Proteoform Identification by Combining RNA-Seq and Top-down Mass Spectrometry

Abstract

In proteogenomic studies, genomic and transcriptomic variants are incorporated into customized protein databases for the identification of proteoforms, especially proteoforms with sample-specific variants. Most proteogenomic research has been focused on combining genomic or transcriptomic data with bottom-up mass spectrometry data. In the last decade, top-down mass spectrometry has attracted increasing attention because of its capacity to identify various proteoforms with alterations.However, top-down proteogenomics, in which genomic or transcriptomic data are combined with topdown mass spectrometry data, has not been widely adopted, and there still lack of software tools for top-down proteogenomic data analysis. In this paper, we introduce TopPG, a proteogenomic tool for identifying proteoforms with genetic alterations and alternative splicing events. Experiments on topdown proteogenomic data of DLD-1 colorectal cancer cells showed that TopPG can confidently identify proteoforms with sample-specific alterations.