Analysis of self-renewal signatures using gene-expression comparison between self-renewing leukemic stem-cells, non-self-renewing leukemic progeny, and normal human hematopoietic stem cells
|has title::Analysis of self-renewal signatures using gene-expression comparison between self-renewing leukemic stem-cells, non-self-renewing leukemic progeny, and normal human hematopoietic stem cells|
|Student name:||student name::Patrick Deelen|
|Supervisor:||Jan Jacob Schuringa|
|Second reader:||has second reader::Sanne Abeln|
|Company:||has company::UMCG, experimental hematology|
Only a small fraction of the leukemic cells are able to self-renew, while the majority of the leukemic cells are unable to do this. It is important to understand this difference since the self-renewing leukemic stem cells (LSC) are the most dangerous and should be the target of therapy. We will investigate the differences in gene expression between the LSCs and the normal leukemic cells. We aim to find genes that can explain why LSCs are able to self-renew so that we can better explain the development of leukemia and identify why LSCs often escape therapy.
We have gene-expression profiles of LSC enriched fractions and non LSC fractions of the leukemic cells from 46 leukemia patients. Furthermore, we have transcriptomes of normal hematopoietic stem cell populations (n=21). The first part of my project will be to design an approach to analysis the gene expression differences between these fractions. The approach will include: normalization of data, perform cluster analysis, perform principle component analysis, search for genes or motifs to discriminate the samples, perform gene ontology analyses and finally we will perform gene set enrichment analyses (GSEA).
Aims and Objectives
This goal will be a list of genes differentially expressed between the LSC and normal leukemic cells.
- Background reading
- Exploring the data
- Write detailed research plan
- Perform and analyze the proposed analysis
- Report writing