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PreprintCC BYbioRxiv

Z-Hunt-DP: accelerating thermodynamic Z-DNA prediction with dynamic programming

  1. 1Brock University

Abstract

Z-DNA is a left-handed DNA conformation implicated in gene regulation and chromatin dynamics. Because it is usually less thermodynamically favorable than canonical B-DNA under physiological conditions, computational tools are needed to identify sequences likely to adopt the Z conformation. Legacy Z-Hunt uses a dinucleotide thermodynamic model, but searches every anti/syn assignment in a window, causing its conformation search to grow exponentially with window size. We present Z-Hunt-DP, an exact dynamic programming reformulation that preserves the original thermodynamic objective while reducing this search from O(2^d) to O(d) for a window of d dinucleotide positions. On benchmark windows, Z-Hunt-DP matched the brute-force minimum energy within numerical tolerance and achieved a 3.30x10^5 speedup at 20 dinucleotides. In an interval-localization benchmark on public human loci with experimentally mapped Z-DNA, it recovered the clipped reference interval in all 24 cases and was the most stable localizer under midpoint-core and expanded-panel analyses. Since the comparison set mixes thermodynamic, heuristic, and learned models, these cross-tool results are interpreted as localization comparisons rather than direct thermodynamic score tests. The source code and benchmark materials are available at https://github.com/Aljumaily/Z-Hunt-DP.

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BibTeX
@misc{jumaily2026zhuntdp,
  title = {{Z-Hunt-DP: accelerating thermodynamic Z-DNA prediction with dynamic programming}},
  author = {M. Al Jumaily and H. Qureshi and H. Yan and Y. Li},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.14.751448},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751448v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Z-Hunt-DP: accelerating thermodynamic Z-DNA prediction with dynamic programming
AU  - M. Al Jumaily
AU  - H. Qureshi
AU  - H. Yan
AU  - Y. Li
PY  - 2026
DA  - 2026/09/14
PB  - bioRxiv
DO  - 10.64898/2026.09.14.751448
UR  - https://www.biorxiv.org/content/10.64898/2026.09.14.751448v1
AB  - Z-DNA is a left-handed DNA conformation implicated in gene regulation and chromatin dynamics. Because it is usually less thermodynamically favorable than canonical B-DNA under physiological conditions, computational tools are needed to identify sequences likely to adopt the Z conformation. Legacy Z-Hunt uses a dinucleotide thermodynamic model, but searches every anti/syn assignment in a window, causing its conformation search to grow exponentially with window size. We present Z-Hunt-DP, an exact dynamic programming reformulation that preserves the original thermodynamic objective while reducing this search from O(2^d) to O(d) for a window of d dinucleotide positions. On benchmark windows, Z-Hunt-DP matched the brute-force minimum energy within numerical tolerance and achieved a 3.30x10^5 speedup at 20 dinucleotides. In an interval-localization benchmark on public human loci with experimentally mapped Z-DNA, it recovered the clipped reference interval in all 24 cases and was the most stable localizer under midpoint-core and expanded-panel analyses. Since the comparison set mixes thermodynamic, heuristic, and learned models, these cross-tool results are interpreted as localization comparisons rather than direct thermodynamic score tests. The source code and benchmark materials are available at https://github.com/Aljumaily/Z-Hunt-DP.
ER  -