Rekonstrukcija funkcionalnih mrež iz dinamike pankreasnih celic beta

Murko, Jakob

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Title:	Rekonstrukcija funkcionalnih mrež iz dinamike pankreasnih celic beta
Authors:	ID Murko, Jakob (Author) ID Marhl, Marko (Mentor) More about this mentor... ID Gosak, Marko (Comentor) ID Stožer, Andraž (Comentor)
Files:	MAG_Murko_Jakob_2019.pdf (3,34 MB) MD5: 39BBB1DEB841961CF0F00F8211AD0D36 PID: 20.500.12556/dkum/b0ffe69e-09d1-41de-9f4b-6431cb41b441
Language:	Slovenian
Work type:	Master's thesis/paper
Typology:	2.09 - Master's Thesis
Organization:	FNM - Faculty of Natural Sciences and Mathematics
Abstract:	V magistrskem delu obravnavamo funkcionalno povezanost celic beta. Te celice se nahajajo v Langerhansovih otočkih v trebušni slinavki in so ključne pri uravnavanju koncentracije glukoze v krvi, saj ob povečani ravni glukoze v organizmu izločajo hormon inzulin. V prvi fazi dela dinamiko električno vzdraženih celic beta simuliramo z modelom, v drugi fazi pa se osredotočimo na analizo eksperimentalno izmerjene dinamike znotrajceličnega kalcija. Za opis dinamike posameznih celic uporabimo fenomenološki model, t.i. iterativno mapo Rulkova. Posamezne Rulkove oscilatorje med seboj povežemo v mrežo, s čimer simuliramo funkcijo presledkovnih stikov, s katerimi so povezane celice beta v realnem tkivu. Da bi naš večcelični model čimbolj približali realnemu obnašanju, vpeljemo tudi naključno in prostorsko definirano heterogenost celic. Na podlagi podatkov aktivnosti celic iz simulacij določimo funkcionalno povezanost le-teh. Predstavimo dve metodi določitve funkcionalne mreže, to je korelacijsko in metodo pseudo-inverza kovariance. Analiza simuliranih podatkov pokaže, da sta obe metodi zanesljivi, zato jih preizkusimo tudi na eksperimentalno pridobljenih podatkih, in sicer na in situ meritvah kalcijeve aktivnosti v svežih tkivnih rezinah mišje trebušne slinavke. Ugotovimo, da sta si funkcionalna mreža na podlagi simulacijskih in eksperimentalnih podatkov podobni, kar nam kaže na natančno obnašanje modela. Z analizo obeh funkcionalnih mrež ustvarjenih na podlagi eksperimentalnih podatkov lahko vsaj delno sklepamo na strukturo povezav presledkovnih stikov v opazovani plasti Langerhansovega otočka. Pomembna je tudi ugotovitev, da v funkcionalni mreži celic beta opazimo celice z nadpovprečnim številom povezav, tudi daljnosežnih, kar je v skladu z ugotovitvami preteklih raziskav.
Keywords:	celice beta, Langerhansov otoček, funkcionalna mreža, Rulkov model, celična heterogenost, korelacijski koeficient, pseudo-inverz kovariance.
Place of publishing:	Maribor
Publisher:	[J. Murko]
Year of publishing:	2019
PID:	20.500.12556/DKUM-74921
UDC:	577(043.2)
COBISS.SI-ID:	24864776
NUK URN:	URN:SI:UM:DK:AELX1YC4
Publication date in DKUM:	05.11.2019
Views:	1875
Downloads:	116
Metadata:
Categories:	FNM
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Licences

License:	CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Link:	http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:	The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:	12.09.2019

Secondary language

Language:	English
Title:	Reconstruction of functional networks from the dynamics of pancreatic beta cells
Abstract:	In master thesis we explore beta cells connectivity. These cells are located in the pancreatic islets of the Langerhans and are crucial in regulating blood glucose levels, as they secrete the hormone insulin as the glucose level in the organism is increased. In the first part of the thesis, we simulate the dynamics of electrically excitable beta cells with a model, and in the second part, we focus on the analysis of the experimentally measured dynamics of intracellular calcium. To describe the dynamics of individual cells, we use a phenomenological model, i.e. the iterative Rulkov map. The individual Rulkov oscillators are interconnected to simulate the function of the gap junctions with which beta cells in real tissue are connected. In order to bring our multicellular model as close to real behaviour as possible, we introduce random and spatially defined cellular heterogeneities. Based on simulated cellular behaviour, we create functional network among simulated beta cells. We introduce two methods for building functional network: the correlation method and the pseudo-inverse covariance method. The analysis of the simulated data shows that both methods are reliable, so they are also tested on experimentally obtained data, namely in in situ measurements of calcium activity in acute pancreatic tissue slices of mice. Functional networks of simulated and experimental data have similar properties, which indicates an accurate behaviour of our computational model. Using information of the functional network structure from real islet of Langerhans, we can at least partially deduce structure of underlying structural gap-junctional connections. Notably, in functional beta cell networks we notice cells with an above-average number of connections, including long-range connections, which is in line with the findings of previous research.
Keywords:	beta cells, islet of Langerhans, functional network, Rulkov model, cell heterogeneity, correlation coefficient, pseudoinverse of covariance.

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