Interpretable Spatial Gradient Analysis for Spatial Transcriptomics Data.

التفاصيل البيبلوغرافية
العنوان: Interpretable Spatial Gradient Analysis for Spatial Transcriptomics Data.
المؤلفون: Liang Q; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center., Soto LS; Department of Translational Molecular Pathology, UT MD Anderson Cancer Center., Haymaker C; Department of Translational Molecular Pathology, UT MD Anderson Cancer Center., Chen K; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 21. Date of Electronic Publication: 2024 Mar 21.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: Cellular anatomy and signaling vary across niches, which can induce gradated gene expressions in subpopulations of cells. Such spatial transcriptomic gradient (STG) makes a significant source of intratumor heterogeneity and can influence tumor invasion, progression, and response to treatment. Here we report Local Spatial Gradient Inference (LSGI), a computational framework that systematically identifies spatial locations with prominent, interpretable STGs from spatial transcriptomic (ST) data. To achieve so, LSGI scrutinizes each sliding window employing non-negative matrix factorization (NMF) combined with linear regression. With LSGI, we demonstrated the identification of spatially proximal yet opposite directed pathway gradients in a glioblastoma dataset. We further applied LSGI to 87 tumor ST datasets reported from nine published studies and identified both pan-cancer and tumor-type specific pathways with gradated expression patterns, such as epithelial mesenchymal transition, MHC complex, and hypoxia. The local gradients were further categorized according to their association to tumor-TME (tumor microenvironment) interface, highlighting the pathways related to spatial transcriptional intratumoral heterogeneity. We conclude that LSGI enables highly interpretable STG analysis which can reveal novel insights in tumor biology from the increasingly reported tumor ST datasets.
Competing Interests: Competing Interests The authors declare no competing interests.
معلومات مُعتمدة: U01 CA247760 United States CA NCI NIH HHS
سلسلة جزيئية: Dryad 10.5061/dryad.h70rxwdmj
تواريخ الأحداث: Date Created: 20240402 Latest Revision: 20240408
رمز التحديث: 20240408
مُعرف محوري في PubMed: PMC10983986
DOI: 10.1101/2024.03.19.585725
PMID: 38562886
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2024.03.19.585725