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A TISSUE DICTIONARY FOR NORMAL AND CANCER TISSUES: A complimentary tool for the Human Protein Atlas
Caroline Kampf*, Julia Bergman*, Per Oksvold # , Anna Asplund*, Sanjay Navani + , Mikaela Wiking # , Emma Lundberg # , Mathias Uhlén # and Fredrik Ponten*
*Department of Immunology, Genetics, Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, #Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden. +Lab Surgpath, Mumbai, India
Background
The Human Protein Atlas project was initiated in 2003 to establish a systematic high-throughput generation of affinity-purified polyclonal antibodies towards all
human proteins and to use these antibodies to map protein localization within the human body. Protein expression data for over 70% of the human protein-coding
genome is currently publically available in the free, online protein atlas database (www.proteinatlas.org ) that contain more than 11 million digital images. The
database is a histology-based map for global visualization of protein expression patterns at a tissue/cellular resolution for over 46 normal tissues, 20 different cancer
types and 47 cell lines and serve as a valuable tool for research and virtual pathology.
Fig. 1. On the overview page all 45
normal tissues, 20 cancer and 18
cell structures that are included in
the dictionary are listed in
alphabetical order. Navigation
between the three dictionary parts
is easily accessible in the
navigation menu. The tissue
specimens keep high quality and
include totally 162 normal tissue
images, 67 IF cells images and 36
IHC cell images. The 173 cancer
images are moreover divided into
20 cancer types and 99 sub groups.
Tissue Dictionary
Browsing the Dictionary
The know-how and experience within the
Human Protein Atlas has made the
creation of a comprehensive and
publically available tissue dictionary
possible. The dictionary covers three
main parts: normal tissues, cancer
tissues and subcellular structures. An
additional anatomical part is included
showing the localization of the organs in
the body. All images and examples
include descriptive text boxes and
supporting background text to facilitate
interpretation of the complex patterns
underlying normal tissue histology,
tumor pathology and cell biology.
Fig. 2A-B. Normal tissues are represented by
the 45 normal tissues used for protein profiling
in the Human Protein Atlas. The images are
displayed with text boxes and arrows to assist
the viewer. Examples show normal colon and
normal breast at three levels of magnification.
The dictionary will be of great use for
Human Protein Atlas users to aid in the
interpretation of human tissues and
cells. It also constitutes a valuable
resource to complement microscopy and
histology teaching as the internet-based
dictionary is easy accessible for lectures
and self-studies 24/7.
The tissue dictionary will be released at
the 2012 HUPO meeting concomitant
with the release of the 10th version of
the Human Protein Atlas.
Fig. 2C-D. Cancer is represented by the cancer
types that are also used for protein profiling in
the Human Protein Atlas. Cases have been
selected to demonstrate the most common
variants of these 20 cancer types. Breast
cancer is eg. represented by four different
cases, selected according to established
pathological classifications. In the figure, one
case of high grade and one case of low-grade
ductal cancer is shown.
Fig. 3. Cells are represented by altogether 18
different subcellular structures and organelles
that are exemplified by images obtained after
IF and IHC depending on which subcellular
structure is visualized. Two examples are
shown with IF and IHC images representing
antibodies targeting proteins in the nucleoli
and the mitochondria respectively.
Acknowledgements
This work was supported by grants from the Knut and Alice
Wallenberg foundation. Pathologists at the Clinical Department
of Pathology, Akademiska Hospital, Uppsala, Sweden is greatly
acknowledged for all expertise supporting the dictionary and
Human Protein Atlas. The authors wish to especially thank
Dijana Djureinovic, Sofie Gustafsson, Elene Karlberg, Dijana
Cerjan and John Juter for assistance with the dictionary work.
References
1. Uhlen M: Antibody-based proteomics for human tissue profiling. Mol Cell Proteomics 2005, 4:384-393. 2. Kampf C: Antibody-based tissue profiling as a tool for clinical proteomics. Clinical Proteomics 2004, 1:285-299. 3. Barbe L: Toward a confocal
subcellular atlas of the human proteome. Mol Cell Proteomics 2008, 7:499-508. 4. Uhlen M: A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteomics 2005, 4:1920-1932. 5. Uhlen M: Towards a
knowledge-based Human Protein Atlas. Nat Biotechnol 2010, 28:1248-1250. 6. Ponten F: The Human Protein Atlas as a proteomic resource for biomarker discovery. Journal of internal medicine 2011, 270:428-446.