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Author:Laajala, Essi
Title:Tyypin 1 diabeteksen biomarkkerit ihmisen kokoveren transkriptomissa
Type 1 diabetes biomarkers in human whole blood transcriptome
Publication type:Master's thesis
Publication year:2011
Pages:iv + 72 s. + liitt. 3      Language:   fin
Department/School:Tietojenkäsittelytieteen laitos
Main subject:Informaatiotekniikka   (T-61)
Supervisor:Lähdesmäki, Harri
Instructor:Kallionpää, Henna
OEVS:
Electronic archive copy is available via Aalto Thesis Database.
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Location:P1 Ark Aalto  920   | Archive
Keywords:type 1 diabetes mellitus
seroconversion
transcriptomics
biomarker
follow-up study
tyypin 1 diabetes mellitus
serokonversio
transkriptomiikka
biomarkkeri
seurantatutkimus
Abstract (eng): This master's thesis is a part of a project, which has (to our knowledge) been the most comprehensive analysis of transcriptional changes associated with type 1 diabetes.
The transcriptome-wide data was collected from 28 case-control pairs in several time points, with the purpose to find transcripts or groups of transcripts, which could be used as biomarkers of type 1 diabetes.
Changes that can be perceived in the earliest stages of the pathogenesis were of particular interest.

Up- and down-regulated transcripts were surveyed with a rank product based method in five time windows, after which the results were grouped for example by testing for enriched signalling pathways.
Interferon response dominated the results in all time windows.

Our results suggest that type 1 diabetes pathogenesis is reflected in human whole blood transcriptome already before seroconversion.
Some of these differentially expressed genes have previously been validated as associated with type 1 diabetes.
In addition, new hypotheses were created for further studies.
Abstract (fin): Tämä diplomityö on osa maailman kattavinta tyypin 1 diabetesta koskevaa geeniekspressiotutkimusta, jonka aineisto on, kerätty 28 tapaus-kontrolliparilta useassa eri aikapisteessä.
Ihmisen kokoveren transkriptomista etsittiin tyypin 1 diabeteksen biomarkkereiksi soveltuvia transkripteja tai transkriptijoukkoja.
Erityisesti patogeneesin varhaisessa vaiheessa havaittavia muutoksia pidettiin kiinnostavina.

Ylös- ja alas säädeltyjä transkripteja kartoitettiin viidessä aikaikkunassa rankituloihin perustuvalla tilastollisella menetelmällä, minkä jälkeen tulokset ryhmiteltiin mm. selvittämällä mielenkiintoisten transkriptien joukossa rikastuneet tunnetut signalointireitit.
Interferonivaste dominoi tuloksia kaikissa aikaikkunoissa.

Tulosten perusteella tyypin 1 diabeteksen patogeneesin kannalta olennaisia muutoksia on mahdollista havaita ihmisen kokoveren transkriptomissa jo ennen serokonversiota.
Joidenkin varhain erilaisesti ekspressoituneiden geenien yhteys tyypin 1 diabeteksen patogeneesiin oli vahvistettu aikaisemmissa julkaisuissa, ja lisäksi luotiin uusia hypoteeseja myöhempää tarkastelua varten.
ED:2011-11-21
INSSI record number: 42980
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