Evaluating the performance of dropout imputation and clustering methods for single-cell RNA sequencing data.

Recent advances in single-cell RNA sequencing (scRNA-seq) provide exciting opportunities for transcriptome analysis at single-cell resolution. Clustering individual cells is a key step to reveal cell subtypes and infer cell lineage in scRNA-seq analysis. Although many dedicated algorithms have been proposed, clustering quality remains a computational challenge for scRNA-seq data, which is exacerbated by inflated zero counts due to various technical noise. To address this challenge, we assess the combinations of nine popular dropout imputation methods and eight clustering methods on a collection of 10 well-annotated scRNA-seq datasets with different sample sizes. Our results show that (i) imputation algorithms do typically improve the performance of clustering methods, and the quality of data visualization using t-Distributed Stochastic Neighbor Embedding; and (ii) the performance of a particular combination of imputation and clustering methods varies with dataset size. For example, the combination of single-cell analysis via expression recovery and Sparse Subspace Clustering (SSC) methods usually works well on smaller datasets, while the combination of adaptively-thresholded low-rank approximation and single-cell interpretation via multikernel learning (SIMLR) usually achieves the best performance on larger datasets.

Least-Squares Support Vector Machine Approach to Viral Replication Origin Prediction.

Replication of their DNA genomes is a central step in the reproduction of many viruses. Procedures to find replication origins, which are initiation sites of the DNA replication process, are therefore of great importance for controlling the growth and spread of such viruses. Existing computational methods for viral replication origin prediction have mostly been tested within the family of herpesviruses. This paper proposes a new approach by least-squares support vector machines (LS-SVMs) and tests its performance not only on the herpes family but also on a collection of caudoviruses coming from three viral families under the order of caudovirales. The LS-SVM approach provides sensitivities and positive predictive values superior or comparable to those given by the previous methods. When suitably combined with previous methods, the LS-SVM approach further improves the prediction accuracy for the herpesvirus replication origins. Furthermore, by recursive feature elimination, the LS-SVM has also helped find the most significant features of the data sets. The results suggest that the LS-SVMs will be a highly useful addition to the set of computational tools for viral replication origin prediction and illustrate the value of optimization-based computing techniques in biomedical applications.