论文题目： Tissue-based map of the human proteome
scholar 引用：1510
页数：11
发表时间：23 Jan 2015
发表刊物：Science
作者：Mathias Uhlén,etc.
摘要：
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.
结论：
- we present a tissue-based map of the hu- man proteome from analyses of 32 tissues and 47 cell lines, with gene expression data on both the RNA and protein level and with supplementary analyses on the protein level for an additional 12 tissues.
- 做了一个交互式的网站
- 意义重大
Introduction：
- aimed to integrate results from many research groups and technical platforms to reach a detailed understanding of each of the ~20,000 human protein-coding genes predicted from the human genome and their corresponding protein isoforms.
正文组织架构：
1. Introduction
2. Results
2.1 Classification of all human protein-coding genes
2.2 Evidence for the human protein-coding genes
2.3 The tissue-elevated proteome
2.4 The human secretome and membrane proteome
2.5 The housekeeping proteome
2.6 The regulatory proteome
2.7 The druggable proteome
2.8 The cancer proteome
2.9 Tissue versus cell lines
2.10 The isoform proteome
2.11 Tissue-based map of human metabolism
3. Discussion
正文部分内容摘录：
a. What type of experiment is it/ What is the study design?
- quantitative transcriptomics on a tissue and organ level combined with protein profiling using microarray-based immunohistochemistry to achieve spatial localization of proteins down to the single-cell level
b. What research problem has been defined/is being investigated?
- Resolving the molecular details of proteome variation in the different tissues and organs of the human body
c. What is the aim/objective of the study?
- a map of the human tissue proteome
d. Do the researcher(s') qualifications/position indicate a degree of knowledge in this particular field? Did the authors explicitly propose a hypothesis – research hypothesis vs. the null hypothesis?
- no
e. Who are the subjects? And how have they been grouped (i.e., randomized into control and treatment, etc.)?
- Samples representing all major tissues and organs (n = 44) in the human body have been analyzed based on 24,028 antibodies corresponding to 16,975 protein-encoding genes, complemented with RNA-sequencing data for 32 of the tissues.
f. What are the dependent and independent variables? Are there any confounding variables?
- no variables concept in this study.
g. How has the research problem been operationalized?
- We report a genome-wide analysis of the tissue specificity of RNA and protein expression covering more than 90% of the putative protein-metabolic enzymes are expressed in all analyzed tissues. The largest number of tissue- enriched genes is found in the testis, followed by the brain and the liver. Analysis of the 618 proteins targeted by clinically approved drugs unexpectedly showed that 30% are expressed in all analyzed tissues. An analysis of metabolic activity based on genome-scale metabolic models (GEMS) revealed liver as the most metabolically active tissue, followed by adipose tissue and skeletal muscle.
h. What is being used to measure the variables/study aim?
- The antibodies have been used to produce more than 13 million tissue-based immunohistochemistry images, each annotated by pathologists for all sampled tissues. To facilitate integration with other biological resources, all data are available for download and cross-referencing.
i. Do the methods of measurement ensure the studies reliability? And does the research reflect the problem being investigated to help ensure the studies validity?
- A freely available interactive resource is presented as part of the Human Protein Atlas portal (www.proteinatlas.org), of- fering the possibility to explore the tissue- elevated proteomes in tissues and organs and to analyze tissue profiles for specific protein classes.
- Comprehensive lists of proteins ex- pressed at elevated levels in the different tis- sues have been compiled to provide a spatial context with localization of the proteins in the subcompartments of each tissue and organ down to the single-cell level
