RT Journal
A1 Blake, Lauren E.
A1 Roux, Julien
A1 Hernando-Herraez, Irene
A1 Banovich, Nicholas E.
A1 Perez, Raquel Garcia
A1 Hsiao, Chiaowen Joyce
A1 Eres, Ittai
A1 Cuevas, Claudia
A1 Marques-Bonet, Tomas
A1 Gilad, Yoav
T1 A comparison of gene expression and DNA methylation patterns across tissues and species
JF Genome Research 
JO Genome Research 
YR 2020 
FD February 01 
VO 30 
IS 2 
SP 250 
OP 262 
DO 10.1101/gr.254904.119 
UL http://genome.cshlp.org/content/30/2/250.abstract 
AB Previously published comparative functional genomic data sets from primates using frozen tissue samples, including many data sets from our own group, were often collected and analyzed using nonoptimal study designs and analysis approaches. In addition, when samples from multiple tissues were studied in a comparative framework, individuals and tissues were confounded. We designed a multitissue comparative study of gene expression and DNA methylation in primates that minimizes confounding effects by using a balanced design with respect to species, tissues, and individuals. We also developed a comparative analysis pipeline that minimizes biases attributable to sequence divergence. Thus, we present the most comprehensive catalog of similarities and differences in gene expression and DNA methylation levels between livers, kidneys, hearts, and lungs, in humans, chimpanzees, and rhesus macaques. We estimate that overall, interspecies and inter-tissue differences in gene expression levels can only modestly be accounted for by corresponding differences in promoter DNA methylation. However, the expression pattern of genes with conserved inter-tissue expression differences can be explained by corresponding interspecies methylation changes more often. Finally, we show that genes whose tissue-specific regulatory patterns are consistent with the action of natural selection are highly connected in both gene regulatory and protein–protein interaction networks.