pwc-archive/papers-with-abstracts huggingface dataset:
A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy
Authors: David Morselli, Giulia Chiari, Federico Frascoli, Marcello E. Delitala
Date: 2024-10-20 00:00:00

The effectiveness of oncolytic virotherapy is significantly affected by several elements of the tumour microenvironment, which reduce the ability of the virus to infect cancer cells. In this work, we focus on the influence of hypoxia on this therapy and develop a novel continuous mathematical model that considers both the spatial and epigenetic heterogeneity of the tumour. We investigate how oxygen gradients within tumours affect the spatial distribution and replication of both the tumour and oncolytic viruses, focusing on regions of severe hypoxia versus normoxic areas. Additionally, we analyse the evolutionary dynamics of tumour cells under hypoxic conditions and their influence on susceptibility to viral infection. Our findings show that the reduced metabolic activity of hypoxic cells may significantly impact the virotherapy effectiveness; the knowledge of the tumour's oxygenation could, therefore, suggest the most suitable type of virus to optimise the outcome. The combination of numerical simulations and theoretical results for the model equilibrium values allows us to elucidate the complex interplay between viruses, tumour evolution and oxygen dynamics, ultimately contributing to developing more effective and personalised cancer treatments.
TockyPrep: Data Preprocessing Methods for Flow Cytometric Fluorescent Timer Analysis
Authors: Masahiro Ono
Date: 2024-11-06 00:00:00

Background: Fluorescent Timer proteins, which display time-dependent changes in their emission spectra, are invaluable for analyzing the temporal dynamics of cellular events at the single-cell level. We previously developed the Timer-of-cell-kinetics-and-activity (Tocky) tools, utilizing a specific Timer protein, Fast-FT, to monitor temporal changes in cellular activities. Despite their potential, the analysis of Timer fluorescence in flow cytometry is frequently compromised by variability in instrument settings and the absence of standardized preprocessing methods. The development and implementation of effective data preprocessing methods remain to be achieved. Results: In this study, we introduce the R package that automates the data preprocessing of Timer fluorescence data from flow cytometry experiments for quantitative analysis at single-cell level. Our aim is to standardize Timer data analysis to enhance reproducibility and accuracy across different experimental setups. The package includes a trigonometric transformation method to elucidate the dynamics of Fluorescent Timer proteins. We have identified the normalization of immature and mature Timer fluorescence data as essential for robust analysis, clarifying how this normalization affects the analysis of Timer maturation. These preprocessing methods are all encapsulated within the TockyPrep R package. Conclusions: TockyPrep is available for distribution via GitHub at https://github.com/MonoTockyLab/TockyPrep, providing tools for data preprocessing and basic visualization of Timer fluorescence data. This toolkit is expected to enhance the utility of experimental systems utilizing Fluorescent Timer proteins, including the Tocky tools.
bursty_dynamics: A Python Package for Exploring the Temporal Properties of Longitudinal Data
Authors: Alisha Angdembe, Wasim A Iqbal, Rebeen Ali Hamad, John Casement, AI-Multiply Consortium, Paolo Missier, Nick Reynolds, Rafael Henkin, Michael R Barnes
Date: 2024-11-05 00:00:00
Tasks: Epidemiology, Time Series Analysis

Understanding the temporal properties of longitudinal data is critical for identifying trends, predicting future events, and making informed decisions in any field where temporal data is analysed, including health and epidemiology, finance, geosciences, and social sciences. Traditional time-series analysis techniques often fail to capture the complexity of irregular temporal patterns present in such data. To address this gap, we introduce bursty_dynamics, a Python package that enables the quantification of bursty dynamics through the calculation of the Burstiness Parameter (BP) and Memory Coefficient (MC). In temporal data, BP and MC provide insights into the irregularity and temporal dependencies within event sequences, shedding light on complex patterns of disease aetiology, human behaviour, or other information diffusion over time. An event train detection method is also implemented to identify clustered events occurring within a specified time interval, allowing for more focused analysis with reduced noise. With built-in visualisation tools, bursty_dynamics provides an accessible yet powerful platform for researchers to explore and interpret the temporal dynamics of longitudinal data. This paper outlines the core functionalities of the package, demonstrates its applications in diverse research domains, and discusses the advantages of using BP, MC, and event train detection for enhanced temporal data analysis.
Impact of genetic polymorphisms on tacrolimus concentrations and intra-individual variability in recipients of heart transplants during the early post-heart transplantation period
Authors: Yuhui Chai, Lili Hu, Danni Quan, Yunyun Yang, Zhuo Wang
Date: 2024-11-04 00:00:00
Tasks: Prognosis

