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Bioinformatics, Computational and Systems Biology

Bioinformatics, Computational and Systems Biology - Poster Session A & B

A6 - ECLIPSE: A Spatial Multi-Omics Platform for Chromatin Architecture, Gene Expression, and Metabolism in Aging Brain

Thursday, October 9, 2025

10:00 AM - 11:00 AM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

Tianyang Xu, M.S.

Ph.D candidate and graduate student researcher
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego
San Diego, California, United States

Co-Author(s)

Zhiliang Bai, PhD

Postdoc Associate
Yale University
New Haven, Connecticut, United States
YL

Yajuan Li, PhD

Postdoctoral Researcher
University of California San Diego, United States

Last Author(s)

SZ

Sheng Zhong

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, United States

Primary Investigator(s)

SZ

Sheng Zhong

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, United States

Co-Author(s)

FH

Fatemeh Hadi

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, United States
RC

Risa Cozza

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego
Chula Vista, United States
TP

Taojin Peng

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, United States
WZ

Wenxin Zhao

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, United States
ZQ

Zhijie Qi

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, United States
QW

Qiuyang Wu

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, United States
YL

Yuan Liu

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, United States
BT

Bo Tao

Department of Pathology, Yale University School of Medicine, United States
Lingyan Shi, PhD

Associate Professor
University of California San Diego
La Jolla, California, United States
RF

Rong Fan

Harold Hodgkinson Professor
Yale University
New Haven, Connecticut, United States

Introduction: : Aging and neurodegeneration involve complex, interconnected changes in nuclear organization, metabolism, and gene expression. The 3D genome architecture orchestrates spatial chromatin folding to regulate gene activity, while metabolic intermediates act as cofactors for epigenetic enzymes that shape chromatin landscapes. The capability to spatially explore this dynamic axis in tissue is critical to decoding the molecular basis of cognitive decline. Here, we developed the ECLIPSE (Epigenomic Chromatin conformation, Label-free metabolic Imaging, and transcriptomics co-Profiling of Spatial Expression) system, a spatial omics innovation method that achieves unbiased concurrent profiling of the transcriptome, metabolites, and multi-way chromatin conformation (3D genome) on the same slide of a tissue section. In addition to the method, we provided a Dockerized web page portal for streamlined data analysis and synchronization between different data modalities. We further applied a series of AD modeling mouse hippocampus sections, as well as four human hippocampus sections. ECLIPSE reveals the patterns and correlations between amyloid plaque formation, DNA architecture disruption, and alterations in RNA expression profiles. The distances correlating these changes are then modeled, suggesting a synchronized profiling method for brain aging, as well as the preceding factors of chromatin topology changes and their relationship to Alzheimer's disease (AD) pathology. ECLIPSE establishes a powerful platform for multimodal spatial omics profiling to uncover molecular determinants of neurodegenerative disease and provides a promising framework for developing spatially targeted neurotherapeutics.

Materials and

Methods: : ECLIPSE starts with ultra-resolution SRS label-free imaging of the sectioned tissues. Spatial barcodes were delivered with Deterministic Barcoding in Tissue (DBiT-Seq) microfluidic system. Interactomes were then labeled by droplet barcoding. The sample was then processed for deep sequencing. We applied 3-month, 6-month, and 9-month 5XFAD mice, along with a wild-type control, for temporal modeling with ECLIPSE, and four female human hippocampus sections. The ECLIPSE data analysis portal was deployed for complete analysis and image registration.

Results, Conclusions, and Discussions:: Applied to hippocampal regions of Alzheimer’s disease (AD) model mice and human AD brain tissues, ECLIPSE revealed spatially coordinated accumulations of amyloid plaques, accompanied by immune remodeling, oxidative dysregulation, and disruptions in local chromatin architecture. We observed reduced short-range DNA interactions and increased chromatin spatial dispersion near plaques, which may reflect differential chromatin responses in astrocytes and neurons. Notably, distortions in chromatin architecture preceded transcriptomic and metabolite alterations during aging, suggesting a key role for genome topology in early local pathology.

Acknowledgements and/or References (Optional)::