Proteogenomics of rare taxonomic phyla: A prospective treasure trove of protein coding genes

Abstract

Sustainable innovations in sequencing technologies have resulted in a torrent of microbial genome sequencing projects. However, the prokaryotic genomes sequenced so far are unequally distributed along their phylogenetic tree; few phyla contain the majority, the rest only a few representatives. Accurate genome annotation lags far behind genome sequencing. While automated computational prediction, aided by comparative genomics, remains a popular choice for genome annotation, substantial fraction of these annotations are erroneous. Proteogenomics utilizes protein level experimental observations to annotate protein coding genes on a genome wide scale. Benefits of proteogenomics include discovery and correction of gene annotations regardless of their phylogenetic conservation. This not only allows detection of common, conserved proteins but also the discovery of protein products of rare genes that may be horizontally transferred or taxonomy specific. Chances of encountering such genes are more in rare phyla that comprise a small number of complete genome sequences. We collated all bacterial and archaeal proteogenomic studies carried out to date and reviewed them in the context of genome sequencing projects. Here, we present a comprehensive list of microbial proteogenomic studies, their taxonomic distribution, and also urge for targeted proteogenomics of underexplored taxa to build an extensive reference of protein coding genes.

Integrating transcriptome and proteome profiling: Strategies and applications

“…However, for this task, proteogenomic methods rely on custom genomic databases, other than the annotated reference proteome, to discover novel peptides indicative of novel translated regions . While genomic databases such as six frame translated genome or ab initio predicted genes may include majority of the novel translation possibilities for a prokaryotic genome , it would have a limited representation of protein isoforms possible from a eukaryotic genome . Proteomic diversity of a eukaryote is largely attributed to alternative mRNA splicing .…”

Advanced Proteomics as a Powerful Tool for Studying Toxins of Human Bacterial Pathogens

“…Peptide information obtained by tandem mass spectrometry may help to establish the presence of a given gene encoding a new polypeptide or better define the translation initiation site of numerous proteins [111]. The integration of proteomics and genomics data collected on the same microorganisms is of interest for detecting such errors and improving the genome annotation quality [112,113], especially for rare taxonomic phyla [114]. Specific proteogenomic experiments could be performed in the future for exploring whether toxin-producing microorganisms are well genome annotated and further characterizing their toxin potential.…”

Current developments to use linear MALDI‐TOF spectra for the identification and typing of bacteria and the characterization of other cells/organisms related to infectious diseases

“…It is therefore straightforward to use ribosomal proteins as biomarkers for bacterial typing by comparison with known gene sequences and their variations. One of the prerequisites of this approach is, however, that the proteins assumed behind the mass peaks of the MALDI‐TOF spectrum have been verified that may be a challenging task . Once identified, the observed mass shifts in comparison to other isolates can be correlated with sequence variations of the respective genes and typing schemes can be implemented on this basis.…”