Targeted transcriptome analysis using synthetic long read sequencing uncovers isoform reprograming in the progression of colon cancer
| Autor: | Michael A Balamotis, Silvia Liu, Baoguo Ren, Indira Wu, Jianhua Luo, Tuval Ben Yehezkel, Yanping Yu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
Colorectal cancer Sequence analysis QH301-705.5 Medicine (miscellaneous) Computational biology Biology General Biochemistry Genetics and Molecular Biology Article Transcriptome 03 medical and health sciences Exon 0302 clinical medicine Text mining Gene expression medicine Humans Protein Isoforms Biology (General) Gene 030304 developmental biology 0303 health sciences business.industry Sequence Analysis RNA Alternative splicing RNA Cancer High-Throughput Nucleotide Sequencing RNA sequencing medicine.disease Alternative Splicing 030220 oncology & carcinogenesis RNA splicing Colonic Neoplasms General Agricultural and Biological Sciences business |
| Zdroj: | Communications Biology Communications Biology, Vol 4, Iss 1, Pp 1-11 (2021) |
| ISSN: | 2399-3642 |
| Popis: | The characterization of human gene expression is limited by short read lengths, high error rates and large input requirements. Here, we used a synthetic long read (SLR) sequencing approach, LoopSeq, to generate accurate sequencing reads that span full length transcripts using standard short read data. LoopSeq identified isoforms from control samples with 99.4% accuracy and a 0.01% per-base error rate, exceeding the accuracy reported for other long-read technologies. Applied to targeted transcriptome sequencing from colon cancers and their metastatic counterparts, LoopSeq revealed large scale isoform redistributions from benign colon mucosa to primary colon cancer and metastatic cancer and identified several previously unknown fusion isoforms. Strikingly, single nucleotide variants (SNVs) occurred dominantly in specific isoforms and some SNVs underwent isoform switching in cancer progression. The ability to use short reads to generate accurate long-read data as the raw unit of information holds promise as a widely accessible approach in transcriptome sequencing. Silvia Liu et al. present LoopSeq, a synthetic long-read sequencing method that generates accurate long-read transcriptome data from short Illumina reads. As an example of possible applications, they use LoopSeq to investigate differential isoform expression, isoform-specific single nucleotide variants, and potential fusion genes in multiple stages of colon cancer. Altogether, LoopSeq is a valuable method for analyzing complex transcriptomes and investigating gene expression at the isoform level. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink