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Abstract Population-scale single-cell RNA sequencing (scRNA-seq) is now viable, enabling finer resolution functional genomics studies and leading to a rush to adapt bulk methods and develop new single-cell-specific methods to perform these studies. Simulations are useful for developing, testing, and benchmarking methods but current scRNA-seq simulation frameworks do not simulate population-scale data with genetic effects. Here, we present splatPop, a model for flexible, reproducible, and well-documented simulation of population-scale scRNA-seq data with known expression quantitative trait loci. splatPop can also simulate complex batch, cell group, and conditional effects between individuals from different cohorts as well as genetically-driven co-expression.

Abstract Recent years have seen a revolution in single-cell RNA-sequencing (scRNA-seq) technologies, datasets, and analysis methods. Since 2016, the scRNA-tools database has cataloged software tools for analyzing scRNA-seq data. With the number of tools in the database passing 1000, we provide an update on the state of the project and the field. This data shows the evolution of the field and a change of focus from ordering cells on continuous trajectories to integrating multiple samples and making use of reference datasets. We also find that open science practices reward developers with increased recognition and help accelerate the field.

Abstract Single-cell RNA-seq datasets are often first analyzed independently without harnessing model fits from previous studies, and are then contextualized with public data sets, requiring time-consuming data wrangling. We address these issues with sfaira, a single-cell data zoo for public data sets paired with a model zoo for executable pre-trained models. The data zoo is designed to facilitate contribution of data sets using ontologies for metadata. We propose an adaption of cross-entropy loss for cell type classification tailored to datasets annotated at different levels of coarseness. We demonstrate the utility of sfaira by training models across anatomic data partitions on 8 million cells.

Abstract Long-read technologies are overcoming early limitations in accuracy and throughput, broadening their application domains in genomics. Dedicated analysis tools that take into account the characteristics of long-read data are thus required, but the fast pace of development of such tools can be overwhelming. To assist in the design and analysis of long-read sequencing projects, we review the current landscape of available tools and present an online interactive database, long-read-tools.org, to facilitate their browsing. We further focus on the principles of error correction, base modification detection, and long-read transcriptomics analysis and highlight the challenges that remain.

Abstract Background Human kidney organoids hold promise for studying development, disease modelling and drug screening. However, the utility of stem cell-derived kidney tissues will depend on how faithfully these replicate normal fetal development at the level of cellular identity and complexity. Methods Here, we present an integrated analysis of single cell datasets from human kidney organoids and human fetal kidney to assess similarities and differences between the component cell types. Results Clusters in the combined dataset contained cells from both organoid and fetal kidney with transcriptional congruence for key stromal, endothelial and nephron cell type-specific markers. Organoid enriched neural, glial and muscle progenitor populations were also evident. Major transcriptional differences between organoid and human tissue were likely related to technical artefacts. Cell type-specific comparisons revealed differences in stromal, endothelial and nephron progenitor cell types including expression of WNT2B in the human fetal kidney stroma. Conclusions This study supports the fidelity of kidney organoids as models of the developing kidney and affirms their potential in disease modelling and drug screening.

Abstract As single-cell RNA sequencing (scRNA-seq) technologies have rapidly developed, so have analysis methods. Many methods have been tested, developed, and validated using simulated datasets. Unfortunately, current simulations are often poorly documented, their similarity to real data is not demonstrated, or reproducible code is not available. Here, we present the Splatter Bioconductor package for simple, reproducible, and well-documented simulation of scRNA-seq data. Splatter provides an interface to multiple simulation methods including Splat, our own simulation, based on a gamma-Poisson distribution. Splat can simulate single populations of cells, populations with multiple cell types, or differentiation paths.