Abstract
The past few decades are characterized by an explosive evolution of genetics and molecular cell biology. Advances in chemistry and engineering have enabled increased data throughput, permitting the study of complete sets of molecules with increasing speed and accuracy using techniques such as genomics, transcriptomics, proteomics, and metabolomics. Prediction of long-term outcomes in transplantation is hampered by the absence of sufficiently robust biomarkers and a lack of adequate insight into the mechanisms of acute and chronic alloimmune injury and the adaptive mechanisms of immunological quiescence that may support transplantation tolerance. Here, we discuss some of the great opportunities that molecular diagnostic tools have to offer both basic scientists and translational researchers for bench-to-bedside clinical application in transplantation medicine, with special focus on genomics and genome-wide association studies, epigenetics (DNA methylation and histone modifications), gene expression studies and transcriptomics (including microRNA and small interfering RNA studies), proteomics and peptidomics, antibodyomics, metabolomics, chemical genomics and functional imaging with nanoparticles. We address the challenges and opportunities associated with the newer high-throughput sequencing technologies, especially in the field of bioinformatics and biostatistics, and demonstrate the importance of integrative approaches. Although this Review focuses on transplantation research and clinical transplantation, the concepts addressed are valid for all translational research.
Key Points
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The omics approach has accelerated biomarker discovery and improved understanding of multifactorial biological processes and diseases
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The complex interplay between the genome, transcriptome, proteome and metabolome has mostly been overlooked in traditional translational research and in the field of transplantation
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In transplantation research, data from high-throughput molecular diagnostic tools are shedding new light on many pathogenic processes (for example, acute cellular rejection, ischemia–reperfusion injury and chronic allograft damage)
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Upcoming high-throughput techniques, such as massively parallel sequencing for genotyping and transcriptomics, are expected to further accelerate the pace at which translational research is performed
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The challenge for the future is to translate the progress that is being made in molecular biology into health gains, an outcome that will only be possible with a holistic approach and integrative data analysis
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Naesens, M., Sarwal, M. Molecular diagnostics in transplantation. Nat Rev Nephrol 6, 614–628 (2010). https://doi.org/10.1038/nrneph.2010.113
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DOI: https://doi.org/10.1038/nrneph.2010.113
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