This study aimed to investigate the effects of genetic polymorphisms on tacrolimus blood levels and intra-individual variability in recipients of heart transplants during the early post-transplantation period. Demographic information, concomitant medications, daily tacrolimus dose, trough concentration, and physiological and biochemical information of 87 Chinese recipients of heart transplants were collected. Trough concentrations were determined using a chemiluminescent micro-particle immunoassay, and 17 selected single nucleic acid polymorphisms were genotyped by direct sequencing. We assessed intra-individual variability by calculating the coefficient of variation of tacrolimus trough concentration and analyzed factors associated with tacrolimus concentration and intra-individual variability. Our study found that low body weight and a high percentage of neutrophils significantly influenced the coefficient of variation of tacrolimus. CYP3A5*1D and CYP3A7 rs776744 haplotypes correlated significantly with an intra-individual coefficient of variation of tacrolimus trough concentration during the early postoperative period. Patients with the CYP3A5*1D rs15524 and CYP3A7 rs776744 TT haplotype had a higher coefficient of variation than carriers of the C allele. Genetic polymorphisms in recipients of heart transplants affect tacrolimus metabolism, significantly affecting tacrolimus blood concentration during the early postoperative period. Genotyping before drug administration can help optimize dosing regimens, reduce intra-individual variability, and improve prognosis.
A Regressor-Guided Graph Diffusion Model for Predicting Enzyme Mutations to Enhance Turnover Number
Authors: Xiaozhu Yu, Kai Yi, Yu Guang Wang, Yiqing Shen
Date: 2024-11-04 00:00:00

Enzymes are biological catalysts that can accelerate chemical reactions compared to uncatalyzed reactions in aqueous environments. Their catalytic efficiency is quantified by the turnover number (kcat), a parameter in enzyme kinetics. Enhancing enzyme activity is important for optimizing slow chemical reactions, with far-reaching implications for both research and industrial applications. However, traditional wet-lab methods for measuring and optimizing enzyme activity are often resource-intensive and time-consuming. To address these limitations, we introduce kcatDiffuser, a novel regressor-guided diffusion model designed to predict and improve enzyme turnover numbers. Our approach innovatively reformulates enzyme mutation prediction as a protein inverse folding task, thereby establishing a direct link between structural prediction and functional optimization. kcatDiffuser is a graph diffusion model guided by a regressor, enabling the prediction of amino acid mutations at multiple random positions simultaneously. Evaluations on BERENDA dataset shows that kcatDiffuser can achieve a {\Delta} log kcat of 0.209, outperforming state-of-the-art methods like ProteinMPNN, PiFold, GraDe-IF in improving enzyme turnover numbers. Additionally, kcatDiffuser maintains high structural fidelity with a recovery rate of 0.716, pLDDT score of 92.515, RMSD of 3.764, and TM-score of 0.934, demonstrating its ability to generate enzyme variants with enhanced activity while preserving essential structural properties. Overall, kcatDiffuser represents a more efficient and targeted approach to enhancing enzyme activity. The code is available at https://github.com/xz32yu/KcatDiffuser.
LaGDif: Latent Graph Diffusion Model for Efficient Protein Inverse Folding with Self-Ensemble
Authors: Taoyu Wu, Yu Guang Wang, Yiqing Shen
Date: 2024-11-04 00:00:00
Tasks: Drug Discovery

