pwc-archive/papers-with-abstracts huggingface dataset:
Enhancing kidney transplantation through multi-agent kidney exchange programs: A comprehensive review and optimization models
Authors: Shayan Sharifi
Date: 2025-02-10 00:00:00
Tasks: Fairness

This paper presents a comprehensive review of the last two decades of research on Kidney Exchange Programs (KEPs), systematically categorizing and classifying key contributions to provide readers with a structured understanding of advancements in the field. The review highlights the evolution of KEP methodologies and lays the foundation for our contribution. We propose three mathematical models aimed at improving both the quantity and quality of kidney transplants. Model 1 maximizes the number of transplants by focusing on compatibility based on blood type and PRA, without additional constraints. Model 2 introduces a minimum Human Leukocyte Antigen (HLA) compatibility threshold to enhance transplant quality, though this leads to fewer matches. Model 3 extends the problem to a Multi-Agent Kidney Exchange Program (MKEP), pooling incompatible donor-recipient pairs across multiple agents, resulting in a higher number of successful transplants while ensuring fairness across agents. Sensitivity analyses demonstrate trade-offs between transplant quantity and quality, with Model 3 striking the optimal balance by leveraging multi-agent collaboration to improve both the number and quality of transplants. These findings underscore the potential benefits of more integrated kidney exchange systems.
Non-asymptotic Analysis of Diffusion Annealed Langevin Monte Carlo for Generative Modelling
Authors: Paula Cordero-Encinar, O. Deniz Akyildiz, Andrew B. Duncan
Date: 2025-02-13 00:00:00

We investigate the theoretical properties of general diffusion (interpolation) paths and their Langevin Monte Carlo implementation, referred to as diffusion annealed Langevin Monte Carlo (DALMC), under weak conditions on the data distribution. Specifically, we analyse and provide non-asymptotic error bounds for the annealed Langevin dynamics where the path of distributions is defined as Gaussian convolutions of the data distribution as in diffusion models. We then extend our results to recently proposed heavy-tailed (Student's t) diffusion paths, demonstrating their theoretical properties for heavy-tailed data distributions for the first time. Our analysis provides theoretical guarantees for a class of score-based generative models that interpolate between a simple distribution (Gaussian or Student's t) and the data distribution in finite time. This approach offers a broader perspective compared to standard score-based diffusion approaches, which are typically based on a forward Ornstein-Uhlenbeck (OU) noising process.
Trend-encoded Probabilistic Multi-order Model: A Non-Machine Learning Approach for Enhanced Stock Market Forecasts
Authors: Peiwan Wang, Chenhao Cui, Yong Li
Date: 2025-02-12 00:00:00
Tasks: Prediction, Stock Market Prediction

In recent years, the dominance of machine learning in stock market forecasting has been evident. While these models have shown decreasing prediction errors, their robustness across different datasets has been a concern. A successful stock market prediction model minimizes prediction errors and showcases robustness across various data sets, indicating superior forecasting performance. This study introduces a novel multiple lag order probabilistic model based on trend encoding (TeMoP) that enhances stock market predictions through a probabilistic approach. Results across different stock indexes from nine countries demonstrate that the TeMoP outperforms the state-of-the-art machine learning models in predicting accuracy and stabilization.
Regularization can make diffusion models more efficient
Authors: Mahsa Taheri, Johannes Lederer
Date: 2025-02-13 00:00:00

Diffusion models are one of the key architectures of generative AI. Their main drawback, however, is the computational costs. This study indicates that the concept of sparsity, well known especially in statistics, can provide a pathway to more efficient diffusion pipelines. Our mathematical guarantees prove that sparsity can reduce the input dimension's influence on the computational complexity to that of a much smaller intrinsic dimension of the data. Our empirical findings confirm that inducing sparsity can indeed lead to better samples at a lower cost.
Model-free Methods for Event History Analysis and Efficient Adjustment (PhD Thesis)
Authors: Alexander Mangulad Christgau
Date: 2025-02-11 00:00:00

