The Human Protein Atlas (HPA) is a publicly accessible scientific effort dedicated to cataloging and mapping all proteins encoded by the human genome. Launched in 2003, the project aims to create a comprehensive biological resource detailing the presence and location of approximately 20,000 human protein-coding genes. By integrating multiple advanced technologies, the HPA provides researchers worldwide with millions of high-resolution images and vast datasets. This data is freely available to accelerate biological and medical discovery by translating the genetic blueprint of the human body into functional knowledge.
The Core Mission of the Atlas
The core mission of the Human Protein Atlas is to understand the spatial distribution of the entire human proteome. This involves precisely mapping where each protein resides—in a specific organ, tissue type, or cellular compartment. This spatial context is paramount because it directly dictates a protein’s function in the body.
If a protein is misplaced or its expression level is abnormal, it can lead to cellular dysfunction and disease. Establishing a baseline map of protein location and quantity in a healthy body is the first step toward understanding the molecular origins of disease. The Atlas provides this foundational reference, allowing scientists to compare protein patterns in a disease state against the established normal profile.
Mapping Protein Location and Expression
The HPA generates its dataset using advanced molecular techniques, primarily focusing on antibody-based imaging. Custom-made antibodies serve as highly specific molecular probes that bind only to their target protein. This method, called immunohistochemistry (IHC), uses antibodies to tag the target protein with a visible color marker.
This visualization allows researchers to see the exact cellular or tissue structure where the protein is present, providing spatial resolution at a microscopic level. The imaging data is combined with transcriptomics, which measures the amount of messenger RNA (mRNA) present in a sample. Since mRNA is the template used to build proteins, measuring its level provides a quantitative estimate of how much protein is being produced.
The integration of visual protein data with quantitative mRNA data offers a comprehensive two-pronged view of protein expression. The resulting high-resolution images and expression profiles are manually annotated and validated by pathologists and scientists. This rigorous process ensures the reliability of the data, which covers a substantial portion of the human proteome.
Navigating the Specialized Atlas Views
The complexity of the human proteome requires the Atlas to be organized into distinct, specialized sections, each addressing a different biological context. This structure allows researchers to focus their queries on specific areas of interest, from whole organs down to individual cellular compartments. Three of the most extensively used sections are the Tissue Atlas, the Cell Atlas, and the Pathology Atlas.
Tissue Atlas
The Tissue Atlas focuses on the distribution of proteins across all major organs and tissues in the human body. It provides expression profiles for dozens of normal tissue types, such as the heart, liver, and brain. Researchers can determine if a protein is widely expressed (a “housekeeping” protein) or highly enriched in a single, specific organ. This resource is essential for understanding tissue specificity and the general physiological role of a protein.
Cell Atlas
The Cell Atlas details the subcellular localization of proteins, taking spatial mapping to a finer level. Using high-resolution immunofluorescence imaging, this section maps proteins to specific cellular compartments, such as the nucleus, the cytoplasm, or the mitochondria. Knowing the precise organelle location is crucial, as a protein’s function is intrinsically linked to its position within the cell.
Pathology Atlas
The Pathology Atlas serves as a specialized resource for cancer research, providing a direct comparison of protein expression in healthy tissues versus various types of cancer tissues. This section correlates protein levels with the clinical outcome and survival data of cancer patients. Researchers use this information to identify proteins whose altered expression levels are associated with a favorable or unfavorable prognosis in tumors.
Impact on Research and Precision Medicine
The Human Protein Atlas is an open-access resource that significantly accelerates scientific discovery and the development of new treatments. By providing a publicly available, detailed map of protein expression, the Atlas allows researchers to quickly validate hypotheses without needing to generate basic expression data themselves. This level of access drastically reduces the time and cost associated with early-stage biomedical research.
Drug Target Identification
One primary impact is in Drug Target Identification, particularly for cancer and other complex diseases. Researchers use the Atlas to pinpoint proteins that are uniquely or highly expressed in diseased cells but are low or absent in healthy tissue. This distinct expression pattern represents a promising therapeutic target, as a drug designed to inhibit it can attack the disease with minimal side effects on healthy tissue.
Diagnostics
The Atlas also aids in the development of new Diagnostics by helping to identify potential biomarkers. For instance, if a protein is released into the blood only when a specific organ is damaged, it could be developed into a blood test for early disease detection. The data allows scientists to select and validate candidate proteins that reliably indicate the presence or progression of a condition.
Precision Medicine
The HPA supports the movement toward Precision Medicine, which aims to tailor medical treatments to the individual characteristics of each patient. By understanding the variability in protein expression across different people and disease subtypes, clinicians can understand why a treatment works well for one patient but not another. This detailed molecular insight helps guide the selection of the most effective therapy based on a patient’s specific protein profile.