Computational analysis of high throughput flow cytometry data of blood cells in cord blood
(2021) BINP52 20202Degree Projects in Bioinformatics
- Abstract
- The genetic regulation of hematopoietic stem and progenitor cells (HSPCs) plays a vital role in the development and function of the immune and circulatory systems. Genetic variants can lead to significant differences in HSPC-related phenotypes, and pathogenic variants can cause blood disorders and other maladies. Discovering these variants and understanding the mechanisms by which they affect an individual’s blood could lead to advances in the treatment of such disorders. HSPCs are commonly studied in adult blood samples where the amount of progenitor cells is very small, making examining HSPCs difficult. However, umbilical cord blood samples extracted from the placenta or the umbilical cord after childbirth contain a much higher... (More)
- The genetic regulation of hematopoietic stem and progenitor cells (HSPCs) plays a vital role in the development and function of the immune and circulatory systems. Genetic variants can lead to significant differences in HSPC-related phenotypes, and pathogenic variants can cause blood disorders and other maladies. Discovering these variants and understanding the mechanisms by which they affect an individual’s blood could lead to advances in the treatment of such disorders. HSPCs are commonly studied in adult blood samples where the amount of progenitor cells is very small, making examining HSPCs difficult. However, umbilical cord blood samples extracted from the placenta or the umbilical cord after childbirth contain a much higher proportion of progenitor cells. Cord blood samples are significantly more challenging to obtain than adult peripheral blood samples, making large cord blood sample data-sets uncommon. In this project, 3020 cord blood samples were analyzed using Flow Cytometry and pattern-recognition based gating. We carried out a replication analysis focusing on 14 SNPs known to have an effect in adult peripheral HSPCs. Additionally, a preliminary Genome-Wide Association Study was completed with 692 samples for which full genotype data was available. We were able to replicate 4 of the effects discovered in adults, and 4 novel loci were discovered containing SNPs in or close to genes that might have an effect in HSPC proliferation. (Less)
- Popular Abstract
- Genetics of blood cell proliferation
Blood stem cells are the cells responsible for producing all other cells in the blood. In some cases, mutations in these stem cells can cause leukemia or other blood diseases. Understanding the genetics of the generation of new blood cells could help curing or preventing these diseases. It is hard to study blood stem cells in adults because most of them are in the bone marrow, and very few in the blood . In contrast, newborn babies have a high amount of stem cells, and blood can be collected from the placenta or the umbilical cord after childbirth. This blood is referred to as cord blood.
In this study, we analyzed 3020 samples of cord blood by looking at the different types of stem cells and... (More) - Genetics of blood cell proliferation
Blood stem cells are the cells responsible for producing all other cells in the blood. In some cases, mutations in these stem cells can cause leukemia or other blood diseases. Understanding the genetics of the generation of new blood cells could help curing or preventing these diseases. It is hard to study blood stem cells in adults because most of them are in the bone marrow, and very few in the blood . In contrast, newborn babies have a high amount of stem cells, and blood can be collected from the placenta or the umbilical cord after childbirth. This blood is referred to as cord blood.
In this study, we analyzed 3020 samples of cord blood by looking at the different types of stem cells and progenitor cells in them. We used a technology called flow cytometry to do so, which is usually an arduous manual task, but instead we wrote code to do it semi-automatically.
We then looked at the genome of these samples, trying to find if there was any correlation between specific genetic variants and the traits we saw. That is, we wanted to see if samples that shared a particular variant also had blood traits in common, e.g. a higher amount of a specific type of progenitor cells. This would give us insight about what genes influence the proliferation of blood cells. We only had genotype data for 692 samples however, which is less than what you generally need for these kinds of studies.
We first looked at a group of variants that had already been discovered in adult blood samples, and checked if we observed the same effects in cord blood. We were able to replicate a few of them.
Afterwards, we performed a Genome Wide Association Study (GWAS) which is a similar assay but checking for correlation with as many variants in the genome as possible (hence “genome wide”). After completing the analysis, we found 4 additional variants that could be affecting the proliferation of blood cells in cord blood.
Master’s Degree Project in Bioinformatics 60 credits 2021
Department of Biology, Lund University
Advisor: Aitzkoa Lopez de Lapuente
Faculty of Medicine / Department of Laboratory Medicine / Division of Hematology and Transfusion Medicine (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9066097
- author
- Lamarca, Antton
- supervisor
- organization
- course
- BINP52 20202
- year
- 2021
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9066097
- date added to LUP
- 2021-09-24 13:54:38
- date last changed
- 2021-09-24 13:54:38
@misc{9066097,
abstract = {{The genetic regulation of hematopoietic stem and progenitor cells (HSPCs) plays a vital role in the development and function of the immune and circulatory systems. Genetic variants can lead to significant differences in HSPC-related phenotypes, and pathogenic variants can cause blood disorders and other maladies. Discovering these variants and understanding the mechanisms by which they affect an individual’s blood could lead to advances in the treatment of such disorders. HSPCs are commonly studied in adult blood samples where the amount of progenitor cells is very small, making examining HSPCs difficult. However, umbilical cord blood samples extracted from the placenta or the umbilical cord after childbirth contain a much higher proportion of progenitor cells. Cord blood samples are significantly more challenging to obtain than adult peripheral blood samples, making large cord blood sample data-sets uncommon. In this project, 3020 cord blood samples were analyzed using Flow Cytometry and pattern-recognition based gating. We carried out a replication analysis focusing on 14 SNPs known to have an effect in adult peripheral HSPCs. Additionally, a preliminary Genome-Wide Association Study was completed with 692 samples for which full genotype data was available. We were able to replicate 4 of the effects discovered in adults, and 4 novel loci were discovered containing SNPs in or close to genes that might have an effect in HSPC proliferation.}},
author = {{Lamarca, Antton}},
language = {{eng}},
note = {{Student Paper}},
title = {{Computational analysis of high throughput flow cytometry data of blood cells in cord blood}},
year = {{2021}},
}