Integrative spatial and genomic analysis of tumor heterogeneity with Tumoroscope
Abstract Spatial and genomic heterogeneity of tumors are crucial factors influencing cancer progression, treatment, and survival. However, a technology for direct mapping the clones in the tumor tissue based on somatic point mutations is lacking. Here, we propose Tumoroscope, the first probabilistic...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53374-3 |
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| author | Shadi Shafighi Agnieszka Geras Barbara Jurzysta Alireza Sahaf Naeini Igor Filipiuk Alicja Rączkowska Hosein Toosi Łukasz Koperski Kim Thrane Camilla Engblom Jeff E. Mold Xinsong Chen Johan Hartman Dominika Nowis Alessandra Carbone Jens Lagergren Ewa Szczurek |
| author_facet | Shadi Shafighi Agnieszka Geras Barbara Jurzysta Alireza Sahaf Naeini Igor Filipiuk Alicja Rączkowska Hosein Toosi Łukasz Koperski Kim Thrane Camilla Engblom Jeff E. Mold Xinsong Chen Johan Hartman Dominika Nowis Alessandra Carbone Jens Lagergren Ewa Szczurek |
| author_sort | Shadi Shafighi |
| collection | DOAJ |
| description | Abstract Spatial and genomic heterogeneity of tumors are crucial factors influencing cancer progression, treatment, and survival. However, a technology for direct mapping the clones in the tumor tissue based on somatic point mutations is lacking. Here, we propose Tumoroscope, the first probabilistic model that accurately infers cancer clones and their localization in close to single-cell resolution by integrating pathological images, whole exome sequencing, and spatial transcriptomics data. In contrast to previous methods, Tumoroscope explicitly addresses the problem of deconvoluting the proportions of clones in spatial transcriptomics spots. Applied to a reference prostate cancer dataset and a newly generated breast cancer dataset, Tumoroscope reveals spatial patterns of clone colocalization and mutual exclusion in sub-areas of the tumor tissue. We further infer clone-specific gene expression levels and the most highly expressed genes for each clone. In summary, Tumoroscope enables an integrated study of the spatial, genomic, and phenotypic organization of tumors. |
| format | Article |
| id | doaj-art-3d9a8629e7334bd7b650d8ad57bae2ee |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-3d9a8629e7334bd7b650d8ad57bae2ee2025-08-20T03:41:47ZengNature PortfolioNature Communications2041-17232024-10-0115111610.1038/s41467-024-53374-3Integrative spatial and genomic analysis of tumor heterogeneity with TumoroscopeShadi Shafighi0Agnieszka Geras1Barbara Jurzysta2Alireza Sahaf Naeini3Igor Filipiuk4Alicja Rączkowska5Hosein Toosi6Łukasz Koperski7Kim Thrane8Camilla Engblom9Jeff E. Mold10Xinsong Chen11Johan Hartman12Dominika Nowis13Alessandra Carbone14Jens Lagergren15Ewa Szczurek16Faculty of Mathematics, Informatics and Mechanics, University of WarsawFaculty of Mathematics, Informatics and Mechanics, University of WarsawFaculty of Mathematics, Informatics and Mechanics, University of WarsawFaculty of Mathematics, Informatics and Mechanics, University of WarsawFaculty of Mathematics, Informatics and Mechanics, University of WarsawFaculty of Mathematics, Informatics and Mechanics, University of WarsawSciLifeLab, School of EECS, KTH Royal Institute of TechnologyDepartment of Pathology, Medical University of WarsawDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Cell and Molecular Biology, Karolinska InstitutetDepartment of Cell and Molecular Biology, Karolinska InstitutetDepartment of Oncology-Pathology, Karolinska InstitutetDepartment of Oncology-Pathology, Karolinska InstitutetLaboratory of Experimental Medicine, Medical University of WarsawSorbonne Universite, CNRS, IBPS, Laboratoire de Biologie Computationnelle et QuantitativeSciLifeLab, School of EECS, KTH Royal Institute of TechnologyFaculty of Mathematics, Informatics and Mechanics, University of WarsawAbstract Spatial and genomic heterogeneity of tumors are crucial factors influencing cancer progression, treatment, and survival. However, a technology for direct mapping the clones in the tumor tissue based on somatic point mutations is lacking. Here, we propose Tumoroscope, the first probabilistic model that accurately infers cancer clones and their localization in close to single-cell resolution by integrating pathological images, whole exome sequencing, and spatial transcriptomics data. In contrast to previous methods, Tumoroscope explicitly addresses the problem of deconvoluting the proportions of clones in spatial transcriptomics spots. Applied to a reference prostate cancer dataset and a newly generated breast cancer dataset, Tumoroscope reveals spatial patterns of clone colocalization and mutual exclusion in sub-areas of the tumor tissue. We further infer clone-specific gene expression levels and the most highly expressed genes for each clone. In summary, Tumoroscope enables an integrated study of the spatial, genomic, and phenotypic organization of tumors.https://doi.org/10.1038/s41467-024-53374-3 |
| spellingShingle | Shadi Shafighi Agnieszka Geras Barbara Jurzysta Alireza Sahaf Naeini Igor Filipiuk Alicja Rączkowska Hosein Toosi Łukasz Koperski Kim Thrane Camilla Engblom Jeff E. Mold Xinsong Chen Johan Hartman Dominika Nowis Alessandra Carbone Jens Lagergren Ewa Szczurek Integrative spatial and genomic analysis of tumor heterogeneity with Tumoroscope Nature Communications |
| title | Integrative spatial and genomic analysis of tumor heterogeneity with Tumoroscope |
| title_full | Integrative spatial and genomic analysis of tumor heterogeneity with Tumoroscope |
| title_fullStr | Integrative spatial and genomic analysis of tumor heterogeneity with Tumoroscope |
| title_full_unstemmed | Integrative spatial and genomic analysis of tumor heterogeneity with Tumoroscope |
| title_short | Integrative spatial and genomic analysis of tumor heterogeneity with Tumoroscope |
| title_sort | integrative spatial and genomic analysis of tumor heterogeneity with tumoroscope |
| url | https://doi.org/10.1038/s41467-024-53374-3 |
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