Identification of small novel coding sequences, a proteogenomics endeavor

Abstract

The identification of small proteins and peptides has consistently proven to be challenging. However, technological advances as well as multiomics endeavors facilitate the identification of novel small coding sequences, leading to new insights. Specifically, the application of next generation sequencing technologies (NGS), providing accurate and sample specific transcriptome / translatome information, into the proteomics field led to more comprehensive results and new discoveries. This book chapter focuses on the inclusion of RNA-Seq and RIBO-Seq also known as ribosome profiling, an RNA-Seq based technique sequencing the +/− 30 bp long fragments captured by translating ribosomes. We emphasize the identification of micropeptides and neo-antigens, two distinct classes of small translation products, triggering our current understanding of biology. RNA-Seq is capable of capturing sample specific genomic variations, enabling focused neo-antigen identification. RIBO-Seq can identify translation events in small open reading frames which are considered to be non-coding, leading to the discovery of micropeptides. The identification of small translation products requires the integration of multi-omics data, stressing the importance of proteogenomics in this novel research area.