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Published on: July 11, 2025
Mapping lncRNAs onto multilevel mRNA co‑expression modules in autism
Chen-Ling Lee1, Geng-Ming Hu2, Yi-Pei Li1
1Department of Life Science, National Taiwan University, Taipei, Taiwan.
Translational Psychiatry
|July 13, 2026
Summary
A new framework, Minimum Span Clustering Network (MSCN), maps autism spectrum disorder (ASD) gene expression hierarchies and links them to long noncoding RNAs (lncRNAs). This reveals neurodevelopmental and immune pathways involved in ASD, offering insights into gene regulation.
Area of Science:
- Genomics
- Neuroscience
- Bioinformatics
Background:
- Autism spectrum disorder (ASD) involves complex genetic and transcriptomic changes.
- Understanding gene co-expression hierarchies and long noncoding RNA (lncRNA) roles in ASD is crucial.
Purpose of the Study:
- To introduce Minimum Span Clustering Network (MSCN), a novel unsupervised framework for analyzing multilevel mRNA co-expression hierarchies.
- To apply MSCN to ASD brain transcriptomes to identify gene modules and their links to lncRNAs.
- To investigate potential regulatory axes involving transcription factors (TFs), lncRNAs, and mRNAs in ASD.
Main Methods:
- Developed and applied the Minimum Span Clustering Network (MSCN) framework to two independent ASD brain transcriptome cohorts.
- Constructed traceable, multilevel mRNA co-expression hierarchies across four resolution levels.
- Mapped lncRNAs to MSCN-derived mRNA modules and performed TF-lncRNA-mRNA mediation analyses.
Main Results:
- MSCN identified hierarchical gene modules related to neuronal, developmental, and immune pathways in ASD.
- The framework demonstrated comparable performance to existing methods (WGCNA, MEGENA) while providing explicit hierarchies.
- Over 11,000 candidate TF-lncRNA-mRNA regulatory axes were identified, including those involving high-confidence ASD genes and named lncRNA mediators.
Conclusions:
- MSCN offers a scalable approach to dissecting ASD transcriptomic architecture and identifying coding-noncoding relationships.
- The identified regulatory axes provide a valuable resource for hypothesis generation and prioritizing ASD research.
- Findings highlight interconnected neurodevelopmental and immune dysregulation programs in ASD, mediated by lncRNAs.
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