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Targeted analysis of serum proteins encoded at known inflammatory bowel disease risk loci
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
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(English)Manuscript (preprint) (Other academic)
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:kth:diva-225979OAI: oai:DiVA.org:kth-225979DiVA, id: diva2:1197224
Note

QC 20180418

Available from: 2018-04-12 Created: 2018-04-12 Last updated: 2018-04-18Bibliographically approved
In thesis
1. Antibody-based bead arrays for high-throughput protein profiling in human plasma and serum
Open this publication in new window or tab >>Antibody-based bead arrays for high-throughput protein profiling in human plasma and serum
2018 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Affinity-based proteomics utilizes affinity binders to detect target proteins in a large-scale manner. This thesis describes a high-throughput method, which enables the search for biomarker candidates in human plasma and serum. A highly multiplexed antibody-based suspension bead array is created by coupling antibodies generated in the Human Protein Atlas project to color-coded beads. The beads are combined for parallel analysis of up to 384 analytes in patient and control samples. This provides data to compare protein levels from the different groups.

In paper I osteoporosis patients are compared to healthy individuals to find disease-linked proteins. An untargeted discovery screening was conducted using 4608 antibodies in 16 cases and 6 controls. This revealed 72 unique proteins, which appeared differentially abundant. A validation screening of 91 cases and 89 controls confirmed that the protein autocrine motility factor receptor (AMFR) is decreased in the osteoporosis patients.

Paper II investigates the risk proteome of inflammatory bowel disease (IBD). Antibodies targeting 209 proteins corresponding to 163 IBD genetic risk loci were selected. To find proteins related to IBD or its subgroups, sera from 49 patients with Crohn’s disease, 51 with ulcerative colitis and 50 matched controls were analyzed. From these targeted assays, the known inflammation-related marker serum amyloid protein A (SAA) was shown to be elevated in the IBD cases. In addition, the protein laccase (multi-copper oxidoreductase) domain containing 1 (LACC1) was found to be decreased in the IBD subjects.

In conclusion, assays using affinity-based bead arrays were developed and applied to screen human plasma and serum samples in two disease contexts. Untargeted and targeted screening strategies were applied to discover disease-associated proteins. Upon further validation, these potential biomarker candidates could be valuable in future disease studies.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2018. p. 58
Series
TRITA-CBH-FOU ; 2018:9
Keyword
proteomics, affinity proteomics, immunoassay, antibody microarray, suspension bead array, protein profiling, plasma, serum, biomarker discovery, osteoporosis, inflammatory bowel disease, Crohn's disease, ulcerative colitis
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-225980 (URN)978-91-7729-739-0 (ISBN)
Presentation
2018-05-04, 10:00 (English)
Opponent
Supervisors
Note

QC 20180412

Available from: 2018-04-12 Created: 2018-04-12 Last updated: 2018-04-12Bibliographically approved

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