Have you ever been lost? When you travel to a place that’s unknown to you, getting lost is easy, frustrating and discouraging – even frightening. And it’s always a waste of time. What you need is a map. A map shows detailed information about the landscape, roads, points of interest and distances. But just looking at the map it is not enough. First of all, you need to choose the correct type of map, be able to understand its features to be able to read it, and most importantly you need to find your location on the map! What if I tell you that there is a map of all the proteins in the human body? Would you be able to read it? This article is here to help you on your way to discovering the potential of this great tool.
A fundamental part of studying and understanding human biology is the study of tissue-specific gene expression and protein levels. Tissue-specific gene expression can result in the presence or absence of a certain protein, leading to the profound functional variation of biological processes among tissues. Thus, the knowledge of protein profiles in a given tissue is critical to understanding the unique characteristics of the various cell types and their functions in the human body.
The expression of all protein-coding genes in all major tissues and organs in the human body can be explored in an interactive database, which includes a catalog of proteins expressed in a tissue-oriented manner. It is the Tissue Atlas. 1
Search, Explore, Learn, Repeat
The Tissue Atlas is part of the Human Protein Atlas database, created by a Swedish-based program initiated in 2003 with the aim to map all the human proteins in cells, tissues and organs using integration of various -omics technologies, including antibody-based imaging, mass spectrometry-based proteomics, transcriptomics and systems biology.
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 tissues and 20 cancer tissues, have been analyzed and the data is presented as knowledge-based annotation of protein expression levels. All images of immunohistochemically stained tissues are available in high resolution, free of charge.
The protein data covers 15,317 genes (78% of all human protein-coding genes). For each gene, there is at least one available antibody that targets a protein expressed by the gene.
All the data in this valuable resource is open access to allow scientists both in academia and industry to freely access the data for exploration of the human proteome.
Figure.1 Schematic representation of the main information available in the Tissue Atlas under each tab.
Depending on where you stand, the view of the world around you can look very different. In fact, the same detail can have different meanings when seen from different perspectives. Another angle allows you to make connections you were previously blind to.
In the Tissue Atlas, there are multiple search tabs and many ways to get information about a protein expression in a particular tissue. Which approach you choose to navigate the Tissue Atlas depends on what kind of information you are looking for and where you want to direct your search.
There are three major ways to look for information while navigating the Tissue Atlas: 1) from a gene/protein perspective; 2) from an organ/tissue perspective and 3) from the proteome perspective. Whatever angle you prefer to start your research with, you will become aware of just how much information, new insights and wisdom about your protein or gene of interest is available.
Let’s briefly take a look at the three different ways.
1. The Gene/Protein Perspective
If you want to read the story from the gene’s perspective, start here by typing the gene name. The search result lists all the genes found by the search function.
Figure.2 An example of list of genes found by the search function for the RNA binding motif protein 3.
The show/hide column function, on the top left, is useful to add columns to the search result list, if you need information such as:
- Gene synonyms, Ensembl Gene Identifier, gene description, chromosomal location and protein class.
- Reliability of the annotated protein expression using IHC-IF staining on human tissues and cell lines.
- Tissue specificity (the distribution of antibody staining or protein expression in human cell types)
- Cell line specificity (the distribution of RNA abundance in cell lines)
- Subcellular location of the protein based on immunofluorescent staining of cell lines.
From the list choose the gene you are interested in: an interactive overview of RNA and protein expression data will appear (Figure.3).
Figure.3 An interactive overview of RNA and protein expression summarizing the data generated in the Human Protein Atlas project is available for each protein. The example image shows RNA and protein expression for the RNA binding motif protein 3.
The analyzed tissues are divided into color-coded groups according to which functional features they have in common. For each group, you can navigate a list of the respective tissues by clicking on group name, group symbol, RNA bar, or protein bar. Each colored bar represents the highest expression score found in a particular group of tissues for both RNA-seq results and protein expression. Subsequent selection of a particular tissue in this list links to the image data page.
On the right-hand side of the page, immunohistochemistry images of selected tissues give a visual summary of the protein expression profile. The gray-colored human body graphic provides links to a histology dictionary when clicking on any part of the graphic. As an example, click here.
