SlideCNA: spatial copy number alteration detection from Slide-seq-like spatial transcriptomics data
Solid tumors are spatially heterogeneous in their genetic, molecular, and cellular composition, but recent spatial profiling studies have mostly charted genetic and RNA variation in tumors separately. To leverage the potential of RNA to identify copy number alterations (CNAs), we develop SlideCNA, a computational tool to extract CNA signals from sparse spatial transcriptomics data with near single cellular resolution. SlideCNA uses expression-aware spatial binning to overcome sparsity limitations while maintaining spatial signal to recover CNA patterns. We test SlideCNA on simulated and real Slide-seq data of (metastatic) breast cancer and demonstrate its potential for spatial subclone detection.
Authors
- Aviv Regev (ORCID: https://orcid.org/0000-0003-3293-3158)
- Jan Watter (ORCID: https://orcid.org/0000-0001-7519-731X)
- Julia Waldman (ORCID: https://orcid.org/0000-0002-0584-5833)
- Judit Jané‐Valbuena (ORCID: https://orcid.org/0000-0002-5651-1745)
- Simon Mages (ORCID: https://orcid.org/0000-0003-1447-6811)
- Åsa Segerstolpe (ORCID: https://orcid.org/0000-0002-3700-9661)
- Orr Ashenberg (ORCID: https://orcid.org/0000-0002-7802-8834)
- Ana Lako (ORCID: https://orcid.org/0000-0003-2931-6212)
- Scott J. Rodig (ORCID: https://orcid.org/0000-0003-1761-9769)
- Nikhil Wagle (ORCID: https://orcid.org/0000-0003-3332-9438)
- Orit Rozenblatt–Rosen (ORCID: https://orcid.org/0000-0001-6313-3570)
- Michal Slyper (ORCID: https://orcid.org/0000-0002-3002-0366)
- Ofir Cohen (ORCID: https://orcid.org/0000-0002-0043-6838)
- Karla Helvie (ORCID: https://orcid.org/0000-0002-3514-0332)
- Ralf Strasser
- Diane Zhang (ORCID: https://orcid.org/0000-0002-0268-4413)
- Daniel L. Abravanel (ORCID: https://orcid.org/0000-0002-0129-1618)
- Johanna Klughammer (ORCID: https://orcid.org/0000-0002-3628-9278)
- Fei Chen (ORCID: https://orcid.org/0000-0003-2308-3649)
- Evan Murray (ORCID: https://orcid.org/0000-0002-9195-7478)
Institutions
- Broad Institute (US)
- Ben-Gurion University of the Negev (IL)
- Brigham and Women's Hospital (US)
- HES-SO Genève (CH)
- Gene Therapy Laboratory (FR)
- Dana-Farber Cancer Institute (US)
- Massachusetts Institute of Technology (US)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Genome biology
- Published
- 2025-05-02
- DOI
- https://doi.org/10.1186/s13059-025-03573-y
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Human Frontier Science Program
- Deutsche Forschungsgemeinschaft
- Else Kröner-Fresenius-Stiftung
- Israel Science Foundation
- Ludwig-Maximilians-Universität München