pwc-archive/papers-with-abstracts huggingface dataset:
Generative Models with ELBOs Converging to Entropy Sums
Authors: Jan Warnken, Dmytro Velychko, Simon Damm, Asja Fischer, Jörg Lücke
Date: 2024-12-25 00:00:00

The evidence lower bound (ELBO) is one of the most central objectives for probabilistic unsupervised learning. For the ELBOs of several generative models and model classes, we here prove convergence to entropy sums. As one result, we provide a list of generative models for which entropy convergence has been shown, so far, along with the corresponding expressions for entropy sums. Our considerations include very prominent generative models such as probabilistic PCA, sigmoid belief nets or Gaussian mixture models. However, we treat more models and entire model classes such as general mixtures of exponential family distributions. Our main contributions are the proofs for the individual models. For each given model we show that the conditions stated in Theorem 1 or Theorem 2 of [arXiv:2209.03077] are fulfilled such that by virtue of the theorems the given model's ELBO is equal to an entropy sum at all stationary points. The equality of the ELBO at stationary points applies under realistic conditions: for finite numbers of data points, for model/data mismatches, at any stationary point including saddle points etc, and it applies for any well behaved family of variational distributions.
COLOR: A compositional linear operation-based representation of protein sequences for identification of monomer contributions to properties
Authors: Akash Pandey, Wei Chen, Sinan Keten
Date: 2025-01-10 00:00:00

The properties of biological materials like proteins and nucleic acids are largely determined by their primary sequence. While certain segments in the sequence strongly influence specific functions, identifying these segments, or so-called motifs, is challenging due to the complexity of sequential data. While deep learning (DL) models can accurately capture sequence-property relationships, the degree of nonlinearity in these models limits the assessment of monomer contributions to a property - a critical step in identifying key motifs. Recent advances in explainable AI (XAI) offer attention and gradient-based methods for estimating monomeric contributions. However, these methods are primarily applied to classification tasks, such as binding site identification, where they achieve limited accuracy (40-45%) and rely on qualitative evaluations. To address these limitations, we introduce a DL model with interpretable steps, enabling direct tracing of monomeric contributions. We also propose a metric ($\mathcal{I}$), inspired by the masking technique in the field of image analysis and natural language processing, for quantitative analysis on datasets mainly containing distinct properties of anti-cancer peptides (ACP), antimicrobial peptides (AMP), and collagen. Our model exhibits 22% higher explainability, pinpoints critical motifs (RRR, RRI, and RSS) that significantly destabilize ACPs, and identifies motifs in AMPs that are 50% more effective in converting non-AMPs to AMPs. These findings highlight the potential of our model in guiding mutation strategies for designing protein-based biomaterials.
Prediction of Binding Affinity for ErbB Inhibitors Using Deep Neural Network Model with Morgan Fingerprints as Features
Authors: La Ode Aman
Date: 2025-01-09 00:00:00
Tasks: Drug Discovery

The ErbB receptor family, including EGFR and HER2, plays a crucial role in cell growth and survival and is associated with the progression of various cancers such as breast and lung cancer. In this study, we developed a deep learning model to predict the binding affinity of ErbB inhibitors using molecular fingerprints derived from SMILES representations. The SMILES representations for each ErbB inhibitor were obtained from the ChEMBL database. We first generated Morgan fingerprints from the SMILES strings and applied AutoDock Vina docking to calculate the binding affinity values. After filtering the dataset based on binding affinity, we trained a deep neural network (DNN) model to predict binding affinity values from the molecular fingerprints. The model achieved significant performance, with a Mean Squared Error (MSE) of 0.2591, Mean Absolute Error (MAE) of 0.3658, and an R-squared value of 0.9389 on the training set. Although performance decreased slightly on the test set (R squared = 0.7731), the model still demonstrated robust generalization capabilities. These results indicate that the deep learning approach is highly effective for predicting the binding affinity of ErbB inhibitors, offering a valuable tool for virtual screening and drug discovery.
The Jungle of Generative Drug Discovery: Traps, Treasures, and Ways Out
Authors: Rıza Özçelik, Francesca Grisoni
Date: 2024-12-24 00:00:00
Tasks: Benchmarking, Deep Learning, Drug Discovery, Navigate