This thesis contains a series of independent contributions to statistics, unified by a model-free perspective. The first chapter elaborates on how a model-free perspective can be used to formulate flexible methods that leverage prediction techniques from machine learning. Mathematical insights are obtained from concrete examples, and these insights are generalized to principles that permeate the rest of the thesis. The second chapter studies the concept of local independence, which describes whether the evolution of one stochastic process is directly influenced by another. To test local independence, we define a model-free parameter called the Local Covariance Measure (LCM). We formulate an estimator for the LCM, from which a test of local independence is proposed. We discuss how the size and power of the proposed test can be controlled uniformly and investigate the test in a simulation study. The third chapter focuses on covariate adjustment, a method used to estimate the effect of a treatment by accounting for observed confounding. We formulate a general framework that facilitates adjustment for any subset of covariate information. We identify the optimal covariate information for adjustment and, based on this, introduce the Debiased Outcome-adapted Propensity Estimator (DOPE) for efficient estimation of treatment effects. An instance of DOPE is implemented using neural networks, and we demonstrate its performance on simulated and real data. The fourth and final chapter introduces a model-free measure of the conditional association between an exposure and a time-to-event, which we call the Aalen Covariance Measure (ACM). We develop a model-free estimation method and show that it is doubly robust, ensuring $\sqrt{n}$-consistency provided that the nuisance functions can be estimated with modest rates. A simulation study demonstrates the use of our estimator in several settings.
Inverse problems with experiment-guided AlphaFold
Authors: Advaith Maddipatla, Nadav Bojan Sellam, Meital Bojan, Sanketh Vedula, Paul Schanda, Ailie Marx, Alex M. Bronstein
Date: 2025-02-13 00:00:00
Tasks: Diversity

Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational heterogeneity revealed by diverse experimental modalities. Here, we present a framework for building experiment-grounded protein structure generative models that infer conformational ensembles consistent with measured experimental data. The key idea is to treat state-of-the-art protein structure predictors (e.g., AlphaFold3) as sequence-conditioned structural priors, and cast ensemble modeling as posterior inference of protein structures given experimental measurements. Through extensive real-data experiments, we demonstrate the generality of our method to incorporate a variety of experimental measurements. In particular, our framework uncovers previously unmodeled conformational heterogeneity from crystallographic densities, and generates high-accuracy NMR ensembles orders of magnitude faster than the status quo. Notably, we demonstrate that our ensembles outperform AlphaFold3 and sometimes better fit experimental data than publicly deposited structures to the Protein Data Bank (PDB). We believe that this approach will unlock building predictive models that fully embrace experimentally observed conformational diversity.
Interpreting and Steering Protein Language Models through Sparse Autoencoders
Authors: Edith Natalia Villegas Garcia, Alessio Ansuini
Date: 2025-02-13 00:00:00

The rapid advancements in transformer-based language models have revolutionized natural language processing, yet understanding the internal mechanisms of these models remains a significant challenge. This paper explores the application of sparse autoencoders (SAE) to interpret the internal representations of protein language models, specifically focusing on the ESM-2 8M parameter model. By performing a statistical analysis on each latent component's relevance to distinct protein annotations, we identify potential interpretations linked to various protein characteristics, including transmembrane regions, binding sites, and specialized motifs. We then leverage these insights to guide sequence generation, shortlisting the relevant latent components that can steer the model towards desired targets such as zinc finger domains. This work contributes to the emerging field of mechanistic interpretability in biological sequence models, offering new perspectives on model steering for sequence design.
Graph-structured Small Molecule Drug Discovery Through Deep Learning: Progress, Challenges, and Opportunities
Authors: Kun Li, Yida Xiong, Hongzhi Zhang, Xiantao Cai, Jia Wu, Bo Du, Wenbin Hu
Date: 2025-02-13 00:00:00
Tasks: Drug Discovery, Out-of-Distribution Generalization

