Proteogenomics: concepts, applications and computational strategies

Abstract

Proteogenomics is an area of research at the interface of proteomics and genomics. In this approach, customized protein sequence databases generated using genomic and transcriptomic information are used to help identify novel peptides (not present in reference protein sequence databases) from mass spectrometry-based proteomic data; in turn, the proteomic data can be used to provide protein-level evidence of gene expression and to help refine gene models. In recent years, owing to the emergence of next generation sequencing technologies such as RNA-Seq and dramatic improvements in the depths and throughput of mass spectrometry-based proteomics, the pace of proteogenomics research has greatly accelerated. Here I review the current state of proteogenomics methods and applications, including computational strategies for building and using customized protein sequence databases. I also draw attention to the challenge of false positives in proteogenomics, and provide guidelines for analyzing the data and reporting the results of proteogenomics studies.

Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry*

“…On the other hand, the original raw MS files are stored in separate repositories (e.g. PeptideAtlas, PRIDE PRoteomics IDEntifications (PRIDE), CHORUS) and more recently, the SWATHAtlas database (82,140). Ideally, this information should be integrated and centralized within the same database.…”

Exploring the potential of public proteomics data

“…However, due to the unconventional sequence population of the databases in proteogenomics, and their often extensive size, the estimation of false positive rates by traditional approaches can be impaired 83, 94. In the near future, it is therefore expected that the creation of such sequence databases will be coupled to ribosome profiling data, to discern the exact start of translation of putative proteins 95.…”

GAPP: A Proteogenomic Software for Genome Annotation and Global Profiling of Post-translational Modifications in Prokaryotes

“…Proteogenomics is defined as the use of proteomic data, often derived from MS, to improve and refine genome annotation (10,11). Pioneering work by Yates et al (12) and Jaffe et al (13) opened new avenues to high-throughput gene annotation.…”

“…Pioneering work by Yates et al (12) and Jaffe et al (13) opened new avenues to high-throughput gene annotation. In recent years, proteogenomics has emerged as a promising and indispensable approach to genome annotation (10,11). It has been applied for genome annotation including identification of novel genes, correction and validation of predicted genes in various organisms (14 -21).…”

“…Over the last few years, computational proteomics has become a dramatically growing field, and a handful of tools have been developed to execute complete proteogenomic analyses (11,46,47). Two excellent reviews have described a comprehensive overview of the various problems commonly encountered and their current solutions for this growing research area (8,11).…”