"How to evaluate de novo designs proposed by a generative model?" Despite the transformative potential of generative deep learning in drug discovery, this seemingly simple question has no clear answer. The absence of standardized guidelines challenges both the benchmarking of generative approaches and the selection of molecules for prospective studies. In this work, we take a fresh $- \textit{critical}$ and $\textit{constructive} -$ perspective on de novo design evaluation. We systematically investigate widely used evaluation metrics and expose key pitfalls ('traps') that were previously overlooked. In addition, we identify tools ('treasures') and strategies ('ways out') to navigate the complex 'jungle' of generative drug discovery, and strengthen the connections between the molecular and deep learning fields along the way. Our systematic and large-scale results are expected to provide a new lens for evaluating the de novo designs proposed by generative deep learning approaches.
Neuroblastoma: nutritional strategies as supportive care in pediatric oncology
Authors: Hafida Hamdache, Alexia Gazeu, Marion Gambart, Nathalie Bendriss-Vermare, Vera Pancaldi
Date: 2025-01-15 00:00:00
Tasks: Nutrition

Neuroblastoma, is a highly heterogeneous pediatric tumour and is responsible for 15% of pediatric cancer-related deaths. The clinical outcomes can vary from spontaneous regression to high metastatic disease. This extracranial tumour arises from a neural crest-derived cell and can harbor different phenotypes. Its heterogeneity may result from variations in differentiation states influenced by genetic and epigenetic factors and individual patient characteristics. This leads downstream to disruption of homeostasis and a metabolic shift in response to the tumour needs. Nutrition can play a key role in influencing various aspects of a tumour behaviour. This review provides an in-depth exploration of the aetiology of neuroblastoma and the different avenues of disease progression, which can be targeted with individualized nutrition intervention strategies to improve the well-being of children and optimize clinical outcomes.
Interplay of Electrostatic Interaction and Steric Repulsion between Bacteria and Gold Surface Influences Raman Enhancement
Authors: Jia Dong, Jeong Hee Kim, Isaac Pincus, Sujan Manna, Jennifer M. Podgorski, Yanmin Zhu, Loza F. Tadesse
Date: 2025-01-12 00:00:00

Plasmonic nanostructures have wide applications in photonics including pathogen detection and diagnosis via Surface-Enhanced Raman Spectroscopy (SERS). Despite major role plasmonics play in signal enhancement, electrostatics in SERS is yet to be fully understood and harnessed. Here, we perform a systematic study of electrostatic interactions between 785 nm resonant gold nanorods designed to harbor zeta potentials of +29, +16, 0 and -9 mV spanning positive neutral and negative domains. SERS activity is tested on representative Gram-negative Escherichia coli and Gram-positive Staphylococcus epidermidis bacteria with zeta potentials of -30 and -23 mV respectively in water. Raman spectroscopy and Cryo-Electron microscopy reveal that +29, +16, 0 and -9 mV nanorods give SERS enhancement of 7.2X, 3.6X, 4.2X, 1.3X to Staphylococcus epidermidis and 3.9X, 2.8X, 2.9X, 1.1X to Escherichia coli. Theoretical results show that electrostatics play the major role among all interaction forces in determining cell-nanorod proximity and signal enhancement. We identify steric repulsion due to cell protrusions to be the critical opposing force. Finally, a design principle is proposed to estimate the electrostatic strength in SERS. Our work provides new insights into the principle of bacteria-nanorod interactions, enabling reproducible and precise biomolecular readouts, critical for next-generation point-of-care diagnostics and smart healthcare applications.
TopoLa: A Universal Framework to Enhance Cell Representations for Single-cell and Spatial Omics through Topology-encoded Latent Hyperbolic Geometry
Authors: Kai Zheng, Shaokai Wang, Yunpei Xu, Qiming Lei, Qichang Zhao, Xiao Liang, Qilong Feng, Yaohang Li, Min Li, Jinhui Xu, Jianxin Wang
Date: 2025-01-14 00:00:00

