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NANO-LUNG
FunderFrench National Research Agency (ANR)
Funder Contribution €754,377.00
DurationFrom 01 Oct 2023
Project codeANR-23-CE17-0052
Open Access mandatePublications: NoResearch data: No
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Description
Despite significant advancements in understanding alloimmune responses, rejection continues to be the primary determinant influencing the longevity of lung allografts. The complexity of histopathologic analysis poses a major challenge in accurately identifying alloimmune-mediated complications, causing histology to be an imperfect gold standard in diagnosing rejection. The integration of formalin-fixed paraffin-embedded-based molecular diagnostics alongside conventional histology may improve the current empirical diagnostic system. To address the unmet need for precision diagnostics, the current proposal aims to enhance lung transplant rejection diagnostics and increase the level of phenotyping of pulmonary rejection using a tissue-based molecular approach. In order to achieve this goal, we will build a highly characterized population-based cohort of lung transplant patients incorporating 750 transbronchial biopsies from three leading French transplant centers. Each biopsy will be contextualized by means of clinical, biological and immunological data. We will sequence and spatially resolve the molecular immune landscape of pulmonary rejection in formalin-fixed paraffin-embedded transbronchial biopsies using a two-tier approach, comprising both bulk transcriptomics and spatial molecular profiling. These complimentary, cutting-edge technologies will precisely identify the molecular signature corresponding to the subtypes of rejection, allowing us to develop gene-expression based classifiers which will provide a more accurate, standardized and reproducible diagnose of cellular and humoral rejection, than conventional histopathology. In addition, integrating gene expression data in unsupervised probabilistic algorithms will enable us to discover novel molecular, clinical entities and correct errors in diagnostic nosology. By merging the clinical experience of Foch hospital and scientific expertise of INSERM U970, the present proposal will establish the groundwork for the development of integrative diagnostic systems which will facilitate the adaptation of gene expression profiling in routine clinical care.
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Despite significant advancements in understanding alloimmune responses, rejection continues to be the primary determinant influencing the longevity of lung allografts. The complexity of histopathologic analysis poses a major challenge in accurately identifying alloimmune-mediated complications, causing histology to be an imperfect gold standard in diagnosing rejection. The integration of formalin-fixed paraffin-embedded-based molecular diagnostics alongside conventional histology may improve the current empirical diagnostic system. To address the unmet need for precision diagnostics, the current proposal aims to enhance lung transplant rejection diagnostics and increase the level of phenotyping of pulmonary rejection using a tissue-based molecular approach. In order to achieve this goal, we will build a highly characterized population-based cohort of lung transplant patients incorporating 750 transbronchial biopsies from three leading French transplant centers. Each biopsy will be contextualized by means of clinical, biological and immunological data. We will sequence and spatially resolve the molecular immune landscape of pulmonary rejection in formalin-fixed paraffin-embedded transbronchial biopsies using a two-tier approach, comprising both bulk transcriptomics and spatial molecular profiling. These complimentary, cutting-edge technologies will precisely identify the molecular signature corresponding to the subtypes of rejection, allowing us to develop gene-expression based classifiers which will provide a more accurate, standardized and reproducible diagnose of cellular and humoral rejection, than conventional histopathology. In addition, integrating gene expression data in unsupervised probabilistic algorithms will enable us to discover novel molecular, clinical entities and correct errors in diagnostic nosology. By merging the clinical experience of Foch hospital and scientific expertise of INSERM U970, the present proposal will establish the groundwork for the development of integrative diagnostic systems which will facilitate the adaptation of gene expression profiling in routine clinical care.
