Towards multiomic analysis of oral mucosal pathologies

Abstract

Oral mucosal pathologies comprise an array of diseases with worldwide prevalence and medical relevance. Affecting a confined space with crucial physiological and social functions, oral pathologies can be mutilating and drastically reduce quality of life. Despite their relevance, treatment for these diseases is often far from curative and remains vastly understudied. While multiple factors are involved in the pathogenesis of oral mucosal pathologies, the host’s immune system plays a major role in the development, maintenance, and resolution of these diseases. Consequently, a precise understanding of immunological mechanisms implicated in oral mucosal pathologies is critical (1) to identify accurate, mechanistic biomarkers of clinical outcomes; (2) to develop targeted immunotherapeutic strategies; and (3) to individualize prevention and treatment approaches. Here, we review key elements of the immune system’s role in oral mucosal pathologies that hold promise to overcome limitations in current diagnostic and therapeutic approaches. We emphasize recent and ongoing multiomic and single-cell approaches that enable an integrative view of these pathophysiological processes and thereby provide unifying and clinically relevant biological signatures.

Reconstrução do fundo de sulco após excisão cirúrgica de hiperplasia fibrosa inflamatória reacional: um relato de caso

“…A mucosa oral é submetida constantemente a estímulos intrínsecos e extrínsecos, como impactos oclusais, impactos de alimentos e alterações do pH no meio bucal, podendo desta maneira surgir patologias e lesões com diferentes fatores etiológicos, dentre eles: fatores de desenvolvimento, de reação (reativa), por causas neoplásicas ou inflamatórias (Shukla, 2014). Sua integridade é fundamental para funções do sistema do corpo humano em geral, como ingestão de alimentos, paladar, fala, estética, respiração, tornando alterações nesta área verdadeiros obstáculos para a qualidade de vida do portador do distúrbio, gerando desconforto em atividades de cotidiano, e impactando assim na qualidade de vida dos pacientes (Zimmermann et al, 2022;Einhaus et al, 2023).…”

Harnessing the n+1 dimensions of single-cell omics data for the prediction and prevention of human diseases

“…This issue further explores how single-cell technologies, particularly those that afford spatial resolution, are currently implemented in clinical outcome studies for the discovery of predictive biomarkers, novel pathobiological mechanisms, or therapeutic targets. Drawing from examples across multiple technologies, such as single-cell RNA sequencing (scR-NAseq), spatial transcriptomics, COdetection by indexing (CODEX), and suspension and imaging mass cytometry (IMC), and diseases (from infectious and neurovascular diseases to transplantation and cancer), all authors contributing to this special issue emphasize important considerations with respect to clinical study design, sample processing, and the choice of machine learning-based analytical pipelines [1][2][3][4][5][6][7][8][9][10].…”

“…In this clinical context, the authors highlight how identification of patient-and organ-specific immune signatures of transplant tolerance may allow patients to reduce their reliance on immunosuppression and facilitate the discovery of new therapeutics for the prevention of graft rejection. Technological and analytical advances in IMC and suspension mass cytometry are also a core focus of Einhaus et al's review of systemic and local immune responses in patients with oral mucosal pathologies, a poorly understood group of diseases comprising not only aggressive malignancies but also severe auto-immune disorders [8]. Finally, Maïer et al examine recent applications of single-cell technologies and multiplex imaging to characterize thrombo-inflammatory events in patients suffering from acute stroke and to derive multi-omics predictive models for the development of hemorrhagic transformation, a devastating complication after revascularization therapy [9].…”

“…In all these reviews, a recurring theme is the need for standardization of sample collection and processing, and for rigorous and reproducible computational pipelines for the analysis of the high-dimensional omics data. For example, Einhaus et al delineate the sequential steps of IMC analysis from sample pre-processing to cell segmentation, marker identification, and systematic extraction of spatial features, a complex process currently at the discretion of the researcher to choose from diverse techniques, software, and analysis pipelines [8]. The same is true for the CODEX multiplex imaging platform, which requires continued fine-tuning of staining protocols, manual or automated cell identification strategies, feature extraction, and data analysis methods detailed in Kuswanto et al [10].…”