Dados do Trabalho

Título

Large-scale proteogenomics characterization of the Mycobacterium tuberculosis hidden microproteome

Introdução

Traditional genome annotation methods exclude Open Reading Frames shorter than 300 codons (smORFs), which leaves a substantial portion of the proteome overlooked. Proteogenomics is a multi-omics approach that merges genomics, transcriptomics and proteomics to identify proteoforms and unannotated proteins from Mass Spectrometry data.

Objetivo (s)

Here, we employed our recently developed proteogenomics pipeline to aid genome annotation and identify hundreds of novel microproteins encoded by smORFs in the genome of Mycobacterium tuberculosis (Mtb).

Material e Métodos

To avoid limitations regarding sensitivity, we used 680 Mass Spectrometry experiments in a large-scale approach, which let us classify the findings by different degrees of confidence using our machine learning model. After integrating the results with RNA-Seq datasets, we explore the biological relevance of the novel sequences and show they are differentially expressed upon starvation and antibiotic treatment, and are co-expressed with many annotated genes that are vital for bacterial virulence. Moreover, some smORFs are located inside essential genomic segments and could be attractive targets for the development of new drugs.

Resultados e Conclusão

Altogether, our results should improve the current annotation of the proteome of Mtb and guide the following studies focusing on studying these microproteins thoroughly.

Palavras-chave

small orfs, microproteins, proteogenomics, tuberculosis

Agradecimentos

This study was funded by National Institute of Science and Technology on Tuberculosis (INCT-TB), Brazil (Grant numbers: 489 421703–2017-2/17–1265-8/14.2.0914.1). CB (310344/2016–6), PM (305203/2018–5) and LB (520182/99–5) are research career awardees of the National Council for Scientific and Technological Development of Brazil (CNPq). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.