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Spatio-temporal analysis of prostate tumours suggests the pre-existence of ADT-resistant expression clones
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
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(English)Manuscript (preprint) (Other academic)
National Category
Bioinformatics (Computational Biology)
Research subject
Biochemistry towards Bioinformatics
Identifiers
URN: urn:nbn:se:su:diva-177920OAI: oai:DiVA.org:su-177920DiVA, id: diva2:1384890
Available from: 2020-01-12 Created: 2020-01-12 Last updated: 2020-02-03Bibliographically approved
In thesis
1. Computational Analysis of Tumour Heterogeneity
Open this publication in new window or tab >>Computational Analysis of Tumour Heterogeneity
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Every tumour is unique and characterised by its genetic, epigenetic, phenotypic, and morphological signature. The diversity observed between and within tumours, and over time, is termed tumour heterogeneity. An increased heterogeneity within a tumour correlates with cancer progression, higher resistance rates, and poorer outcome. Heterogeneity between tumours explains aspects of a treatment’s ineffectiveness. Depending on a tumour’s unique signature, common processes like unhindered cell proliferation, invasiveness, or treatment resistance characterise tumour progression. Studying tumour heterogeneity aims to understand cancer causes and evolution, and eventually to improve cancer treatment outcomes. 

This thesis presents application and development of computational methods to study tumour heterogeneity. Papers I and II concern the in-depth investigation of clinical tissue samples taken from prostate cancer patients. The findings range from spatial expansion of gene expression patterns based on high-resolution data to a gene expression signature of non-responding cancer cells revealed by spatio-temporal analysis. These cells underwent a transition from an epithelial to a mesenchymal phenotype pre-treatment. Papers III and IV present tools to detect fusion transcripts and copy number variations, respectively. Both tools, applicable to high-resolution data, enable the in-depth study of mutations, which are the driving force behind tumour heterogeneity.

The results in this thesis demonstrate how the beneficial combination of high-resolution data and computational methods leads to novel insights of tumour heterogeneity. 

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2020. p. 79
Keywords
tumour heterogeneity, human genome and gene expression analyses, pathway annotation, fusion transcript detection, copy number calling, and high-resolution data
National Category
Bioinformatics (Computational Biology)
Research subject
Biochemistry towards Bioinformatics
Identifiers
urn:nbn:se:su:diva-176074 (URN)978-91-7797-943-2 (ISBN)978-91-7797-944-9 (ISBN)
Public defence
2020-03-20, Wangari, Widerströmska huset (KI), Tomtebodavägen 18, Solna, 14:00 (English)
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Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript. Paper 4: Manuscript.

Available from: 2020-02-26 Created: 2020-01-12 Last updated: 2020-02-19Bibliographically approved

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Friedrich, StefanieSonnhammer, Erik
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