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Advanced modeling of circadian systems and forensic DNA interpretation
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An, Zheming. Advanced modeling of circadian systems and forensic DNA interpretation. Retrieved from https://doi.org/doi:10.7282/t3-8yhf-cn80

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TitleAdvanced modeling of circadian systems and forensic DNA interpretation
NameAn, Zheming (author); Piccoli, Benedetto (chair); Lee, Kwangwon (internal member); Grgicak, Catherine (internal member); Garin, Federica (outside member); Rutgers University; Camden Graduate School
Date Created2021
Other Date2021-05 (degree)
SubjectMathematical modeling, Computational and Integrative Biology
Extent1 online resource (ix, 152 pages)
DescriptionWe model and analyze two systems in this thesis: Circadian Rhythm and Forensic interpretation of DNA processing. Mathematical modeling of a process is necessary in order to use analytical and computational tools to study its dynamics. The primary purpose of this thesis is to develop advanced mathematical modeling to examine two biochemical systems: circadian rhythm and forensic interpretation of DNA processing.

One of the essential characteristics of a circadian clock is that the free-running period maintains a cycle of approximately 24 hours. When organisms are ex- posed to an external environmental signal called a zeitgeber, such as the light-dark cycle and temperature changes, the endogenous oscillators synchronize to the zeitgeber in a process known as entrainment. We first developed a two-step entrainment model to explain a range of period-phase relationships, not explained by previous models but observed experimentally. We proved the existence and stability of periodic orbits for our model and gave analytical expressions for the range of entrainment. There are two main approaches to model entrainment process of circadian clocks, parametric and non-parametric. The parametric model focuses on the gradual changes of the clock parameters in response to the changing ambient condition, whereas the non-parametric model focuses on the instantaneous change of the phase of the clock in response to the zeitgeber. To encompass both parametric and non-parametric approaches, we then developed a dynamic CIRC (dCIRC) model that describes clock parameters of molecular and overt circadian rhythms, and it predicts the phase of entrainment in zeitgeber cycles. The unified model dCIRC provides new insights into how circadian clocks of diverse organisms function in a natural habitat. This type of model is useful in the advent of chronotherapies.

Secondly, we investigated the forensic DNA interpretation process. In casework involving complex forensic evidence containing a mixture of DNA with low copy number, the evaluation and interpretation of the mixture evidence are difficult due to various reasons, which include allele dropout and allele stacking among contributors. The interpretation of the results vary among different laboratory protocols. Based on the mechanisms proposed in previous works, we created a mathematical model with essential improvements to simulate, analyze, and standardize the forensic DNA interpretation process. We showed how the experimental settings and the processing approaches (bulk and single-cell processes) were related to the dropout rates and missing detection rates of alleles.
NotePh.D.
NoteIncludes bibliographical references
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/t3-8yhf-cn80
LanguageEnglish
CollectionCamden Graduate School Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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