PuSH - Publikationsserver des Helmholtz Zentrums München: CaClust: Linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants.

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Oksza-Orzechowski, K.* ; Quinten, E.* ; Shafighi, S.* ; Kiełbasa, S.M.* ; van Kessel, H.W.* ; de Groen, R.A.L.* ; Vermaat, J.S.P.* ; Sepúlveda Yáñez, J.H.* ; Navarrete, M.A.* ; Veelken, H.* ; van Bergen, C.A.M.* ; Szczurek, E.

CaClust: Linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants.

Genome Biol. 25:286 (2024)

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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.

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