The Human Protein Atlas program is a scientific research program with the goal to explore the whole human proteome using an antibody-based approach. The program was started at the Royal Institute of Technology, Sweden, in 2003 and funded by the non-profit organization Knut and Alice Wallenberg Foundation (KAW).
The project has a gene-centric approach with the effort to map and characterize a representative protein for each protein-coding human gene (approximately 20,000 genes). Antibodies, both in-house produced and external (commercial and from collaborators), are validated in the Human Protein Atlas workflow and used for protein characterization. The data is released annually in a publicly available information database portal.
The database includes protein expression profiles from 44 different normal and 20 different cancer tissues, 56 cell lines, subcellular localization and transcript expression levels. The database is searchable for a specific gene or protein. Functionalities added to the The Human Protein Atlas in later versions allow for combined searches, e.g. to find all proteins expressed in a certain organ or tissue or proteins differentially expressed in a specific tumor type.
History
The Human Protein Atlas program was started in 2003 and funded by the non-profit organization Knut and Alice Wallenberg Foundation (KAW). The main site of the project is the Royal Institute of Technology (KTH), School of Biotechnology (Stockholm, Sweden). Professor Mathias Uhlén is the director of the program.
The research underpinning the start of the exploration of the whole human proteome in the Human Protein Atlas program was carried out in the late 1990s and early 2000s. A pilot study employing an affinity proteomics strategy using affinity-purified antibodies raised against recombinant human protein fragments was carried out for a chromosome-wide protein profiling of chromosome 21. Other projects were also carried out to establish processes for parallel and automated affinity purification of mono-specific antibodies and their validation.,
Research
Antibodies and antigens, produced in the Human Protein Atlas workflow, are used in research projects to study potential biomarkers in various diseases, such as breast cancer, prostate cancer, colon cancer, diabetes, autoimmune diseases, ovarian cancer and renal failure.
The Human Protein Atlas consists of three sub-atlases:
·The Tissue Atlas: contains information regarding the expression profiles of human genes both on the mRNA and protein level. The protein expression data is derived from antibody-based protein profiling using immunohistochemistry. Altogether 76 different cell types, corresponding to 44 normal human tissue types, have been analyzed and the data is presented as pathology-based annotation of protein expression levels. All underlying images of immunohistochemistry stained normal tissues are available as high-resolution images in the normal tissue atlas. The protein data covers 15297 genes (78%) for which there are available antibodies.
·The Cell Atlas: provides high-resolution insights into the spatial distribution of proteins within cells. The protein expression data is derived from antibody-based profiling using immunofluorescence confocal microscopy. A panel of 56 cell lines, selected to represent various cell populations in different organs of the human body, forms the basis of the Cell Atlas. In this cell line panel the mRNA expression of all human genes have been characterized using deep RNA-sequencing. The subcellular distribution of proteins is investigated in a subset of the cell lines, and classified into 32 different organelles and fine cellular structures. The cell atlas covers 12036 genes (61%) for which there are available antibodies.
·The Cancer Atlas: contains gene expression data based on protein expression patterns in 216 different cancer samples representing the 20 most common forms of human cancer. Protein expression data is derived from antibody-based protein profiling using immunohistochemistry. The data is presented as pathology-based annotation of protein expression levels. All underlying images of immunohistochemistry stained cancer tissues are available as high-resolution images in the cancer tissue atlas together with basic information regarding age, gender and tumor phenotype.
Collaborations
The Human Protein Atlas program is participating in 9 EU research projects ENGAGE, PROSPECTS, BIO_NMD, AFFINOMICS, CAGEKID, EURATRANS, ITFoM, DIRECT and PRIMES.