Research projects in Human Protein Atlas

In addition to the high-throughput protein profiling core project, several projects with more specific research objectives are run based on the resources generated within the Human Protein Atlas, in collaboration with Swedish or international researchers. Below is a short description of such selected projects.

Antibody validation, performance and characterization

PIs: Cecilia Lindskog Bergström and Fredrik Pontén
Research group members involved: Feria Hikmet Noraddin, Jonas Gustavsson, Emil Lindström and Dennis Kesti
Collaborators: Ulf Landegren (UU), Max Backman (UU), Evelina Sjöstedt (KI), Fredrik Edfors (SciLifeLab), Andreas Hober (SciLifeLab), Åsa Sivertsson (SciLifeLab), Emma Lundberg (SciLifeLab), Cecilia Williams (SciLifeLab) and Mathias Uhlén (SciLifeLab).
Objective: The objective of these technical development projects is to develop assays and strategies for further validation of antibodies in tissues and cells. Strategies include refinement of guidelines for antibody validation using standardized immunohistochemistry, but also method development of new techniques, such as multiplexed detection of proteins in paraffin-embedded tissue sections using immunofluorescence. Other techniques used for antibody validation include proximity ligation assay. The techniques used have different advantages and disadvantages regarding sensitivity, specificity, resolution, and implementation in a high-throughput workflow.

Machine learning for cancer diagnostics

PI: Cecilia Lindskog Bergström
Research group members involved: Jonas Gustavsson, Feria Hikmet Noraddin
Collaborators: Lars Björk (ContextVision), Kristian Eurén (ContextVision), Marc Rassy (UU), Patrick Micke (UU) and Max Backman (UU).
ObjectiveThe project's objective is to create an algorithm for detection of cancer tissues in certain organs, such as prostate and lung. Immunofluorescence is used to mark specific proteins associated with cancer and normal tissues. After scanning the tissues are stained with hematoxylin and eosin (H&E) and scanned in brightfield. The immunofluorescence staining is overlaid with H&E and used as ground truth for machine learning to detect and outline cancer areas.  

Organ-specific proteomes

PIs: Cecilia Lindskog Bergström and Fredrik Pontén
Research group members involved: Andreas Digre, Feria Hikmet Noraddin, Borbala Katona, Emil Lindström and Åsa Edvinsson
Collaborators: Evelina Sjöstedt (KI), Jan Mulder (KI), Linn Fagerberg (ScilIfeLab), Cheng Zhang (SciLifeLab), Åsa Sivertsson (SciLifeLab) and Mathias Uhlén (SciLifeLab).
Objective: Global RNA expression levels across 37 different normal tissues and organs has allowed for classification of all human genes into categories based on abudance and distribution. Genes elevated or specifically expressed in certain organs provide interesting starting points for tissue specific research in health and disease. Several ongoing projects focus on such genes, combined with strategies aiming at determining the cell type specific localization in the tissue using antibody-based techniques.

Single cell imaging of reproductive organs

PI: Cecilia Lindskog Bergström
Research group members involved: Feria Hikmet Noraddin, Andreas Digre, Åsa Edvinsson, Loren Méar, Jimmy Vuu, Rutger Schutten and Jonas Gustafsson
Collaborators: Charles Pineau (INSERM), Roser Vento (Wellcome Sanger Institute), Carlos Simon (Valencia University), Linn Fagerberg (SciLifeLab), Cheng Zhang (SciLifeLab) and Mathias Uhlén (SciLifeLab).
Objective: A large proportion of genes elevated in certain organs belong to male and female reproductive organs, and studies have shown that many of the corresponding proteins have an unknown function. Using organ-specific antibody panels and multiplexed imaging tools, high-resolution spatial protein maps of human tissues are built in order to determine the exact location of cell type-specific expression patterns, and how these genes and proteins are related to reproductive biology in health and disease. 

Cancer biomarkers

PI: Fredrik Pontén
Research group members involved: IngMarie Olsson, Borbala Katona, Feria Hikmet Noraddin, Leo Nore and Cecilia Lindskog Bergström.
Collaborators: Per-Henrik Edqvist (UCAN, UU), Tobias Sjöblom (UCAN, UU), Anna Dimberg (UU), Rose-Marie Amini (UU), Mattias Berglund (UU), Lena Claeson-Welsh (UU), Patrick Micke (UAS), Olivera Casar-Borota (UAS), Karin Jirström (MAS), Anja Smits (GU), Irma Fredriksson (KI/KS), Cecilia Williams (SciLifeLab) and Mathias Uhlén (SciLifeLab).
Objective: In several projects the aim is to further analyze the role of proteins identified as potential cancer biomarkers in the screening effort performed within the Human Protein Atlas project. Tumor material from well-defined patient cohorts with tumors representing several major forms of human cancer are being collected and assembled into tissue microarrays. In addition to tumor material, clinical data is also collected to create databases allowing for testing and validation of protein expression patterns of importance for diagnostics, prognosis and functional tumor biology studies. Special emphasis is put on colorectal cancer, breast cancer and lung cancer, but several collaborations are run related to other cancer types.

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