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Cooper Stansbury

Publications and source records attributed to Cooper Stansbury.

9 recordsLinked to original sources

Language Model Powered Digital Biology with BRAD

Recent advancements in Large Language Models (LLMs) are transforming biology, computer science, engineering, and every day life. However, integrating the wide array of computational tools, databases, and scientific literature continues to pose a challenge to biological research. LLMs are well-suited for unstructured integration, efficient information retrieval, and automating standard workflows and actions from these diverse resources. To harness these capabilities in bioinformatics, we present a prototype Bioinformatics Retrieval Augmented Digital assistant (BRAD). BRAD is a chatbot and agentic system that integrates a variety of bioinformatics tools. The Python package implements an AI \texttt{Agent} that is powered by LLMs and connects to a local file system, online databases, and a user's software. The \texttt{Agent} is highly configurable, enabling tasks such as Retrieval-Augmented Generation, searches across bioinformatics databases, and the execution of software pipelines. BRAD's coordinated integration of bioinformatics tools delivers a context-aware and semi-autonomous system that extends beyond the capabilities of conventional LLM-based chatbots. A graphical user interface (GUI) provides an intuitive interface to the system.

cs.AI

Dynamic Sensor Selection for Biomarker Discovery

Advances in methods of biological data collection are driving the rapid growth of comprehensive datasets across clinical and research settings. These datasets provide the opportunity to monitor biological systems in greater depth and at finer time steps than was achievable in the past. Classically, biomarkers are used to represent and track key aspects of a biological system. Biomarkers retain utility even with the availability of large datasets, since monitoring and interpreting changes in a vast number of molecules remains impractical. However, given the large number of molecules in these datasets, a major challenge is identifying the best biomarkers for a particular setting Here, we apply principles of observability theory to establish a general methodology for biomarker selection. We demonstrate that observability measures effectively identify biologically meaningful sensors in a range of time series transcriptomics data. Motivated by the practical considerations of biological systems, we introduce the method of dynamic sensor selection (DSS) to maximize observability over time, thus enabling observability over regimes where system dynamics themselves are subject to change. This observability framework is flexible, capable of modeling gene expression dynamics and using auxiliary data, including chromosome conformation, to select biomarkers. Additionally, we demonstrate the applicability of this approach beyond genomics by evaluating the observability of neural activity These applications demonstrate the utility of observability-guided biomarker selection for across a wide range of biological systems, from agriculture and biomanufacturing to neural applications and beyond.

q-bio.MN

Geometric Aspects of Observability of Hypergraphs

In this paper we consider aspects of geometric observability for hypergraphs, extending our earlier work from the uniform to the nonuniform case. Hypergraphs, a generalization of graphs, allow hyperedges to connect multiple nodes and unambiguously represent multi-way relationships which are ubiquitous in many real-world networks including those that arise in biology. We consider polynomial dynamical systems with linear outputs defined according to hypergraph structure, and we propose methods to evaluate local, weak observability.

math.DS

Kronecker Product of Tensors and Hypergraphs: Structure and Dynamics

Hypergraphs and tensors extend classic graph and matrix theory to account for multiway relationships, which are ubiquitous in engineering, biological, and social systems. While the Kronecker product is a potent tool for analyzing the coupling of systems in graph or matrix contexts, its effectiveness in capturing multiway interactions remains elusive. In this article, we present a comprehensive exploration of algebraic, structural, and spectral properties of the tensor Kronecker product. We express Tucker and tensor train decompositions and various tensor eigenvalues in terms of the tensor Kronecker product. Additionally, we utilize the tensor Kronecker product to form Kronecker hypergraphs, a tensor-based hypergraph product, and investigate the structure and stability of polynomial dynamics on Kronecker hypergraphs. Finally, we provide numerical examples to demonstrate the utility of the tensor Kronecker product in computing Z-eigenvectors, various tensor decompositions, and determining the stability of polynomial systems.

