23 March 2017 in BMC Bioinformatics
Gene regulatory networks reveal how genes work together to carry out their biological functions. Reconstructions of gene networks from gene expression data greatly facilitate our understanding of underlying biological mechanisms and provide new opportunities for biomarker and drug discoveries. In gene networks, a gene that has many interactions with other genes is called a hub gene, which usually plays an essential role in gene regulation and biological processes. In this study, we developed a method for reconstructing gene networks using a partial correlation-based approach that incorporates prior information about hub genes. Through simulation studies and two real-data examples, we compare the performance in estimating the network structures between the existing methods and the proposed method. In simulation studies, we show that the proposed strategy reduces errors in estimating network structures compared to the existing methods. When applied to Escherichia coli, the regulation network constructed by our proposed ESPACE method is more consistent with current biological knowledge than the SPACE method. Furthermore, application of the proposed method in lung cancer has identified hub genes whose mRNA expression predicts cancer progress and patient response to treatment. We have demonstrated that incorporating hub gene information in estimating network structures can improve the performance of the existing methods.
6 January 2021 in Nature Methods
22 August 2017 in Briefings in Bioinformatics
Rank aggregation (RA), the process of combining multiple ranked lists into a single ranking, has played an important role in integrating information from individual genomic studies that address the same biological question. In previous research, attention has been focused on aggregating full lists. However, partial and/or top ranked lists are prevalent because of the great heterogeneity of genomic studies and limited resources for follow-up investigation. To be able to handle such lists, some ad hoc adjustments have been suggested in the past, but how RA methods perform on them (after the adjustments) has never been fully evaluated. In this article, a systematic framework is proposed to define different situations that may occur based on the nature of individually ranked lists. A comprehensive simulation study is conducted to examine the performance characteristics of a collection of existing RA methods that are suitable for genomic applications under various settings simulated to mimic practical situations. A non-small cell lung cancer data example is provided for further comparison. Based on our numerical results, general guidelines about which methods perform the best/worst, and under what conditions, are provided. Also, we discuss key factors that substantially affect the performance of the different methods.
3 September 2024 in Nature Methods
1 April 2023 in Nature Communications
While experimental and informatic techniques around single cell sequencing (scRNA-seq) are advanced, research around mass cytometry (CyTOF) data analysis has severely lagged behind. CyTOF data are notably different from scRNA-seq data in many aspects. This calls for the evaluation and development of computational methods specific for CyTOF data. Dimension reduction (DR) is one of the critical steps of single cell data analysis. Here, we benchmark the performances of 21 DR methods on 110 real and 425 synthetic CyTOF samples. We find that less well-known methods like SAUCIE, SQuaD-MDS, and scvis are the overall best performers. In particular, SAUCIE and scvis are well balanced, SQuaD-MDS excels at structure preservation, whereas UMAP has great downstream analysis performance. We also find that t-SNE (along with SQuad-MDS/t-SNE Hybrid) possesses the best local structure preservation. Nevertheless, there is a high level of complementarity between these tools, so the choice of method should depend on the underlying data structure and the analytical needs.
28 June 2008 in Biometrics