Inferring a Transcriptional Regulatory Network from Gene Expression Data Using Nonlinear Manifold Embedding

Transcriptional networks consist of multiple regulatory layers corresponding to the activity of global regulators, specialized repressors and activators of transcription as well as proteins and enzymes shaping the DNA template. Such intrinsic multi-dimensionality makes uncovering connectivity patterns difficult and unreliable and it calls for adoption of methodologies commensurate with the underlying organization of the data source. Here we present a new computational method that predicts interactions between transcription factors and target genes using a compendium of microarray gene expression data and the knowledge of known interactions between genes and transcription factors. The proposed method called Kernel Embedding of REgulatory Networks (KEREN) is based on the concept of gene-regulon association and it captures hidden geometric patterns of the network via manifold embedding. We applied KEREN to reconstruct gene regulatory interactions in the model bacteria E.coli on a genome-wide scale. Our method not only yields accurate prediction of verifiable interactions, which outperforms on certain metrics comparable methodologies, but also demonstrates the utility of a geometric approach to the analysis of high-dimensional biological data. We also describe the general application of kernel embedding techniques to some other function and network discovery algorithms

A glance at the applications of Singular Spectrum Analysis in gene expression data

AbstractIn recent years Singular Spectrum Analysis (SSA) has been used to solve many biomedical issues and is currently accepted as a potential technique in quantitative genetics studies. Presented in this article is a review of recent published genetics studies which have taken advantage of SSA. Since Singular Value Decomposition (SVD) is an important stage of this technique which can also be used as an independent analytical method in gene expression data, we also briefly touch upon some areas of the application of SVD. The review finds that at present, the most prominent area of applying SSA in genetics is filtering and signal extraction, which proves that SSA can be considered as a valuable aid and promising method for genetics analysis