# A transcriptomic and proteomic map of primary human cell types

## TL;DR

This study maps the transcriptome and proteome of 28 primary human cell types, revealing molecular patterns and novel post-translational modifications.

## Contribution

The study introduces a comprehensive proteomic and transcriptomic map with novel insights into PTMs and genome annotation refinement.

## Key findings

- Three major cell clusters (epithelial, endothelial, mesenchymal) were identified at both transcriptomic and proteomic levels.
- Novel PTMs like serine O-acetylation and histidine methylation were identified, along with oxidative mitochondria subunits.
- Translational readthrough isoforms of LDHB and MDH1 were detected for the first time at the peptide level.

## Abstract

Molecular profiling of human primary cell types is essential for understanding human biology. We present a transcriptome and proteome map of 28 primary human cell types. Three major clusters of epithelial, endothelial, and mesenchymal cell types were observed in both the transcriptome and proteome levels along with the discovery of cell type enriched molecules including GRAP and C1orf116. The epithelial cell specific protein C1orf116 was further validated using immunohistochemistry across various human tissues. An exhaustive protein database search considering 39 post-translational modifications (PTMs) revealed novel insights into the PTM landscape including identification of understudied PTMs such as serine O-acetylation and histidine methylation. This also enabled comprehensive characterization of proteins with diverse PTMs. Interestingly, an unexpectedly higher frequency of dioxidation on tryptophan compared to methionine led to the identification of oxidative mitochondria complex subunit proteins. Further, a search strategy accounting for alternative translational start sites, splice junctions and translational readthrough refined genome annotation using proteomic evidence. For example, peptides from translational readthrough including extended sequence of LDHB and MDH1 were detected representing the first peptide-level evidence of these protein readthrough isoforms. Our comprehensive transcriptome and proteome data revealed cell type-specific molecular cues and heterogeneity, offering new insights into disease mechanisms often overlooked by tissue proteomics.

Graphical Abstract