Due to their excellent drug-like and pharmacokinetic properties, small molecule drugs are widely used to treat various diseases, making them a critical component of drug discovery. In recent years, with the rapid development of deep learning (DL) techniques, DL-based small molecule drug discovery methods have achieved excellent performance in prediction accuracy, speed, and complex molecular relationship modeling compared to traditional machine learning approaches. These advancements enhance drug screening efficiency and optimization and provide more precise and effective solutions for various drug discovery tasks. Contributing to this field's development, this paper aims to systematically summarize and generalize the recent key tasks and representative techniques in graph-structured small molecule drug discovery in recent years. Specifically, we provide an overview of the major tasks in small molecule drug discovery and their interrelationships. Next, we analyze the six core tasks, summarizing the related methods, commonly used datasets, and technological development trends. Finally, we discuss key challenges, such as interpretability and out-of-distribution generalization, and offer our insights into future research directions for small molecule drug discovery.
Persistent Sheaf Laplacian Analysis of Protein Flexibility
Authors: Nicole Hayes, Xiaoqi Wei, Hongsong Feng, Ekaterina Merkurjev, Guo-Wei Wei
Date: 2025-02-12 00:00:00
Tasks: Drug Discovery, Protein Design, Topological Data Analysis

Protein flexibility, measured by the B-factor or Debye-Waller factor, is essential for protein functions such as structural support, enzyme activity, cellular communication, and molecular transport. Theoretical analysis and prediction of protein flexibility are crucial for protein design, engineering, and drug discovery. In this work, we introduce the persistent sheaf Laplacian (PSL), an effective tool in topological data analysis, to model and analyze protein flexibility. By representing the local topology and geometry of protein atoms through the multiscale harmonic and non-harmonic spectra of PSLs, the proposed model effectively captures protein flexibility and provides accurate, robust predictions of protein B-factors. Our PSL model demonstrates an increase in accuracy of 32% compared to the classical Gaussian network model (GNM) in predicting B-factors for a dataset of 364 proteins. Additionally, we construct a blind machine learning prediction method utilizing global and local protein features. Extensive computations and comparisons validate the effectiveness of the proposed PSL model for B-factor predictions.
Trajectory Inference for Single Cell Omics
Authors: Alexandre Hutton, Jesse G. Meyer
Date: 2025-02-13 00:00:00

Trajectory inference is used to order single-cell omics data along a path that reflects a continuous transition between cells. This approach is useful for studying processes like cell differentiation, where a stem cell matures into a specialized cell type, or investigating state changes in pathological conditions. In the current article, we provide a general introduction to trajectory inference, explaining the concepts and assumptions underlying the different methods. We then briefly discuss the strengths and weaknesses of different trajectory inference methods. We also describe best practices for using trajectory inference, such as how to validate the results and how to interpret them in the context of biological knowledge. Finally, the article will discuss some of the applications of trajectory inference in single-cell omics research. These applications include studying cell differentiation, development, and disease. We provide examples of how trajectory inference has been used to gain new insights into these processes.
$^{18}$F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: substrate for persistent/delayed disorders?
Authors: Eric Guedj, Matthieu Million, Pierre Dudouet, Hervé Tissot-Dupont, Fabienne Bregeon, Serge Cammilleri, Didier Raoult
Date: 2025-02-13 00:00:00
Tasks: Hippocampus

