Advances-in molecular biology that have enabled the development of high throughput technologies for assaying gene expression, very large numbers of single nucleotide polymorphisms (SNPs), proteins, metabolic profiles etc. have revolutionized our ability to understand the biological basis of complex human disorders. As a consequence, we have now developed gene expression profiles that can predict treatment outcomes, and identified SNPs that are reproducibly associated with complex human diseases, findings that had previously been all but intractable. But it is difficult to be satisfied with the progress we have made when there is still so much that we do not know or understand about how common disorders arise and develop. We believe that we can learn much more from the systematic organization of the totality of the information developed through genome-wide interrogation of gene expression and DNA polymorphism than we have yet appreciated. Thus we propose to focus our expertise in statistical methods and algorithms for mining the data generated from genome-wide platforms toward a better understanding of the molecular architecture of psychiatric phenotypes. We will achieve this through a dynamic process of data acquisition, integration, phenotype deconstruction, and the development of a database, software and associated web browser that should provide the next logical step in merging the information that has started to become available from large throughput genotyping , sequencing, comparative genomic hybridization, and expression technology. The database will contain detailed annotation of all known genetic variants (including general information on location, conservation and local recombination rates, population characteristics such as frequency and evidence for selection, as well as association data on clinical and expression phenotypes), and of all genes (including general characteristics of location and variants within, information on pathways associated to the gene, as well as known SNPs and phenotypes associated with the gene). This project will build on an existing effort at University of Chicago called SCAN (SNP and CNV Annotation Network, www.scandb.org).
The project uses mathematical modeling to account for complex interactions among genetic aberrations in a human genome and the influence of prescription drugs as environmental factors. The mathematical modeling employs knowledge about molecular interactions between genes and proteins. This project focuses on complex neuropsychiatric disorders, such as autism, schizophrenia and depression.
|Manrai, Arjun K; Funke, Birgit H; Rehm, Heidi L et al. (2016) Genetic Misdiagnoses and the Potential for Health Disparities. N Engl J Med 375:655-65|
|Nazeen, Sumaiya; Palmer, Nathan P; Berger, Bonnie et al. (2016) Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities. Genome Biol 17:228|
|Lykins, Joseph; Wang, Kanix; Wheeler, Kelsey et al. (2016) Understanding Toxoplasmosis in the United States Through ""Large Data"" Analyses. Clin Infect Dis 63:468-75|
|Somekh, Judith; Peleg, Mor; Eran, Alal et al. (2016) A model-driven methodology for exploring complex disease comorbidities applied to autism spectrum disorder and inflammatory bowel disease. J Biomed Inform 63:366-378|
|Mallory, Emily K; Zhang, Ce; RÃ©, Christopher et al. (2016) Large-scale extraction of gene interactions from full-text literature using DeepDive. Bioinformatics 32:106-13|
|Bagley, Steven C; Sirota, Marina; Chen, Richard et al. (2016) Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants. PLoS Comput Biol 12:e1004885|
|Li, Yong Fuga; Xin, Fuxiao; Altman, Russ B (2016) SEPARATING THE CAUSES AND CONSEQUENCES IN DISEASE TRANSCRIPTOME. Pac Symp Biocomput 21:381-92|
|Gamazon, Eric R; Wheeler, Heather E; Shah, Kaanan P et al. (2015) A gene-based association method for mapping traits using reference transcriptome data. Nat Genet 47:1091-8|
|Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M et al. (2015) Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD. Am J Psychiatry 172:82-93|
|Kohane, Isaac S (2015) An autism case history to review the systematic analysis of large-scale data to refine the diagnosis and treatment of neuropsychiatric disorders. Biol Psychiatry 77:59-65|
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