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

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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
status: finished
Master: project within::Bioinformatics
Student name: student name::Patrick Deelen
Dates
Start start date:=2011/07/15
End end date:=2012/01/15
Supervision
Supervisor: Jan Jacob Schuringa
Second reader: has second reader::Sanne Abeln
Company: has company::UMCG, experimental hematology

Signature supervisor



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Abstract

Background

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.

Approach

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.

Time line

Month 1

  • Background reading
  • Exploring the data
  • Write detailed research plan

Month 2/3/4

  • Perform and analyze the proposed analysis

Month 5

  • Report writing