Quantitative Methods

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Showing new listings for Monday, 19 October 2026

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Cross submissions (showing 1 of 1 entries)

[1] CCCURJ:2610.00014 (cross-list from q-bio.GN) [pdf]

Research in progress Guide reselection expands canonical PAM candidates in an HGD editing resource for alkaptonuria

William Zane Duncan, Annie de Paula Bento, Laura Nadia Cabrera, Quoc Huy Hoang, Maddison Lila Kahn, Zhuolang Li, Raj Mathur, Malaika Theresa Mekkattuparamban, Cristian Emanuel Vasquez, Yuritzia Alexandra Zaragoza, Giorgio Lagna

Comments: 20 pages. Republished from a Research Square preprint (posted September 22, 2026) under CC BY 4.0; not submitted to CCCURJ

Subjects: Genomics (q-bio.GN); Quantitative Methods (q-bio.QM)

Rare monogenic diseases offer defined molecular targets, but sequence-level editing options require explicit selection and verification. Using artificial intelligence assisted analysis and public tools within a community-college research cohort, we assembled an editing resource for the homogentisate 1,2-dioxygenase gene (HGD) in alkaptonuria. The inventory contained 278 variants and represented 268 of 271 eligible records in a defined ClinVar census. We compared filtering fixed prime-editing designs with re-selection requiring canonical NGG protospacer-adjacent motifs at both guide targets. Re-selection preserved 93 compatible configurations and added 140, all using a second nick without predicted edited-allele discrimination (PE3), while retaining 92 predicted allele-discriminating configurations (PE3b). Under a shared genomic count screen including NGG, NAG and NGA sites, 70 preserved and 79 added configurations remained. With an unchanged base-editing arm, combined representation increased from 110 to 188 variants, or 106 to 180 of 271 eligible ClinVar records. Preserving fixed configurations makes nonnegative gain structural; a 33-setting threshold grid quantified additional representation, with gains of 2–121. Conservative base-window exclusions and a prime-only control retained the increase. Sequence reconstruction and independent PrimeDesign comparisons checked component conventions. The result identifies nicking-guide selection as a source of additional canonical candidates and motivates planned tests of editing activity, product purity and restoration of HGD function.