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However, the limited diversity and accuracy of \u201cgold standard\u201d datasets hindered the effectiveness and fairness of benchmarking rapidly growing ST analysis tools.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>To address this issue, we proposed Spider, a flexible and comprehensive framework for simulating ST data without requiring real ST data as a reference. By characterizing the spatial patterns using cell type proportions and transition matrix between adjacent cells, Spider can produce more realistic and diverse simulated data and offer enhanced modeling flexibility compared to existing simulation methods. Additionally, Spider provides interactive features for customizing the spatial domain, such as zone segmentation and integration of histology imaging data. Benchmark analyses demonstrate that Spider outperforms other simulation tools in preserving the spatial characteristics of real ST data and facilitating the evaluation of downstream analysis methods. Spider is implemented in Python and available at https:\/\/github.com\/YANG-ERA\/Spider.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>All codes, simulated ST data in this paper are publicly available at https:\/\/github.com\/YANG-ERA\/Spider.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf562","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:11:59Z","timestamp":1763125919000},"source":"Crossref","is-referenced-by-count":1,"title":["Spider: a flexible and unified framework for simulating spatial transcriptomics data"],"prefix":"10.1093","volume":"42","author":[{"given":"Jiyuan","family":"Yang","sequence":"first","affiliation":[{"name":"School of Mathematical Sciences, Shanghai Jiao Tong University , Shanghai, 200240,","place":["China"]}]},{"given":"Nana","family":"Wei","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute , Beijing, 100142,","place":["China"]},{"name":"Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine , Shanghai, 200025,","place":["China"]}]},{"given":"Yang","family":"Qu","sequence":"additional","affiliation":[{"name":"The Guangxi Key Laboratory of Intelligent Precision Medicine, Guangxi Zhuang Autonomous Region , Nanning, 530007,","place":["China"]}]},{"given":"Congcong","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Mathematical and Information Sciences, Shaoxing University , Shaoxing, Zhejiang 312000,","place":["China"]}]},{"given":"Weiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Mathematical and Information Sciences, Shaoxing University , Shaoxing, Zhejiang 312000,","place":["China"]}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Natural Sciences, MOE-LSC, School of Mathematical Sciences, CMA-Shanghai, SJTU-Yale Joint Center for Biostatistics and Data Science, Shanghai Jiao Tong University , Shanghai, 200240,","place":["China"]}]},{"given":"Hua-Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute , Beijing, 100142,","place":["China"]},{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, 100191,","place":["China"]},{"name":"Center for Precision Medicine Multi-Omics Research, Institute of Advanced Clinical Medicine, Peking University , Beijing, 100191,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5438-7277","authenticated-orcid":false,"given":"Xiaoqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine , Shanghai, 200025,","place":["China"]},{"name":"Hainan International Medical Center, Shanghai Jiao Tong University School of Medicine , Hainan, 571400,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"2026011114021709900_btaf562-B1","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1093\/nar\/gkaa740","article-title":"SpaGE: spatial gene enhancement using scRNA-seq","volume":"48","author":"Abdelaal","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2026011114021709900_btaf562-B2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s42003-020-01247-y","article-title":"Single-cell and spatial transcriptomics 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