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Understanding DNA double-strand breaks and genome fragility across neurodifferentiation

Eriksson, Gustaw (2020) BINP51 20192
Degree Projects in Bioinformatics
Abstract
The development of new sequencing methods requires new computational pipelines to handle and analyse raw data. One recently developed method is Breaks Labelling In Situ and Sequencing (BLISS), which localise and quantifies DNA double-strand breaks (DSB). Coupling this technique, with RNA sequencing, the interaction of gene expression and accumulation of DSBs can be studied. The RNA-BLISS data analysis pipeline has been programmed to handle and analyse data generated by BLISS and RNA sequencing. It allows the user to first analyse the datasets individually, to thereafter do a joint analysis to investigate the relation between them. Applying the RNA-BLISS data analysis on BLISS and RNA sequencing data derived from in vitro model of... (More)
The development of new sequencing methods requires new computational pipelines to handle and analyse raw data. One recently developed method is Breaks Labelling In Situ and Sequencing (BLISS), which localise and quantifies DNA double-strand breaks (DSB). Coupling this technique, with RNA sequencing, the interaction of gene expression and accumulation of DSBs can be studied. The RNA-BLISS data analysis pipeline has been programmed to handle and analyse data generated by BLISS and RNA sequencing. It allows the user to first analyse the datasets individually, to thereafter do a joint analysis to investigate the relation between them. Applying the RNA-BLISS data analysis on BLISS and RNA sequencing data derived from in vitro model of neurodifferentiation, we reveal differential gene expression and genome-wide patterns of DSBs across neurodifferentiation. Combining the data sets, we illustrate the impact of gene expression on the accumulation of DSBs. (Less)
Popular Abstract
Quantifying genome fragility and gene expression of the brain

A new data analysis program jointly handles data generated by the BLISS method, that maps genome fragility by detecting DNA double-strand breaks and by RNA-sequencing, that
measures gene expression. The program analyses the data to investigate if genes with high
expression are more prone to accumulate double-strand breaks. Applying the program on data produced from brain development experiment, revealed new insights about the interaction of gene expression and genome fragility across brain development.

Every cell in the human body carries a molecule called DNA, containing genetic information for the function and development of the cell. The sum of all DNA in the cell... (More)
Quantifying genome fragility and gene expression of the brain

A new data analysis program jointly handles data generated by the BLISS method, that maps genome fragility by detecting DNA double-strand breaks and by RNA-sequencing, that
measures gene expression. The program analyses the data to investigate if genes with high
expression are more prone to accumulate double-strand breaks. Applying the program on data produced from brain development experiment, revealed new insights about the interaction of gene expression and genome fragility across brain development.

Every cell in the human body carries a molecule called DNA, containing genetic information for the function and development of the cell. The sum of all DNA in the cell is called the genome which consists of genes that are regions that keep the most important genetic information. To extract the genetic information, the genes are processed by the cell and the information is expressed. If DNA is damaged, the genetic information can be corrupted and have an impact on the development and function of the cell, causing diseases such as cancer and neurodevelopmental disorders.

Every day, DNA is the victim of biological and chemical assault that causes damage. One of the most lethal forms of DNA damage is DSB (double-strand breaks) that break the double-stranded structure of DNA. Most DSB events, are repaired by cells own repair system, but when not, diseases can arise. Much of the DNA damage is caused by external sources, such as UV-radiation and lifestyle habits. However, DNA damage, including DSBs, appear in healthy cells, where certain regions of it, are more prone to damage. When genes in these regions are expressed at a high rate, DSBs accumulate at the gene start.

To find these fragile regions, the BLISS (Breaks Labelling In Situ and Sequencing) method was developed. BLISS allows for the mapping and quantification of DSB throughout the genome, by capturing and counting the number of DSB in DNA. By coupling BLISS, with an already established method called RNA-sequencing, which measures how much genes are expressed, the relationship between expressed genes and fragility could be explored. To analyse the datasets individually and together, a new RNA-BLISS data analysis tool was developed.

The RNA-BLISS data analysis tool in action
In a recent experiment, the RNA-BLISS data analysis tool was applied to data generated when applying BLISS and RNA-sequencing on cells extracted across brain development. The experiment generated
insights on how genes are expressed and the frequency DSBs accumulate across the genome during
different stages of brain development. In brain stem cells, the data showed that the frequency of DSB at the start of genes increased with the expression of genes. The result raises new questions about whether this pattern continues across brain development and if more of these fragile regions can be mapped. If mapped, it will add to our understanding of how DSB cause diseases and how to cure them.

Master’s Degree Project in Bioinformatics 45 credits 2020
Department of Biology, Lund University

Supervisor: Nicola Crosetto
Department of Medical biochemistry and biophysics, Karolinska Institute (Less)
Please use this url to cite or link to this publication:
author
Eriksson, Gustaw
supervisor
organization
course
BINP51 20192
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9031392
date added to LUP
2020-10-27 12:29:37
date last changed
2020-10-27 12:29:37
@misc{9031392,
  abstract     = {{The development of new sequencing methods requires new computational pipelines to handle and analyse raw data. One recently developed method is Breaks Labelling In Situ and Sequencing (BLISS), which localise and quantifies DNA double-strand breaks (DSB). Coupling this technique, with RNA sequencing, the interaction of gene expression and accumulation of DSBs can be studied. The RNA-BLISS data analysis pipeline has been programmed to handle and analyse data generated by BLISS and RNA sequencing. It allows the user to first analyse the datasets individually, to thereafter do a joint analysis to investigate the relation between them. Applying the RNA-BLISS data analysis on BLISS and RNA sequencing data derived from in vitro model of neurodifferentiation, we reveal differential gene expression and genome-wide patterns of DSBs across neurodifferentiation. Combining the data sets, we illustrate the impact of gene expression on the accumulation of DSBs.}},
  author       = {{Eriksson, Gustaw}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Understanding DNA double-strand breaks and genome fragility across neurodifferentiation}},
  year         = {{2020}},
}