Phenotype-tissue expression and exploration (PTEE) resource facilitates the choice of tissue for RNA-seq-based clinical genetics studies
Akhil Velluva,
Maximillian Radtke,
Susanne Horn,
Bernt Popp,
Konrad Platzer,
Erind Gjermeni,
Chen-Ching Lin,
Johannes R. Lemke,
Antje Garten,
Torsten Schöneberg,
Matthias Blüher,
Rami Abou Jamra,
Diana Le Duc
Affiliations
Akhil Velluva
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology
Maximillian Radtke
Institute of Human Genetics, University Medical Center Leipzig
Susanne Horn
Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, University of Leipzig
Bernt Popp
Institute of Human Genetics, University Medical Center Leipzig
Konrad Platzer
Institute of Human Genetics, University Medical Center Leipzig
Erind Gjermeni
Department of Electrophysiology, Heart Center Leipzig at University of Leipzig
Chen-Ching Lin
Institute of Biomedical Informatics, National Yang Ming Chiao Tung University
Johannes R. Lemke
Institute of Human Genetics, University Medical Center Leipzig
Antje Garten
Pediatric Research Center, University Hospital for Children and Adolescents, Leipzig University
Torsten Schöneberg
Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, University of Leipzig
Matthias Blüher
Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig
Rami Abou Jamra
Institute of Human Genetics, University Medical Center Leipzig
Diana Le Duc
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology
Abstract Background RNA-seq emerges as a valuable method for clinical genetics. The transcriptome is “dynamic” and tissue-specific, but typically the probed tissues to analyze (TA) are different from the tissue of interest (TI) based on pathophysiology. Results We developed Phenotype-Tissue Expression and Exploration (PTEE), a tool to facilitate the decision about the most suitable TA for RNA-seq. We integrated phenotype-annotated genes, used 54 tissues from GTEx to perform correlation analyses and identify expressed genes and transcripts between TAs and TIs. We identified skeletal muscle as the most appropriate TA to inquire for cardiac arrhythmia genes and skin as a good proxy to study neurodevelopmental disorders. We also explored RNA-seq limitations and show that on-off switching of gene expression during ontogenesis or circadian rhythm can cause blind spots for RNA-seq-based analyses. Conclusions PTEE aids the identification of tissues suitable for RNA-seq for a given pathology to increase the success rate of diagnosis and gene discovery. PTEE is freely available at https://bioinf.eva.mpg.de/PTEE/
