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| Status |
Public on Oct 03, 2024 |
| Title |
CaClust: a probabilistic model for intraclonal heterogeneity (K6B) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Clones in the cancer tissue exhibit different genotypes and phenotypes, which can be linked with their evolution, future progression, and possible treatment methods. The development of single-cell RNA sequencing allowed for the measurement of single-cell phenotypes, but without a genotype-phenotype map the phenotypes of the clones cannot be obtained. We introduce CaClust, a probabilistic graphical model that integrates whole exome, ultra-deep single-cell RNA and B-cell receptor sequencing data, to infer clonal genotypes, cell-to-clone mapping, and single-cell genotyping, enabling the combined study of clonal genotypes and phenotypes. CaClust outperforms a state-of-the-art model on simulated and experimental datasets of follicular lymphoma patients. CaClust results on patient data give insights into effects of driver mutations, follicular lymphoma evolution, and possible therapeutic targets. CaClust single-cell genotyping agrees with genotypes observed in an independent targeted resequencing experiment. In short, CaClust enables the first study of genotype-to-phenotype links in follicular lymphoma of such depth and scale.
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| Overall design |
Dataset K6B: 10X Genomics of flowcytometry purified follicular lymphoma cells, 5' chemistry, full transcriptome and BCR enrichment; targeted amplification of selected genes on sc cDNA samples and full length single molecule PacBio sequencing
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| Contributor(s) |
van Bergen C, Veelken H, Oksza-Orzechowski K, Szczurek E |
| Citation missing |
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| Submission date |
Jan 03, 2024 |
| Last update date |
Oct 04, 2024 |
| Contact name |
Cornelis A.M. van Bergen |
| E-mail(s) |
c.a.m.van_bergen@lumc.nl
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| Organization name |
Leiden University Medical Center
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| Department |
Hematology
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| Street address |
Albinusdreef 2
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| City |
Leiden |
| ZIP/Postal code |
2333ZA |
| Country |
Netherlands |
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| Platforms (2) |
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| Samples (3) |
| GSM8001071 |
lymph node S13530_s1309520 scRNAseq BCR enriched |
| GSM8001072 |
lymph node S13530_s1309520 scRNAseq full transcriptome |
| GSM8001073 |
lymph node S13530_s1309520 scRNA targeted resequencing |
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| Relations |
| BioProject |
PRJNA1060612 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE252416_RAW.tar |
116.4 Mb |
(http)(custom) |
TAR (of CSV, FASTA, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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