2. The Organ/Tissue Proteome Perspective
To direct the Tissue Atlas, say, to a particular tissue, use the organ/tissue proteome perspective to separate the information based on common features, or based on the fraction of elevated transcripts in different tissues and organs. All human genes (approximately 20,000) are classified according to their expression across a large number of tissues representing all major organs and tissue types in the human body. The amount of tissue elevated genes (i.e. genes expressed at elevated levels in certain tissues) is highly variable among the analyzed tissue types.
To explore the proteomes of specific tissues and organs, start here.
Each tissue tab links to a comprehensive list of genes expressed at elevated levels. The Tissue Atlas provides quantitative expression profiles, including deep-sequencing transcriptomics complemented with IHC images.
Each chapter also includes a basic description of a defined proteome with analyses of expression patterns, gene lists, and examples of protein expression on a cellular level.
Figure 4 The expression for all protein-coding genes in all major tissues and organs in the human body can be explored in the interactive Tissue Atlas database, including numerous catalogs of proteins expressed in a tissue-restricted manner.
Through this perspective, you will learn that almost half of the genes appear as housekeeping genes with detectable levels of transcripts in all analyzed tissues, while approximately 40% (n=7,904) show some level of elevated expression in one of the analyzed tissues. The genes with an elevated expression in a particular tissue are interesting as a starting point to understand the biology and function of this part of the human body, although only a few of these genes show a strict expression in a single tissue or organ.
Figure.5 Distribution of genes in the different RNA-based categories of gene expression. A total of 7,904 genes (tissue enriched + group enriched + tissue enhanced) are elevated in at least one of the analyzed tissues.
3. The Sub-Proteome Perspective
To tell the story from another perspective, use the sub-proteome approach. Seven separate chapters provide a knowledge-based analysis and entry into the Human Protein Atlas from different defined transections of the human tissue proteome: tissue-specific, housekeeping, regulatory, secretome, isoform, cancer and druggable proteomes.
Here you can find amazing content.
For example, do you want to know the cellular localization of all the 672 human protein targets for the food and drug administration (FDA) approved drugs? Explore the druggable proteome!
The regulatory proteome includes genes involved in the regulation of gene expression as well as different post-translational modifications that control activity, stability, localization or degradation of the protein. Transcription factors, differentially expressed in different parts of the human body, constitute an important class of regulatory proteins. Their main job is to determine when genes are switched on and off.
Figure 6 The various sub-proteomes can be explored in this interactive database including numerous catalogues of protein-coding genes with detailed information regarding expression and localization of the corresponding proteins.
Click here to find out more about the various sub-proteomes.
It Is Not About Which Protein You Have But How Much Of It You Have
Tissue specificity is achieved by precise regulation of protein levels in space and time, and different tissues in the body acquire their unique characteristics by controlling not which kind of proteins are expressed but how much of each protein is produced.
A high fraction of the human proteins is present in every single cell type in the human body and, surprisingly, only very few proteins are expressed in a single or a few types of cells. In other words, proteins expressed in a narrow, well-defined set of cell types are most likely important for the function of the given cells.
These findings suggest that the phenotype of a cell is determined by localization, modifications and fluctuations in concentrations of a large portion of the proteome, and not by a simple “ON/OFF” protein expression.
Explore The Proteome Like A Boss
Now that you know how to read the Tissue Atlas and you are aware what a great resource this protein map is, take your time to go deeper in your search but don’t stick with one perspective throughout. Explore all the ways offered to you. This makes it easier to find all the information you need. Always be sure to filter the data independently on the search input and to look at the images that support the data.
A step-by-step guide on how to navigate the Tissue Atlas is ready and waiting for you to download.
Understand how to find, evaluate, and use the resources in the Tissue Atlas to explore a topic in depth. Learn how to discover in which tissues the human proteins are expressed, and how to explore antibody staining in both normal and cancer tissues. All images in the guide are example images from the Human Protein Atlas portal.
So…enjoy the adventure that awaits you.
Download the guide and get exploring.
1 Uhlén M et al, 2015. Tissue-based map of the human proteome. Science Vol. 347, Issue 6220
2.Ponten et al., 2009, A global view of protein expression in human cells, tissues, and organs. Mol Syst Biol. 5: 337