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- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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- Wang, ZC, et al.
(författare)
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A diagnostic model for predicting type 2 nasal polyps using biomarkers in nasal secretion
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1054201-
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Tidskriftsartikel (refereegranskat)abstract
- Predicting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) may help for selection of appropriate surgical procedures or pharmacotherapies in advance. However, an accurate non-invasive method for diagnosis of type 2 CRSwNP is presently unavailable.MethodsTo optimize the technique for collecting nasal secretion (NasSec), 89 CRSwNP patients were tested using nasal packs made with four types of materials. Further, Th2low and Th2highCRSwNP defined by clustering analysis in another 142 CRSwNP patients using tissue biomarkers, in the meanwhile, inflammatory biomarkers were detected in NasSec of the same patients collected by the selected nasal pack. A diagnostic model was established by machine learning algorithms to predict Th2highCRSwNP using NasSecs biomarkers.ResultsConsidering the area under receiver operating characteristic curve (AUC) for IL-5 in NasSec, nasal pack in polyvinyl alcohol (PVA) was superior to other materials for NasSec collection. When Th2low and Th2highCRSwNP clusters were defined, logistic regression and decision tree model for prediction of Th2highCRSwNP demonstrated high AUCs values of 0.92 and 0.90 respectively using biomarkers of NasSecs. Consequently, the pre-pruned decision tree model; based on the levels of IL-5 in NasSec (≤ 15.04 pg/mL), blood eosinophil count (≤ 0.475*109/L) and absence of comorbid asthma; was chosen to define Th2lowCRSwNP from Th2highCRSwNP for routine clinical use.ConclusionsTaken together, a decision tree model based on a combination of NasSec biomarkers and clinical features can accurately define type 2 CRSwNP patients and therefore may be of benefit to patients in receiving appropriate therapies in daily clinical practice.
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