentiation of fibroblast-like pancreatic progenitors. This study starts with human fibroblast-like pancreatic progenitor (hFLPP) cells derived from an endocrine depleted pancreatic preparation. Each of eight aliquots is grown in either suspension or normal adherent culture. The RNA is then extracted and biotin-labeled for hybridization on an Affymetrix chip.
Gene Expression in pancreatic cells
On each gene page we provide information on evidence about that gene being expressed in certain pancreatic cells. This evidence can come from Beta Cell Genomics studies, BCBC bioimages, or literature.
This is in the section "Where is this gene expressed" on the gene pages. In this section a table is displayed with columns for each of: pancreas, acinar cells, islets, alpha and beta cells, as well as endocrine progenitor cells. For each such tissue/cell type, if there is evidence of expression for that gene in that tissue/cell type, a clickable icon appears. Different icons correspond to different types of evidence. Clicking on an icon, the details about all lines of evidence of that type are shown. If the evidence comes from a microarray study in Beta Cell Genomics, it has been computationally derived based on thresholds calculated from expression values of blanks or controls. A red question mark over such an icon indicates that, upon manual review of this evidence, this is questionable and could be due, for example, to contaminats. This section also contains links to external resources (Novartis and Array Expressed) with expression evidence data.
The example shown displays expression evidence details for mouse Pdx1 in islets. The studies from which this evidence was derived and the methods used to make the calls are illustrated.
Genetic Markers and Key Transcriptional Cascades in Pancreatic Development
Using data from published sources and feedback from members of the BCBC we have manually curated and drawn a series of interactive visualizations that summarize the timing of expression, influence and interaction among key transcriptional regulators that characterize or affect the formation of pancreatic cells during development.
We provide two types of visual summaries of these data. The first allows you to trace the timing and impact of the expression of key transcriptional regulators during the specification or differentiation of pancreatic endoderm, exocrine and endocrine cells, and the endocrine pancreas (Marker Characteristics). The second tracks the known transcriptional cascades underlying islet differentiation by illustrating manually curated networks of interactions among known key transcription factors (Transcriptional Regulatory Networks). Both types of visualizations are fully interactive, allowing users to zoom in on regions of particular interest and mouse over elements to see additional details, such as explanatory text or references to the primary literature. Elements may also provide links to related BCBC resources (e.g., gene or relationship detail pages on Beta Cell Genomics). The illustrated data are fully accessible through the relationship searches on Beta Cell Genomics and the manually curated transcriptional networks are incorporated in the gene-interaction database underlying the Gene Network Visualization tool.
TRAFEX - TRAnscription Factor EXpression survey
TRAFEX is a searchable database of gene expression data.
A global survey of RNA from 14 fetal and 12 adult human organs by RT-PCR determined the expression patterns of 790 genes encoding DNA-binding transcription factors. The data can be searched and sorted to identify sets of transcription factors with expression restricted to a given organ or to particular organ groups. These data are a resource to help define the spectrum of transcription factor control, contribute to the elucidation of transcription factor cascades responsible for the development and maintenance of each organ, and provide a baseline to study the effects of disease or developmental defects.