Proteins are the fundamental “workhorses” within the human body, carrying out nearly all cellular functions. These complex molecules are responsible for building tissues, fighting infections, and transmitting signals. Understanding their roles and locations is important for comprehending human health and disease. To systematically map these components, scientists embarked on the Human Protein Atlas project.
What is the Human Protein Atlas?
The Human Protein Atlas (HPA) is a Swedish-based program initiated in 2003 to map all human proteins. It aims to determine the location and abundance of proteins within cells, tissues, and organs. The HPA integrates various “omics” technologies, including antibody-based imaging, mass spectrometry-based proteomics, and transcriptomics, to characterize the human proteome.
This resource is openly accessible, providing data for scientists and the general public. The HPA has become one of the most visited biological databases, featuring millions of high-resolution images showing protein spatial distribution. Launched in 2005 with data on 700 antibodies, the atlas is continuously updated with new data and functionalities.
Exploring the Protein Landscape
The Human Protein Atlas is organized into several sections, providing information on protein expression and localization. The data covers 76% to 87% of human protein-coding genes for which antibodies are available.
Tissue Atlas
The Tissue Atlas shows protein distribution across normal human tissues and organs. It includes expression profiles of human genes at both protein and mRNA levels. Protein expression data comes from immunohistochemical analysis of approximately 44 normal human tissue types, encompassing 76 different cell types.
Cell Atlas
The Cell Atlas illustrates protein subcellular localization within different cell types. This resource presents the distribution of thousands of proteins based on high-resolution immunofluorescence images of cell lines. Proteins are mapped to subcellular structures, including organelles like the nucleus, mitochondria, endoplasmic reticulum, and Golgi apparatus.
Pathology Atlas
The Pathology Atlas focuses on protein expression in cancer types and its correlation with patient survival. This section contains protein expression and mRNA data for common human cancers, allowing researchers to explore protein levels in individual tumors. It also includes Kaplan-Meier plots, showing the relationship between mRNA expression levels of human protein genes and cancer patient survival.
Blood Atlas
The Blood Atlas provides information on proteins found in human blood, particularly those relevant for diagnostics. This section details proteins in individual blood cells and those secreted into the blood. It includes data on protein levels in plasma across diseases and profiles of immune cell populations.
Brain Atlas
The Brain Atlas maps proteins in different regions of the human brain. This resource provides spatial profiling of the brain, integrating data from human, pig, and mouse brains. It allows exploration of protein presence or absence in the human brain and helps identify differences in protein profiles across these mammalian brains.
The methodologies employed across these atlases involve antibody-based proteomics, such as immunohistochemistry (IHC) and immunofluorescence (IF), for visualizing protein expression and localization. These antibody-based approaches are combined with transcriptomics data, derived from high-throughput mRNA sequencing (RNA-seq), to provide a comprehensive overview of gene and protein expression profiles.
Impact on Biomedical Research and Health
The Human Protein Atlas significantly impacts biomedical research and human health. This data resource serves as a valuable tool for scientists globally, enabling them to explore questions about human biology. Its open-access nature ensures information is readily available to researchers and clinicians, supporting discoveries.
Disease Understanding
The atlas aids understanding of molecular disease mechanisms, including cancer, neurological disorders, and infectious diseases. By providing information on protein expression and localization, it helps researchers identify abnormal or misplaced proteins contributing to disease development. For instance, the Pathology Atlas identifies proteins up- or down-regulated in specific cancer types, linking them to patient outcomes. This resource enables exploration of cell type-specific expression patterns and differences in expression between organs, revealing insights into disease progression.
Drug Discovery and Development
The HPA is a valuable resource for identifying new drug targets and biomarkers for diagnosis and prognosis. Nearly all approved drugs target proteins, making the atlas’s mapping of protein locations and functions relevant for pharmaceutical development. By revealing where specific proteins are expressed, the atlas guides the development of targeted therapies and helps predict drug side effects. It also assists in discovering biomarkers, useful for early disease detection and monitoring treatment effectiveness.
Personalized Medicine
Insights from protein expression patterns contribute to personalized medicine and tailored treatments. The HPA’s data helps develop approaches where medical interventions are customized to an individual’s protein profile. Understanding variations in protein expression among individuals and in different disease states can lead to more effective therapies with fewer adverse reactions. Ongoing HPA efforts, such as the new Disease Blood Atlas, aim to profile blood samples from patients with various diseases for early detection and patient stratification.
The Human Protein Atlas continues to evolve, regularly incorporating new datasets and functionalities. This expansion ensures it remains a current and robust resource for the scientific community. The project’s commitment to open access and its integration of diverse “omics” technologies underscore its role in advancing our understanding of the human proteome and its implications for health and disease.