math.DS

Hypergraph Analysis Toolbox for Chromosome Conformation

Recent advances in biological technologies, such as multi-way chromosome conformation capture (3C), require development of methods for analysis of multi-way interactions. Hypergraphs are mathematically tractable objects that can be utilized to precisely represent and analyze multi-way interactions. Here we present the Hypergraph Analysis Toolbox (HAT), a software package for visualization and analysis of multi-way interactions in complex systems.

q-bio.QM

RAILS: A Robust Adversarial Immune-inspired Learning System

Adversarial attacks against deep neural networks (DNNs) are continuously evolving, requiring increasingly powerful defense strategies. We develop a novel adversarial defense framework inspired by the adaptive immune system: the Robust Adversarial Immune-inspired Learning System (RAILS). Initializing a population of exemplars that is balanced across classes, RAILS starts from a uniform label distribution that encourages diversity and uses an evolutionary optimization process to adaptively adjust the predictive label distribution in a manner that emulates the way the natural immune system recognizes novel pathogens. RAILS' evolutionary optimization process explicitly captures the tradeoff between robustness (diversity) and accuracy (specificity) of the network, and represents a new immune-inspired perspective on adversarial learning. The benefits of RAILS are empirically demonstrated under eight types of adversarial attacks on a DNN adversarial image classifier for several benchmark datasets, including: MNIST; SVHN; CIFAR-10; and CIFAR-10. We find that PGD is the most damaging attack strategy and that for this attack RAILS is significantly more robust than other methods, achieving improvements in adversarial robustness by $\geq 5.62\%, 12.5\%$, $10.32\%$, and $8.39\%$, on these respective datasets, without appreciable loss of classification accuracy. Codes for the results in this paper are available at https://github.com/wangren09/RAILS.

cs.NE

Expressing and Executing Informed Consent Permissions Using SWRL: The All of Us Use Case

The informed consent process is a complicated procedure involving permissions as well a variety of entities and actions. In this paper, we discuss the use of Semantic Web Rule Language (SWRL) to further extend the Informed Consent Ontology (ICO) to allow for semantic machine-based reasoning to manage and generate important permission-based information that can later be viewed by stakeholders. We present four use cases of permissions from the All of Us informed consent document and translate these permissions into SWRL expressions to extend and operationalize ICO. Our efforts show how SWRL is able to infer some of the implicit information based on the defined rules, and demonstrate the utility of ICO through the use of SWRL extensions. Future work will include developing formal and generalized rules and expressing permissions from the entire document, as well as working towards integrating ICO into software systems to enhance the semantic representation of informed consent for biomedical research.

cs.DL

Immuno-mimetic Deep Neural Networks (Immuno-Net)

Biomimetics has played a key role in the evolution of artificial neural networks. Thus far, in silico metaphors have been dominated by concepts from neuroscience and cognitive psychology. In this paper we introduce a different type of biomimetic model, one that borrows concepts from the immune system, for designing robust deep neural networks. This immuno-mimetic model leads to a new computational biology framework for robustification of deep neural networks against adversarial attacks. Within this Immuno-Net framework we define a robust adaptive immune-inspired learning system (Immuno-Net RAILS) that emulates, in silico, the adaptive biological mechanisms of B-cells that are used to defend a mammalian host against pathogenic attacks. When applied to image classification tasks on benchmark datasets, we demonstrate that Immuno-net RAILS results in improvement of as much as 12.5% in adversarial accuracy of a baseline method, the DkNN-robustified CNN, without appreciable loss of accuracy on clean data.

cs.NE

Understanding Memory B Cell Selection

The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own immunological objectives. The affinity maturation process is widely viewed as a heuristic to solve the global optimization problem of finding B cells with high affinity to the antigen. However, memory B cells appear to be purposely selected earlier in the affinity maturation process and have lower affinity. We propose that this memory B cell selection process may be an approximate solution to two optimization problems: optimizing for affinity to similar antigens in the future despite mutations or other minor differences, and optimizing to warm start the generation of plasma B cells in the future. We use simulations to provide evidence for our hypotheses, taking into account data showing that certain B cell mutations are more likely than others. Our findings are consistent with memory B cells having high-affinity to mutated antigens, but do not provide strong evidence that memory B cells will be more useful than selected naive B cells for seeding the secondary germinal centers.

q-bio.CB