Objectives: We have investigated autism from a systems biology perspective with the aim of defining protein interaction networks/pathways/functional modules that connect this diverse set of genes.
Methods: Our integrative approach consisted of (1) cloning autism candidate genes from normal adult and fetal brain RNA; (2) Screening these genes against the hORFeome (~15,000 clones) by yeast-two-hybrid (Y2H) experiments to detect protein-protein interactions; (3) building interactome of autism candidate genes; (4) interactome analysis to define key functional modules.
Results: (a) We selected 191 autism candidate genes and successfully cloned 124. We added 45 clones from the hORFeome collection; (b) We performed Y2H for 169 genes and detected interactions between 75 autism candidate genes and 272 human proteins that were retested positively four times; (c) We have constructed autism interactome with 492 unique interactions; (d) 93% of the detected interactions are novel and have not been previously reported in the public databases.
Conclusions: (a) We have detected interaction partners (preys) that are shared between autism candidate genes, thereby implicating new gene targets in autism; (b) We have detected new interactions between well-known autism candidate genes; (c) We have identified preys that connect genes from different autism CNVs on a protein level; (d) Autism network is enriched in preys with autism CNV membership; (e) Autism network is significantly enriched in co-expressed genes; (f) Autism network is enriched in differentially expressed genes, specifically in down-regulated genes.
Our new autism interactome represents a valuable resource for the research community and for future autism studies.