Department of Computer Science & Engineering

Our study harnesses a CRISPR-based method to examine ecDNA biogenesis, uncovering efficient circularization between double-strand breaks. ecDNAs and their corresponding chromosomal scars can form via nonhomologous end joining or microhomology-mediated end joining, but the ecDNA and scar formation processes are distinct. Based on our findings, we establish a mechanistic model of excisional ecDNA formation.

We present Generic Refinement Types: a way to write modular higher-order specifications that abstract invariants over function contracts, while preserving automatic SMT-decidable verification. We show how generic refinements let us write a variety of modular higher-order specifications, including specifications for Rust's traits which abstract over the concrete refinements that hold for different trait implementations. We formalize generic refinements in a core calculus and show how to synthesize the generic instantiations algorithmically at usage sites via a combination of syntactic unification and constraint solving. We give semantics to generic refinements via the intuition that they correspond to ghost parameters, and we formalize this intuition via a type-preserving translation into the polymorphic contract calculus to establish the soundness of generic refinements. Finally, we evaluate generic refinements by implementing them in Flux and using it for two case studies. First, we show how generic refinements let us write modular specifications for Rust's vector indexing API that lets us statically verify the bounds safety of a variety of vector-manipulating benchmarks from the literature. Second, we use generic refinements to refine Rust's Diesel ORM library to track the semantics of the database queries issued by client applications, and hence, statically enforce data-dependent access-control policies in several database-backed web applications.

OBJECTIVE: To study the association between dietary patterns and subgingival microbiota. METHODS: Participants (n = 651) who were enrolled in the Oral Infections, Glucose Intolerance, and Insulin Resistance Study (ORIGINS) with subgingival plaque sampling (n = 890 plaques) and a dietary assessment were included. 16S rRNA gene amplicon sequences of subgingival plaque from sites with either probing depth <4 or ≥4 mm were processed separately and used to obtain α-diversity metrics (Faith, Shannon, Simpson, Observed) and taxa ratios (Red Complex to Corynebacterium [RCLR], Treponema to Corynebacterium [TCLR], and Treponema to Neisseria [TNLR]). Food frequency questionnaires (FFQs) were processed to calculate Alternate Healthy Eating Index (AHEI) and A Priori Diet Quality Score (APDQS) scores. Mixed regression models examined the mean levels of microbial metrics across quartiles of diet quality. Means ± standard errors are reported along with p-values. RESULTS: In multivariable models assessing the association between diet scores and α-diversity metrics, higher AHEI values were significantly associated with lower Faith (p-value = 0.01) and Observed (p-value = 0.04) diversity values; similar findings were observed for APDQS (p-value = 0.01, p-value = 0.04). In multivariable models assessing the association between diet scores (AHEI and APDQS) and taxa ratios (RCLR, TCLR and TNLR), as the AHEI quartile increased, all taxa ratios decreased significantly as follows: -1.06 ± 0.093 in Q1 to -1.34 ± 0.099 in Q4 (RCLR), -0.43 ± 0.077 in Q1 to -0.64 ± 0.083 in Q4 (TCLR) and -0.09 ± 0.083 in Q1 to -0.38 ± 0.089 in Q4 (TNLR), respectively. In contrast, as the APDQS quartiles increased, only TNLR decreased significantly from -0.08 ± 0.085 in Q1 to -0.34 ± 0.091 in Q4. CONCLUSION: Diets rich in fruits, vegetables, whole grains and other nutritionally rich plant foods are associated with lower oral microbial diversity and favourable ratios of pathogenic to commensal microbiota.

Citizen science video games are designed primarily for users already inclined to contribute to science, which severely limits their accessibility for an estimated community of 3 billion gamers worldwide. We created Borderlands Science (BLS), a citizen science activity that is seamlessly integrated within a popular commercial video game played by tens of millions of gamers. This integration is facilitated by a novel game-first design of citizen science games, in which the game design aspect has the highest priority, and a suitable task is then mapped to the game design. BLS crowdsources a multiple alignment task of 1 million 16S ribosomal RNA sequences obtained from human microbiome studies. Since its initial release on 7 April 2020, over 4 million players have solved more than 135 million science puzzles, a task unsolvable by a single individual. Leveraging these results, we show that our multiple sequence alignment simultaneously improves microbial phylogeny estimations and UniFrac effect sizes compared to state-of-the-art computational methods. This achievement demonstrates that hyper-gamified scientific tasks attract massive crowds of contributors and offers invaluable resources to the scientific community.

Longitudinal studies are crucial for understanding complex microbiome dynamics and their link to health. We introduce TEMPoral TEnsor Decomposition (TEMPTED), a time-informed dimensionality reduction method for high-dimensional longitudinal data that treats time as a continuous variable, effectively characterizing temporal information and handling varying temporal sampling. TEMPTED captures key microbial dynamics, facilitates beta-diversity analysis, and enhances reproducibility by transferring learned representations to new data. In simulations, it achieves 90% accuracy in phenotype classification, significantly outperforming existing methods. In real data, TEMPTED identifies vaginal microbial markers linked to term and preterm births, demonstrating robust performance across datasets and sequencing platforms.

