SegCorr: a statistical procedure for the detection of genomic regions of correlated expression

TL;DR

SegCorr is a statistical method that segments and detects highly correlated gene regions in genomic data, accounting for known confounding factors, to identify potential regulatory mechanisms in cancer.

Contribution

It introduces a unified framework combining segmentation and significance testing for correlated regions, with an efficient correction for confounding effects.

Findings

Effective detection of correlated genomic regions in cancer data

Correction for copy number variation reveals methylation-linked regions

Robust performance demonstrated on simulated and real data

Abstract

Motivation: Detecting local correlations in expression between neighbor genes along the genome has proved to be an effective strategy to identify possible causes of transcriptional deregulation in cancer. It has been successfully used to illustrate the role of mechanisms such as copy number variation (CNV) or epigenetic alterations as factors that may significantly alter expression in large chromosomic regions (gene silencing or gene activation). Results: The identification of correlated regions requires segmenting the gene expression correlation matrix into regions of homogeneously correlated genes and assessing whether the observed local correlation is significantly higher than the background chromosomal correlation. A unified statistical framework is proposed to achieve these two tasks, where optimal segmentation is efficiently performed using dynamic programming algorithm, and detection of highly correlated regions is then achieved using an exact test procedure. We also propose a simple and efficient procedure to correct the expression signal for mechanisms already known to impact expression correlation. The performance and robustness of the proposed procedure, called SegCorr, are evaluated on simulated data. The procedure is illustrated on cancer data, where the signal is corrected for correlations possibly caused by copy number variation. The correction permitted the detection of regions with high correlations linked to DNA methylation. Availability and implementation: R package SegCorr is available on the CRAN.