Protein inverse folding aims to identify viable amino acid sequences that can fold into given protein structures, enabling the design of novel proteins with desired functions for applications in drug discovery, enzyme engineering, and biomaterial development. Diffusion probabilistic models have emerged as a promising approach in inverse folding, offering both feasible and diverse solutions compared to traditional energy-based methods and more recent protein language models. However, existing diffusion models for protein inverse folding operate in discrete data spaces, necessitating prior distributions for transition matrices and limiting smooth transitions and gradients inherent to continuous spaces, leading to suboptimal performance. Drawing inspiration from the success of diffusion models in continuous domains, we introduce the Latent Graph Diffusion Model for Protein Inverse Folding (LaGDif). LaGDif bridges discrete and continuous realms through an encoder-decoder architecture, transforming protein graph data distributions into random noise within a continuous latent space. Our model then reconstructs protein sequences by considering spatial configurations, biochemical attributes, and environmental factors of each node. Additionally, we propose a novel inverse folding self-ensemble method that stabilizes prediction results and further enhances performance by aggregating multiple denoised output protein sequence. Empirical results on the CATH dataset demonstrate that LaGDif outperforms existing state-of-the-art techniques, achieving up to 45.55% improvement in sequence recovery rate for single-chain proteins and maintaining an average RMSD of 1.96 {\AA} between generated and native structures. The code is public available at https://github.com/TaoyuW/LaGDif.
Radical-mediated Electrical Enzyme Assay For At-home Clinical Test
Authors: Hyun-June Jang, Hyou-Arm Joung, Xiaoao Shi, Rui Ding, Justine Wagner, Erting Tang, Wen Zhuang, Byunghoon Ryu, Guanmin Chen, Kiang-Teck Jerry Yeo, Jun Huang, Junhong Chen
Date: 2024-11-03 00:00:00

To meet the growing demand for accurate, rapid, and cost-effective at-home clinical testing, we developed a radical-mediated enzyme assay (REEA) integrated with a paper fluidic system and electrically read by a handheld field-effect transistor (FET) device. The REEA utilizes horseradish peroxidase (HRP) to catalyze the conversion of aromatic substrates into radical forms, producing protons detected by an ion-sensitive FET for biomarker quantification. Through screening 14 phenolic compounds, halogenated phenols emerged as optimal substrates for the REEA. Encased in an affordable cartridge ($0.55 per test), the system achieved a detection limit of 146 fg/mL for estradiol (E2), with a coefficient of variation (CV) below 9.2% in E2-spiked samples and an r2 of 0.963 across a measuring range of 19 to 4,551 pg/mL in clinical plasma samples, providing results in under 10 minutes. This adaptable system not only promises to offer a fast and reliable platform, but also holds significant potential for expansion to a wide array of biomarkers, paving the way for broader clinical and home-based applications.
GatingTree: Pathfinding Analysis of Group-Specific Effects in Cytometry Data
Authors: Masahiro Ono
Date: 2024-10-31 00:00:00

Advancements in cytometry technologies have led to a remarkable increase in the number of markers that can be analyzed simultaneously, presenting significant challenges in data analysis. Traditional approaches, such as dimensional reduction techniques and computational clustering, although popular, often face reproducibility challenges due to their heavy reliance on inherent data structures, preventing direct translation of their outputs into gating strategies to be used in downstream experiments. Here we propose the novel Gating Tree methodology, a pathfinding approach that investigates the multidimensional data landscape to unravel group-specific features without the use of dimensional reduction. This method employs novel measures, including enrichment scores and gating entropy, to effectively identify group-specific features within high-dimensional cytometric datasets. Our analysis, applied to both simulated and real cytometric datasets, demonstrates that the Gating Tree not only identifies group-specific features comprehensively but also produces outputs that are immediately usable as gating strategies for unequivocally identifying cell populations. In conclusion, the Gating Tree facilitates a comprehensive analysis of the multidimensional data landscape and provides experimentalists with practical, successive gating strategies that enhance cross-experimental comparisons and downstream analyses such as flow cytometric sorting.
Revolutionizing Personalized Cancer Vaccines with NEO: Novel Epitope Optimization Using an Aggregated Feed Forward and Recurrent Neural Network with LSTM Architecture
Authors: Nishanth Basava
Date: 2024-10-31 00:00:00

