Biology subjects

Boone, J.

Publications and source records attributed to Boone, J..

3 recordsLinked to original sources

bioRxiv2025

Task-Geometry Alignment: a design principle forparameter-free, accurate genomic search

Standard alignment-based DNA barcoding falters because rigid geometric assumptions clash with biological realities, particularly insertions/deletions (indels) and fragment-to-reference asymmetry. To address this, we propose Task-Geometry Alignment (TGA), a design principle that structurally aligns the algorithm with the intrinsic geometry of the biological task. We implement TGA in TGAO_SCPLOWLIGNC_SCPLOW, a parameter-free tool that tiles reference databases into windows, applies gap-robust syncmer sketching, and indexes them for approximate nearest neighbor search. Across five benchmarks encompassing COI, 16S, and ITS markers, TGAO_SCPLOWLIGNC_SCPLOW achieves 9% higher accuracy and up to 10x faster query speeds than the leading aligner. Crucially, ablation studies confirm this architectural tiling is the causal driver of performance, allowing the tool to automatically match expert-parameterized configurations on fragment identification tasks. AvailabilitySource code and data are available at https://github.com/JustinBooneLab/TGAlign

molecular biology↗

bioRxiv2025

High-Accuracy, Ultrafast DNA Barcode Identification via Statistical Sketching and Approximate Nearest Neighbor Search

High-throughput DNA barcoding, a cornerstone of modern biodiversity and environmental genomics, is critically limited by the computational cost of traditional, alignment-based identification methods. While faster alignment-free approaches have been proposed, first-generation techniques based on k-mer hashing are fundamentally unreliable due to their inherent sensitivity to insertions and deletions (indels), a common form of sequence variation. Here, we introduce DNA-Sketch, a novel alignment-free framework that overcomes this limitation. DNA-Sketch transforms a DNA sequence into a robust statistical fingerprint by vectorizing its binned dinucleotide frequencies. These high-dimensional "sketches" are then indexed for ultrafast similarity search using an Approximate Nearest Neighbor (ANN) library. We benchmarked a single-pass sketch and a "Multi-Sketch Ensemble" against the state-of-the-art aligner VSEARCH on a large, challenging benchmark simulating real-world noise and intra-species variation. The Multi-Sketch Ensemble achieved 100% accuracy, perfectly matching VSEARCH, while delivering a 31-fold speed improvement. The single-pass sketch achieved 99.98% accuracy with a 95-fold speedup. DNA-Sketch resolves the classic speed-versus-accuracy trade-off, demonstrating that by pairing robust feature extraction with high-performance ANN indexing, it is possible to achieve the accuracy of gold-standard alignment at a fraction of the computational cost, providing a powerful and highly scalable solution for modern bioinformatics.

bioinformatics↗

bioRxiv2021

Development of a novel, pan-variant aerosol intervention for COVID-19

To develop a universal strategy to block SARS-CoV-2 cellular entry and infection represents a central aim for effective COVID-19 therapy. The growing impact of emerging variants of concern increases the urgency for development of effective interventions. Since ACE2 is the critical SARS-CoV-2 receptor and all tested variants bind to ACE2, some even at much increased affinity (see accompanying paper), we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here we show that intranasal administration of APN01 in a mouse model of SARS-CoV-2 infection dramatically reduced weight loss and prevented animal death. As a prerequisite to a clinical trial, we evaluated both virus binding activity and enzymatic activity for cleavage of Ang II following aerosolization. We report successful aerosolization for APN01, retaining viral binding as well as catalytic RAS activity. Dose range-finding and IND-enabling repeat-dose aerosol toxicology testing were conducted in dogs. Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers can now be initiated, with subsequent Phase II testing in individuals with SARS-CoV-2 infection. This strategy could be used to develop a viable and rapidly actionable therapy to prevent and treat COVID-19, against all current and future SARS-CoV-2 variants. One Sentence SummaryPreclinical development and evaluation of aerosolized soluble recombinant human ACE2 (APN01) administered as a COVID-19 intervention is reported.

pharmacology and toxicology↗