Kuemmerle, Louis B. and Luecken, Malte D. and Firsova, Alexandra B. and Barros de Andrade e Sousa, Lisa and Strasser, Lena and Mekki, Ilhem Isra and Campi, Francesco and Heumos, Lukas and Shulman, Maiia and Beliaeva, Valentina and Hediyeh-Zadeh, Soroor and Schaar, Anna C. and Mahbubani, Krishnaa T. and Sountoulidis, Alexandros and Balassa, Tamás and Kovacs, Ferenc and Horváth, Péter and Piraud, Marie and Erturk, Ali and Samakovlis, Christos and Theis, Fabian J. (2024) Probe set selection for targeted spatial transcriptomics. NATURE METHODS, 21 (12). pp. 2260-2270. ISSN 1548-7091
|
Text
KuemmerleL_Probeset.pdf - Published Version Available under License Creative Commons Attribution. Download (16MB) | Preview |
Abstract
Targeted spatial transcriptomic methods capture the topology of cell types and states in tissues at single-cell and subcellular resolution by measuring the expression of a predefined set of genes. The selection of an optimal set of probed genes is crucial for capturing the spatial signals present in a tissue. This requires selecting the most informative, yet minimal, set of genes to profile (gene set selection) for which it is possible to build probes (probe design). However, current selections often rely on marker genes, precluding them from detecting continuous spatial signals or new states. We present Spapros, an end-to-end probe set selection pipeline that optimizes both gene set specificity for cell type identification and within-cell type expression variation to resolve spatially distinct populations while considering prior knowledge as well as probe design and expression constraints. We evaluated Spapros and show that it outperforms other selection approaches in both cell type recovery and recovering expression variation beyond cell types. Furthermore, we used Spapros to design a single-cell resolution in situ hybridization on tissues (SCRINSHOT) experiment of adult lung tissue to demonstrate how probes selected with Spapros identify cell types of interest and detect spatial variation even within cell types. Spapros is a probe set selection pipeline for targeted spatial transcriptomics that optimizes for both transcriptional and within-cell type variation.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Agency and Grant Number: Virological and immunological determinants of COVID-19 pathogenesis - lessons to get prepared for future pandemics [KA1-Co-02 'COVIPA']; Helmholtz Association's Initiative and Networking Fund; European Union [874656] Funding text: We are grateful to all members of the Theis and Ertuerk laboratories as well as the discovAIR consortium for frequent discussions of the project. We thank E. Madissoon and K. Meyer for provision and discussion of the scRNA-seq lung reference datasets. We thank P. Barbry for provision of the airway marker list. We thank J. Theelke for testing the probe design pipeline. We thank X. Abalo for helping with tissue sectioning and tissue quality control. We thank W. Timens for histopathological tissue evaluation. This work was supported by the project 'Virological and immunological determinants of COVID-19 pathogenesis - lessons to get prepared for future pandemics (KA1-Co-02 'COVIPA')', a grant from the Helmholtz Association's Initiative and Networking Fund. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement 874656. |
| Uncontrolled Keywords: | gene-expression; cell atlas |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia Q Science / természettudomány > QH Natural history / természetrajz > QH426 Genetics / genetika, örökléstan |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 14 Apr 2025 09:49 |
| Last Modified: | 14 Apr 2025 09:49 |
| URI: | https://real.mtak.hu/id/eprint/217748 |
Actions (login required)
 |
Edit Item |
