{"title":"nsDCC: dual-level contrastive clustering with nonuniform sampling for scRNA-seq data analysis.","authors":"Linjie Wang, Wei Li, Fanghui Zhou, Kun Yu, Chaolu Feng, Dazhe Zhao","doi":"10.1093/bib/bbae477","DOIUrl":null,"url":null,"abstract":"<p><p>Dimensionality reduction and clustering are crucial tasks in single-cell RNA sequencing (scRNA-seq) data analysis, treated independently in the current process, hindering their mutual benefits. The latest methods jointly optimize these tasks through deep clustering. However, contrastive learning, with powerful representation capability, can bridge the gap that common deep clustering methods face, which requires pre-defined cluster centers. Therefore, a dual-level contrastive clustering method with nonuniform sampling (nsDCC) is proposed for scRNA-seq data analysis. Dual-level contrastive clustering, which combines instance-level contrast and cluster-level contrast, jointly optimizes dimensionality reduction and clustering. Multi-positive contrastive learning and unit matrix constraint are introduced in instance- and cluster-level contrast, respectively. Furthermore, the attention mechanism is introduced to capture inter-cellular information, which is beneficial for clustering. The nsDCC focuses on important samples at category boundaries and in minority categories by the proposed nearest boundary sparsest density weight assignment algorithm, making it capable of capturing comprehensive characteristics against imbalanced datasets. Experimental results show that nsDCC outperforms the six other state-of-the-art methods on both real and simulated scRNA-seq data, validating its performance on dimensionality reduction and clustering of scRNA-seq data, especially for imbalanced data. Simulation experiments demonstrate that nsDCC is insensitive to \"dropout events\" in scRNA-seq. Finally, cluster differential expressed gene analysis confirms the meaningfulness of results from nsDCC. In summary, nsDCC is a new way of analyzing and understanding scRNA-seq data.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427072/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Briefings in bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/bib/bbae477","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Dimensionality reduction and clustering are crucial tasks in single-cell RNA sequencing (scRNA-seq) data analysis, treated independently in the current process, hindering their mutual benefits. The latest methods jointly optimize these tasks through deep clustering. However, contrastive learning, with powerful representation capability, can bridge the gap that common deep clustering methods face, which requires pre-defined cluster centers. Therefore, a dual-level contrastive clustering method with nonuniform sampling (nsDCC) is proposed for scRNA-seq data analysis. Dual-level contrastive clustering, which combines instance-level contrast and cluster-level contrast, jointly optimizes dimensionality reduction and clustering. Multi-positive contrastive learning and unit matrix constraint are introduced in instance- and cluster-level contrast, respectively. Furthermore, the attention mechanism is introduced to capture inter-cellular information, which is beneficial for clustering. The nsDCC focuses on important samples at category boundaries and in minority categories by the proposed nearest boundary sparsest density weight assignment algorithm, making it capable of capturing comprehensive characteristics against imbalanced datasets. Experimental results show that nsDCC outperforms the six other state-of-the-art methods on both real and simulated scRNA-seq data, validating its performance on dimensionality reduction and clustering of scRNA-seq data, especially for imbalanced data. Simulation experiments demonstrate that nsDCC is insensitive to "dropout events" in scRNA-seq. Finally, cluster differential expressed gene analysis confirms the meaningfulness of results from nsDCC. In summary, nsDCC is a new way of analyzing and understanding scRNA-seq data.
期刊介绍:
Briefings in Bioinformatics is an international journal serving as a platform for researchers and educators in the life sciences. It also appeals to mathematicians, statisticians, and computer scientists applying their expertise to biological challenges. The journal focuses on reviews tailored for users of databases and analytical tools in contemporary genetics, molecular and systems biology. It stands out by offering practical assistance and guidance to non-specialists in computerized methodologies. Covering a wide range from introductory concepts to specific protocols and analyses, the papers address bacterial, plant, fungal, animal, and human data.
The journal's detailed subject areas include genetic studies of phenotypes and genotypes, mapping, DNA sequencing, expression profiling, gene expression studies, microarrays, alignment methods, protein profiles and HMMs, lipids, metabolic and signaling pathways, structure determination and function prediction, phylogenetic studies, and education and training.