Metagenomic tools and applications toward Type 1 Diabetes

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Arvo building, auditorium F114, address: Arvo Ylpön katu 34.


Doctoral defence of MSc Jake Lin

Metagenomic tools and applications toward Type 1 Diabetes

The field of science of the dissertation is Bioinformatics.

The opponent is PhD Anna Heintz-Buschart (German Centre for Integrative Biodiversity Research, Germany). Professor Matti Nykter acts as the custos.

The language of the dissertation defence is English.

Computational detection of environmental microbial populations with assessment in Type 1 Diabetes stool samples

Human autoimmune diseases stem from abnormal responses towards normal cells. Relatively common, there are many types of autoimmune diseases. For example, Type 1 diabetes impacting children and teenagers, is caused by gradual immune targeting and subsequent destruction of pancreatic beta cells. The exact reasons, or triggers for the initial targeting of the beta cells are not known but there have been multiple reports citing microbes, particularly certain virus infections and gut bacteria population shifts as possible culprits.

The introduction of metagenomics together with advances in next generation sequencing technologies have enabled detection of genetic material directly from the environmental samples such as soil, water and human stool. Prior to metagenomics, most bacterial microbes are not detectable as they do not grow outside of their native environments. The improved sensitivity and reduction in cost of modern computer sequencing technologies have also promoted virus related metagenomics studies. Virome sequencing data generated from these studies required advanced bioinformatics solutions and forms the core of this thesis.

The study introduces Vipie, a secured and fully web based tool to profile multiple samples with interactive profile maps, quality and assembly reports and virus profile table. This thesis also reports results from analysis of virus and bacteria populations found in stool samples from Finnish children enrolled in Type 1 Diabetes Prediction and Prevention (DIPP) Study. The analysis reported more phage bacterial correlations, presented as interactive networks, in stools taken from autoimmune positive children compared to negative controls.

Metagenomics experiments have great potential to investigate immune disorders via systematic detection of microbes and viruses from human matter. This thesis contributes to the field via Vipie, an easy to use web based tool for multi-sample virus profiling. Impressively, investigators from more than 20 countries have registered and used Vipie. An offline high parallel computing (HPC) platform version of Vipie have been successfully applied to more than 10,000 stool samples. With preliminary promising results, Vipie profiles are the central parameters for statistical virome modelling in this large international diabetes cohort. Moreover, this thesis also reports novel results from analysis of sequencing based gut bacteria and viral dynamics associated with Type 1 Diabetes autoimmunity development.                                               

The dissertation is published in the publication series of Acta Universitatis Tamperensis; 2388, Tampere University Press, Tampere 2018. The dissertation is also published in the e-series Acta Electronica Universitatis Tamperensis; 1897, Tampere University Press 2018.

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