CaClust: linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants
Tumours exhibit high genotypic and transcriptional heterogeneity. Both affect cancer progression and treatment, but have been predominantly studied separately in follicular lymphoma. To comprehensively investigate the evolution and genotype-to-phenotype maps in follicular lymphoma, we introduce CaClust, a probabilistic graphical model integrating deep whole exome, single-cell RNA and B-cell receptor sequencing data to infer clone genotypes, cell-to-clone mapping, and single-cell genotyping. CaClust outperforms a state-of-the-art model on simulated and patient data. In-depth analyses of single cells from four samples showcase effects of driver mutations, follicular lymphoma evolution, possible therapeutic targets, and single-cell genotyping that agrees with an independent targeted resequencing experiment.
Authors
- Julieta Sepúlveda-Yáñez (ORCID: https://orcid.org/0000-0001-6354-3609)
- Szymon M. Kiełbasa (ORCID: https://orcid.org/0000-0003-2805-6535)
- Cornelis A.M. van Bergen (ORCID: https://orcid.org/0000-0001-6386-4517)
- Edwin Quinten (ORCID: https://orcid.org/0000-0001-9470-9683)
- Marcelo A. Navarrete (ORCID: https://orcid.org/0000-0002-2044-9548)
- Ewa Szczurek (ORCID: https://orcid.org/0000-0002-1320-6695)
- Shadi Darvish Shafighi (ORCID: https://orcid.org/0000-0003-0367-8864)
- Hendrik Veelken (ORCID: https://orcid.org/0000-0002-9108-3125)
- Joost S.P. Vermaat (ORCID: https://orcid.org/0000-0002-1628-6256)
- Ruben A. L. de Groen (ORCID: https://orcid.org/0000-0002-2998-2066)
- Kazimierz Oksza-Orzechowski
- Hugo W. van Kessel
Institutions
- Leiden University Medical Center (NL)
- Center for Environmental Health (US)
- Helmholtz Zentrum München (DE)
- Cancer Research UK Cambridge Center (GB)
- University of Warsaw (PL)
- Universidad de Magallanes (CL)
Publication Details
- Journal
- Genome biology
- Published
- 2024-11-05
- DOI
- https://doi.org/10.1186/s13059-024-03417-1
- Citations
- 1
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.42
Funders
- Universiteit Leiden
- Narodowe Centrum Nauki
- KWF Kankerbestrijding
- Leids Universitair Medisch Centrum
- Agencia Nacional de Investigación y Desarrollo