Despite many years of research, no biomarkers for stroke are available to use in clinical practice. Progress in high-throughput technologies has provided new opportunities to understand the pathophysiology of this complex disease, and these studies have generated large amounts of data and information at different molecular levels. The integration of these multi-omics data means that thousands of proteins (proteomics), genes (genomics), RNAs (transcriptomics) and metabolites (metabolomics) can be studied simultaneously, revealing interaction networks between the molecular levels. Integrated analysis of multi-omics data will provide useful insight into stroke pathogenesis, identification of therapeutic targets and biomarker discovery. In this Review, we detail current knowledge on the pathology of stroke and the current status of biomarker research in stroke. We summarize how proteomics, metabolomics, transcriptomics and genomics are all contributing to the identification of new candidate biomarkers that could be developed and used in clinical stroke management.
Biomarkers of stroke could improve diagnosis and management, but standardization or harmonization of procedures is needed before translation of biomarkers to clinical practice to ensure results are comparable and reliable.
Studies of the proteome of the brain, cerebrospinal fluid and brain extracellular fluid after ischaemic stroke have led to identification of candidate biomarkers for stroke management.
Most studies of stroke genetics have focused on common or low-frequency single-nucleotide polymorphisms; other types of variation, such as rare single-nucleotide variants or structural variations, have been insufficiently explored.
Changes in RNA levels in stroke have the potential to aid stroke diagnosis and provide insight into stroke aetiology.
Circulating metabolites provide information about local and systemic events after stroke, and therefore could serve as biomarkers of stroke and for differentiation of major stroke aetiologies.
Integrated analysis of data obtained with different omics approaches will enable implementation of biomarkers at several stages in the stroke care pathway, with the potential to transform stroke management.
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The Neurovascular Research Laboratory acknowledges funding from grants PI15/00354 and PI18/00804 from Fondo de Investigaciones Sanitarias of the Instituto de Salud Carlos III (co-financed by the European Regional Development Fund, FEDER). The Neurovascular Research Laboratory is also a member of the Spanish stroke research network INVICTUS+ (RD16/0019). L.R. is supported by a predoctoral fellowship grant from the Instituto de Salud Carlos III (IFI17/00012). A.B. is supported by a Juan Rodes research grant from Instituto de Salud Carlos III (JR16/00008).
Members of the neurovascular research laboratory (A.S., A.B., J.M. and L.R.) are inventors of a family of patents for biomarkers to differentiate ischaemic from haemorrhagic stroke, to predict stroke outcome and to establish stroke aetiology. J.-C.S. and J.M. are co-founders of ABCDx, a spin-off company of the University of Geneva (http://www.abcdx.ch).
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- Ischaemic core
The region of the brain with the most severe blood flow deficits (blood flow below 10–25%), resulting in rapid progression of cell death.
- Embolic stroke of undetermined source
Ischaemic stroke with an unknown origin; these strokes are non-lacunar and non-atherosclerotic strokes of an undetermined embolic source.
A phenomenon that occurs when a statistical model describes random error or noise instead of the underlying relationship.
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Montaner, J., Ramiro, L., Simats, A. et al. Multilevel omics for the discovery of biomarkers and therapeutic targets for stroke. Nat Rev Neurol 16, 247–264 (2020). https://doi.org/10.1038/s41582-020-0350-6
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