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Towards Precision Oncology : Advancing Multiomic Biomarker Discovery with Mass Spectrometry Proteomics

Mosquim Junior, Sergio LU (2024)
Abstract
Over the past couple of decades, considerable advances in automation and high-throughput omics technologies have contributed to the generation of unprecedented amounts of molecular data, challenging the traditional “one size fits all” approach in favour of personalised medicine, where the individual needs of patients are addressed.
However, the speed at which such molecular data is being acquired does not translate in a proportional number of clinical implementations. One way in which the molecular data can contribute to individualised treatment is by the discovery of novel and more robust biomarkers.
Proteins are interesting biomarker candidates, as they mediate most processes in living organisms, and are by far the most utilised... (More)
Over the past couple of decades, considerable advances in automation and high-throughput omics technologies have contributed to the generation of unprecedented amounts of molecular data, challenging the traditional “one size fits all” approach in favour of personalised medicine, where the individual needs of patients are addressed.
However, the speed at which such molecular data is being acquired does not translate in a proportional number of clinical implementations. One way in which the molecular data can contribute to individualised treatment is by the discovery of novel and more robust biomarkers.
Proteins are interesting biomarker candidates, as they mediate most processes in living organisms, and are by far the most utilised molecules in clinical use. For these reasons, global analysis of proteins could contribute to the development of better biomarkers.
By combining mass spectrometry-based proteomics with automation solutions, workflows that can potentially improve biomarker discovery are discussed and showcased in this thesis. Such workflows are exemplified in (i) the multiplexed enrichment of blood plasma, allowing higher throughput and a unique platform for automation of affinity enrichment, (ii) the acquisition of matching multiomics data from a large number of breast cancer patient samples, allowing the optimisation of data acquisition strategies and utilisation of such data for functional analyses of the intrinsic subtypes, (iii) and the multiomics data analysis of patient samples, contributing to the most comprehensive molecular profile of metastatic processes in oestrogen receptor-positive breast cancer utilising transcriptomics, proteomics, phosphoproteomics and immune infiltration data acquired from the same tumour samples.
In summary, the work presented in this thesis highlights strategies incorporating mass spectrometry-based proteomics and automation, allowing a greater number of samples to be analysed, more data to be extracted from samples and making better use of these data, which would hopefully improve biomarkers discovery, contributing to the field of personalised medicine. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof. Jimenez, Connie, Amsterdam University Medical Center, The Netherlands.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
multi-omics, Data integration, Proteomics, Affinity Enrichment, Phosphoproteomics, Mass Spectrometry, Breast Cancer, Blood Plasma, Deconvolution, Automation
pages
94 pages
publisher
Department of Immunotechnology, Lund University
defense location
Lecture Hall Sharience, building The Spark, Medicon Village, Scheeletorget 1, Faculty of Engineering LTH, Lund University, Lund
defense date
2024-09-13 09:00:00
ISBN
978-91-8104-115-6
978-91-8104-116-3
language
English
LU publication?
yes
id
d7fc2332-5b15-49ff-924d-6a7e11e027f0
date added to LUP
2024-08-19 10:42:03
date last changed
2024-08-20 08:45:39
@phdthesis{d7fc2332-5b15-49ff-924d-6a7e11e027f0,
  abstract     = {{Over the past couple of decades, considerable advances in automation and high-throughput omics technologies have contributed to the generation of unprecedented amounts of molecular data, challenging the traditional “one size fits all” approach in favour of personalised medicine, where the individual needs of patients are addressed.<br/>However, the speed at which such molecular data is being acquired does not translate in a proportional number of clinical implementations. One way in which the molecular data can contribute to individualised treatment is by the discovery of novel and more robust biomarkers.<br/>Proteins are interesting biomarker candidates, as they mediate most processes in living organisms, and are by far the most utilised molecules in clinical use. For these reasons, global analysis of proteins could contribute to the development of better biomarkers.<br/>By combining mass spectrometry-based proteomics with automation solutions, workflows that can potentially improve biomarker discovery are discussed and showcased in this thesis. Such workflows are exemplified in (i) the multiplexed enrichment of blood plasma, allowing higher throughput and a unique platform for automation of affinity enrichment, (ii) the acquisition of matching multiomics data from a large number of breast cancer patient samples, allowing the optimisation of data acquisition strategies and utilisation of such data for functional analyses of the intrinsic subtypes, (iii) and the multiomics data analysis of patient samples, contributing to the most comprehensive molecular profile of metastatic processes in oestrogen receptor-positive breast cancer utilising transcriptomics, proteomics, phosphoproteomics and immune infiltration data acquired from the same tumour samples.<br/>In summary, the work presented in this thesis highlights strategies incorporating mass spectrometry-based proteomics and automation, allowing a greater number of samples to be analysed, more data to be extracted from samples and making better use of these data, which would hopefully improve biomarkers discovery, contributing to the field of personalised medicine.}},
  author       = {{Mosquim Junior, Sergio}},
  isbn         = {{978-91-8104-115-6}},
  keywords     = {{multi-omics; Data integration; Proteomics; Affinity Enrichment; Phosphoproteomics; Mass Spectrometry; Breast Cancer; Blood Plasma; Deconvolution; Automation}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Department of Immunotechnology, Lund University}},
  school       = {{Lund University}},
  title        = {{Towards Precision Oncology : Advancing Multiomic Biomarker Discovery with Mass Spectrometry Proteomics}},
  url          = {{https://lup.lub.lu.se/search/files/193533966/e-nailing_ex_sergio.pdf}},
  year         = {{2024}},
}