Shanrong Zhao
Pfizer Worldwide Research & Development
Title: Isoform quantification in RNA sequencing: challenges and applications
Biography
Biography: Shanrong Zhao
Abstract
Due to alternative splicing, over 90% of human genes have multiple transcript isoforms. Isoforms of the same gene can play distinct or even opposite biological rules. For instance, gene TP53 has an important role in oncology and different cancer types show different expression profiles of its transcript isoforms. Therefore, it is tempting to quantify RNA-Seq experiments at transcript level, rather than at the gene level. However, estimating the expression of individual isoform is intrinsically challenging because different isoforms of a gene usually have a high proportion of genomic overlap.
Recently, a number of tools have been developed for RNA-seq isoform quantification, including RSEM, Cufflinks, eXpress, Tigar2, Kallisto, Salmon and Sailfish. We performed a systematic evaluation on those methods using both simulated dataset and UHRR and HBRR, and furthermore investigated the impact of gene/isoform structures on the accuracy of isoform quantification. Besides, the library size and relative abundance of different isoforms also influence the quantification results. We determined why RNA-seq is unable to detect less abundant TP53 transcripts and discussed its implications for the general interpretation of RNA-seq data.