Compressed spectral screening for large-scale differential correlation analysis with application in selecting Glioblastoma gene modules

Abstract

Differential coexpression analysis has been widely applied by scientists in understanding the biological mechanisms of diseases. However, the unknown differential patterns are often complicated; thus, models based on simplified parametric assumptions can be ineffective in identifying the differences. Meanwhile, the gene expression data involved in such analysis are in extremely high dimensions by nature, whose correlation matrices may not even be computable. Such a large scale seriously limits the application of most well-studied statistical methods. This paper introduces a simple yet powerful approach to the differential correlation analysis problem called compressed spectral screening. By leveraging spectral structures and random sampling techniques, our approach could achieve a highly accurate screening of features with complicated differential patterns while maintaining the scalability to analyze correlation matrices of ${10}^4$–${10}^5$ variables within a few minutes on a standard personal computer. We have applied this screening approach in comparing a TCGA data set about Glioblastoma with normal subjects. Our analysis successfully identifies multiple functional modules of genes that exhibit different coexpression patterns. The findings reveal new insights about Glioblastoma’s evolving mechanism. The validity of our approach is also justified by a theoretical analysis, showing that the compressed spectral analysis can achieve variable screening consistency.