The visualization of transcription-factor/transcription-factor direct regulatory interactions below are determined by ChIP-seq experiments for the ChEA and ENCODE networks. The node sizes are linearly scaled based on the number of links for each node in that network. The colors are based on tiers of node size.

ChEA ENCODE

Developed | in | the Ma'ayan Lab |

by | Yan Kou | |

Edward Chen | ||

Neil Clark | ||

Christopher Tan | ||

Avi Ma'ayan |

**Contents**[hide]

ChEA2 uses a list of Entrez gene symbols as input. Each symbol in the input must be on its own line. You can upload the list by either selecting the text file that contains the list or just simply pasting in the list into the text box.

It is recommended to enter a description for your list so that multiple lists can be differentiated from each other if you choose to save or share your list.

If you are using a touch device, you can swipe left or right to navigate between the different tabs at the top.

On the results page, the analysis is divided into different categories of enrichment; in the example, the transcription category is shown. On a mobile device, you can switch between the categories by swiping left or right. Within each category, the enrichment analyses of various gene-set libraries are listed.

You can open a particular analysis by tapping on the name of the gene-set library, presenting a multitude of visualizations. On a mobile device, you can switch between the visualizations by swiping left or right. To return to switching categories on a mobile device, tap the name of the gene-set library to close the analysis.

The first visualization is the bar graph. You can sort the bar graph by the different score methods by clicking on the bar graph.

The length of the bar represents the significance of that specific gene-set or term. In addition, the brighter the color, the more significant that term is.

You can export the bar graph as a figure by clicking on one of the image format buttons to the top right of the bar graph.

The data table gives you a raw view of the data. By clicking on the column header, you can sort the table by the term, p-value, z-score, or combined score. Furthermore, you can filter the results by searching for a specific term.

Hovering over each row shows you the genes from the input that were found to be associated with that term. If the term name is highlighted in red, it means that you can click on the term name for additional information from external sites.

You can also get the table information in tab-delimited format by clicking on the "Export to Table" button.

Each grid square represents a term and is arranged based on its gene-set similarity with other terms. It shows only the top 10 terms sorted by combined score. The brighter the square, the more significant that term is. Clicking on the grid allows you to toggle to an alternate view that colors the grid based on its correlation score with neighbors with white dots representing the significant terms.

The z-score and p-value is a measure of how clustered the top 10 terms are on the grid

NOTE: The network may not be available for all gene-set libraries.

Each node represents a term and a link between two nodes means that the two terms have some gene content similarity.

Initially, the network is force directed, but if you drag the node to a fixed position, it will stay there.

Like the other SVG figures, the network can be exported in three image formats.

By default, all the figures have a red color scheme. However, you can change the color scheme by clicking on the cog-shaped icon to bring up a color picker. Selecting a color will change the color scheme of the bar graph, grid, and network figures.

ChEA2 implements three approaches to compute enrichment. The first one is a standard method implemented within most enrichment analysis tools: the Fisher exact test. This is a proportion test that assumes a binomial distribution and independence for probability of any gene belonging to any set. The second test is a correction to the Fisher exact test that we developed based on intuition. We first compute enrichment using the Fisher exact test for many random gene sets in order to compute a mean rank and standard deviation from the expected rank for each term in the gene-set library. Then using a lookup table of expected ranks with their variances, we compute a z-score for deviation from this expected rank, this can be a new corrected score for ranking terms. Alternatively, we combined the p-value computed using the Fisher exact test with the z-score of the deviation from the expected rank by multiplying these two numbers as follows:

c = log(p) × z

Where c is the combined score, p is the p-value computed using the Fisher exact test, and z is the z-score computed to assess the deviation from the expected rank. ChEA2 provides all three options for sorting enriched terms. In the results section, we show how we evaluated the quality of each of these three enrichment methods by examining how the methods rank terms that we know should be highly ranked.

ChEA2 is in active development so it is possible that something can break during our updates. If it is a cosmetic bug, please try refreshing your browser (by pressing Ctrl+F5/Shift+F5/Command+F5). If that does not fix the problem, please send us your input file and how you reproduced the bug to help us fix the problem. When reporting a bug, please also include screenshots and the browser that you used. You can find our contact email on the about page.

Since we are always looking for ways to improve ChEA2, please use our contact email on the about page to send us feature suggestions.

ChEA2 uses SVG to generate the figures and since Internet Explorer (IE) versions prior to IE 9 do not render SVG properly, ChEA2 does not work with these browsers. In addition, the stock browser in Android 2.3.7 (Gingerbread) or below does not support SVG either; however, Firefox for Android and Opera for Android are viable alternatives. You can see a complete table of SVG compatibility across various browsers here.