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How to Use LENS

LENS is a web-based tool for interactome analysis of human genes. It takes one or two gene lists, builds a protein-protein interaction network that connects them, and computes enrichment statistics against diseases, drugs, pathways, and GWASs.

Go to the interactive tutorial

The Basics

On the home page, input a list of genes for analysis, separated by commas, spaces, or new lines. LENS accepts HGNC symbols, UniProt identifiers, and Entrez identifiers. If you would rather analyze genes associated with a disease, drug, pathway, or GWAS, type a partial name in the right-hand box. Auto-complete options will appear, and selecting one will populate the gene list automatically.

Candidate genes are the genes entered here.

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Analysis with two lists of genes

Sometimes it is useful to see whether the interactome of candidate genes connects closely to another set of genes (target genes), such as those from a pathway or disease. To enter a target list, click the "Add Target Gene Set" button beneath the candidate list. You can enter target genes by ID or by selecting a pathway or dataset from the right-hand box.

The Network

The network consists of:

  • Protein-protein interactions of the candidate genes.
  • Shortest paths from each candidate gene to the nearest target gene (if provided), or to the nearest candidate gene when only candidates are given.

Interactome visualization

Red nodes: Candidate genes and their immediate interactors.

If only the candidate list is given, LENS connects them by finding shortest paths between candidates.

Blue nodes: Target genes (no immediate interactors included).

When target genes are given, LENS connects candidate genes to target genes instead of to each other.

Orange nodes: Genes present in both candidate and target lists.

Gray nodes: Genes not in candidate or target lists.

Interacting with the network

The network is interactive. Click and drag nodes to reposition them. Hold shift and drag to select multiple nodes. Selected nodes are outlined in green and can be moved, scaled, or re-laid out together.

The initial layout uses a force-directed algorithm. Click Auto Layout to re-apply it. If nodes are selected, only those nodes are re-laid out.

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Use the mouse wheel to scale the network edges.

Use Hide Non-Connecting Nodes to remove gray nodes that do not connect candidate and target genes.

Use Hide linker labels to toggle labels for gray nodes.

Labels default to the identifier type you used for input. Use Display ID to switch between symbols, UniProt IDs, or Entrez IDs at any time.

You can investigate any gene or interaction by clicking on nodes or edges. This opens annotations in Wiki-Pi.

Network statistics

Beneath the network are tabs with additional information. The Network Statistics tab reports minimum shortest path length, average shortest path length, and disconnected nodes for the generated network and for random reference networks.

Network Min. Shortest Path Length Avg. Shortest Path Length Disconnected Nodes
Given Candidates 4 4 0
Random Candidates 17 17 2

Minimum shortest path length is the smallest distance between candidate and target genes (or between candidates when only one list is given). A value of 17 means no shortest path could be found. The average shortest path length is computed across candidate pairs or candidate-to-target distances. Disconnected nodes count candidate genes without shortest paths.

Network Min. Shortest Path Length Avg. Shortest Path Length Disconnected Nodes
Candidate to Target 3 3.5 0
Candidate to Random 8.6 8.8 0.8
Random to Target 13.4 13.4 1.6
Random to Random 17 17 2

When a target list is provided, LENS compares candidate-to-target distances against three sets of random reference networks.

GWASs, disease, drugs, and pathways tabs

These tabs display overlap significance between the generated network and gene lists from the NHGRI GWAS Catalogue, KEGG Diseases, DrugBank Drugs, and Reactome Pathways. You can view results for candidate genes only or for the entire network.

Items appear as buttons with p (p-value) and n (number of overlapping genes). Sorting by p-value is available at the top of each tab.

Downloads

All download options are in the menu beneath the network visualization. You can download SIF files for Cytoscape (entire network or shortest paths), a text file of all genes, an SVG of the raw network, or a high-quality PNG image.

Customizing

The Notes tab lets you save your own annotations. You can also click the page title ("Network Analysis Pipeline (LENS)") to rename it.

Nuts and bolts