The Signaling Pathways Project, an integrated 'omics knowledgebase for mammalian cellular signaling pathways

Area of Science:

• Molecular Biology
• Bioinformatics
• Genomics

Background:

• Mammalian cellular signaling pathways are complex and not fully understood.
• Integrating public transcriptomic and ChIP-Seq (cistromic) datasets offers a powerful approach to explore these pathways.
• Existing research literature has gaps in understanding specific pathway functions.

Purpose of the Study:

• To develop a comprehensive web knowledgebase, the Signaling Pathways Project (SPP), for exploring mammalian cellular signaling pathways.
• To enable the prediction of transcriptional regulatory relationships between pathway nodes and target genes.
• To provide researchers with a tool for data mining and discovery in signaling biology.

Main Methods:

• Designed the Signaling Pathways Project (SPP) web knowledgebase.
• Incorporated community classifications of signaling pathway nodes and bioactive small molecules.
• Mapped over 10,000 public transcriptomic or cistromic experiments to pathway nodes or biosamples.
• Generated consensus 'omics signatures (consensomes) to rank genes based on differential expression or promoter occupancy.
• Validated consensomes using literature, integrated omics data, and bench experiments.

Main Results:

• Developed SPP, a knowledgebase integrating diverse omics data for signaling pathways.
• Generated consensomes to predict novel gene target regulatory relationships.
• Validated predictions through literature alignment and experimental confirmation.
• Created a web browser interface for accessible data mining.

Conclusions:

• The SPP knowledgebase facilitates the discovery of novel functions in mammalian cellular signaling pathways.
• Consensomes are a validated method for predicting node-gene target transcriptional regulatory relationships.
• SPP provides a valuable resource for researchers investigating signaling biology and gene regulation.