Biomedical subjects

Christina Boucher

Publications and source records attributed to Christina Boucher.

6 recordsLinked to original sources

PubMed2026

Primer design through submodular function estimation.

MOTIVATION: Multiplex PCR-based enrichment is widely used in viral genome sequencing and pathogen surveillance. However, designing large sets of primers that maximize genome coverage while minimizing primer-primer interactions remains a major computational challenge. Existing methods such as SADDLE and Olivar use heuristics to optimize a Badness score for primer dimers but lack theoretical guarantees on solution quality. RESULTS: We introduce PRISM, a new framework that formulates multiplex primer design as a constrained submodular maximization problem. Our method defines an objective that balances genome coverage and dimer risk, and applies a local search algorithm with a constant-factor approximation guarantee. Evaluations on viral genome datasets demonstrate that PRISM consistently achieves lower Badness scores compared to PrimalScheme, Olivar, and primerJinn. These results highlight the scalability and theoretical rigor of submodular optimization in primer design. AVAILABILITY: PRISM is open-source and available at https://github.com/yhhan19/PRISM-new. The experimental data, scripts, and results used in this paper are archived on Figshare at https://doi.org/10.6084/m9.figshare.32806499.

Algorithms↗

PubMed2026

RAmpSim: a thermodynamic simulator for hybridization capture in metagenomic sequencing.

MOTIVATION: Simulators that generate synthetic datasets help address the lack of ground truth for developing and benchmarking computational tools. Many read simulators assume uniform sampling across reference genomes; however, for newer capture-based sequencing technologies (e.g. TELSeq), this assumption is intentionally broken to oversample regions of interest. Along with systematic biases arising from probe multiplicity, sequence composition, and species abundances inherent to capture-based sequencing, this mismatch between modeling assumptions and the characteristics of real data necessitates the design of a new capture-based sequencing-specific simulator. RESULTS: We present RAmpSim, a fast simulator that models bait-target hybridization and fragment capture using a thermodynamic nearest-neighbor energy model and Boltzmann-weighted sampling of binding sites. Fragments are generated through multinomial sampling parameterized by bait concentration, binding energy, and genomic abundance before being passed to existing models of platform-specific errors. Implemented in Rust, RAmpSim reproduces empirical within-genome coverage and cross-species enrichment patterns observed in capture-based metagenomic datasets. RAmpSim generally outperforms a uniform baseline with respect to position-based earth mover's distance when compared against the empirical coverage distribution. Classification analysis also shows high recall in recovering empirical high-coverage regions while outperforming a uniform baseline. AVAILABILITY: Code, example scripts, and data sources are available at https://github.com/az002/RAmpSim.git.

Metagenomics↗

PubMed2026

Response to: "best practices when benchmarking CATCH for the design of genome enrichment probes".

We clarify the design principles and evaluation choices underlying Syotti, a robust and scalable probe-design tool developed to support large, heterogeneous bacterial datasets with minimal parameter tuning. We highlight Syotti's ability to perform simultaneous large-scale designs and its effectiveness as a reliable alternative when existing tools such as CATCH are not well suited to the problem setting.

Genomics↗

PubMed2025

Enhanced barrier precautions to prevent transmission of Staphylococcus aureus and Carbapenem-resistant organisms in nursing home chronic ventilator units.

OBJECTIVE: Assess the feasibility and effect of Enhanced Barrier Precautions (EBP) on the transmission of Staphylococcus aureus (SA) and carbapenem-resistant organisms (CRO) among residents in nursing home chronic ventilator units (NH-CVU). DESIGN: Pre-post interventional study. SETTING: Two community-based nursing homes with CVUs in Maryland. A total of 56 residents were enrolled in the baseline period and 64 residents were enrolled in the intervention period. METHODS: During a 3-month baseline and intervention period, residents were swabbed monthly to estimate SA and CRO acquisition. During a 2-month training period, EBP was implemented for residents with chronic wounds, medical devices, or history of multidrug-resistant organism (MDRO) colonization. During the subsequent 3-month intervention period, healthcare personnel (HCP) wore gowns and gloves for high-contact care activities when residents were on EBP. Whole genome sequencing assessed resident-to-resident transmission. RESULTS: At baseline, NH-CVU1 used gowns and gloves for all direct contact, while NH-CVU2 used EBP only for residents with a history of MDRO colonization. After training, the proportion of NH-CVU2 residents on EBP increased from 65% in the baseline period to 87% in the intervention period. Glove use was high (93-98%) in both NH-CVUs. Gown use increased from 39% to 77% in NH-CVU1 and from 26% to 72% in NH-CVU2. Resident-to-resident transmission of SA or CRO decreased by 25% in NH-CVU1 (p = 0.60) and by 67% in NH-CVU2 (p = 0.05). CRO transmission decreased by 33% in NH-CVU1 (p = 0.54) and by 83% in NH-CVU2 (p = 0.02). CONCLUSIONS: EBP is feasible and potentially decreases overall and CRO transmission in nursing home CVUs.

Humans↗

PubMed2006

Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity.

The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED(50) of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.

Administration, Oral↗

PubMed2006

Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.

The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection. In this paper, we describe the synthesis, structure-activity relationships, and pharmacological characterization of 2-aminopyrimidine carbamates, a new class of compounds with potent and selective inhibition of Lck. The most promising compound of this series, 2,6-dimethylphenyl 2-((3,5-bis(methyloxy)-4-((3-(4-methyl-1-piperazinyl)propyl)oxy)phenyl)amino)-4-pyrimidinyl(2,4-bis(methyloxy)phenyl)carbamate (43) exhibits good activity when evaluated in in vitro assays and in an in vivo model of T cell activation.

Administration, Oral↗