Abstract
Autism spectrum disorders are early childhood neurodevelopmental disorders, it is not a disease but rather a syndrome that is characterized by a multifactorial type of inheritance and a rapid annual increase in prevalence. In some cases autism spec- trum disorders are one of the symptoms of monogenic or chromosomal pathology, and can also be a symptom of inherited metabol- ic disorders. A reconstruction of human mitochondrial metabolic network has been used to model insufficiency of some genes encoded proteins to observe the consequences at metabolic network scale and propose approaches for the development of diagnostics. Flux variabil- ity analysis of mitochondrial metabolic network reconstruction is performed maximizing ATP production. It is found that deletion of SUCLG2 gene reduces the maximal production of ATP by 50% with wide flux variability range for most of reactions. Deletion of gene SLC25A12 reduces the maximal ATP production just by 1% but the new state is very fragile as most of reactions have very narrow flux variability range and any disturbance would cause reduction of ATP production that can not be compensated by other reactions. Detection of insufficiency of genes SUCLG2 and SLC25A12 is suggested by observing of fluxes of specific reactions found by flux variability analysis. The reactions with non-overlapping flux variability range can be very informative for the diagnostics of deficiency of particular gene. Still the experiments demonstrated that there are just few reactions with non-overlapping range. The analysis of wide flux variability range in case of deletion also can be perspective as detection of zero flux could be easier task for experimental detection. Pathway scale analysis could bring new constraints for improvement of the model and increase the number of reactions with non-overlapping flux variability range.
Published Version
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