iMPI: An Integrative Database for MicroProteins Encoded by Intron Retention in Tumors

Research advancements made in the last decade have shed light on the dysregulation of cellular mechanisms that lead to aberrant and pathologic intron retention (IR). IR is not merely a mechanism of gene regulation but may also play a potential role in cancer pathogenesis and therapeutic resistance across various human cancers. Despite its potential significance, there remains a notable gap in comprehensive database resources for introns within tumors. Therefore, we investigated whether the retained introns contain undiscovered protein-coding ORFs and whether they can encode proteins. We conducted a genome-wide search for underlying translatable intron ORFs (iORFs) and validated them at the protein level via large-scale proteomic mass spectrometry (MS) data. Furthermore, we developed the first comprehensive resource, iMPI (an integrative database for MicroProteins encoded by introns), to provide an accessible source of iORF-encoded microproteins. Our genome-wide search identified 209,091 introns in the human GRCh38 genome, among which 15,975 were confirmed as candidates with strong coding potential. On the basis of the proteomic MS search, 4751 introns containing a total of 5823 iORFs across 27 cancer types were validated. Detailed annotations, including intron information, coding evidence, subcellular location and structures, were integrated. iMPI is a user-friendly web interface that is freely available at https://impi.omicsbio.info/, making it a valuable tool for researchers investigating the spectrum of IR in human cancers.