The T2T-CHM13 reference genome has more accurate sequences for immunoglobulin genes than GRCh38
Nie, J.; Tellier, J.; Tarasova, I.; Nutt, S. L.; Smyth, G. K.
Show abstract
Antibody production by B-cells is essential for protective immunity. The clonal selection theory posits that each mature B cell has a unique immunoglobulin receptor generated through random gene recombination and, when stimulated to differentiate into an antibody-secreting cell, has the capacity to produce only a single antibody specificity. It follows from this "one-cell-one-antibody" dogma, that single-cell RNA-seq profiling of antibody-secreting cells should find that each cell expresses only a single form of each of the immunoglobulin heavy and light chains. However, when using GRCh38 as the genome reference, we found that many antibody-secreting cells appeared to express multiple immunoglobulin isotypes. When the newly published T2T-CHM13 genome was used instead as the genome reference, every antibody-secreting cell was found to express a unique isotype, and read mapping quality was also improved. We show that the superior performance of T2T-CHM13 was due to its European origin matching the genetic background of the query samples. On the other hand, T2T-CHM13 failed to appropriately fit the "one-cell-one-antibody" dogma when applied to data derived from East Asia. Our results show that read assignment to human immunoglobulin isotype genes is very sensitive to the ancestral origin of the genome reference.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- CaClust: linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants 94%
- Comprehensive characterization of single cell full-length isoforms in human and mouse with long-read sequencing 94%
- SCAPTURE: a deep learning-embedded pipeline that captures polyadenylation information from 3' tag-based RNA-seq of single cells 93%
Similar papers in this journal
- Benchmarking computational methods for B-cell receptor reconstruction from single-cell RNA-seq data 95%
- Platypus: an open-access software for integrating lymphocyte single-cell immune repertoires with transcriptomes 94%
- ViCloD, an interactive web tool for visualizing B cell repertoires and analyzing intra-clonal diversities: application to human B-cell tumors 93%
Similar papers in this journal
- Probability of stealth multiplets in sample-multiplexing for droplet-based single-cell analysis 93%
- Revealing the Prevalence of Suboptimal Cells and Organs in Reference Cell Atlases: An Imperative for Enhanced Quality Control 92%
- Dual indexed design of in-Drop single-cell RNA-seq libraries improves sequencing quality and throughput 92%
Similar papers in this journal
Similar papers in this journal
- LINE-1 Retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5'-single cell RNA-Seq 93%
- Polymorphisms in immunoglobulin heavy chain variable genes and their upstream regions 92%
- MarcoPolo: a clustering-free approach to the exploration of differentially expressed genes along with group information in single-cell RNA-seq data 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.