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

IF 10.1 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Genome Biology Pub Date : 2024-11-05 DOI:10.1186/s13059-024-03417-1
Kazimierz Oksza-Orzechowski, Edwin Quinten, Shadi Shafighi, Szymon M. Kiełbasa, Hugo W. van Kessel, Ruben A. L. de Groen, Joost S. P. Vermaat, Julieta H. Sepúlveda Yáñez, Marcelo A. Navarrete, Hendrik Veelken, Cornelis A. M. van Bergen, Ewa Szczurek
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Abstract

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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CaClust:利用 BCR 和外显子变异将滤泡淋巴瘤的基因型与转录异质性联系起来
肿瘤表现出高度的基因型和转录异质性。两者都会影响癌症的进展和治疗,但在滤泡性淋巴瘤中主要是单独研究。为了全面研究滤泡性淋巴瘤的进化和基因型到表型图谱,我们引入了CaClust,这是一种概率图形模型,整合了深度全外显子组、单细胞RNA和B细胞受体测序数据,用于推断克隆基因型、细胞到克隆图谱和单细胞基因分型。在模拟数据和患者数据上,CaClust 的表现优于最先进的模型。对四个样本的单细胞进行的深入分析显示了驱动突变的影响、滤泡淋巴瘤的演变、可能的治疗靶点以及与独立的靶向重测序实验一致的单细胞基因分型。
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来源期刊
Genome Biology
Genome Biology Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
21.00
自引率
3.30%
发文量
241
审稿时长
2 months
期刊介绍: Genome Biology stands as a premier platform for exceptional research across all domains of biology and biomedicine, explored through a genomic and post-genomic lens. With an impressive impact factor of 12.3 (2022),* the journal secures its position as the 3rd-ranked research journal in the Genetics and Heredity category and the 2nd-ranked research journal in the Biotechnology and Applied Microbiology category by Thomson Reuters. Notably, Genome Biology holds the distinction of being the highest-ranked open-access journal in this category. Our dedicated team of highly trained in-house Editors collaborates closely with our esteemed Editorial Board of international experts, ensuring the journal remains on the forefront of scientific advances and community standards. Regular engagement with researchers at conferences and institute visits underscores our commitment to staying abreast of the latest developments in the field.
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