Work

Covariance-based sample selection for heterogeneous data: Applications to gene expression and autism risk gene detection

Year: 2018

Type: preprint

Abstract: Risk for autism can be influenced by genetic mutations in hundreds of genes. Based on findings showing that genes with highly correlated gene expressions are functionally interrelated, "guilt by association" methods such as DAWN have been developed to identify these autism risk genes. Previous research analyzes the BrainSpan dataset, which contains gene expression of brain tissues from varying regions and developmental periods. Since the spatiotemporal properties of brain tissue is known to affect the gene expression's covariance, previous research have focused only on a specific subset of samples to avoid the issue of heterogeneity. This leads to a potential loss of power when detecting risk genes. In this article, we develop a new method called COBS (COvariance-Based sample Selection) to find a larger and more homogeneous subset of samples that share the same population covariance matrix for the downstream DAWN analysis. To demonstrate COBS's effectiveness, we utilize genetic risk scores from two sequential data freezes obtained in 2014 and 2019. We show COBS improves DAWN's ability to predict risk genes detected in the newer data freeze when utilizing the risk scores of the older data freeze as input.

Source: arXiv (Cornell University)

DOI: 10.48550/arxiv.1812.08147

Authors: Lin, Kevin Z., Liu, Han, Roeder, Kathryn

Institutions: Carnegie Mellon University, Northwestern University

Language: English

Topic: Gene expression and cancer classification

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Science Foundation, Defense Advanced Research Projects Agency, National Institute of Mental Health