FusionPro, a versatile proteogenomic tool for identification of novel fusion transcripts and their potential translation products in cancer cells

Chae Yeon Kim, Keun Na, Saeram Park, Seul Ki Jeong, Jin Young Cho, Heon Shin, Min Jung Lee, Gyoonhee Han, Young Ki Paik

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Fusion proteoforms are translation products derived from gene fusion. Although very rare, the fusion proteoforms play important roles in biomedical science. For example, fusion proteoforms influence the development of tumors by serving as cancer markers or cell cycle regulators. Although numerous studies have reported bioinformatics tools that can predict fusion transcripts, few proteogenomic tools are available that can predict and identify proteoforms. In this study, we develop a versatile proteogenomic tool “FusionPro,” which facilitates the identification of fusion transcripts and their potential translatable peptides. FusionPro provides an independent gene fusion prediction module and can build sequence databases for annotated fusion proteoforms. FusionPro shows greater sensitivity than the available fusion finders when analyzing simulated or real RNA sequencing data sets. We use FusionPro to identify 18 fusion junction peptides and three potential fusion-derived peptides by MS/ MS-based analysis of leukemia cell lines (Jurkat and K562) and ovarian cancer tissues from the Clinical Proteomic Tumor Analysis Consortium. Among the identified fusion proteins, we molecularly validate two fusion junction isoforms and a translation product of FAM133B: CDK6. Moreover, sequence analysis suggests that the fusion protein participates in the cell cycle progression. In addition, our prediction results indicate that fusion transcripts often have multiple fusion junctions and that these fusion junctions tend to be distributed in a nonrandom pattern at both the chromosome and gene levels. Thus, FusionPro allows users to detect various types of fusion translation products using a transcriptome-informed approach and to gain a comprehensive understanding of the formation and biological roles of fusion proteoforms.

Original languageEnglish
Pages (from-to)1651-1668
Number of pages18
JournalMolecular and Cellular Proteomics
Volume18
Issue number8
DOIs
Publication statusPublished - 2019 Jan 1

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'FusionPro, a versatile proteogenomic tool for identification of novel fusion transcripts and their potential translation products in cancer cells'. Together they form a unique fingerprint.

  • Cite this