Shaked Briller

Inter-tissue gene expression coordination pattern changes in aging

Shaked Briller, Judith Somekh
Department of Information Systems, University of Haifa

Aging is one of the most important biological processes and is a known risk factor for many death-causing diseases in human [1]. As aging is a concordant process involving multiple tissues [2], generating a global view of age-related inter-tissue expression can provide valuable information for a holistic understanding of this fundamental process.

Although most genomic studies focus on finding factors associated to aging within tissue, the understanding of their intricate molecular mechanisms in all tissues is still lacking.

The goal of this research is to study the possible effects of aging on whole-body gene expression coordination patterns by combining transcriptional and network-level gene expression analysis. We aim to develop a system-level approach to detect cross tissue changes in coordination patterns with age. We use the publicly available gene expression data from the Genotype-Tissue Expression (GTEx) project comprising 54 tissue types from thousand post-mortem donors of RNA-seq gene expression [3].

We study the inter-tissue coordination using two approaches. In the first, we analyzed how direct gene expression correlations and transcriptional noise changes across tissues between age groups. As a measure of variance, we used the coefficient of variation (CoV) across tissues for each individual.

Then we developed a novel cross-tissue weighted gene co-expression network which captures gene activities both within and across tissues in different age groups. This cross-tissue network was applied to three tissues: Adipose- subcutaneous, Muscle-skeletal and Brain-cortex.

We found an increase correlation between two adipose tissues: Adipose-subcutaneous and Adipose-visceral in the young group in a subset of metabolic genes. In addition, we saw a decrease in noise synchronization and a connectivity loss associated with aging indicating that the young group network is more robust.

Our approach provides an important understanding that inter-tissue coordination is an essential feature of biological systems and one that influences biological aging.



[1] Ageing as a Risk Factor for Disease. TeresaNiccoli, LindaPartridge. 17, s.l. : Current Biology, .2012, Vol. Volume 22

[2] Inter-tissue coexpression network analysis reveals DPP4 as an important gene in heart to blood communication. Long, Q., Argmann, C., Houten, S.M. et al. s.l. : Genome Medicine, 2016, Vols. 8, 15

[3] The Genotype-Tissue Expression (GTEx) project. . Lonsdale, J. et al. s.l. s.l. : Nat. Genet, 2013, .Vols. Vols. 45, 580–585