Purpose: Several brain complications of SARS-CoV-2 infection have been reported. It has been moreover speculated that this neurotropism could potentially cause a delayed outbreak of neuropsychiatric and neurodegenerative diseases of neuroinflammatory origin. A propagation mechanism has been proposed across the cribriform plate of the ethmoid bone, from the nose to the olfactory epithelium, and possibly afterward to other limbic structures, and deeper parts of the brain including the brainstem. Methods: Review of clinical examination, and whole-brain voxel-based analysis of $^{18}$F-FDG PET metabolism in comparison with healthy subjects (p voxel<0.001, p-cluster<0.05, uncorrected), of two patients with confirmed diagnosis of SARS-CoV-2 explored at the post-viral stage of the disease. Results: Hypometabolism of the olfactory/rectus gyrus was found on the two patients, especially one with 4-week prolonged anosmia. Additional hypometabolisms were found within amygdala, hippocampus, parahippocampus, cingulate cortex, pre-/post-central gyrus, thalamus/hypothalamus, cerebellum, pons, and medulla in the other patient who complained of delayed onset of a painful syndrome. Conclusion: These preliminary findings reinforce the hypotheses of SARS-CoV-2 neurotropism through the olfactory bulb and the possible extension of this impairment to other brain structures. $^{18}$F-FDG PET hypometabolism could constitute a cerebral quantitative biomarker of this involvement. Post-viral cohort studies are required to specify the exact relationship between such hypometabolisms and the possible persistent disorders, especially involving cognitive or emotion disturbances, residual respiratory symptoms, or painful complaints.
Neuronal Correlates of Semantic Event Classes during Presentation of Complex Naturalistic Stimuli: Anatomical Patterns, Context-Sensitivity, and Potential Impact on shared Human-Robot Ontologies
Authors: Florian Ahrens, Mihai Pomarlan, Daniel Beßler, Michael Beetz, Manfred Herrmann
Date: 2025-02-12 00:00:00

The present study forms part of a research project that aims to develop cognition-enabled robotic agents with environmental interaction capabilities close to human proficiency. This approach is based on human-derived neuronal data in combination with a shared ontology to enable robots to learn from human experiences. To gain further insight into the relation between human neuronal activity patterns and ontological classes, we introduced General Linear Model (GLM) analyses on fMRI data of participants who were presented with complex naturalistic video stimuli comparable to the robot tasks. We modeled four event classes (pick, place, fetch and deliver) attached to different environmental and object-related context and employed a Representational Similarity Analysis (RSA) on associated brain activity patterns as a starting point for an automatic hierarchical clustering. Based on the default values for the Hemodynamic Response Function (HRF), the activity patterns were reliably grouped according to their parent classes of object interaction and navigation. Although fetch and deliver events were also distinguished by neuronal patterns, pick and place events demonstrated higher ambiguity with respect to neuronal activation patterns. Introducing a shorter HRF time-to-peak leads to a more reliable grouping of all four semantic classes, despite contextual factors. These data might give novel insights into the neuronal representation of complex stimuli and may enable further research in ontology validation in cognition-enabled robotics.
Normative Cerebral Perfusion Across the Lifespan
Authors: Xinglin Zeng, Yiran Li, Lin Hua, Ruoxi Lu, Lucas Lemos Franco, Peter Kochunov, Shuo Chen, John A Detre, Ze Wang
Date: 2025-02-12 00:00:00
Tasks: Additive models

Cerebral perfusion plays a crucial role in maintaining brain function and is tightly coupled with neuronal activity. While previous studies have examined cerebral perfusion trajectories across development and aging, precise characterization of its lifespan dynamics has been limited by small sample sizes and methodological inconsistencies. In this study, we construct the first comprehensive normative model of cerebral perfusion across the human lifespan (birth to 85 years) using a large multi-site dataset of over 12,000 high-quality arterial spin labeling (ASL) MRI scans. Leveraging generalized additive models for location, scale, and shape (GAMLSS), we mapped nonlinear growth trajectories of cerebral perfusion at global, network, and regional levels. We observed a rapid postnatal increase in cerebral perfusion, peaking at approximately 7.1 years, followed by a gradual decline into adulthood. Sex differences were evident, with distinct regional maturation patterns rather than uniform differences across all brain regions. Beyond normative modeling, we quantified individual deviations from expected CBF patterns in neurodegenerative and psychiatric conditions, identifying disease-specific perfusion abnormalities across four brain disorders. Using longitudinal data, we established typical and atypical cerebral perfusion trajectories, highlighting the prognostic value of perfusion-based biomarkers for detecting disease progression. Our findings provide a robust normative framework for cerebral perfusion, facilitating precise characterization of brain health across the lifespan and enhancing the early identification of neurovascular dysfunction in clinical populations.
Some things to know about achieving artificial general intelligence
Authors: Herbert Roitblat
Date: 2025-02-10 00:00:00