As cancer cases continue to rise, with a 2023 study from Zhejiang and Harvard predicting a 31 percent increase in cases and a 21 percent increase in deaths by 2030, the need to find more effective treatments for cancer is greater than ever before. Traditional approaches to treating cancer, such as chemotherapy, often kill healthy cells because of their lack of targetability. In contrast, personalized cancer vaccines can utilize neoepitopes - distinctive peptides on cancer cells that are often missed by the body's immune system - that have strong binding affinities to a patient's MHC to provide a more targeted treatment approach. The selection of optimal neoepitopes that elicit an immune response is a time-consuming and costly process due to the required inputs of modern predictive methods. This project aims to facilitate faster, cheaper, and more accurate neoepitope binding predictions using Feed Forward Neural Networks (FFNN) and Recurrent Neural Networks (RNN). To address this, NEO was created. NEO requires next-generation sequencing data and uses a stacking ensemble method by calculating scores from state-of-the-art models (MHCFlurry 1.6, NetMHCstabpan 1.0, and IEDB). The model's architecture includes an FFNN and an RNN with LSTM layers capable of analyzing both sequential and non-sequential data. The results from both models are aggregated to produce predictions. Using this model, personalized cancer vaccines can be produced with improved results (AUC = 0.9166, recall = 91.67 percent).
What the %PCSA? Addressing Diversity in Lower-Limb Musculoskeletal Models: Age- and Sex-related Differences in PCSA and Muscle Mass
Authors: R. Maarleveld, H. E. J. Veeger, F. C. T. van der Helm, J. Son, R. L. Lieber, E. van der Kruk
Date: 2024-10-31 00:00:00
Tasks: Diversity

Musculoskeletal (MSK) models offer a non-invasive way to understand biomechanical loads on joints and tendons, which are difficult to measure directly. Variations in muscle strength, especially relative differences between muscles, significantly impact model outcomes. Typically, scaled generic MSK models use maximum isometric forces that are not adjusted for different demographics, raising concerns about their accuracy. This review provides an overview on experimentally derived strength parameters, including physiological cross-sectional area (PCSA), muscle mass (Mm), and relative muscle mass (%Mm), which is the relative distribution of muscle mass across the leg. We analysed differences by age and sex, and compared open-source lower limb MSK model parameters with experimental data from 57 studies. Our dataset, with records dating back to 1884, shows that uniformly increasing all maximum isometric forces in MSK models does not capture key muscle ratio differences due to age and sex. Males have a higher proportion of muscle mass in the rectus femoris and semimembranosus muscles, while females have a greater relative muscle mass in the pelvic (gluteus maximus and medius) and ankle muscles (tibialis anterior, tibialis posterior, and extensor digitorum longus). Older adults have a higher relative muscle mass in the gluteus medius, while younger individuals show more in the gastrocnemius. Current MSK models do not accurately represent muscle mass distribution for specific age or sex groups, and none of them accurately reflect female muscle mass distribution. Further research is needed to explore musculotendon age- and sex differences.
Logistic Regression Analysis on the Dietary Behavior and the Risk of Nutritional Deficiency Dermatosis: The Case of Bicol Region, Philippines
Authors: John Ben S Temones
Date: 2024-10-31 00:00:00
Tasks: Diversity, Nutrition, regression

This study explores the link between dietary behavior and the risk of nutritional deficiency dermatoses (NDD) in the Bicol region, where malnutrition remains a concern. Using regression analysis on FNRI data, it examines food purchase patterns, particularly riboflavin intake. Findings show an NDD risk prevalence of 15.75%, with Masbate and Camarines Sur contributing over half of cases. While rice (1590.93 g/day) and plant-based diets (523.30 g/day) are not rich in riboflavin, they still reduce NDD odds by 0.3% per gram. Riboflavin-rich foods like meat, eggs, and dairy lower risks by up to 3% per gram. The logistic regression model demonstrated strong performance (Nagelkerke = 0.765, accuracy = 94.1%, precision = 84.5%). Findings highlight the need for nutrition interventions, including enriched rice, better market access, and food diversity education to improve riboflavin intake and mitigate NDD risks.
Whack-a-mole Online Learning: Physics-Informed Neural Network for Intraday Implied Volatility Surface
Authors: Kentaro Hoshisashi, Carolyn E. Phelan, Paolo Barucca
Date: 2024-11-04 00:00:00

