Integrative spatial and genomic analysis of tumor heterogeneity with Tumoroscope

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 and Ewa Szczurek ()
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Shadi Shafighi: University of Warsaw
Agnieszka Geras: University of Warsaw
Barbara Jurzysta: University of Warsaw
Alireza Sahaf Naeini: University of Warsaw
Igor Filipiuk: University of Warsaw
Alicja Rączkowska: University of Warsaw
Hosein Toosi: KTH Royal Institute of Technology
Łukasz Koperski: Medical University of Warsaw
Kim Thrane: KTH Royal Institute of Technology
Camilla Engblom: Karolinska Institutet
Jeff E. Mold: Karolinska Institutet
Xinsong Chen: Karolinska Institutet
Johan Hartman: Karolinska Institutet
Dominika Nowis: Medical University of Warsaw
Alessandra Carbone: Laboratoire de Biologie Computationnelle et Quantitative
Jens Lagergren: KTH Royal Institute of Technology
Ewa Szczurek: University of Warsaw

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53374-3

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