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Identifier

000444154

Title

Cancer as an evolutionary process : Identification and Modeling of driver mutations using computational simulations

Alternative Title

Μελέτη του καρκίνου από εξελικτική σκοπιά

Author

Δασκαλάκη, Μαρία-Όλγα

Thesis advisor

Παυλίδης, Παύλος
Καραλή, Γεωργία
Χαρμανδάρης , Βαγγέλης

Abstract

From an evolutionary perspective cancer can be considered as the product of natural selection within our bodies. Cells can be seen as populations of individuals with constant cycle of mature, reproduction, mutation and finally death. Under some probability a mutation with functional impact could lead to fitness advantage of the cell bearing it, resulting in its constant and uncontrollable division causing its genotype to be fixed among the whole tissue and the creation of aggressive tumors. The responsible mutations that drive this uncontrollable proliferation are called driver mutations. Their identification could lead to targeted therapy contributing both to the prevention of cancer and the increase in survival chance of a patient. For this purpose, in this thesis, we created a simulator of cells cycle, based on Wright-Fisher model of genetic variation. The Wright-Fisher model was expanded using cellular automata and different fitness functions as a way to depict the environmental pressures that also affect the cell cycle and consequently its probability of extinction or fixation. Simulation results were analyzed using both statistical and machine learning methods in order to study cancer from an evolutionary perspective by computing metrics of fixation probabilities, needed time for a genotype to be fixed,competition and tumor size and eventually combine all the above for the construction of the evolutionary trajectory of each mutation, feature that could be the factor of characterization as driver or passenger.

Language

English

Subject

Fixation

Passenger

Probabilities

Μεταλλάξεις

Πιθανότητες

Issue date

2021-12-01

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses