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Green, O.

Publications and source records attributed to Green, O..

4 recordsLinked to original sources

Rapid-PFP: Accelerating Prefix-Free Parsing with GPU Parallelism

Prefix-Free Parsing (PFP) is widely used in genomic data processing to construct compressed indexes on massive, highly repetitive datasets. However, existing CPU implementations are constrained by sequential bottlenecks, limiting their ability to scale to large-scale modern pangenomic collections. We introduce RAPID-PFP, a redesigned implementation of the PFP algorithm that takes advantage of the massive parallelism and high memory bandwidth of modern GPUs. RAPID-PFP parallelizes trigger-string detection, phrase parsing, dictionary construction, and parse generation through custom CUDA kernels and GPU-resident data structures built using cuDF, CuPy, and Numba-CUDA. The algorithm operates entirely within GPU memory, minimizes host interaction, and dynamically adapts to available VRAM, enabling efficient processing in a range of hardware configurations. Across E. coli and Human Pangenome (HPRC) datasets, RAPID-PFP produces identical output to established CPU pipelines while delivering an order-of-magnitude acceleration. On 3,682 E. coli assemblies, RAPID-PFP reduces runtime from 552 seconds to 17 seconds compared to PFP-FL (32.1 times) and from 1,078 seconds to 17 seconds compared to PFP-ITL (62.6 times). On the complete 46-sample HPRC dataset, RAPID-PFP achieves a 33.4 time speedup and successfully processes scales that PFP-ITL cannot handle. Performance improves with dataset size, reflecting that PFP maps naturally onto thousands of CUDA cores, yielding sublinear scaling relative to CPU implementations. RAPID-PFP demonstrates that foundational compressed-indexing algorithms can be re-engineered for accelerators, enabling scalable and practical preprocessing for large-scale genomic indexing workflows.

bioinformatics↗

Scalable machine learning improves resistance prediction and identifies novel determinants in Mycobacterium tuberculosis

Multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis (MTB) represents a growing global health crisis, characterized by limited treatment options and high mortality rates. Rapid and accurate prediction of resistance profiles is critical to guide effective therapy and curb transmission. Whole-genome sequencing (WGS) offers promise for individualized resistance profiling, yet existing computational tools remain constrained by predefined mutation catalogs and prohibitive resource requirements for large-scale analyses. Here, we present AURA, a GPU-accelerated, pangenome-scale machine learning framework for de novo resistance prediction. Trained on 12,185 globally diverse MTB isolates, AURA predicts resistance to 13 first-line, second-line, and repurposed antibiotics with high precision and identifies 59 novel resistance-associated loci, including variants in katG, pncA, rpoC, and members of the PE/PGRS gene family. By enabling model training on an unprecedented genomic scale, AURA provides new insights into the genetic architecture of resistance and establishes a scalable platform for precision-guided therapy and global surveillance of MTB.

bioinformatics↗

SAMHD1 controls nucleoside-based cancer therapeutics, deoxyguanosine toxicity, and inflammation

SAMHD1 is a key regulator of dNTP metabolism, being activated by dGTP and converting dNTPs into their respective nucleosides. As a result, it plays a significant role in several distinct diseases. Not only is SAMHD1 a restriction factor for HIV-1 replication, which requires dNTPs for replication, but it is also required for genome stability, is mutated in multiple cancers, and loss of function mutations cause Acardi-Goutieres Syndrome, an early-onset inherited encephalopathy. In this paper we knock out the SAMHD1 gene in pluripotent stem cells, and show that it also affects nucleoside analogue sensitivity of dividing cells and deoxyguanosine toxicity in a cell cycle-independent manner. Comparing wild type and gene-edited macrophages, we also show that deoxyguanosine toxicity is associated with pro-inflammatory cell death, modifications in uric acid production and the formation of monosodium urate crystals within the macrophages. These novel features of the SAMHD1-/- phenotype provide unique insights into the aetiology of Acardi-Goutieres Syndrome, and have implications for certain chemotherapeutic agents.

pharmacology and toxicology↗

A chemiluminescent protease probe for rapid, sensitive, and inexpensive detection of live Mycobacterium tuberculosis

Tuberculosis (TB) is a top-ten cause of death worldwide. Successful treatment is often limited by insufficient diagnostic capabilities, especially at the point of care in low-resource settings. The ideal diagnostic must be fast, cheap, and require minimal clinical resources while providing high sensitivity, selectivity, and the ability to differentiate live from dead bacteria. We describe here the development of a Fast, Luminescent, and Affordable Sensor of Hip1 (FLASH) for the diagnosis and monitoring of drug sensitivity of Mycobacterium tuberculosis (Mtb). FLASH is a selective chemiluminescent substrate for the Mtb protease Hip1 that when processed, produces visible light that can be measured with a high signal to noise ratio using inexpensive sensors. FLASH is sensitive to fmol of recombinant Hip1 enzyme in vitro and can detect as few as thousands of Mtb cells in culture or in human sputum samples within minutes. The probe is highly selective for Mtb compared to other non-tuberculous mycobacteria and can distinguish live from dead cells. Importantly, FLASH can be used to measure antibiotic killing of Mtb in culture with greatly accelerated timelines compared to traditional protocols. Overall, FLASH has the potential to enhance both TB diagnostics and drug resistance monitoring in resource-limited settings. One Sentence SummaryA luminescent probe enables sensitive detection of Mycobacterium tuberculosis for diagnostics, treatment monitoring, and drug susceptibility testing.

microbiology↗