Journal Article

Z-GENIE: a user-friendly R/Shiny resource for predicting Z-DNA forming regions in DNA

Garza Reyna, Angel, Pisetsky, David S., Fuentes, Melany

2025

Overview

Background Z-DNA is a left-handed DNA conformation with a zigzag backbone whose formation depends on base composition, modifications, and environmental factors. Although energetically unfavorable, Z-DNA has been implicated in both normal physiology and disease. The Z-Hunt algorithm predicts Z-DNA potential from thermodynamic principles, but its command-line interface and plain-text outputs limit adoption by users without coding expertise. Results We introduce Z-GENIE, an R/Shiny GUI that automates Z-Hunt execution, parses its output, and presents interactive visualizations. Z-GENIE accepts FASTA files, NCBI accession IDs, or manual sequences and produces CSV and BED summaries compatible with genomic browsers. In benchmarks on small to medium genomes (< 20 Mb), Z-Hunt completes in minutes and the full Z-GENIE pipeline (data retrieval, parsing, visualization) finishes in under five minutes. For large genomes (> 50 Mb), Z-Hunt may require up to two hours, whereas Z-GENIE’s parsing and BED-file export take < 2 min. In a human ADAM12 case study, Z-GENIE reproduced a published Z-score (3.0 × 10^7) and uncovered orientation-dependent Z-DNA clusters. Another case study compared predictions for Z-DNA in the rice genome ( Oryza sativa ) with experimental ZIP-Seq and CUT&Tag data; this study highlights the complementarity between in silico and in vivo approaches. Conclusions By encapsulating Z-Hunt within an intuitive GUI and offering flexible inputs and downstream-ready outputs, Z-GENIE democratizes genome-wide Z-DNA analysis. Its rapid performance and advanced visualization features should broaden exploration of Z-DNA’s roles in health and disease.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Algorithms / Analysis / Animal Genetics and Genomics / Applications software / Base composition / Benchmarks / Biomedical and Life Sciences / Case studies / Complementarity / Computational Biology - methods / Conformation / Data retrieval / Deoxyribonucleic acid / DNA / DNA structure / DNA, Z-Form - chemistry / DNA, Z-Form - genetics / Environmental factors / Genetic research / Genomes / Genomic analysis / Genomics / Genomics - methods / GUI / Handedness / Humans / Immune response / In vivo methods and tests / Life Sciences / Line interfaces / Linux / Microarrays / Microbial Genetics and Genomics / Nucleic Acid Conformation / Oryza - genetics / Physiological aspects / Plant Genetics and Genomics / Proteins / Proteomics / Sequence motifs / Shiny application / Software / Standard scores / Structure / User interface / User-Computer Interface / Visualization / Visualization (Computers) / Web browsers / Z-DNA genomic data visualization / Z-form / Z-GENIE / Z-Hunt