Dataset Information

SECANT: a biology-guided semi-supervised method for clustering, classification, and annotation of single-cell multi-omics.

ABSTRACT: The recent advance of single cell sequencing (scRNA-seq) technology such as Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) allows researchers to quantify cell surface protein abundance and RNA expression simultaneously at single cell resolution. Although CITE-seq and other similar technologies have gained enormous popularity, novel methods for analyzing this type of single cell multi-omics data are in urgent need. A limited number of available tools utilize data-driven approach, which may undermine the biological importance of surface protein data. In this study, we developed SECANT, a biology-guided SEmi-supervised method for Clustering, classification, and ANnoTation of single-cell multi-omics. SECANT is used to analyze CITE-seq data, or jointly analyze CITE-seq and scRNA-seq data. The novelties of SECANT include (1) using confident cell type label identified from surface protein data as guidance for cell clustering, (2) providing general annotation of confident cell types for each cell cluster, (3) utilizing cells with uncertain or missing cell type label to increase performance, and (4) accurate prediction of confident cell types for scRNA-seq data. Besides, as a model-based approach, SECANT can quantify the uncertainty of the results through easily interpretable posterior probability, and our framework can be potentially extended to handle other types of multi-omics data. We successfully demonstrated the validity and advantages of SECANT via simulation studies and analysis of public and in-house datasets from multiple tissues. We believe this new method will be complementary to existing tools for characterizing novel cell types and make new biological discoveries using single-cell multi-omics data.

SUBMITTER: Wang X

PROVIDER: S-EPMC9491696 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

SECANT: a biology-guided semi-supervised method for clustering, classification, and annotation of single-cell multi-omics.

Wang Xinjun X Xu Zhongli Z Hu Haoran H Zhou Xueping X Zhang Yanfu Y Lafyatis Robert R Chen Kong K Huang Heng H Ding Ying Y Duerr Richard H RH Chen Wei W

PNAS nexus 20220819 4

The recent advance of single cell sequencing (scRNA-seq) technology such as Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) allows researchers to quantify cell surface protein abundance and RNA expression simultaneously at single cell resolution. Although CITE-seq and other similar technologies have gained enormous popularity, novel methods for analyzing this type of single cell multi-omics data are in urgent need. A limited number of available tools utilize data-driven ...[more]

PMID: 36157595

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Project description:BACKGROUND:Electrogram-guided ablation procedures have been proposed as an alternative strategy consisting of either mapping and ablating focal sources or targeting complex fractionated electrograms in atrial fibrillation (AF). However, the incomplete understanding of the mechanism of AF makes difficult the decision of detecting the target sites. To date, feature extraction from electrograms is carried out mostly based on the time-domain morphology analysis and non-linear features. However, their combination has been reported to achieve better performance. Besides, most of the inferring approaches applied for identifying the levels of fractionation are supervised, which lack of an objective description of fractionation. This aspect complicates their application on EGM-guided ablation procedures. METHODS:This work proposes a semi-supervised clustering method of four levels of fractionation. In particular, we make use of the spectral clustering that groups a set of widely used features extracted from atrial electrograms. We also introduce a new atrial-deflection-based feature to quantify the fractionated activity. Further, based on the sequential forward selection, we find the optimal subset that provides the highest performance in terms of the cluster validation. The method is tested on external validation of a labeled database. The generalization ability of the proposed training approach is tested to aid semi-supervised learning on unlabeled dataset associated with anatomical information recorded from three patients. RESULTS:A joint set of four extracted features, based on two time-domain morphology analysis and two non-linear dynamics, are selected. To discriminate between four considered levels of fractionation, validation on a labeled database performs a suitable accuracy (77.6 %). Results show a congruence value of internal validation index among tested patients that is enough to reconstruct the patterns over the atria to located critical sites with the benefit of avoiding previous manual classification of AF types. CONCLUSIONS:To the best knowledge of the authors, this is the first work reporting semi-supervised clustering for distinguishing patterns in fractionated electrograms. The proposed methodology provides high performance for the detection of unknown patterns associated with critical EGM morphologies. Particularly, obtained results of semi-supervised training show the advantage of demanding fewer labeled data and less training time without significantly compromising accuracy. This paper introduces a new method, providing an objective scheme that enables electro-physiologist to recognize the diverse EGM morphologies reliably.

Dataset Information

SECANT: a biology-guided semi-supervised method for clustering, classification, and annotation of single-cell multi-omics.

Publications

SECANT: a biology-guided semi-supervised method for clustering, classification, and annotation of single-cell multi-omics.

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