Recent advances in cellular research demonstrate that scRNA-seq characterizes cellular heterogeneity, while spatial transcriptomics reveals the spatial distribution of gene expression. Cell representation is the fundamental issue in the two fields. Here, we propose Topology-encoded Latent Hyperbolic Geometry (TopoLa), a computational framework enhancing cell representations by capturing fine-grained intercellular topological relationships. The framework introduces a new metric, TopoLa distance (TLd), which quantifies the geometric distance between cells within latent hyperbolic space, capturing the network's topological structure more effectively. With this framework, the cell representation can be enhanced considerably by performing convolution on its neighboring cells. Performance evaluation across seven biological tasks, including scRNA-seq data clustering and spatial transcriptomics domain identification, shows that TopoLa significantly improves the performance of several state-of-the-art models. These results underscore the generalizability and robustness of TopoLa, establishing it as a valuable tool for advancing both biological discovery and computational methodologies.
Data mining the functional architecture of the brain's circuitry
Authors: Adam S. Charles
Date: 2025-01-16 00:00:00
Tasks: Anatomy

The brain is a highly complex organ consisting of a myriad of subsystems that flexibly interact and adapt over time and context to enable perception, cognition, and behavior. Understanding the multi-scale nature of the brain, i.e., how circuit- and moleclular-level interactions build up the fundamental components of brain function, holds incredible potential for developing interventions for neurodegenerative and psychiatric diseases, as well as open new understanding into our very nature. Historically technological limitations have forced systems neuroscience to be local in anatomy (localized, small neural populations in single brain areas), in behavior (studying single tasks), in time (focusing on specific stages of learning or development), and in modality (focusing on imaging single biological quantities). New developments in neural recording technology and behavioral monitoring now provide the data needed to break free of local neuroscience to global neuroscience: i.e., understanding how the brain's many subsystem interact, adapt, and change across the multitude of behaviors animals and humans must perform to thrive. Specifically, while we have much knowledge of the anatomical architecture of the brain (i.e., the hardware), we finally are approaching the data needed to find the functional architecture and discover the fundamental properties of the software that runs on the hardware. We must take this opportunity to bridge between the vast amounts of data to discover this functional architecture which will face numerous challenges from low-level data alignment up to high level questions of interpretable mathematical models of behavior that can synthesize the myriad of datasets together.
Causal Spike Timing Dependent Plasticity Prevents Assembly Fusion in Recurrent Networks
Authors: Xinruo Yang, Brent Doiron
Date: 2025-01-16 00:00:00
Tasks: Specificity

The organization of neurons into functionally related assemblies is a fundamental feature of cortical networks, yet our understanding of how these assemblies maintain distinct identities while sharing members remains limited. Here we analyze how spike-timing-dependent plasticity (STDP) shapes the formation and stability of overlapping neuronal assemblies in recurrently coupled networks of spiking neuron models. Using numerical simulations and an associated mean-field theory, we demonstrate that the temporal structure of the STDP rule, specifically its degree of causality, critically determines whether assemblies that share neurons maintain segregation or merge together after training is completed. We find that causal STDP rules, where potentiation/depression occurs strictly when presynaptic spikes precede/proceed postsynaptic spikes, allow assemblies to remain distinct even with substantial overlap in membership. This stability arises because causal STDP effectively cancels the symmetric correlations introduced by common inputs from shared neurons. In contrast, acausal STDP rules lead to assembly fusion when overlap exceeds a critical threshold, due to unchecked growth of common input correlations. Our results provide theoretical insight into how spike-timing-dependent learning rules can support distributed representation where individual neurons participate in multiple assemblies while maintaining functional specificity.
A UDP Packet Format Establishing Adress Event Representation Communication Between Remote Neuromorphic and Biological Setups
Authors: Christian Georg Mayr, Richard Miru George, Mattia Tambaro, Giacomo Indiveri
Date: 2025-01-15 00:00:00

