The human cardiac translatome

The human cardiac translatome app was developed by the Hubner lab at the Max Delbrück Center in Berlin.

Gene expression in human tissue has primarily been studied on the transcriptional level, largely neglecting translational regulation. Here, we analyze the translatomes of 80 human hearts to identify new translation events and quantify the effect of translational regulation. We show extensive translational control of cardiac gene expression, which is orchestrated in a process-specific manner. Translation downstream of predicted disease-causing protein-truncating variants appears to be frequent, suggesting inefficient translation termination. We identify hundreds of previously undetected microproteins, expressed from lncRNAs and circRNAs, for which we validate the protein products in vivo . The translation of microproteins is not restricted to the heart and prominent in the translatomes of human kidney and liver. We associate these microproteins with diverse cellular processes and compartments and find that many locate to the mitochondria. Importantly, dozens of microproteins are translated from lncRNAs with well-characterized noncoding functions, indicating previously unrecognized biology.

This online tool offers an easy way to expore the human cardiac translatome data published in the accompanying paper:

van Heesch S., Witte F., Schneider-Lunitz V., Schultz J.F., Adami E., et al. (2019) The Translational Landscape of the Human Heart. Cell In Press .

version: 1.1 (last updated: 2019-06-11)

Inspect your translated genes and ORFs of interest using the Integrative Genomics Viewer (IGV)

The datasets generated in our study, The translational landscape of the human heart (van Heesch et al., 2019) can be downloaded and explored using the Integrative Genomics Viewer (IGV) (Robinson et al. 2011) .

Here you can download a fasta file containing all ORFs that were detected in this study (this can be used as a proteomics search database): hs_cardiacTranslatome.fasta

To view the data in IGV, please perform the following steps:

  1. If IGV is not installed locally, download and install it:

  2. Acquire IGV

  3. Download an IGV session file.

  4. Human left ventricle [hg38]:

    Rat left ventricle [rn6.0]:

    Mouse left ventricle [mm38]:

  5. Extract zip file.

  6. Open IGV session file (XML format) in a text editor.

  7. Within the XML file, change the value of "/path/to/IGV/folder/" to the path where the folder is located and the XML file is saved.

  8. Save the XML file.

  9. Open IGV, click on: File —> Open Session… —> Select adjusted XML file.

This is what a typical IGV session looks like for human left ventricle:

Transcriptional and translational regulation in cardiac health and disease

Here you can download an excel file containing the raw and DESeq normalized Ribo-seq and mRNA-seq counts: cardiacTranslatome_counts.xlsx

Or upload a file containing gene symbols or gene IDs and select the parameters accordingly:

Download example files:

DCM associated genes [line break separated Gene IDs]: DCM associated Gene IDs

Oxphos genes [comma-separated Gene Symbols]: OXPHOS Gene Symbols

Differential expression results

This table lists the differential expression results of all selected genes.

Fold change (FC) plots of selected genes

This plot shows all selected genes sorted from left to right based on the delta FC (DCM vs. control) of translation (Ribo-seq) over mRNA expression levels (mRNA-seq). For each gene, corresponding fold changes are depicted below the delta FC plot with color coding reflecting the intensity of the expression change, with genes upregulated in DCM in red and genes downregulated in blue.

Download Files

Download the text file of the differential expression table

Download the PDF with a box plot for each selected gene to visualize the mRNA-seq and Ribo-seq data individually.

Download the PDF with the fold change plot.

Information on translated lncRNAs (microproteins)

sORF information

This table contains ORF specific information that was derived using RiboTaper (Calviello et al. 2016) .

LncRNA expression and translation in the heart and other tissues or cell types

This plot shows gene-based expression levels of the selected translated lncRNA across different datasets.

LncRNA and sORF conservation to other species

This table summarizes the conservation of the translated lncRNA gene (positional conservation) and sORF (PhyloCSF and translation initiation site (TIS) conservation) in comparison to other vertebrates (PhyloCSF) and to the translatomes of mouse and rat left ventricles.

Summary of predicted peptide characteristics

This table lists predicted peptide characteristics including signal cleavage site (SignalP), localization (TargetP and DeepLoc) and transmembrane domain prediction (TMHMM).

In vitro and in vivo evidence for microproteins

This table summarizes the evidence for microprotein production obtained with in vitro translation assays and in vivo public mass spectrometry searches (Doll et al. 2017) or targeted selected reaction monitoring (SRM).

I-TASSER protein structure prediction results

Genetic Associations

We performed genetic association testing of all translated genes in our dataset. Genetic variants with at least 5 samples showing the reference allele and 5 samples showing the alternative allele have been considered. Association testing was performed using MatrixEQTL (Shabalin et al. 2012) on transcription, translation and translation efficiency. More detailed information can be found in the methods section of The translational landscape of the human heart (van Heesch et al., 2019).

List of all genetic associations for selected gene

All significant associations (FDR ≤ 0.05) for the selected gene are listed here.

Gene expression of the most significant association separated by genotype