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Peer-Reviewed Publication
Nat Commun2026June 13, 2026Journal Article

Spatial architecture of autism pathogenesis reveals mosaic structural disarray during early development.

Li Lin1, Tzuen Yih Saw2, Nigel Chou2, Jie Lin Jolene Goh2, Jing Eugene Kwa2, Wan Kee Chock2, Vipul Singhal2,3, Zheng Li2, Mike J Huang2, Huck Hui Ng2,4,5,6,7,8, Chiea Chuen Khor2,9,10, Hwee Lee Kuan1,5,11,12,13, Kok Hao Chen2, Shyam Prabhakar14,15, Jinyue Liu16
1Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
2Genome Institute of Singapore (GIS), Agency for Science Technology and Research (A*STAR), Singapore, Republic of Singapore.
3Terray Therapeutics Inc., Monrovia, CA, USA.
4Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Republic of Singapore.
5School of Biological Sciences, Nanyang Technological University, Singapore, Republic of Singapore.
6Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
7Department of Biological Sciences, National University of Singapore, Singapore, Republic of Singapore.
8School of Medicine, Nazarbayev University, Astana, Republic of Kazakhstan.
9Singapore Eye Research Institute (SERI), Singapore, Republic of Singapore.
10SingHealth and Duke-NUS Ophthalmology & Visual Sciences Academic Clinical Programme (EYE ACP), Singapore, Republic of Singapore.
11School of Computing, National University of Singapore, Singapore, Republic of Singapore.
12International Research Laboratory on Artificial Intelligence, Institute for Infocomm Research, Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
13Centre for Frontier AI Research (CFAR), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
14Genome Institute of Singapore (GIS), Agency for Science Technology and Research (A*STAR), Singapore, Republic of Singapore. prabhakars@a-star.edu.sg.
15National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, Republic of Singapore. prabhakars@a-star.edu.sg.
16Genome Institute of Singapore (GIS), Agency for Science Technology and Research (A*STAR), Singapore, Republic of Singapore. liu_jinyue@a-star.edu.sg.
PubMed DOI

Abstract

Autism spectrum disorder (ASD) has been associated with diverse genetic factors and molecular changes. Yet, how pathophysiology emerges during development and contributes to clinical heterogeneity remains unclear. Here we use spatial and single-cell transcriptomics of genetically diverse patient-derived organoids of the prenatal cortex to map the spatial architecture of ASD pathogenesis. We find a…

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