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Gastrointestinal (GI) motility disorders are not well understood, resulting in patient management that typically controls symptoms. Patients suffer from reduced quality of life and incur large costs from chronic GI disorders. It is imperative to elucidate underlying mechanisms causing GI motility disorders that, in turn, can facilitate development of treatment such as drug therapeutics. To this end, we seek to use multi-scale computational models to better understand GI motility in health and disease. An initial computational framework was established to study genetic perturbation in causing a phenotypical change at the GI tissue level. Computer models describing a couple of genetic perturbations were developed and examined in the multi-scale framework. Preliminary findings suggest alterations to phenotype that may adversely affect GI motility. However, much work remains, given the tissue complexity and uncertainties in our knowledge of the GI organs. A future direction will be to incorporate multi-scale mechanical models in the current framework.