Dataset Information

BATMAN: Fast and Accurate Integration of Single-Cell RNA-Seq Datasets via Minimum-Weight Matching.

ABSTRACT: Single-cell RNA-sequencing (scRNA-seq) is a set of technologies used to profile gene expression at the level of individual cells. Although the throughput of scRNA-seq experiments is steadily growing in terms of the number of cells, large datasets are not yet commonly generated owing to prohibitively high costs. Integrating multiple datasets into one can improve power in scRNA-seq experiments, and efficient integration is very important for downstream analyses such as identifying cell-type-specific eQTLs. State-of-the-art scRNA-seq integration methods are based on the mutual nearest neighbor paradigm and fail to both correct for batch effects and maintain the local structure of the datasets. In this paper, we propose a novel scRNA-seq dataset integration method called BATMAN (BATch integration via minimum-weight MAtchiNg). Across multiple simulations and real datasets, we show that our method significantly outperforms state-of-the-art tools with respect to existing metrics for batch effects by up to 80% while retaining cell-to-cell relationships.

SUBMITTER: Mandric I

PROVIDER: S-EPMC7276436 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

BATMAN: Fast and Accurate Integration of Single-Cell RNA-Seq Datasets via Minimum-Weight Matching.

Mandric Igor I Hill Brian L BL Freund Malika K MK Thompson Michael M Halperin Eran E

iScience 20200520 6

Single-cell RNA-sequencing (scRNA-seq) is a set of technologies used to profile gene expression at the level of individual cells. Although the throughput of scRNA-seq experiments is steadily growing in terms of the number of cells, large datasets are not yet commonly generated owing to prohibitively high costs. Integrating multiple datasets into one can improve power in scRNA-seq experiments, and efficient integration is very important for downstream analyses such as identifying cell-type-specif ...[more]

PMID: 32504875

Similar Datasets

Project description:MotivationMicroRNA (miRNA) precursor arms give rise to multiple isoforms simultaneously called 'isomiRs.' IsomiRs from the same arm typically differ by a few nucleotides at either their 5' or 3' termini or both. In humans, the identities and abundances of isomiRs depend on a person's sex and genetic ancestry as well as on tissue type, tissue state and disease type/subtype. Moreover, nearly half of the time the most abundant isomiR differs from the miRNA sequence found in public databases. Accurate mining of isomiRs from deep sequencing data is thus important.ResultsWe developed isoMiRmap, a fast, standalone, user-friendly mining tool that identifies and quantifies all isomiRs by directly processing short RNA-seq datasets. IsoMiRmap is a portable 'plug-and-play' tool, requires minimal setup, has modest computing and storage requirements, and can process an RNA-seq dataset with 50 million reads in just a few minutes on an average laptop. IsoMiRmap deterministically and exhaustively reports all isomiRs in a given deep sequencing dataset and quantifies them accurately (no double-counting). IsoMiRmap comprehensively reports all miRNA precursor locations from which an isomiR may be transcribed, tags as 'ambiguous' isomiRs whose sequences exist both inside and outside of the space of known miRNA sequences and reports the public identifiers of common single-nucleotide polymorphisms and documented somatic mutations that may be present in an isomiR. IsoMiRmap also identifies isomiRs with 3' non-templated post-transcriptional additions. Compared to similar tools, isoMiRmap is the fastest, reports more bona fide isomiRs, and provides the most comprehensive information related to an isomiR's transcriptional origin.Availability and implementationThe codes for isoMiRmap are freely available at https://cm.jefferson.edu/isoMiRmap/ and https://github.com/TJU-CMC-Org/isoMiRmap/. IsomiR profiles for the datasets of the 1000 Genomes Project, spanning five population groups, and The Cancer Genome Atlas (TCGA), spanning 33 cancer studies, are also available at https://cm.jefferson.edu/isoMiRmap/.Supplementary informationSupplementary data are available at Bioinformatics online.

Project description:RNA-sequencing (RNA-seq) provides a comprehensive quantification of transcriptomic activities in biological samples. Formalin-Fixed Paraffin-Embedded (FFPE) samples are collected as part of routine clinical procedure, and are the most widely available biological sample format in medical research and patient care. Normalization is an essential step in RNA-seq data analysis. A number of normalization methods, though developed for RNA-seq data from fresh frozen (FF) samples, can be used with FFPE samples as well. The only extant normalization method specifically designed for FFPE RNA-seq data, MIXnorm, which has been shown to outperform the normalization methods, but at the cost of a complex mixture model and a high computational burden. It is therefore important to adapt MIXnorm for simplicity and computational efficiency while maintaining superior performance. Furthermore, it is critical to develop an integrated tool that performs commonly used normalization methods for both FF and FFPE RNA-seq data. We developed a new normalization method for FFPE RNA-seq data, named SMIXnorm, based on a simplified two-component mixture model compared to MIXnorm to facilitate computation. The expression levels of expressed genes are modeled by normal distributions without truncation, and those of non-expressed genes are modeled by zero-inflated Poisson distributions. The maximum likelihood estimates of the model parameters are obtained by a nested Expectation-Maximization algorithm with a less complicated latent variable structure, and closed-form updates are available within each iteration. Real data applications and simulation studies show that SMIXnorm greatly reduces computing time compared to MIXnorm, without sacrificing the performance. More importantly, we developed a web-based tool, RNA-seq Normalization (RSeqNorm), that offers a simple workflow to compute normalized RNA-seq data for both FFPE and FF samples. It includes SMIXnorm and MIXnorm for FFPE RNA-seq data, together with five commonly used normalization methods for FF RNA-seq data. Users can easily upload a raw RNA-seq count matrix and select one of the seven normalization methods to produce a downloadable normalized expression matrix for any downstream analysis. The R package is available at https://github.com/S-YIN/RSEQNORM. The web-based tool, RSeqNorm is available at http://lce.biohpc.swmed.edu/rseqnorm with no restriction to use or redistribute.

Dataset Information

BATMAN: Fast and Accurate Integration of Single-Cell RNA-Seq Datasets via Minimum-Weight Matching.

Publications

BATMAN: Fast and Accurate Integration of Single-Cell RNA-Seq Datasets via Minimum-Weight Matching.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets