Silvia Liu and Jianhua Luo, co-directors of the PLRC GSBC along with PLRC members Alina Ostrowska and Alex Soto-Gutierrez of the HSLBC, publish an article in eLife entitled, ” Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells“.
Silvia Liu, Yan-Ping Yu, Bao-Guo Ren, Tuval Ben-Yehezkel, Caroline Obert, Mat Smith, Wenjia Wang, Alina Ostrowska, Alejandro Soto-Gutierrez, Jian-Hua Luo (2024) Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells eLife 12:RP87607: https://doi.org/10.7554/eLife.87607.3
ABSTRACT:
The protein diversity of mammalian cells is determined by arrays of isoforms from genes. Genetic mutation is essential in species evolution and cancer development. Accurate long-read transcriptome sequencing at single-cell level is required to decipher the spectrum of protein expressions in mammalian organisms. In this report, we developed a synthetic long-read single-cell sequencing technology based on LOOPSeq technique. We applied this technology to analyze 447 transcriptomes of hepatocellular carcinoma (HCC) and benign liver from an individual. Through Uniform Manifold Approximation and Projection analysis, we identified a panel of mutation mRNA isoforms highly specific to HCC cells. The evolution pathways that led to the hyper-mutation clusters in single human leukocyte antigen molecules were identified. Novel fusion transcripts were detected. The combination of gene expressions, fusion gene transcripts, and mutation gene expressions significantly improved the classification of liver cancer cells versus benign hepatocytes. In conclusion, LOOPSeq single-cell technology may hold promise to provide a new level of precision analysis on the mammalian transcriptome.
