Exceptions to Broad Tissue-Specific Transcriptomic Interdependence: Searching for Independence in Expression of Genes

Area of Science:

• Genomics
• Gene Expression Analysis
• Bioinformatics

Background:

• Gene correlation within tissues is well-studied.
• Genes with Independent In Expression (INDIE) patterns are poorly understood.
• INDIE genes may indicate tissue admixtures or novel regulatory mechanisms.

Purpose of the Study:

• To identify INDIE genes across various human tissues.
• To investigate the replicability of INDIE genes in external datasets.
• To explore the potential of INDIE genes as biomarkers.

Main Methods:

• Calculated biweight midcorrelation for gene pairs in GTEx v8 dataset.
• Defined INDIE genes using absolute (r) and relative (Z-score) thresholds.
• Validated INDIE gene findings in external whole blood and ileum datasets.

Main Results:

• One gene, RPL13P12, was INDIE across all GTEx tissues but lacked external validation.
• HIST1H2AD and TMEM176B were INDIE in GTEx whole blood and replicated across four external datasets.
• ACAT2 and HBB showed replication in external ileal datasets, highlighting tissue heterogeneity's role.

Conclusions:

• Described a set of genes with independent expression patterns across GTEx tissues.
• External validation confirmed specific INDIE genes, such as HIST1H2AD and TMEM176B.
• Findings suggest both tissue heterogeneity and novel gene expression regulatory mechanisms contribute to INDIE patterns.