Tissue-based map of the human proteome¶
Why this mattered¶
This paper mattered because it shifted human proteomics from gene-by-gene or tissue-limited measurement toward a systematically navigable, body-wide atlas. By integrating RNA-seq across tissues with antibody-based immunohistochemistry, Uhlén and colleagues made it possible to ask not only whether a protein-coding gene was expressed, but where its product localized in human tissues and, often, in which cell types. The scale was the central change: detecting expression evidence for more than 90% of putative protein-coding genes across 32 tissues and organs turned the human proteome into a reference map rather than a collection of isolated observations.
The work also made tissue specificity operational for biomedical discovery. Researchers could identify proteins enriched in particular organs, survey the secretome and membrane proteome for biomarkers or therapeutic targets, and relate metabolic, cancer-associated, or druggable proteins to their normal tissue context. That context was crucial: a proposed disease marker or drug target could now be evaluated against a broad baseline of healthy human expression, helping distinguish tissue-restricted biology from broadly expressed housekeeping function and exposing likely sites of on-target toxicity.
Its influence is visible in later atlas-scale biology. The Human Protein Atlas became a widely used infrastructure for interpreting genomics, cancer biology, pathology, drug discovery, and single-cell datasets. Subsequent breakthroughs in single-cell transcriptomics, spatial biology, and proteogenomics did not replace the 2015 map so much as build on its premise: that human biology is best understood through integrated, spatially resolved reference atlases connecting genes, proteins, tissues, and disease states.
Abstract¶
Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.
Related¶
- cite → Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation — The human proteome map uses RNA-seq transcript quantification methods such as Cufflinks-style assembly to compare protein expression with transcript abundance.
- cite → An integrated encyclopedia of DNA elements in the human genome — The tissue-based proteome map complements ENCODE by adding protein-level tissue expression evidence to genome-wide functional annotation.
- cite → Comprehensive molecular characterization of human colon and rectal cancer — The proteome map uses cancer genomics resources such as TCGA colorectal cancer profiles to contextualize tissue proteins in disease biology.
- enables ← Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation — RNA-Seq transcript quantification and isoform discovery provided tissue expression evidence that the Human Proteome Map used to connect proteins to transcripts.