In the field of brain-machine interfaces, biohybrids offer an interesting new perspective, as in them, the technological side acts like a closed-loop extension or real counterpart of biological tissue, instead of the usual open loop approaches in tranditional BMI. To achieve a credible counterpart to biological tissue, biohybrids usually employ one or several neuromorphic components as the hardware half of the biohybrid. However, advanced neuromorphic circuit such as memristor crossbars usually operate best in a dedicated lab with corresponding support equipment. The same is true for biological tissue, which makes co-locating all of the parts of a biohybrid in the same lab challenging. Here, we present as solution to this co-location issue a simple method to connect biohybrids via the internet by a custom UDP packet format. We show that the characteristics achieved with our solution (jitter, delay, packet loss, packet reordering) on a standard internet connection are compatible with various biohybrid processing paradigms, and we present a short three-ways experiment as proof-of-concept. The described UDP format has been employed to link biohybrids and neuromorphic circuits in four different EC-funded projects.
Inferring collective synchrony observing spiking of one or several neurons
Authors: Arkady Pikovsky, Michael Rosenblum
Date: 2025-01-13 00:00:00
Tasks: Spike Sorting

We tackle a quantification of synchrony in a large ensemble of interacting neurons from the observation of spiking events. In a simulation study, we efficiently infer the synchrony level in a neuronal population from a point process reflecting spiking of a small number of units and even from a single neuron. We introduce a synchrony measure (order parameter) based on the Bartlett covariance density; this quantity can be easily computed from the recorded point process. This measure is robust concerning missed spikes and, if computed from observing several neurons, does not require spike sorting. We illustrate the approach by modeling populations of spiking or bursting neurons, including the case of sparse synchrony.
The tardigrade as an emerging model organism for systems neuroscience
Authors: Ana M. Lyons, Saul Kato
Date: 2025-01-11 00:00:00

We present the case for developing the tardigrade (Hypsibius exemplaris) into a model organism for systems neuroscience. These microscopic, transparent animals (~300-500 microns) are among the smallest known to possess both limbs (eight) and eyes (two), with a nervous system of only a few hundred neurons organized into a multi-lobed brain, ventral nerve cord, and a series of ganglia along the body. Despite their neuroanatomical simplicity, tardigrades exhibit complex behaviors, including multi-limbed walking gaits, individual limb grasping, phototaxis, and transitions between active and dormant states. These behaviors position tardigrades as a uniquely powerful system for addressing certain fundamental questions in systems neuroscience, such as: How do nervous systems coordinate multi-limbed behaviors? How are top-down and bottom-up motor control systems integrated? How is stereovision-guided navigation implemented? What mechanisms underlie neural resilience and recovery during environmental stress? We review current knowledge of tardigrade neuroanatomy, behavior, and genomics, and we identify opportunities and challenges for leveraging their unique biology. We propose developing essential neuroscientific tools for tardigrades, including genetic engineering and live neuroimaging, alongside behavioral assays linking neural activity to outputs. Leveraging their evolutionary ties to Caenorhabditis elegans and Drosophila melanogaster, we can adapt existing toolkits to accelerate tardigrade research - providing a bridge between simpler invertebrate systems and more complex neural architectures.
High-throughput digital twin framework for predicting neurite deterioration using MetaFormer attention
Authors: Kuanren Qian, Genesis Omana Suarez, Toshihiko Nambara, Takahisa Kanekiyo, Yongjie Jessica Zhang
Date: 2024-12-18 00:00:00
Tasks: Synthetic Data Generation

Neurodevelopmental disorders (NDDs) cover a variety of conditions, including autism spectrum disorder, attention-deficit/hyperactivity disorder, and epilepsy, which impair the central and peripheral nervous systems. Their high comorbidity and complex etiologies present significant challenges for accurate diagnosis and effective treatments. Conventional clinical and experimental studies are time-intensive, burdening research progress considerably. This paper introduces a high-throughput digital twin framework for modeling neurite deteriorations associated with NDDs, integrating synthetic data generation, experimental images, and machine learning (ML) models. The synthetic data generator utilizes an isogeometric analysis (IGA)-based phase field model to capture diverse neurite deterioration patterns such as neurite retraction, atrophy, and fragmentation while mitigating the limitations of scarce experimental data. The ML model utilizes MetaFormer-based gated spatiotemporal attention architecture with deep temporal layers and provides fast predictions. The framework effectively captures long-range temporal dependencies and intricate morphological transformations with average errors of 1.9641% and 6.0339% for synthetic and experimental neurite deterioration, respectively. Seamlessly integrating simulations, experiments, and ML, the digital twin framework can guide researchers to make informed experimental decisions by predicting potential experimental outcomes, significantly reducing costs and saving valuable time. It can also advance our understanding of neurite deterioration and provide a scalable solution for exploring complex neurological mechanisms, contributing to the development of targeted treatments.
An Asymptotic Analysis of Bivalent Monoclonal Antibody-Antigen Binding
Authors: Luke A Heirene, Helen M Byrne, James W T Yates, Eamonn A Gaffney
Date: 2025-01-16 00:00:00
Tasks: parameter estimation

