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Swain, A. K.

Publications and source records attributed to Swain, A. K..

2 recordsLinked to original sources

Comparison of Dimensionality Reduction and Clustering Methods for Single-Cell Transcriptomics Data

Dimensionality reduction (DR) methods are applied to extract relevant features from inherently high dimensional and noisy single-cell RNA sequencing (scRNA-seq) data. Choice of DR method could influence the performance of clustering algorithm and subsequent analysis outcomes. We performed a benchmarking study of seven popular DR methods and four clustering algorithms widely used for scRNA-seq datasets. For this purpose, we used three publicly available real scRNA-seq datasets. The performance was evaluated using two clustering metrics viz. adjusted random index (ARI) and normalized mutual index (NMI). We also compared our results with a similar study published by Xiang and colleagues. Overall, we observed higher ARI and NMI scores for DR methods when compared with Xiangs study. We also noticed several differences between our and Xiangs study. Noteworthy, three methods, namely, Independent Component Analysis (ICA), t-Distributed Stochastic Neighbor Embedding (t-SNE) and Uniform Manifold Approximation and Projection (UMAP) performed consistently well across three datasets. Linear method ICA was best performer on Segerstolpe dataset, while nonlinear methods UMAP and t-SNE best performed on Deng and Chu datasets, respectively. Neural network-based methods Variational Autoencoder (VAE) and Deep Count Autoencoder (DCA) could not perform well probably due to their sensitivity to hyperparameters and overfitting. Among clustering methods, Gaussian Mixture Models (GMMs) performed consistently well across datasets. This might be because GMMs are the universal approximators of posterior probability densities. We conclude that performance of different DR methods is more dataset dependent and for various scRNA-seq datasets different algorithms are more suited and there is no one-fit-all method.

bioinformatics↗

Single-Cell Transcriptome Analysis Identifies Novel Biomarkers Involved in Major Liver Cancer Subtypes

Liver cancers including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are leading cause of death worldwide. Single-cell transcriptomics studies have vast potential in advancing our understanding of cancers by defining the cellular composition of different solid tumor types. We peformed an integrated analysis using single-cell RNA sequencing (scRNA-seq) data from cancerous and healthy liver tissues in order to identify the molecular progression and intercellular heterogeneity across cell types in the liver cancer. Moreover, we performed a subtype specific analyses, separately for HCC and ICC, to identify any molecular drivers uniquely associated with these liver cancers. The scRNA-seq dataset comprising 5 healthy controls and 19 liver cancer patients were collected from Human Cell Atlas and Gene Expression Omnibus (GEO), respectively. Our analyses confirmed upregulation of four previously known malignant cell marker genes, namely, EPCAM, KRT19, KRT7 and S100P in the cancerous liver cells. Of these, KRT7 gene has been reported to be associated with ovarian cancer in the past studies. Noteworthy, four marker genes specific to the G1/S (MCM5 and PCNA) and G2/M phases (HMGB2 and CKS2) of the cell cycle were upregulated in the cancerous liver cells. This indicates that these four marker genes are actively dividing in these two phases in cancerous cells as compared to normal liver cells. Our differential expression analysis identified 2 upregulated genes (ATF3 and S100A11) and 2 downregulated genes (FCN3 and FGB) in the liver cancer. Our subtype based differential expression analysis identified 4 genes (HSPA6, LMNA, ATP1B1 and DCXR) specific to HCC and 3 genes (HSPB1, APOC3 and APOA1) specific to ICC. CD4+ T-cell, Hepatocyte, neutrophil, mesenchymal cells and liver bud hepatic cells are the predominant cell-types in liver cells. Our scRNA-seq study revealed the mesenchymal cells as potential malignant cell types in liver cancers. Our work suggests future research on developing liver cancer subtypes therapies could target these cell types and associated molecular markers.

genomics↗