Human transcriptional gene regulatory network compiled from 14 data resources

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• The transcriptional regulatory network (TRN) governs gene expression for cellular functions.
• Transcription factors (TF) and target genes (TG) are key components of TRNs.
• Existing databases catalog human TRNs, but lack comparative assessments.

Purpose of the Study:

• To conduct a comparative assessment of human TRN resources.
• To assemble a comprehensive human TRN by integrating data from multiple databases.
• To provide a reliable resource for understanding transcriptional regulation.

Main Methods:

• Compared over 2.2 million regulatory pairs from 14 different resources.
• Analyzed TF and TG commonality, expression correlation, gene ontology overlap, and PubMed co-citations.
• Developed a confidence score for each TF-TG regulatory pair based on its presence across databases.

Main Results:

• TF and TG were common across resources, but regulatory pairs varied significantly.
• TF-TG pairs showed weak expression correlation and low representation of transcriptional repression.
• Assembled a comprehensive human TRN with 2,246,598 TF-TG pairs, including 44,284 with activation/repression information.

Conclusions:

• This study provides the most complete human TRN assembled to date.
• The integrated network highlights inconsistencies in regulatory pair data across resources.
• The TRN serves as a valuable resource for benchmarking prediction tools and advancing functional genomics research.