Dataset Information

ScINSIGHT for interpreting single-cell gene expression from biologically heterogeneous data.

ABSTRACT: The increasing number of scRNA-seq data emphasizes the need for integrative analysis to interpret similarities and differences between single-cell samples. Although different batch effect removal methods have been developed, none are suitable for heterogeneous single-cell samples coming from multiple biological conditions. We propose a method, scINSIGHT, to learn coordinated gene expression patterns that are common among, or specific to, different biological conditions, and identify cellular identities and processes across single-cell samples. We compare scINSIGHT with state-of-the-art methods using simulated and real data, which demonstrate its improved performance. Our results show the applicability of scINSIGHT in diverse biomedical and clinical problems.

SUBMITTER: Qian K

PROVIDER: S-EPMC8935111 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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scINSIGHT for interpreting single-cell gene expression from biologically heterogeneous data.

Qian Kun K Fu Shiwei S Li Hongwei H Li Wei Vivian WV

Genome biology 20220321 1

The increasing number of scRNA-seq data emphasizes the need for integrative analysis to interpret similarities and differences between single-cell samples. Although different batch effect removal methods have been developed, none are suitable for heterogeneous single-cell samples coming from multiple biological conditions. We propose a method, scINSIGHT, to learn coordinated gene expression patterns that are common among, or specific to, different biological conditions, and identify cellular ide ...[more]

PMID: 35313930

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Project description:BackgroundThere are many methods for analyzing microarray data that group together genes having similar patterns of expression over all conditions tested. However, in many instances the biologically important goal is to identify relatively small sets of genes that share coherent expression across only some conditions, rather than all or most conditions as required in traditional clustering; e.g. genes that are highly up-regulated and/or down-regulated similarly across only a subset of conditions. Equally important is the need to learn which conditions are the decisive ones in forming such gene sets of interest, and how they relate to diverse conditional covariates, such as disease diagnosis or prognosis.ResultsWe present a method for automatically identifying such candidate sets of biologically relevant genes using a combination of principal components analysis and information theoretic metrics. To enable easy use of our methods, we have developed a data analysis package that facilitates visualization and subsequent data mining of the independent sources of significant variation present in gene microarray expression datasets (or in any other similarly structured high-dimensional dataset). We applied these tools to two public datasets, and highlight sets of genes most affected by specific subsets of conditions (e.g. tissues, treatments, samples, etc.). Statistically significant associations for highlighted gene sets were shown via global analysis for Gene Ontology term enrichment. Together with covariate associations, the tool provides a basis for building testable hypotheses about the biological or experimental causes of observed variation.ConclusionWe provide an unsupervised data mining technique for diverse microarray expression datasets that is distinct from major methods now in routine use. In test uses, this method, based on publicly available gene annotations, appears to identify numerous sets of biologically relevant genes. It has proven especially valuable in instances where there are many diverse conditions (10's to hundreds of different tissues or cell types), a situation in which many clustering and ordering algorithms become problematic. This approach also shows promise in other topic domains such as multi-spectral imaging datasets.

Dataset Information

ScINSIGHT for interpreting single-cell gene expression from biologically heterogeneous data.

Publications

scINSIGHT for interpreting single-cell gene expression from biologically heterogeneous data.

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