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

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 top-down mass spectrometry data, has not been
widely adopted, and there is still a lack of software tools for top-down
proteogenomic data analysis. In this paper, we introduce TopPG, a
proteogenomic tool for generating proteoform sequence databases with
genetic alterations and alternative splicing events. Experiments on
top-down proteogenomic data of DLD-1 colorectal cancer cells showed
that TopPG coupled with database search confidently identified proteoforms
with sample-specific alterations.