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. 2014 Jul;42(Web Server issue):W449-60.
doi: 10.1093/nar/gku476. Epub 2014 Jun 6.

LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures

Qiaonan Duan  1 , Corey Flynn  2 , Mario Niepel  3 , Marc Hafner  3 , Jeremy L Muhlich  3 , Nicolas F Fernandez  1 , Andrew D Rouillard  1 , Christopher M Tan  1 , Edward Y Chen  1 , Todd R Golub  2 , Peter K Sorger  3 , Aravind Subramanian  2 , Avi Ma'ayan  4
Affiliations

LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures

Qiaonan Duan et al. Nucleic Acids Res. 2014 Jul.

Abstract

For the Library of Integrated Network-based Cellular Signatures (LINCS) project many gene expression signatures using the L1000 technology have been produced. The L1000 technology is a cost-effective method to profile gene expression in large scale. LINCS Canvas Browser (LCB) is an interactive HTML5 web-based software application that facilitates querying, browsing and interrogating many of the currently available LINCS L1000 data. LCB implements two compacted layered canvases, one to visualize clustered L1000 expression data, and the other to display enrichment analysis results using 30 different gene set libraries. Clicking on an experimental condition highlights gene-sets enriched for the differentially expressed genes from the selected experiment. A search interface allows users to input gene lists and query them against over 100 000 conditions to find the top matching experiments. The tool integrates many resources for an unprecedented potential for new discoveries in systems biology and systems pharmacology. The LCB application is available at http://www.maayanlab.net/LINCS/LCB. Customized versions will be made part of the http://lincscloud.org and http://lincs.hms.harvard.edu websites.

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Figures

Figure 1.
Figure 1.
LCB search interface. Two textboxes are available to insert lists of up and down regulated genes. The search interface provides a link to the Enrichr software. Clicking this button passes the input gene lists to Enrichr for independent enrichment analysis in a new web page. The Example button fills the textboxes with sample lists. The Aggravate/Reverse slider swaps the up list with the down list so that the search is done in reverse mode. The result panel displays the top 50 matching experiments in a table where only 10 entries are displayed per page. The screenshot is from Case Study 1: searching for perturbations that could potentially reverse breast cancer progression and recurrence given a pre-compiled list of 374 breast cancer prognosis biomarker genes.
Figure 2.
Figure 2.
LCB browse interface. The browse interface has two types of canvases: The experiment canvases on the left and the enrichment canvases on the right. The experiment canvases are made of all experiments for a specific cell line in a specific batch. Each tile represents one condition and the tiles are arranged by gene content similarity. On the right the enrichment canvases display gene set enrichment results where each tile on these canvases represent a gene-set from a gene-set library. Gene-sets are arranged on the canvas based on their gene content similarity and enriched terms for the selected condition from the experiment canvas are highlighted in circles. Users can search for a specific condition using the search bar on the top, select a specific batch or cell type using the dropdown lists near the experiment canvases, and select a gene-set library using the dropdown menu on top of the enrichment canvases.
Figure 3.
Figure 3.
Four views of the clustered experimental data. (A) Tiles represent individual conditions and are colored by their average change where bright red indicates more change. A slider below the canvas controls contrast. (B) The time point view colors the canvas by time points. (C) The drug view colors tiles by drug or ligand types, and a dropdown menu beneath the canvas allows users to highlight tiles of the same drug or ligand perturbations. (D) Gene-set enrichment analysis results, applied to the differentially expressed genes of the clicked tile, are displayed on the MGI-MP gene-set library enrichment canvas. Each tile on this canvas represents a gene-set, and circles highlight the enriched terms. Bright tiles represent high similarity among gene sets in the local region of the bright tile. A list box on top of the canvas allows user to switch between 30 different gene set libraries. The canvases fold on themselves such that the edges are connected to opposite edges forming a torus.
Figure 4.
Figure 4.
Example for a search query using LCB. The search for all experiments that use the MCF10A cell line, have a perturbation name that ends with ‘atinib’ and a time-point of 6 h is applied with the query ‘*atinib * 6 h MCF10A’. Users can then select one of the entries to see their position within their associated canvas.
Figure 5.
Figure 5.
Visualization of enrichment analyses of selected perturbations from the results shown in Figure 1: (A–C) PD0332991; (D–F) Tyrophostin AG 1478 and (G–I) the Benezensulfonamide derivative.
Figure 6.
Figure 6.
Top perturbations that match the top 100 genes significantly up-regulated by IL-1 (A) or IL-6 (B) treatment of monocyte derived macrophages.
Figure 7.
Figure 7.
Canvases for the top ranked IL-1 perturbation: IL-1 applied to MCF7 cells at a concentration of 100 ng/μl for 3 h. (A) The selected perturbation is surrounded by similar perturbations which are either IL-1 or TNF-alpha treatments. (B) Visualization of the enriched terms using the MGI mammalian phenotypes gene set library.
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