Calibrating the time-dependent Implied Volatility Surface (IVS) using sparse market data is an essential challenge in computational finance, particularly for real-time applications. This task requires not only fitting market data but also satisfying a specified partial differential equation (PDE) and no-arbitrage conditions modelled by differential inequalities. This paper proposes a novel Physics-Informed Neural Networks (PINNs) approach called Whack-a-mole Online Learning (WamOL) to address this multi-objective optimisation problem. WamOL integrates self-adaptive and auto-balancing processes for each loss term, efficiently reweighting objective functions to ensure smooth surface fitting while adhering to PDE and no-arbitrage constraints and updating for intraday predictions. In our experiments, WamOL demonstrates superior performance in calibrating intraday IVS from uneven and sparse market data, effectively capturing the dynamic evolution of option prices and associated risk profiles. This approach offers an efficient solution for intraday IVS calibration, extending PINNs applications and providing a method for real-time financial modelling.
Evaluating Company-specific Biases in Financial Sentiment Analysis using Large Language Models
Authors: Kei Nakagawa, Masanori Hirano, Yugo Fujimoto
Date: 2024-11-01 00:00:00
Tasks: General Knowledge, Sentiment Analysis

This study aims to evaluate the sentiment of financial texts using large language models~(LLMs) and to empirically determine whether LLMs exhibit company-specific biases in sentiment analysis. Specifically, we examine the impact of general knowledge about firms on the sentiment measurement of texts by LLMs. Firstly, we compare the sentiment scores of financial texts by LLMs when the company name is explicitly included in the prompt versus when it is not. We define and quantify company-specific bias as the difference between these scores. Next, we construct an economic model to theoretically evaluate the impact of sentiment bias on investor behavior. This model helps us understand how biased LLM investments, when widespread, can distort stock prices. This implies the potential impact on stock prices if investments driven by biased LLMs become dominant in the future. Finally, we conduct an empirical analysis using Japanese financial text data to examine the relationship between firm-specific sentiment bias, corporate characteristics, and stock performance.
AI in Investment Analysis: LLMs for Equity Stock Ratings
Authors: Kassiani Papasotiriou, Srijan Sood, Shayleen Reynolds, Tucker Balch
Date: 2024-10-30 00:00:00

Investment Analysis is a cornerstone of the Financial Services industry. The rapid integration of advanced machine learning techniques, particularly Large Language Models (LLMs), offers opportunities to enhance the equity rating process. This paper explores the application of LLMs to generate multi-horizon stock ratings by ingesting diverse datasets. Traditional stock rating methods rely heavily on the expertise of financial analysts, and face several challenges such as data overload, inconsistencies in filings, and delayed reactions to market events. Our study addresses these issues by leveraging LLMs to improve the accuracy and consistency of stock ratings. Additionally, we assess the efficacy of using different data modalities with LLMs for the financial domain. We utilize varied datasets comprising fundamental financial, market, and news data from January 2022 to June 2024, along with GPT-4-32k (v0613) (with a training cutoff in Sep. 2021 to prevent information leakage). Our results show that our benchmark method outperforms traditional stock rating methods when assessed by forward returns, specially when incorporating financial fundamentals. While integrating news data improves short-term performance, substituting detailed news summaries with sentiment scores reduces token use without loss of performance. In many cases, omitting news data entirely enhances performance by reducing bias. Our research shows that LLMs can be leveraged to effectively utilize large amounts of multimodal financial data, as showcased by their effectiveness at the stock rating prediction task. Our work provides a reproducible and efficient framework for generating accurate stock ratings, serving as a cost-effective alternative to traditional methods. Future work will extend to longer timeframes, incorporate diverse data, and utilize newer models for enhanced insights.