RT Journal
A1 Li, Hao
A1 Rukina, Daria
A1 David, Fabrice P.A.
A1 Li, Terytty Yang
A1 Oh, Chang-Myung
A1 Gao, Arwen W.
A1 Katsyuba, Elena
A1 Bou Sleiman, Maroun
A1 Komljenovic, Andrea
A1 Huang, Qingyao
A1 Williams, Robert W.
A1 Robinson-Rechavi, Marc
A1 Schoonjans, Kristina
A1 Morgenthaler, Stephan
A1 Auwerx, Johan
T1 Identifying gene function and module connections by the integration of multispecies expression compendia
JF Genome Research 
JO Genome Research 
YR 2019 
FD December 01 
VO 29 
IS 12 
SP 2034 
OP 2045 
DO 10.1101/gr.251983.119 
UL http://genome.cshlp.org/content/29/12/2034.abstract 
AB The functions of many eukaryotic genes are still poorly understood. Here, we developed and validated a new method, termed GeneBridge, which is based on two linked approaches to impute gene function and bridge genes with biological processes. First, Gene-Module Association Determination (G-MAD) allows the annotation of gene function. Second, Module-Module Association Determination (M-MAD) allows predicting connectivity among modules. We applied the GeneBridge tools to large-scale multispecies expression compendia—1700 data sets with over 300,000 samples from human, mouse, rat, fly, worm, and yeast—collected in this study. G-MAD identifies novel functions of genes—for example, DDT in mitochondrial respiration and WDFY4 in T cell activation—and also suggests novel components for modules, such as for cholesterol biosynthesis. By applying G-MAD on data sets from respective tissues, tissue-specific functions of genes were identified—for instance, the roles of EHHADH in liver and kidney, as well as SLC6A1 in brain and liver. Using M-MAD, we identified a list of module-module associations, such as those between mitochondria and proteasome, mitochondria and histone demethylation, as well as ribosomes and lipid biosynthesis. The GeneBridge tools together with the expression compendia are available as an open resource, which will facilitate the identification of connections linking genes, modules, phenotypes, and diseases.