Transcriptomic Analysis in Autism Spectrum Disorder Suggests Three Molecular Subtypes with Distinct Phenotypic Profiles and Functional Pathways
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2026
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| author | Tao |
| author_facet | Tao |
| contents | <p><strong><span lang="EN-US">Background</span></strong></p> <p><span lang="EN-US">Autism spectrum disorder (ASD) is highly heterogeneous. Molecular subtyping of ASD based on gene expression data will help address the biological heterogeneity of ASD. </span></p> <p><strong><span lang="EN-US">Methods</span></strong></p> <p><span lang="EN-US">We analyzed RNA-seq data from 1,711 ASD samples, employing unsupervised non-negative matrix factorization (NMF) to identify subtypes, and characterized them with five categories: overall ASD symptoms, social-communication deficits, restricted-repetitive-stereotyped behaviors, cognitive-adaptive function and behavior problems. We also explored subtype-specific differentially expressed genes, functional pathways, and spatiotemporal/cell-type characteristics.</span></p> <p><strong><span lang="EN-US">Results</span></strong></p> <p><span lang="EN-US">NMF analysis identified three ASD subtypes. The three subtypes exhibited different phenotypic patterns: Cluster 1 had severe restricted and repetitive behaviors, Cluster 3 mainly had social communication impairments, Cluster 2 presented milder symptoms and better cognitive function. Differential expressed genes analysis linked Cluster 1 and Cluster3 to nervous system dysfunctions and morphogenesis of a branching structure, while Cluster 2 to immune system processes. The clusters also exhibited distinct gene expression patterns across brain regions, developmental stages, and cell types. Validation in two independent datasets confirmed the reproducibility of the distinct clusters.<strong> </strong></span></p> <p><strong><span lang="EN-US">Conclusions</span></strong></p> <p><span lang="EN-US">This molecular subtyping reveals biologically and clinically distinct subtypes of ASD, helping to understand the atypical mechanisms underlying ASD heterogeneity. It also contributes to the development of personalized therapeutic strategies for distinct subtypes. <span> </span></span></p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_19124179 |
| institution | Zenodo |
| language | |
| publishDate | 2026 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Transcriptomic Analysis in Autism Spectrum Disorder Suggests Three Molecular Subtypes with Distinct Phenotypic Profiles and Functional Pathways Tao <p><strong><span lang="EN-US">Background</span></strong></p> <p><span lang="EN-US">Autism spectrum disorder (ASD) is highly heterogeneous. Molecular subtyping of ASD based on gene expression data will help address the biological heterogeneity of ASD. </span></p> <p><strong><span lang="EN-US">Methods</span></strong></p> <p><span lang="EN-US">We analyzed RNA-seq data from 1,711 ASD samples, employing unsupervised non-negative matrix factorization (NMF) to identify subtypes, and characterized them with five categories: overall ASD symptoms, social-communication deficits, restricted-repetitive-stereotyped behaviors, cognitive-adaptive function and behavior problems. We also explored subtype-specific differentially expressed genes, functional pathways, and spatiotemporal/cell-type characteristics.</span></p> <p><strong><span lang="EN-US">Results</span></strong></p> <p><span lang="EN-US">NMF analysis identified three ASD subtypes. The three subtypes exhibited different phenotypic patterns: Cluster 1 had severe restricted and repetitive behaviors, Cluster 3 mainly had social communication impairments, Cluster 2 presented milder symptoms and better cognitive function. Differential expressed genes analysis linked Cluster 1 and Cluster3 to nervous system dysfunctions and morphogenesis of a branching structure, while Cluster 2 to immune system processes. The clusters also exhibited distinct gene expression patterns across brain regions, developmental stages, and cell types. Validation in two independent datasets confirmed the reproducibility of the distinct clusters.<strong> </strong></span></p> <p><strong><span lang="EN-US">Conclusions</span></strong></p> <p><span lang="EN-US">This molecular subtyping reveals biologically and clinically distinct subtypes of ASD, helping to understand the atypical mechanisms underlying ASD heterogeneity. It also contributes to the development of personalized therapeutic strategies for distinct subtypes. <span> </span></span></p> |
| title | Transcriptomic Analysis in Autism Spectrum Disorder Suggests Three Molecular Subtypes with Distinct Phenotypic Profiles and Functional Pathways |
| url | https://doi.org/10.5281/zenodo.19124179 |