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1. scSampler: fast diversity-preserving subsampling of large-scale single-cell transcriptomic data

   https://doi.org/10.1093/bioinformatics/btac271  

   Song, Dongyuan; Xi, Nan_Miles; Li, Jingyi_Jessica; Wang, Lin; Vitek, ed., Olga (April 2022, Bioinformatics)

   Abstract SummaryThe number of cells measured in single-cell transcriptomic data has grown fast in recent years. For such large-scale data, subsampling is a powerful and often necessary tool for exploratory data analysis. However, the easiest random subsampling is not ideal from the perspective of preserving rare cell types. Therefore, diversity-preserving subsampling is required for fast exploration of cell types in a large-scale dataset. Here, we propose scSampler, an algorithm for fast diversity-preserving subsampling of single-cell transcriptomic data. Availability and implementationscSampler is implemented in Python and is published under the MIT source license. It can be installed by “pip install scsampler” and used with the Scanpy pipline. The code is available on GitHub: https://github.com/SONGDONGYUAN1994/scsampler. An R interface is available at: https://github.com/SONGDONGYUAN1994/rscsampler. Supplementary informationSupplementary data are available at Bioinformatics online. 

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2. ACTIVA : realistic single-cell RNA-seq generation with automatic cell-type identification using introspective variational autoencoders

   https://doi.org/10.1093/bioinformatics/btac095  

   Heydari, A. Ali; Davalos, Oscar A.; Zhao, Lihong; Hoyer, Katrina K.; Sindi, Suzanne S.; Mathelier, ed., Anthony (February 2022, Bioinformatics)

   Abstract MotivationSingle-cell RNA sequencing (scRNAseq) technologies allow for measurements of gene expression at a single-cell resolution. This provides researchers with a tremendous advantage for detecting heterogeneity, delineating cellular maps or identifying rare subpopulations. However, a critical complication remains: the low number of single-cell observations due to limitations by rarity of subpopulation, tissue degradation or cost. This absence of sufficient data may cause inaccuracy or irreproducibility of downstream analysis. In this work, we present Automated Cell-Type-informed Introspective Variational Autoencoder (ACTIVA): a novel framework for generating realistic synthetic data using a single-stream adversarial variational autoencoder conditioned with cell-type information. Within a single framework, ACTIVA can enlarge existing datasets and generate specific subpopulations on demand, as opposed to two separate models [such as single-cell GAN (scGAN) and conditional scGAN (cscGAN)]. Data generation and augmentation with ACTIVA can enhance scRNAseq pipelines and analysis, such as benchmarking new algorithms, studying the accuracy of classifiers and detecting marker genes. ACTIVA will facilitate analysis of smaller datasets, potentially reducing the number of patients and animals necessary in initial studies. ResultsWe train and evaluate models on multiple public scRNAseq datasets. In comparison to GAN-based models (scGAN and cscGAN), we demonstrate that ACTIVA generates cells that are more realistic and harder for classifiers to identify as synthetic which also have better pair-wise correlation between genes. Data augmentation with ACTIVA significantly improves classification of rare subtypes (more than 45% improvement compared with not augmenting and 4% better than cscGAN) all while reducing run-time by an order of magnitude in comparison to both models. Availability and implementationThe codes and datasets are hosted on Zenodo (https://doi.org/10.5281/zenodo.5879639). Tutorials are available at https://github.com/SindiLab/ACTIVA. Supplementary informationSupplementary data are available at Bioinformatics online. 

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3. ASTRAL-Pro 2: ultrafast species tree reconstruction from multi-copy gene family trees

   https://doi.org/10.1093/bioinformatics/btac620  

   Zhang, Chao; Mirarab, Siavash; Schwartz, ed., Russell (September 2022, Bioinformatics)

   Abstract MotivationSpecies tree inference from multi-copy gene trees has long been a challenge in phylogenomics. The recent method ASTRAL-Pro has made strides by enabling multi-copy gene family trees as input and has been quickly adopted. Yet, its scalability, especially memory usage, needs to improve to accommodate the ever-growing dataset size. ResultsWe present ASTRAL-Pro 2, an ultrafast and memory efficient version of ASTRAL-Pro that adopts a placement-based optimization algorithm for significantly better scalability without sacrificing accuracy. Availability and implementationThe source code and binary files are publicly available at https://github.com/chaoszhang/ASTER; data are available at https://github.com/chaoszhang/A-Pro2_data. Supplementary informationSupplementary data are available at Bioinformatics online. 

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4. Differential Expression Gene Explorer (DrEdGE): a tool for generating interactive online visualizations of gene expression datasets

   https://doi.org/10.1093/bioinformatics/btz972  

   Tintori, Sophia C.; Golden, Patrick; Goldstein, Bob; Wren, ed., Jonathan (January 2020, Bioinformatics)

   Abstract SummaryDifferential Expression Gene Explorer (DrEdGE) is a web-based tool that guides genomicists through easily creating interactive online data visualizations, which colleagues can query according to their own conditions to discover genes, samples or patterns of interest. We demonstrate DrEdGE’s features with three example websites generated from publicly available datasets—human neuronal tissue, mouse embryonic tissue and Caenorhabditis elegans whole embryos. DrEdGE increases the utility of large genomics datasets by removing technical obstacles to independent exploration. Availability and implementationFreely available at http://dredge.bio.unc.edu. Supplementary informationSupplementary data are available at Bioinformatics online. 

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5. Single-cell generalized trend model (scGTM): a flexible and interpretable model of gene expression trend along cell pseudotime

   https://doi.org/10.1093/bioinformatics/btac423  

   Cui, Elvis Han; Song, Dongyuan; Wong, Weng Kee; Li, Jingyi Jessica; Mathelier, ed., Anthony (June 2022, Bioinformatics)

   Abstract MotivationModeling single-cell gene expression trends along cell pseudotime is a crucial analysis for exploring biological processes. Most existing methods rely on nonparametric regression models for their flexibility; however, nonparametric models often provide trends too complex to interpret. Other existing methods use interpretable but restrictive models. Since model interpretability and flexibility are both indispensable for understanding biological processes, the single-cell field needs a model that improves the interpretability and largely maintains the flexibility of nonparametric regression models. ResultsHere, we propose the single-cell generalized trend model (scGTM) for capturing a gene’s expression trend, which may be monotone, hill-shaped or valley-shaped, along cell pseudotime. The scGTM has three advantages: (i) it can capture non-monotonic trends that are easy to interpret, (ii) its parameters are biologically interpretable and trend informative, and (iii) it can flexibly accommodate common distributions for modeling gene expression counts. To tackle the complex optimization problems, we use the particle swarm optimization algorithm to find the constrained maximum likelihood estimates for the scGTM parameters. As an application, we analyze several single-cell gene expression datasets using the scGTM and show that scGTM can capture interpretable gene expression trends along cell pseudotime and reveal molecular insights underlying biological processes. Availability and implementationThe Python package scGTM is open-access and available at https://github.com/ElvisCuiHan/scGTM. Supplementary informationSupplementary data are available at Bioinformatics online. 

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