paRDal: bioinformatics framework for a parallel RNA and DNA NGS analysis in hereditary cancer diagnostics
- 1Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague , ,
- 2Department of Clinical Neurosciences, Faculty of Medicine, University of PJ Safarik in Kosice , ,
- 3Department of Medical Genetics, Oslo University Hospital , ,
Abstract
Germline next-generation sequencing (NGS) is the gold standard for hereditary cancer diagnostics. However, clinical utility is limited by variants of uncertain significance (VUS), which may disrupt mRNA processing; consequences invisible to DNA NGS alone but identifiable by parallel RNA NGS. Here, we present paRDal (parallel RNA/DNA analytical workflow), a containerized, modular framework that integrates matched germline DNA and RNA NGS data into a single diagnostic pipeline. paRDal implements allele-aware two-pass alignment, automated splicing and expression outlier detection, allele-specific expression analysis, and comprehensive variant annotation. A bidirectionally reactive filtering engine enables both DNA-centric (variant-to-function) and RNA-centric (function-to-variant) workflows. An R/Shiny application consolidates multilayered evidence per patient and across cohorts, linking in silico predictions with observed transcriptomic consequences without requiring specialized bioinformatic expertise. As demonstrated in 204 individuals undergoing hereditary cancer genetic testing, paRDal facilitates the standardized application of RNA-based ACMG/AMP criteria [PVS1(RNA), PS3, PP3, BP7(RNA)] supporting VUS resolution.
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BibTeX
@article{matejkova2026pardal,
title = {{paRDal: bioinformatics framework for a parallel RNA and DNA NGS analysis in hereditary cancer diagnostics}},
author = {Katerina Matejkova and Petr Nehasil and Petra Kleiblova and Tatana Ptackova and Marta Cerna and Pavel Just and Ondrej Vit and Petra Zemankova and Mária Giertlova and Marketa Janatova and Jana Soukupova and Ina Skaara Brorson and Zdenek Kleibl},
journal = {Frontiers in bioinformatics},
year = {2026},
month = oct,
doi = {10.3389/fbinf.2026.1944540},
url = {https://europepmc.org/article/PMC/PMC13728347},
note = {CC BY},
}
RIS
TY - JOUR
TI - paRDal: bioinformatics framework for a parallel RNA and DNA NGS analysis in hereditary cancer diagnostics
AU - Katerina Matejkova
AU - Petr Nehasil
AU - Petra Kleiblova
AU - Tatana Ptackova
AU - Marta Cerna
AU - Pavel Just
AU - Ondrej Vit
AU - Petra Zemankova
AU - Mária Giertlova
AU - Marketa Janatova
AU - Jana Soukupova
AU - Ina Skaara Brorson
AU - Zdenek Kleibl
PY - 2026
DA - 2026/10/20
JO - Frontiers in bioinformatics
DO - 10.3389/fbinf.2026.1944540
UR - https://europepmc.org/article/PMC/PMC13728347
AB - Germline next-generation sequencing (NGS) is the gold standard for hereditary cancer diagnostics. However, clinical utility is limited by variants of uncertain significance (VUS), which may disrupt mRNA processing; consequences invisible to DNA NGS alone but identifiable by parallel RNA NGS. Here, we present paRDal (parallel RNA/DNA analytical workflow), a containerized, modular framework that integrates matched germline DNA and RNA NGS data into a single diagnostic pipeline. paRDal implements allele-aware two-pass alignment, automated splicing and expression outlier detection, allele-specific expression analysis, and comprehensive variant annotation. A bidirectionally reactive filtering engine enables both DNA-centric (variant-to-function) and RNA-centric (function-to-variant) workflows. An R/Shiny application consolidates multilayered evidence per patient and across cohorts, linking in silico predictions with observed transcriptomic consequences without requiring specialized bioinformatic expertise. As demonstrated in 204 individuals undergoing hereditary cancer genetic testing, paRDal facilitates the standardized application of RNA-based ACMG/AMP criteria [PVS1(RNA), PS3, PP3, BP7(RNA)] supporting VUS resolution.
SN - 2673-7647
ER -