Functional annotation of synonymous genetic variants in breast cancer
(2021) BINP50 20211Degree Projects in Bioinformatics
- Abstract
- DNA sequence variation can have different effects on the amino acid sequence of a protein, depending on what type of alteration is made and the position of it. While missense and nonsense variants can substitute one amino acid for another or lead to a premature stop codon respectively, synonymous variation does not directly alter the amino acid sequence of a protein. Though synonymous variants seem to be harmless at first glance, accumulating evidence shows that they can affect messenger RNA (mRNA) splicing, translational rate and efficiency and, in turn, protein folding and conformation. Together with improvements in sequencing technologies, more research into synonymous codon usage has led researchers to new knowledge about the important... (More)
- DNA sequence variation can have different effects on the amino acid sequence of a protein, depending on what type of alteration is made and the position of it. While missense and nonsense variants can substitute one amino acid for another or lead to a premature stop codon respectively, synonymous variation does not directly alter the amino acid sequence of a protein. Though synonymous variants seem to be harmless at first glance, accumulating evidence shows that they can affect messenger RNA (mRNA) splicing, translational rate and efficiency and, in turn, protein folding and conformation. Together with improvements in sequencing technologies, more research into synonymous codon usage has led researchers to new knowledge about the important role synonymous variants might have in human disease. This project has contributed to the creation of an annotation pipeline for synonymous variants in sequencing data. We first compared phyloP evolutionary conservation scores obtained using two different multiple sequence alignments (20-way mammalian and 100-way vertebrate) and then created tools for identification of alternative splicing events and exon-inclusion ratio calculations. These tools were tested on gene expression data for 16 samples with associated variant calling files from the Sweden Cancerome Analysis Network – Breast (SCAN-B) initiative. Annotated alternative splicing events consisted of alternative acceptors or donors and cassette exons and the Percent Spliced in Index (PSI) was used to determine how genetic variation may affect exon’s inclusion ratio, hypothesizing that variants in genomic positions near splice sites may lead to changes in splicing patterns. These measures can be part of a pipeline for researching synonymous variants and their effects on phenotypical manifestations. (Less)
- Popular Abstract
- Annotation of synonymous genetic variants in breast cancer
Breast cancer is one of the four most common cancers worldwide and if the treatment is administered at an early stage the chances of survival can reach as high as 100%. The search for new biomarkers and ways to identify new therapies in order to personalize treatment has been gaining more attention, especially fast-spreading and aggressive tumors being at the center of focus.
Research in the Functional breast cancer genomics group is focused on investigation of genetic variants that were assumed to be harmless in the past (synonymous genetic variants). Although they do not change the encoded amino acid in the primary protein structure, new evidence suggests they can alter the... (More) - Annotation of synonymous genetic variants in breast cancer
Breast cancer is one of the four most common cancers worldwide and if the treatment is administered at an early stage the chances of survival can reach as high as 100%. The search for new biomarkers and ways to identify new therapies in order to personalize treatment has been gaining more attention, especially fast-spreading and aggressive tumors being at the center of focus.
Research in the Functional breast cancer genomics group is focused on investigation of genetic variants that were assumed to be harmless in the past (synonymous genetic variants). Although they do not change the encoded amino acid in the primary protein structure, new evidence suggests they can alter the way proteins are built in our bodies. The group’s research programme is based on analysis of genetic variants in sequencing data from the SCAN-B breast cancer cohort with more than 9000 sequenced breast tumors.
This project has contributed to the creation of a method, which could help identify interesting “silent” genetic variants in breast cancer. We used measures to predict how evolutionary conserved some parts of the genome are, hypothesizing that genetic variation at conserved sites may have stronger impact. During this project, we compared two different multiple sequence alignments for evolutionary conservation scores calculations (phyloP) to evaluate which alignment is more suitable for the annotation pipeline. Furthermore, we created tools for alternative splicing events annotation and calculations of exon inclusion ratios into transcripts, which can give insights on how a genetic variant may change splicing patterns.
The mentioned measures greatly enhance the knowledge about synonymous variants in breast cancer, but more information can be added to the annotation pipeline in order to select the most promising variants. The next step could be appending information about predicted effects on splicing based on overlap with known exonic splicing enhancer (ESE) and exonic splicing silencer (ESS) motifs or investigating overlaps with binding sites for RNA-binding proteins.
Master’s Degree Project in Biology/Molecular Biology/Bioinformatics 30 credits 2021
Department of Biology, Lund University
Advisor: Helena Persson
Department of Clinical Sciences, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9055233
- author
- Kurgonaitė, Monika
- supervisor
- organization
- course
- BINP50 20211
- year
- 2021
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9055233
- date added to LUP
- 2021-06-16 14:02:57
- date last changed
- 2021-06-16 14:02:57
@misc{9055233,
abstract = {{DNA sequence variation can have different effects on the amino acid sequence of a protein, depending on what type of alteration is made and the position of it. While missense and nonsense variants can substitute one amino acid for another or lead to a premature stop codon respectively, synonymous variation does not directly alter the amino acid sequence of a protein. Though synonymous variants seem to be harmless at first glance, accumulating evidence shows that they can affect messenger RNA (mRNA) splicing, translational rate and efficiency and, in turn, protein folding and conformation. Together with improvements in sequencing technologies, more research into synonymous codon usage has led researchers to new knowledge about the important role synonymous variants might have in human disease. This project has contributed to the creation of an annotation pipeline for synonymous variants in sequencing data. We first compared phyloP evolutionary conservation scores obtained using two different multiple sequence alignments (20-way mammalian and 100-way vertebrate) and then created tools for identification of alternative splicing events and exon-inclusion ratio calculations. These tools were tested on gene expression data for 16 samples with associated variant calling files from the Sweden Cancerome Analysis Network – Breast (SCAN-B) initiative. Annotated alternative splicing events consisted of alternative acceptors or donors and cassette exons and the Percent Spliced in Index (PSI) was used to determine how genetic variation may affect exon’s inclusion ratio, hypothesizing that variants in genomic positions near splice sites may lead to changes in splicing patterns. These measures can be part of a pipeline for researching synonymous variants and their effects on phenotypical manifestations.}},
author = {{Kurgonaitė, Monika}},
language = {{eng}},
note = {{Student Paper}},
title = {{Functional annotation of synonymous genetic variants in breast cancer}},
year = {{2021}},
}