In silico cholinergic pathway analysis indicates possible role for exogenous choline in modulating sensory processing in autism spectrum disorder Audrey Olson1,2, MS; Fuquan Zhang3, PhD; Hongbao Cao1,4, PhD; Ancha Baranova1, PhD; Margaret Slavin2, PhD, RDN 1Department of Bioinformatics and Computational Biology, School of Systems Biology, College of Science, George Mason University, Manassas, VA; 2Department of Nutrition and Food Studies, College of Health and Human Services, George Mason University, Fairfax VA; 3Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China; 4Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi Province, China 1. Ashburner et al. Gene ontology: tool for the unification of biology. Nat Genet. May 2000; 25(1):25-9. http://geneontology.org/ 2. The Gene Ontology Consortium. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res. Jan 2019; 47(D1):D330-D338. http://geneontology.org/ 3. Liu, S., Rao, S., Xu, Y. et al. Identifying common genome-wide risk genes for major psychiatric traits. Hum Genet 139, 185–198 (2020). https://doi- org.mutex.gmu.edu/10.1007/s00439-019-02096-4 4. Molecular Signatures Database, MSig-DB, https://www.gsea-msigdb.org/gsea/msigdb 5. Elsevier’s Pathway Studio https://www.elsevier.com/solutions/pathway-studio-biological-research 6. Oliveros, J.C. (2007-2015) Venny. An interactive tool for comparing lists with Venn's diagrams. https://bioinfogp.cnb.csic.es/tools/venny/index.html o Sensory processing dysfunction is common in ASD. o Sensory processing relies upon sensory gating – ligand-activated, ion-channel- mediated pathways built upon cholinergic signals. o Acetylcholine plays roles in sensory processing, including auditory signal pathways, as well as cognitive function, memory, and learning. o Gene set enrichment analysis was conducted to identify Gene Ontology database1,2 pathways shared between MSig-DB curated cholinergic pathway gene sets (345 genes total) and a set of 53 autism genes identified by meta-analysis of genome- wide association studies3,4. o Ontologies associated with both the autism GWAS set and the MSig-DB functional pathway sets were identified using gene ontology association analysis within Pathway Studio (Elsevier)5. The lists of ontologies assigned to each of these gene sets were trimmed at approximately the lowest 100 p-values (p <0.01), while using a shift in p-value order of magnitude as the final determinant in list cutoff. o The gene ontology lists’ respective areas of overlap were identified using Venny6. o Associated pathways and ontologies were integrated graphically, using Pathway Studio to both illustrate and model the potential influence of dietary choline deficiency sensory pathways affected in autism. o To investigate a potential role of dietary choline intake as a means for bolstering sensory processing function, through use of scientific literature analysis using natural language processing (NLP) as a means for assessing potential gene ontological overlap between autism spectrum disorder (ASD) associated genes and cholinergic signaling pathways. o Because acetylcholine has long been identified as a modulator of ion transport throughout the body, the findings highlight a potential use for adequate dietary choline intake as a means to bolster acetylcholine supply, and therefore, ion transport related functionality across sensory domains. o Future study of sensory processing associated with autism should not only include identified genetic components, but also associated sensory processing pathway components, including acetylcholine, and its exogenous precursor, dietary choline. This project was funded by a research grant from the American Egg Board / Egg Nutrition Center. OBJECTIVES BACKGROUND METHODS RESULTS CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES Figure 3. Subsequent analysis was conducted within Pathway Studio