Ligand-receptor interactions are fundamental to many biological processes. For example in antibody-based immunotherapies, the dynamics of an antibody binding with its target antigen directly influence the potency and efficacy of monoclonal antibody (mAb) therapies. In this paper, we present an asymptotic analysis of an ordinary differential equation (ODE) model of bivalent antibody-antigen binding in the context of mAb cancer therapies, highlighting the added complexity associated with bivalency of the antibody. To understand what drives the complex temporal dynamics of bivalent antibody-antigen binding, we construct asymptotic approximations to the model's solutions at different timescales and antibody concentrations that are in good agreement with numerical simulations of the full model. We show how the dynamics differ between two scenarios; a region where unbound antigens are abundant, and one where the number of unbound antigens is small such that the dominant balance within the model equations changes. Of particular importance to the potency and efficacy of mAb treatments are the values of quantities such as antigen occupancy and bound antibody number. We use the results of our asymptotic analysis to approximate the long-time values of these quantities that could be combined with experimental data to facilitate parameter estimation.
Être mineur non accompagné à Paris: exploration des facteurs déterminants des besoins en santé physique et mentale par une étude qualitative
Authors: Lignon Lignon, Juan Diego Poveda, Stéphanie Wakap Nguengang, Lara Gautier
Date: 2025-01-15 00:00:00

In France, government protection of unaccompanied minors (UMs) depends upon the recognition of their minority status and often result in a rejection. A significant proportion of UMs therefore find themselves unprotected. This qualitative study explores the contextual and individual factors that shape the physical and mental health needs of unprotected UMs in Paris. Interviews were conducted with UMs (n=12) and those working with them (n=36). A deductive-inductive thematic analysis was carried out. The study contributes to the analysis of the health determinants of unprotected UMs. It shows that institutional barriers limit the scope for action by civil society in the palliative care they receive. The consequence for them is living in conditions of instability and precariousness, with very little prospects for the future, which has a negative impact on their physical and mental health.
On the stability of competitive ecological communities with pairwise and higher-order interactions
Authors: Marc Duran-Sala, Sandro Meloni, Violeta Calleja-Solanas
Date: 2025-01-15 00:00:00

Ecological communities intrigue researchers seeking to explain the emergence of biodiversity observed in nature. This raises a fundamental question. What sustains the stability and coexistence of species within these ecosystems? Traditional ecological models have largely been based on the assumption that species primarily engage in pairwise interactions. However, interactions in ecological systems may involve groups of three or more individuals, i.e. higher-order interactions. As a result, the question of how the combined effects of pairwise and higher-order interactions shape the stability of large ecological communities remains unresolved. This work addresses this gap by analyzing a model of competitive communities that incorporates both pairwise and higher-order interactions. Using analytical techniques and numerical simulations, we find that higher-order interactions alone are not always sufficient to foster and maintain coexistence. When species are identical (i.e., have the same physiological rates), even a small proportion of higher-order interactions can stabilize their dynamics. However, when more realistic factors, such as varied birth and death rates or complex interaction structures are introduced, a finite fraction of higher-order interactions may not be sufficient to achieve stable coexistence. Our findings challenge the role of higher-order interactions as a universal stabilizing mechanism in ecological communities and open new avenues for research into the interplay of different factors that underpin biodiversity and ecosystem stability.