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Meta-Analysis of Integrated Proteomic and Transcriptomic Data Discerns Structure-Activity Relationship of Carbon Materials with Different Morphologies.

ABSTRACT: The Fiber Pathogenicity Paradigm (FPP) establishes connections between fiber structure, durability, and disease-causing potential observed in materials like asbestos and synthetic fibers. While emerging nanofibers are anticipated to exhibit pathogenic traits according to the FPP, their nanoscale diameter limits rigidity, leading to tangling and loss of fiber characteristics. The absence of validated rigidity measurement methods complicates nanofiber toxicity assessment. By comprehensively analyzing 89 transcriptomics and 37 proteomics studies, this study aims to enhance carbon material toxicity understanding and proposes an alternative strategy to assess morphology-driven toxicity. Carbon materials are categorized as non-fibrous, high aspect ratio with shorter lengths, tangled, and rigid fibers. Mitsui-7 serves as a benchmark for pathogenic fibers. The meta-analysis reveals distinct cellular changes for each category, effectively distinguishing rigid fibers from other carbon materials. Subsequently, a robust random forest model is developed to predict morphology, unveiling the pathogenicity of previously deemed non-pathogenic NM-400 due to its secondary structures. This study fills a crucial gap in nanosafety by linking toxicological effects to material morphology, in particular regarding fibers. It demonstrates the significant impact of morphology on toxicological behavior and the necessity of integrating morphological considerations into regulatory frameworks.

SUBMITTER: Dumit VI

PROVIDER: S-EPMC10916575 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Meta-Analysis of Integrated Proteomic and Transcriptomic Data Discerns Structure-Activity Relationship of Carbon Materials with Different Morphologies.

Dumit Verónica I VI Liu Yuk-Chien YC Bahl Aileen A Kohonen Pekka P Grafström Roland C RC Nymark Penny P Müller-Graf Christine C Haase Andrea A Pink Mario M

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231220 9

The Fiber Pathogenicity Paradigm (FPP) establishes connections between fiber structure, durability, and disease-causing potential observed in materials like asbestos and synthetic fibers. While emerging nanofibers are anticipated to exhibit pathogenic traits according to the FPP, their nanoscale diameter limits rigidity, leading to tangling and loss of fiber characteristics. The absence of validated rigidity measurement methods complicates nanofiber toxicity assessment. By comprehensively analyz ...[more]

PMID: 38116877

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Project description:Yersinia pseudotuberculosis is one of the three pathogenic species of the genus Yersinia. Most studies regarding pathogenesis of Y. pseudotuberculosis are based on the proteins related to Type III secretion system, which is a well-known primary virulence factor in pathogenic Gram-negative bacteria, including Y. pseudotuberculosis. Information related to the factors involved in Y. pseudotuberculosis granuloma formation is scarce. In the present study we have used a computational approach to identify proteins that might be potentially involved in formation of Y. pseudotuberculosis granuloma. A comparative proteome analysis and conserved orthologous protein identification was performed between two different genera of bacteria - Mycobacterium and Yersinia, their only common pathogenic trait being ability to form necrotizing granuloma. Comprehensive analysis of orthologous proteins was performed in proteomes of seven bacterial species. This included M. tuberculosis, M. bovis and M. avium paratuberculosis - the known granuloma forming Mycobacterium species, Y. pestis and Y. frederiksenii - the non-granuloma forming Yersinia species and, Y. enterocolitica - that forms micro-granuloma and, Y. pseudotuberculosis - a prominent granuloma forming Yersinia species. In silico proteome analysis indicated that seven proteins (UniProt id A0A0U1QT64, A0A0U1QTE0, A0A0U1QWK3, A0A0U1R1R0, A0A0U1R1Z2, A0A0U1R2S7, A7FMD4) might play some role in Y. pseudotuberculosis granuloma. Validation of the probable involvement of the seven proposed Y. pseudotuberculosis granuloma proteins was done using transcriptome data analysis and, by mapping on a composite protein-protein interaction map of experimentally proved M. tuberculosis granuloma proteins (RD1 locus proteins, ESAT-6 secretion system proteins and intra-macrophage secreted proteins). Though, additional experiments involving knocking out of each of these seven proteins are required to confirm their role in Y. pseudotuberculosis granuloma our study can serve as a basis for further studies on Y. pseudotuberculosis granuloma.

Dataset Information

Meta-Analysis of Integrated Proteomic and Transcriptomic Data Discerns Structure-Activity Relationship of Carbon Materials with Different Morphologies.

Publications

Meta-Analysis of Integrated Proteomic and Transcriptomic Data Discerns Structure-Activity Relationship of Carbon Materials with Different Morphologies.

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