Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies.

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Abstract

With increasing significance of developmental programming effects associated with placental dysfunction, more investigations are devoted to improving the characterization and understanding of placental signatures in health and disease. The placenta is a transitory but dynamic organ adapting to the shifting demands of fetal development and available resources of the maternal supply throughout pregnancy. Trophoblasts (cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts) are placental-specific cell types responsible for the main placental exchanges and adaptations. Transcriptomic studies with single-cell resolution have led to advances in understanding the placenta's role in health and disease. These studies, however, often show discrepancies in characterization of the different placental cell types.

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SCANPY : large-scale single-cell gene expression data analysis

F. Alexander Wolf, Philipp Angerer, Fabian Theis (2018)

Scanpy is a scalable toolkit for analyzing single-cell gene expression data. It includes methods for preprocessing, visualization, clustering, pseudotime and trajectory inference, differential expression testing, and simulation of gene regulatory networks. Its Python-based implementation efficiently deals with data sets of more than one million cells (https://github.com/theislab/Scanpy). Along with Scanpy, we present AnnData, a generic class for handling annotated data matrices (https://github.com/theislab/anndata).

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The GTEx Consortium atlas of genetic regulatory effects across human tissues

(2020)

The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue specificity of genetic effects and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.

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DoubletFinder: Doublet Detection in Single-Cell RNA Sequencing Data Using Artificial Nearest Neighbors

Christopher S McGinnis, Lyndsay Murrow, Zev J. Gartner (2019)

Single-cell RNA sequencing (scRNA-seq) data are commonly affected by technical artifacts known as “doublets,” which limit cell throughput and lead to spurious biological conclusions. Here, we present a computational doublet detection tool—Doublet-Finder—that identifies doublets using only gene expression data. DoubletFinder predicts doublets according to each real cell’s proximity in gene expression space to artificial doublets created by averaging the transcriptional profile of randomly chosen cell pairs. We first use scRNA-seq datasets where the identity of doublets is known to show that DoubletFinder identifies doublets formed from transcriptionally distinct cells. When these doublets are removed, the identification of differentially expressed genes is enhanced. Second, we provide a method for estimating DoubletFinder input parameters, allowing its application across scRNA-seq datasets with diverse distributions of cell types. Lastly, we present “best practices” for DoubletFinder applications and illustrate that DoubletFinder is insensitive to an experimentally validated kidney cell type with “hybrid” expression features. scRNA-seq data interpretation is confounded by technical artifacts known as doublets—single-cell transcriptome data representing more than one cell. Moreover, scRNA-seq cellular throughput is purposefully limited to minimize doublet formation rates. By identifying cells sharing expression features with simulated doublets, DoubletFinder detects many real doublets and mitigates these two limitations.