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Open AccessJournal ArticleDOI

Transcriptional and Cellular Diversity of the Human Heart

Nathan R. Tucker, +17 more
- 04 Aug 2020 - 
- Vol. 142, Iss: 5, pp 466-482
TLDR
Using large-scale single nuclei RNA sequencing, the transcriptional and cellular diversity in the normal human heart was defined and the identification of discrete cell subtypes and differentially expressed genes within the heart will ultimately facilitate the development of new therapeutics for cardiovascular diseases.
Abstract: 
Background: The human heart requires a complex ensemble of specialized cell types to perform its essential function. A greater knowledge of the intricate cellular milieu of the heart is critical to...

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Citations
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Journal ArticleDOI

Cells of the adult human heart.

Monika Litviňuková, +43 more
- 24 Sep 2020 - 
TL;DR: The state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes are used to construct a cellular atlas of the human heart that will aid further research into cardiac physiology and disease and provides a valuable reference for future studies.

Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

Anubha Mahajan, +113 more
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%, 14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.
Journal ArticleDOI

Systemic and organ-specific immune-related manifestations of COVID-19.

Manuel Ramos-Casals, +2 more
- 26 Apr 2021 - 
TL;DR: The signs and symptoms associated with this excessive immune response are very diverse and can resemble some autoimmune or inflammatory diseases, with the clinical phenotype that is seemingly influenced by epidemiological factors such as age, sex or ethnicity.
Journal ArticleDOI

Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions

Michael R. Filbin, +56 more
TL;DR: In this paper, the authors analyzed several thousand plasma proteins longitudinally in 306 severe coronavirus disease 2019 (COVID-19) patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-2019.
Journal ArticleDOI

Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

Gökcen Eraslan, +25 more
- 13 May 2022 - 
TL;DR: A framework for multitissue human cell atlases is established and an atlas of 209,126 snRNA-seq profiles from eight tissue types across 16 individuals, archived as frozen tissue as part of the Genotype-Tissue Expression (GTEx) project is generated.
References
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Fitting Linear Mixed-Effects Models Using lme4

Douglas M. Bates, +3 more
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Adam Auton, +517 more
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Journal ArticleDOI

Comprehensive Integration of Single-Cell Data.

Tim Stuart, +9 more
- 13 Jun 2019 - 
TL;DR: A strategy to "anchor" diverse datasets together, enabling us to integrate single-cell measurements not only across scRNA-seq technologies, but also across different modalities.
Journal ArticleDOI

Integrating single-cell transcriptomic data across different conditions, technologies, and species.

Andrew Butler, +4 more
- 02 Apr 2018 - 
TL;DR: An analytical strategy for integrating scRNA-seq data sets based on common sources of variation is introduced, enabling the identification of shared populations across data sets and downstream comparative analysis.
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Cells of the adult human heart.

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