Fig 1.
QuIN allows users to upload diverse data types and formats and it enables building, querying, annotating, and analyzing chromatin interaction networks. QuIN also integrates publically available databases for network annotation and enrichment.
Fig 2.
A screenshot of QuIN’s web interface highlighting its features.
(1) menus for uploading data and building networks, (2) options for visualizing and annotating a network, (3) target discovery menu for visualizing and exporting direct and indirect targets from source annotations to target annotations (4) network visualization panel, (5) options for searching, querying, or exporting the network, (6) the menu for performing GO Enrichment Analysis on the current subnetwork, (7) tools for summarizing network construction statistics, centrality measures and enrichment of interactions between annotations, (8) dialog box showing additional information about a selected node, including centrality measures, SNPs, and associated diseases.
Fig 3.
A breast cancer case study with QuIN.
(A) Workflow of the case study analysis. (1) Upload the DNASE-Seq and Interaction data into QuIN, constructing an MCF-7 interaction network where each node represents an open chromatin site. (2) Annotate the network with Non-Coding Variants (NCVs) in MCF-7 and cancer associated gene lists. (3) Perform target discovery between NCVs (source) and promoters and cancer gene lists (targets) and find all direct and indirect associations between NCVs and their gene targets. (B) A simplified network example showing the interactions between a node harboring an NCV (shown in purple) and known oncogenes (green), genes associated with poor prognosis in breast cancer (red), and tumor suppressor genes (blue). Nodes shown were selected based on their overlap with an annotation or if the node is necessary to connect the NCV to the annotated node. Width of the edges correspond to the relative number of paired end tags supporting the edge.
Fig 4.
Comparison of ChIA-PET gene targets with nearest gene targets.
(A) A cartoon describing different approaches to associate NCVs with gene targets (Nearest TSS, Direct Targets, & Indirect Targets). (B) Enrichment p-values (based on Fisher’s exact test) of cancer related genes (known oncogenes (green), tumor suppressor genes (blue), poor prognosis genes (red), and the combined gene list (purple)) among NCV gene targets obtained via nearest TSS, direct target, indirect target associations. (C) Boxplot showing the differential expression (between cancer and normal tissues) for NCV target genes obtained via nearest TSS, direct target, indirect target associations.