The application of terminomics for the identification of protein start sites and proteoforms in bacteria

Berry, Iain J.; Steele, Joel R.; Padula, Matthew P.; Djordjevic, Steven P.

doi:10.1002/pmic.201500319

Cited by 28 publications

(27 citation statements)

References 169 publications

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“…Functional RNAs which are not yet well understood include structured noncoding RNAs such as riboswitches (Stav et al, 2019, Hücker et al, 2017. Proteins with alternative start sites, designated isoforms or 'proteoforms', have also been reported in a few bacterial systems (Berry et al, 2016, Nakahigashi et al, 2016, Meydan et al, 2019. These genetic elements are all yet to be incorporated into genome annotation files and gene prediction algorithms.…”

Section: The Context: Unexpected Complexitymentioning

confidence: 99%

Are Antisense Proteins in Prokaryotes Functional?

Ardern

Neuhaus

Scherer

2020

Preprint

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Many prokaryotic RNAs are transcribed from loci outside of annotated protein coding genes.Across bacterial species hundreds of short open reading frames antisense to annotated genes show evidence of both transcription and translation, for instance in ribosome profiling data. Determining the functional fraction of these protein products awaits further research, including insights from studies of molecular interactions and detailed evolutionary analysis.There are multiple lines of evidence however that many of these newly discovered proteins are of use to the organism. Condition-specific phenotypes have been characterised for a few. These proteins should be added to genome annotations, and the methods for predicting them standardised. Evolutionary analysis of these typically young sequences also may provide important insights into gene evolution. This research should be prioritised for its exciting potential to uncover large numbers of novel proteins with extremely diverse potential practical uses, including applications in synthetic biology and responding to pathogens.

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Section: The Context: Unexpected Complexitymentioning

confidence: 99%

Are Antisense Proteins in Prokaryotes Functional?

Ardern

Neuhaus

Scherer

2020

Preprint

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“…More recently, degradomics has been applied to study bacteria, recently reviewed by Berry et al (74). The degradomes of 10 eubacterial species (75–83) and at least three archaeal species (84–86) have been studied.…”

Section: Microbial Degradomicsmentioning

confidence: 99%

Sharpening Host Defenses during Infection: Proteases Cut to the Chase

Marshall

Finlay

Overall

2017

Molecular & Cellular Proteomics

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The human immune system consists of an intricate network of tightly controlled pathways, where proteases are essential instigators and executioners at multiple levels. Invading microbial pathogens also encode proteases that have evolved to manipulate and dysregulate host proteins, including host proteases during the course of disease. The identification of pathogen proteases as well as their substrates and mechanisms of action have empowered significant developments in therapeutics for infectious diseases. Yet for many pathogens, there remains a great deal to be discovered. Recently, proteomic techniques have been developed that can identify proteolytically processed proteins across the proteome. These “degradomics” approaches can identify human substrates of microbial proteases during infection in vivo and expose the molecular-level changes that occur in the human proteome during infection as an operational network to develop hypotheses for further research as well as new therapeutics. This Perspective Article reviews how proteases are utilized during infection by both the human host and invading bacterial pathogens, including archetypal virulence-associated microbial proteases, such as the Clostridia spp. botulinum and tetanus neurotoxins. We highlight the potential knowledge that degradomics studies of host–pathogen interactions would uncover, as well as how degradomics has been successfully applied in similar contexts, including use with a viral protease. We review how microbial proteases have been targeted in current therapeutic approaches and how microbial proteases have shaped and even contributed to human therapeutics beyond infectious disease. Finally, we discuss how, moving forward, degradomics research can greatly contribute to our understanding of how microbial pathogens cause disease in vivo and lead to the identification of novel substrates in vivo, and the development of improved therapeutics to counter these pathogens.

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“…Alternative proteoform usage can also be investigated by specific mass spectrometry protocols measuring N-terminal peptides [21,22]. Although the technology is recognized, it suffers from drawbacks (e.g.…”

Section: Introductionmentioning

confidence: 99%

DeepRibo: precise gene annotation of prokaryotes using deep learning and ribosome profiling data

Clauwaert

Menschaert

Waegeman

2018

Preprint

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Annotation of gene expression in prokaryotes often finds itself corrected due to small variations of the annotated gene regions observed between different (sub)species. It has become apparent that traditional sequence alignment algorithms, used for the curation of genomes, are not able to map the full complexity of the genomic landscape. We present DeepRibo, a novel neural network applying ribosome profiling data that shows to be a precise tool for the delineation and annotation of expressed genes in prokaryotes. The neural network combines recurrent memory cells and convolutional layers, adapting the information gained from both the high-throughput ribosome profiling data and Shine-Dalgarno region into one model. DeepRibo is designed as a single model trained on a variety of ribosome profiling experiments, and is therefore evaluated on independent datasets. Through extensive validation of the model, including the use of multiple species sequence similarity and mass spectrometry, the effectiveness of the model is highlighted.

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The application of terminomics for the identification of protein start sites and proteoforms in bacteria

Cited by 28 publications

References 169 publications

Are Antisense Proteins in Prokaryotes Functional?

Are Antisense Proteins in Prokaryotes Functional?

Sharpening Host Defenses during Infection: Proteases Cut to the Chase

DeepRibo: precise gene annotation of prokaryotes using deep learning and ribosome profiling data

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