Mathematical modeling of obsessive compulsive disorder

Abstract only availableWe all at some point become fixated with certain actions or ideas. However, for the two to three percent of the world population with obsessive compulsive disorder (OCD), these fixations become so intense that the individual is debilitated. The exact obsessions the patients experience vary from case to case, but most obsessions fall within five categories: contamination, hoarding, ordering / symmetry, religious, and danger. Suffers of OCD usually recognize that their obsessions are unreasonable and illogical, yet are unable to prevent them. To alleviate these obsessions, the patients perform compulsions or ritualistic acts. Functional imaging studies have consistently implicated the caudate nucleus, the anterior cingulate gyrus, and the orbitofrontal cortex as the major causes of OCD. All three parts of the brain show hyperactivity in OCD patients and decreased activity of patients post treatment. The caudate nucleus is a part of the basal ganglia and is connected to the neocortex through a series of thalamocortical loops. These loops start in certain parts of the neocortex, such as the anterior cingulate gyrus and the orbitofrontal cortex, and run through the basal ganglia to the thalamus and then back to the neocortex. OCD patients appear to become stuck in one of these loops. In an attempt to better understand the loops, a mathematical model is being constructed to represent the OCD network pathway. GEneral NEural SImulation System (GENESIS) is a computer program being employed in the construction of the network. Currently, the framework for the OCD model has been constructed. This model will be enhanced in the coming months to create a more biologically realistic model. We hope to be able to show the reoccurring loop of OCD patients. Ultimately, a better understanding of the thalamocortical loop may lead to better treatment of OCD.NSF-REU Biosystems Modelin

Quantitative analysis of mammalian translation initiation sites by FACS‐seq

Abstract An approach combining fluorescence‐activated cell sorting and high‐throughput DNA sequencing (FACS‐seq) was employed to determine the efficiency of start codon recognition for all possible translation initiation sites (TIS) utilizing AUG start codons. Using FACS‐seq, we measured translation from a genetic reporter library representing all 65,536 possible TIS sequences spanning the −6 to +5 positions. We found that the motif RYMRMVAUGGC enhanced start codon recognition and translation efficiency. However, dinucleotide interactions, which cannot be conveyed by a single motif, were also important for modeling TIS efficiency. Our dataset combined with modeling allowed us to predict genome‐wide translation initiation efficiency for all mRNA transcripts. Additionally, we screened somatic TIS mutations associated with tumorigenesis to identify candidate driver mutations consistent with known tumor expression patterns. Finally, we implemented a quantitative leaky scanning model to predict alternative initiation sites that produce truncated protein isoforms and compared predictions with ribosome footprint profiling data. The comprehensive analysis of the TIS sequence space enables quantitative predictions of translation initiation based on genome sequence