Journal Article

A deep proteome and transcriptome abundance atlas of 29 healthy human tissues

Meng, Chen, Hahne, Hannes, Eraslan, Basak, Zecha, Jana, Uhlen, Mathias, Schnatbaum, Karsten, Wieland, Thomas, Wang, Dongxue, Frejno, Martin, Hallström, Björn, Schmidt, Tobias, Hopf, Thomas, Wilhelm, Mathias, Ponten, Frederik, Li, Li‐hua, Zolg, Daniel Paul, Asplund, Anna, Gagneur, Julien, Kuster, Bernhard

2019

Overview

Genome‐, transcriptome‐ and proteome‐wide measurements provide insights into how biological systems are regulated. However, fundamental aspects relating to which human proteins exist, where they are expressed and in which quantities are not fully understood. Therefore, we generated a quantitative proteome and transcriptome abundance atlas of 29 paired healthy human tissues from the Human Protein Atlas project representing human genes by 18,072 transcripts and 13,640 proteins including 37 without prior protein‐level evidence. The analysis revealed that hundreds of proteins, particularly in testis, could not be detected even for highly expressed mRNAs, that few proteins show tissue‐specific expression, that strong differences between mRNA and protein quantities within and across tissues exist and that protein expression is often more stable across tissues than that of transcripts. Only 238 of 9,848 amino acid variants found by exome sequencing could be confidently detected at the protein level showing that proteogenomics remains challenging, needs better computational methods and requires rigorous validation. Many uses of this resource can be envisaged including the study of gene/protein expression regulation and biomarker specificity evaluation. Synopsis Proteome and transcriptome quantification across tissues reveals which human genes exist as transcripts and proteins, where they are expressed and in which approximate quantities. Tissue‐specific protein expression is found to be a rare and quantitative rather than qualitative characteristic. The study presents the most comprehensive atlas of protein expression to date, across 29 healthy human tissues. Protein level evidence is provided for 13,640 genes and 15,257 isoforms, including 37 missing proteins. Tissue‐specific protein expression is rare and quantitative rather than qualitative characteristic. Proteogenomics is still challenging and needs rigorous validation by synthetic peptides. Graphical Abstract Proteome and transcriptome quantification across tissues reveals which human genes exist as transcripts and proteins, where they are expressed and in which approximate quantities. Tissue‐specific protein expression is found to be a rare and quantitative rather than qualitative characteristic.

• Publisher: Nature Publishing Group UK,EMBO Press,John Wiley and Sons Inc,Springer Nature
• Subject: Amino acids / Biomarkers / Brain research / Computer applications / EMBO17 / EMBO22 / Gene expression / Gene Expression Regulation - genetics / Genes / Genome, Human - genetics / Genomes / human proteome / Human tissues / human transcriptome / Humans / Isoforms / Mass spectrometry / Mass Spectrometry - methods / Ontology / Peptides / Protein expression / Proteins / proteogenomics / Proteome - genetics / Proteomes / Proteomics / Proteomics - methods / Qualitative analysis / quantitative mass spectrometry / RNA, Messenger - genetics / RNA-Seq / Scientific imaging / Sequence Analysis, RNA - methods / Synthetic peptides / Tissue Distribution - genetics / Tissues / Transcriptome - genetics / Transcriptomes