[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331616-105":59,"doc-detail-331616-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","inferring-allele-specific-copy-number-aberrations-and-tumor-phylogeography-from-spatially-resolved-transcriptomics","Inferring allele-specific copy number aberrations and tumor phylogeography from spatially resolved transcriptomics","","Analyzing somatic evolution across time and within physical space is a central challenge in cancer research. Spatially resolved transcriptomics (SRT) measures gene expression at thousands of tissue locations but does not directly reveal genomic aberrations. CalicoST is introduced to infer allele-specific copy number aberrations and reconstruct tumor phylogeography jointly from SRT. The method detects CNAs that total copy number analysis cannot see, including copy-neutral loss of heterozygosity and mirrored subclonal CNAs, using nine Human Tumor Atlas Network patients.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/inferring-allele-specific-copy-number-aberrations-and-tumor-phylogeography-from-spatially-resolved-transcriptomics/331616/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/inferring-allele-specific-copy-number-aberrations-and-tumor-phylogeography-from-spatially-resolved-transcriptomics/331616.png","ImageObject",300,407,{"name":92,"@type":93},"Clementine","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does CalicoST address in spatially resolved transcriptomics?","Question",{"text":112,"@type":113},"SRT measures gene expression but cannot directly reveal genomic aberrations. CalicoST infers allele-specific copy number aberrations and reconstructs tumor evolution in space from SRT data.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which copy number aberration classes can CalicoST detect that total copy number analysis misses?",{"text":117,"@type":113},"CalicoST identifies important CNA classes, including copy-neutral loss of heterozygosity and mirrored subclonal CNAs.",{"name":119,"@type":110,"acceptedAnswer":120},"How does CalicoST reconstruct tumor phylogeography?",{"text":121,"@type":113},"It jointly models allele-specific copy number states across clones and uses spatial modeling (including correlations across neighboring genomic regions and neighboring spatial locations) to produce a phylogeographic expansion model in 3D space.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331616,1790119329,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1374391974564,"https://ap-avatar.wpscdn.com/avatar/14000253aa45c000a9e?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779874745381141002","nature methods  \nArticle [https://doi.org/10.1038/s41592-024-02438-9](https://doi.org/10.1038/s41592-024-02438-9)  \nInferring allele-specific copy number aberrationsand tumorphylogeography from spatially resolved transcriptomics  \n\n| Received: 2 November 2023\u003Cbr>Accepted: 4 September 2024\u003Cbr>Published online: 30 October 2024  Check for updates | Cong Ma1, Metin Balaban  1, Jingxian Liu2,3, Siqi Chen2,3, Michael J. Wilson4, Christopher H. Sun  5, Li Ding  2,3,6,7  & Benjamin J. Raphael  1 \u003Cbr>Analyzing somatic evolution within a tumor overtime and across space is a key challenge in cancer research. Spatially resolved transcriptomics (SRT) measures gene expression at thousands of spatial locations ina tumor, but does not directly reveal genomic aberrations. We introduce CalicoST, an algorithm to simultaneously infer allele-specific copy number aberrations (CNAs) andreconstruct spatial tumor evolution, orphylogeography, from SRT data. CalicoST identifies important classes ofCNAs—including copy-neutral loss of heterozygosity and mirrored subclonalCNAs—that are invisible to total copy number analysis. Using nine patients’data from the Human Tumor Atlas Network, CalicoST achievesan average accuracy of 86%, approximately 21% higher than existing methods. CalicoST reconstructsatumorphylogeography in three-dimensional space for two patients with multiple adjacent slices. CalicoST analysis of multipleSRT slices from a cancerous prostate organ reveals mirrored subclonalCNAson the two sides of the prostate, forming a bifurcating phylogeography in both genetic and physical space. |  |\n| --- | --- | --- |\n| Tumors evolve through acquisition of somatic mutations—including single nucleotide variations (SNVs), CNAs and large-scale structural variations. Sequencing of somatic mutations in bulk tumors1,2 or disassociated single cells3–5has revealed the genetic heterogeneity within tumorsand enabled thereconstruction of a tumor’s evolutionary history6–8. Atthe same time, tumors exhibit heterogeneity and undergo evolution within physical space, expanding and regressing based on interactions with other cells and the local microenvironment. Incorporating the spatial perspective into somatic evolution studies\u003Cbr>is a key challenge9, but has been hampered by a lack of spatial data.\u003Cbr>Recent technological advances in spatial sequencing provide a promising direction for studies ofspatiotemporal tumor evolution. While high-quality spatial DNA sequencing would provide the ideal dataset for spatiotemporal evolution studies, such technologies remain |  | inactive development10 and are not yet widely applied. However, SRT technologies that measure RNA simultaneously from thousands of spatial locations in a tissue have found extensive applications in analyzing the spatial organization of transcriptionally defined cell types within a tumor11–14. Eventhough somatic mutations occur in DNA and are not directly measured by SRT, large CNAs leave a signature in gene expression; namely, a deletion of a genomic region tends to result in underexpression of genes in the region, while an amplification tends to result in overexpression. Thus, identification ofCNAs from transcriptomic data is a promising direction for analysis of somatic evolution in tumors.\u003Cbr>Inferring CNAs from single-cell or spatially resolved transcriptomics is challenging as there are multiple explanations for an observed gene expression change, such as chromatin accessibility |\n| 1Department of Computer Science, Princeton University, Princeton, NJ, USA. 2Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. 3McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA. 4Department of Astrophysical Sciences, Princeton University, Princeton, NJ, USA. 5Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA. 6Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA. 7Department of Genetics, Washingto","cbCain74H9zgK9O7","https://ap.wps.com/l/cbCain74H9zgK9O7","pdf",10902268,23,"English","# Introduction\n## CalicoST approach and modeling\n## Performance and patient case studies","[{\"question\":\"What problem does CalicoST address in spatially resolved transcriptomics?\",\"answer\":\"SRT measures gene expression but cannot directly reveal genomic aberrations. CalicoST infers allele-specific copy number aberrations and reconstructs tumor evolution in space from SRT data.\"},{\"question\":\"Which copy number aberration classes can CalicoST detect that total copy number analysis misses?\",\"answer\":\"CalicoST identifies important CNA classes, including copy-neutral loss of heterozygosity and mirrored subclonal CNAs.\"},{\"question\":\"How does CalicoST reconstruct tumor phylogeography?\",\"answer\":\"It jointly models allele-specific copy number states across clones and uses spatial modeling (including correlations across neighboring genomic regions and neighboring spatial locations) to produce a phylogeographic expansion model in 3D space.\"}]","Inferring allele-specific copy number aberrations and tumor phylogeography from spatially resolved transcriptomics | PDF",1789994325,58]