Current and foreseeable GenAI models are not capable of achieving artificial general intelligence because they are burdened with anthropogenic debt. They depend heavily on human input to provide well-structured problems, architecture, and training data. They cast every problem as a language pattern learning problem and are thus not capable of the kind of autonomy needed to achieve artificial general intelligence. Current models succeed at their tasks because people solve most of the problems to which these models are directed, leaving only simple computations for the model to perform, such as gradient descent. Another barrier is the need to recognize that there are multiple kinds of problems, some of which cannot be solved by available computational methods (for example, "insight problems"). Current methods for evaluating models (benchmarks and tests) are not adequate to identify the generality of the solutions, because it is impossible to infer the means by which a problem was solved from the fact of its solution. A test could be passed, for example, by a test-specific or a test-general method. It is a logical fallacy (affirming the consequent) to infer a method of solution from the observation of success.
Enhancing Olfactory Perception Through Large Language Models: Integrating Sensory Data for Advanced Odor Recognition
Authors: Ravirajan K, Arvind Sundararajan
Date: 2025-01-28 00:00:00

The integration of biological principles into artificial olfactory systems has led to significant advancements in odor detection and classification. Inspired by the intricate mechanisms of natural olfaction, researchers are developing sophisticated systems that mimic the functionality of biological olfactory pathways. These systems utilize high-density chemoresistive sensor arrays (HCSA) combined with advanced computational techniques, such as FPGA-accelerated glomerular convergence circuits (FGCC) and hierarchical graph neural networks (HGNN). This bioinspired approach enables real-time adaptive responses to volatile organic compounds (VOCs), enhancing the accuracy and efficiency of odor identification. At the core of these innovations is the multiparametric sigmoidal sensor activation (MPSA), which quantifies VOCs by leveraging the diverse responses of sensor arrays. The implementation of lateral inhibition via programmable synaptic crossbars (LIPSC) further refines odor processing by mimicking neural interactions found in biological systems. Additionally, temporal self-organizing maps (TSOM) facilitate dynamic clustering of odor patterns, allowing for a nuanced understanding of complex odor environments. A novel aspect of this research lies in the Grassmannian manifold embedding (GME) of odor profiles, which provides a mathematical framework for representing and analyzing the multidimensional nature of odors. Coupled with Hamiltonian Monte Carlo-optimized feedback (HMC-FB), this system effectively compensates for drift in sensor readings, ensuring consistent performance over time. By bridging the gap between biological inspiration and technological innovation, these artificial olfactory systems are poised to revolutionize applications ranging from environmental monitoring to food safety and healthcare diagnostics.
Conditional Success of Adaptive Therapy: The Role of Treatment-Holiday Thresholds Revealed by Mathematical Modeling
Authors: Lanfei Sun, Haifeng Zhang, Kai Kang, Xiaoxin Wang, Leyi Zhang, Yanan Cai, Changjing Zhuge, Lei Zhang
Date: 2025-02-13 00:00:00
Tasks: Management

Adaptive therapy (AT) improves cancer treatment by controlling the competition between sensitive and resistant cells through treatment holidays. This study highlights the critical role of treatment-holiday thresholds in AT for tumors composed of drug-sensitive and resistant cells. Using a Lotka-Volterra model, the research compares AT with maximum tolerated dose therapy and intermittent therapy, showing that AT's success largely depends on the threshold at which treatment is paused and resumed, as well as on the competition between sensitive and resistant cells. Three scenarios of comparison between AT and other therapies are identified: uniform-decline, conditional-improve, and uniform-improve, illustrating that optimizing the treatment-holiday threshold is crucial for AT effectiveness. Tumor composition, including initial tumor burden and the proportion of resistant cells, influences outcomes. Adjusting threshold values enables AT to suppress resistant subclones, preserving sensitive cells, ultimately improving progression-free survival. These findings emphasize the importance of personalized treatment strategies potentially enhancing long-term therapeutic outcomes.