Dark-field microscopy (DFM) is a widely used imaging tool, due to its high-contrast capability in imaging label-free specimens. Traditional DFM requires optical alignment to block the oblique illumination, and the resolution is diffraction-limited to the wavelength scale. In this work, we present deep-learning assisted plasmonic dark-field microscopy (DAPD), which is a single-frame super-resolution method using plasmonic dark-field (PDF) microscopy and deep-learning assisted image reconstruction. Specifically, we fabricated a designed PDF substrate with surface plasmon polaritons (SPPs) illuminating specimens on the substrate. Dark field images formed by scattered light from the specimen are further processed by a pretrained convolutional neural network (CNN) using a simulation dataset based on the designed substrate and parameters of the detection optics. We demonstrated a resolution enhancement of 2.8 times on various label-free objects with a large potential for future improvement. We highlight our technique as a compact alternative to traditional DFM with a significantly enhanced spatial resolution.

OBJECTIVES: Implicit bias perpetuates health care inequities and manifests in patient-provider interactions, particularly nonverbal social cues like dominance. We investigated the use of artificial intelligence (AI) for automated communication assessment and feedback during primary care visits to raise clinician awareness of bias in patient interactions. MATERIALS AND METHODS: (1) Assessed the technical performance of our AI models by building a machine-learning pipeline that automatically detects social signals in patient-provider interactions from 145 primary care visits. (2) Engaged 24 clinicians to design usable AI-generated communication feedback for their workflow. (3) Evaluated the impact of our AI-based approach in a prospective cohort of 108 primary care visits. RESULTS: Findings demonstrate the feasibility of AI models to identify social signals, such as dominance, warmth, engagement, and interactivity, in nonverbal patient-provider communication. Although engaged clinicians preferred feedback delivered in personalized dashboards, they found nonverbal cues difficult to interpret, motivating social signals as an alternative feedback mechanism. Impact evaluation demonstrated fairness in all AI models with better generalizability of provider dominance, provider engagement, and patient warmth. Stronger clinician implicit race bias was associated with less provider dominance and warmth. Although clinicians expressed overall interest in our AI approach, they recommended improvements to enhance acceptability, feasibility, and implementation in telehealth and medical education contexts. DISCUSSION AND CONCLUSION: Findings demonstrate promise for AI-driven communication assessment and feedback systems focused on social signals. Future work should improve the performance of this approach, personalize models, and contextualize feedback, and investigate system implementation in educational workflows. This work exemplifies a systematic, multistage approach for evaluating AI tools designed to raise clinician awareness of implicit bias and promote patient-centered, equitable health care interactions.

Objective

Methods

Results

Conclusions

Science-informed decisions are best guided by the objective synthesis of the totality of evidence around a particular question and assessing its trustworthiness through systematic processes. However, there are major barriers and challenges that limit science-informed food and nutrition policy, practice, and guidance. First, insufficient evidence, primarily due to acquisition cost of generating high-quality data, and the complexity of the diet-disease relationship. Furthermore, the sheer number of systematic reviews needed across the entire agriculture and food value chain, and the cost and time required to conduct them, can delay the translation of science to policy. Artificial intelligence offers the opportunity to (i) better understand the complex etiology of diet-related chronic diseases, (ii) bring more precision to our understanding of the variation among individuals in the diet-chronic disease relationship, (iii) provide new types of computed data related to the efficacy and effectiveness of nutrition/food interventions in health promotion, and (iv) automate the generation of systematic reviews that support timely decisions. These advances include the acquisition and synthesis of heterogeneous and multimodal datasets. This perspective summarizes a meeting convened at the National Academy of Sciences, Engineering, and Medicine. The purpose of the meeting was to examine the current state and future potential of artificial intelligence in generating new types of computed data as well as automating the generation of systematic reviews to support evidence-based food and nutrition policy, practice, and guidance.

Cellular metabolism is a complex process involving the consumption and production of metabolites, as well as the regulation of enzyme synthesis and activity. Modeling of metabolic processes is important to understand the underlying mechanisms, with a wide range of applications in metabolic engineering and health sciences. Cybernetic modeling is a powerful technique that accounts for unknown intricate regulatory mechanisms in complex cellular processes. It models regulation as goal-oriented, where the levels and activities of enzymes are modulated by the cybernetic control variables to achieve the cybernetic objective. This study used cybernetic model to study the enzyme competition between arachidonic acid (AA) and eicosapentaenoic acid (EPA) metabolism in murine macrophages. AA and EPA compete for the shared enzyme cyclooxygenase. Upon external stimuli, AA produces proinflammatory 2-series prostaglandins and EPA metabolizes to antiinflammatory 3-series prostaglandins, where proinflammatory and antiinflammatory responses are necessary for homeostasis. The cybernetic model adequately captured the experimental data for control and EPA-supplemented conditions. The model is validated by performing an F-test, conducting leave-one-out-metabolite cross-validation, and predicting an unseen experimental condition. The cybernetic variables provide insights into the competition between AA and EPA for the cyclooxygenase enzyme. Predictions from our model suggest that the system undergoes a switch from a predominantly proinflammatory state in the control to an antiinflammatory state with EPA-supplementation. The model can also be used to analytically determine the AA and EPA concentrations required for the switch to occur. The quantitative outcomes enhance understanding of proinflammatory and antiinflammatory metabolism in RAW 264.7 macrophages.