Dataset Information

Integrating Deep Supervised, Self-Supervised and Unsupervised Learning for Single-Cell RNA-seq Clustering and Annotation.

ABSTRACT: As single-cell RNA sequencing technologies mature, massive gene expression profiles can be obtained. Consequently, cell clustering and annotation become two crucial and fundamental procedures affecting other specific downstream analyses. Most existing single-cell RNA-seq (scRNA-seq) data clustering algorithms do not take into account the available cell annotation results on the same tissues or organisms from other laboratories. Nonetheless, such data could assist and guide the clustering process on the target dataset. Identifying marker genes through differential expression analysis to manually annotate large amounts of cells also costs labor and resources. Therefore, in this paper, we propose a novel end-to-end cell supervised clustering and annotation framework called scAnCluster, which fully utilizes the cell type labels available from reference data to facilitate the cell clustering and annotation on the unlabeled target data. Our algorithm integrates deep supervised learning, self-supervised learning and unsupervised learning techniques together, and it outperforms other customized scRNA-seq supervised clustering methods in both simulation and real data. It is particularly worth noting that our method performs well on the challenging task of discovering novel cell types that are absent in the reference data.

SUBMITTER: Chen L

PROVIDER: S-EPMC7397036 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Integrating Deep Supervised, Self-Supervised and Unsupervised Learning for Single-Cell RNA-seq Clustering and Annotation.

Chen Liang L Zhai Yuyao Y He Qiuyan Q Wang Weinan W Deng Minghua M

Genes 20200714 7

As single-cell RNA sequencing technologies mature, massive gene expression profiles can be obtained. Consequently, cell clustering and annotation become two crucial and fundamental procedures affecting other specific downstream analyses. Most existing single-cell RNA-seq (scRNA-seq) data clustering algorithms do not take into account the available cell annotation results on the same tissues or organisms from other laboratories. Nonetheless, such data could assist and guide the clustering process ...[more]

PMID: 32674393

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Project description:BackgroundSingle-cell RNA sequencing (scRNA-seq) has emerged has a main strategy to study transcriptional activity at the cellular level. Clustering analysis is routinely performed on scRNA-seq data to explore, recognize or discover underlying cell identities. The high dimensionality of scRNA-seq data and its significant sparsity accentuated by frequent dropout events, introducing false zero count observations, make the clustering analysis computationally challenging. Even though multiple scRNA-seq clustering techniques have been proposed, there is no consensus on the best performing approach. On a parallel research track, self-supervised contrastive learning recently achieved state-of-the-art results on images clustering and, subsequently, image classification.ResultsWe propose contrastive-sc, a new unsupervised learning method for scRNA-seq data that perform cell clustering. The method consists of two consecutive phases: first, an artificial neural network learns an embedding for each cell through a representation training phase. The embedding is then clustered in the second phase with a general clustering algorithm (i.e. KMeans or Leiden community detection). The proposed representation training phase is a new adaptation of the self-supervised contrastive learning framework, initially proposed for image processing, to scRNA-seq data. contrastive-sc has been compared with ten state-of-the-art techniques. A broad experimental study has been conducted on both simulated and real-world datasets, assessing multiple external and internal clustering performance metrics (i.e. ARI, NMI, Silhouette, Calinski scores). Our experimental analysis shows that constastive-sc compares favorably with state-of-the-art methods on both simulated and real-world datasets.ConclusionOn average, our method identifies well-defined clusters in close agreement with ground truth annotations. Our method is computationally efficient, being fast to train and having a limited memory footprint. contrastive-sc maintains good performance when only a fraction of input cells is provided and is robust to changes in hyperparameters or network architecture. The decoupling between the creation of the embedding and the clustering phase allows the flexibility to choose a suitable clustering algorithm (i.e. KMeans when the number of expected clusters is known, Leiden otherwise) or to integrate the embedding with other existing techniques.

Project description:This work aimed to identify pre-existing health conditions of patients with traumatic brain injury (TBI) and develop predictive models for the first TBI event and its external causes by employing a combination of unsupervised and supervised learning algorithms. We acquired up to five years of pre-injury diagnoses for 488,107 patients with TBI and 488,107 matched control patients who entered the emergency department or acute care hospitals between April 1st, 2002, and March 31st, 2020. Diagnoses were obtained from the Ontario Health Insurance Plan (OHIP) database which contains province-wide claims data by physicians in Ontario, Canada for inpatient and outpatient services. A screening process was conducted on the OHIP diagnostic codes to limit the subsequent analysis to codes that were predictive of TBI, which concluded that 314 codes were significantly associated with TBI. The Latent Dirichlet Allocation (LDA) model was applied to the diagnostic codes and generated an optimal number of 19 topics that concur with published literature but also suggest other unexplored areas. Estimated word-topic probabilities from the LDA model helped us detect pre-morbid conditions among patients with TBI by uncovering the underlying patterns of diagnoses, meanwhile estimated document-topic probabilities were utilized in variable creation as form of a dimension reduction. We created 19 topic scores for each patient in the cohort which were utilized along with socio-demographic factors for Random Forest binary classifier models. Test set performances evaluated using area under the receiver operating characteristic curve (AUC) were: TBI event (AUC = 0.85), external cause of injury: falls (AUC = 0.85), struck by/against (AUC = 0.83), cyclist collision (AUC = 0.76), motor vehicle collision (AUC = 0.83). Our analysis successfully demonstrated the feasibility of using machine learning to predict TBI due to various external causes and identified the most important factors that contribute to this prediction.

Dataset Information

Integrating Deep Supervised, Self-Supervised and Unsupervised Learning for Single-Cell RNA-seq Clustering and Annotation.

Publications

Integrating Deep Supervised, Self-Supervised and Unsupervised Learning for Single-Cell RNA-seq Clustering and Annotation.

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