Expression2Kinases: Genome-wide mRNA profiling provides a snapshot of the global state of cells under different conditions. However, mRNA levels do not provide direct understanding of upstream regulatory mechanisms. Here, we present a new approach called Expression2Kinases (X2K) to identify upstream regulators likely responsible for observed patterns in genome-wide gene expression. By integrating ChIP-seq/chip and position-weight-matrices (PWMs) data, protein-protein interactions, and kinase-substrate phosphorylation reactions, we can better identify regulatory mechanisms upstream of genome-wide differences in gene expression. We validated X2K by applying it to recover drug targets of FDA approved drugs from drug perturbations followed by mRNA expression profiling; to map the regulatory landscape of 44 stem cells and their differentiating progeny; to profile upstream regulatory mechanisms of 327 breast cancer tumors; and to detect pathways from profiled hepatic stellate cells and hippocampal neurons. The X2K approach can advance our understanding of cell signaling and unravel drugs mechanisms of action.
Website: X2K | PMID: 22080467

Lists2Networks (Integrated Analysis for Lists of Mammalian Genes) is a web-based system that allows users to upload and analyze lists of mammalian gene-sets in a client-server software application. Within their workspace users can examine the overlap among the lists they upload, manipulate lists with different set operations, expand lists using existing mammalian networks of protein-protein, co-expression correlations, or background knowledge annotation correlations, and apply simple gene-set enrichment analyses on many gene lists at once against a plethora of prior knowledge datasets.
Website: List2Networks | PMID: 20152038

GATE (Grid Analysis of Time-series Expression) is a computational software platform for integrated visualization and analysis of expression time-series. Given a high-dimensional time-series dataset, GATE employs a clustering algorithm which creates movies of expression dynamics by assigning individual genes/proteins to hexagons on a hexagonal array and dynamically coloring each hexagon according to the expression level of the molecular species to which it is associated. Additionally, in order to infer potential regulatory control mechanisms from patterns of time-series correlations, GATE allows interactive interrogation of the movies with a wide variety of background knowledge datasets.
Website: GATE | PMID: 19892805

KEA (Kinase Enrichment Analysis) is a web-based tool with an underlying database providing users with the ability to link lists of mammalian proteins/genes with the kinases that phosphorylate them. The system draws from several available kinase-substrate databases to computes kinase enrichment probability based on the distribution of kinase-substrate proportions in the background kinase-substrate database compared with kinases found to be associated with an input list of genes/proteins.
Websites: KEA web-interface | KEA command-line version | PMID: 19176546

ChEA (ChIP-X Enrichment Analysis) database contains manually extracted datasets of transcription-factor/target-gene interactions from over 100 experiments such as ChIP-chip, ChIP-seq, ChIP-PET applied to mammalian cells. We use the database to analyze mRNA expression data where we perform gene-list enrichment analysis as the prior biological knowledge gene-list library. The system is delivered as web-based interactive software. With this software users can input lists of mammalian genes for which the program computes over-representation of transcription factor targets from the ChEA database.
Websites: ChEA web interface | ChEA command-line version | PMID: 20709693

Genes2Networks is a command-line software tool that can be used to place lists of mammalian genes in the context of a background mammalian signalome and interactome networks. The input to the program is a list of human Entrez Gene gene symbols and background networks in SIG format, while the output includes: (a) all identified interactions for the genes/proteins, (b) a subnetwork connecting the genes/proteins using intermediate components that are used to connect the genes, (c) ranking of the specificity of intermediate components to interact with the list of genes/proteins.
Websites: Genes2Networks command-line version | Genes2Networks web interface | PMID: 17916244

AVIS (AJAX Viewer for Signaling Networks) is a visualization tool for viewing and sharing intracellular signaling, gene regulation and protein interaction networks. AVIS is implemented as an AJAX enabled syndicated Google gadget. It allows any webpage to render an image from a text file representation of signaling, gene regulatory, or protein interaction networks.
Website: AVIS | PMID: 17855420

SNAVI (Signaling Networks Analysis and Visualization) is a Windows-based desktop application that implements standard network analysis methods to compute the clustering, connectivity distribution, and detection of network motifs, as well as provides means to visualize networks and network motifs. SNAVI is capable of generating linked web pages from network datasets loaded in text format. SNAVI can also create networks from lists of gene or protein names. SNAVI is a useful tool for analyzing, visualizing and sharing cell signaling data. SNAVI is open source free software.
Website: SNAVI | PMID: 19154595

Sig2BioPAX is a command-line Java program that can be used to convert structured text files describing molecular interactions into the BioPAX Level 3 standard format.
Website: Sig2BioPAX | PMID: 21418653