ESPRESSO: Robust discovery and quantification of transcript isoforms from error-prone long-read RNA-seq data

作者：Yuan Gao, Feng Wang, Robert Wang, Eric Kutschera, Yang Xu, Stephan Xie, Yuanyuan Wang, Kathryn E. Kadash-Edmondson, Lan Lin, Yi Xing · 发表于：Science Advances · 年份：2023 · DOI：10.1126/sciadv.abq5072 · 被引用次数：94 · 研究领域：Cancer-related molecular mechanisms research、RNA modifications and cancer、RNA and protein synthesis mechanisms

Long-read RNA sequencing (RNA-seq) holds great potential for characterizing transcriptome variation and full-length transcript isoforms, but the relatively high error rate of current long-read sequencing platforms poses a major challenge. We present ESPRESSO, a computational tool for robust discovery and quantification of transcript isoforms from error-prone long reads. ESPRESSO jointly considers alignments of all long reads aligned to a gene and uses error profiles of individual reads to improve the identification of splice junctions and the discovery of their corresponding transcript isoforms. On both a synthetic spike-in RNA sample and human RNA samples, ESPRESSO outperforms multiple contemporary tools in not only transcript isoform discovery but also transcript isoform quantification. In total, we generated and analyzed ~1.1 billion nanopore RNA-seq reads covering 30 human tissue samples and three human cell lines. ESPRESSO and its companion dataset provide a useful resource for studying the RNA repertoire of eukaryotic transcriptomes.