The intricate interplay between host organisms and their gut microbiota has catalyzed research into the microbiome's role in disease, shedding light on novel aspects of disease pathogenesis. However, the mechanisms through which the microbiome exerts its influence on disease remain largely unclear. In this study, we first introduce a structural equation model to delineate the pathways connecting the microbiome, metabolome, and disease processes, utilizing a target multiview microbiome data. To mitigate the challenges posed by hidden confounders, we further propose an integrative approach that incorporates data from an external microbiome cohort. This method also supports the identification of disease-specific and microbiome-associated metabolites that are missing in the target cohort. We provide theoretical underpinnings for the estimations derived from our integrative approach, demonstrating estimation consistency and asymptotic normality. The effectiveness of our methodologies is validated through comprehensive simulation studies and an empirical application to inflammatory bowel disease, highlighting their potential to unravel the complex relationships between the microbiome, metabolome, and disease.
Longitudinal imaging is able to capture both static anatomical structures and dynamic changes in disease progression towards earlier and better patient-specific pathology management. However, conventional approaches for detecting diabetic retinopathy (DR) rarely take advantage of longitudinal information to improve DR analysis. In this work, we investigate the benefit of exploiting self-supervised learning with a longitudinal nature for DR diagnosis purposes. We compare different longitudinal self-supervised learning (LSSL) methods to model the disease progression from longitudinal retinal color fundus photographs (CFP) to detect early DR severity changes using a pair of consecutive exams. The experiments were conducted on a longitudinal DR screening dataset with or without those trained encoders (LSSL) acting as a longitudinal pretext task. Results achieve an AUC of 0.875 for the baseline (model trained from scratch) and an AUC of 0.96 (95% CI: 0.9593-0.9655 DeLong test) with a p-value < 2.2e-16 on early fusion using a simple ResNet alike architecture with frozen LSSL weights, suggesting that the LSSL latent space enables to encode the dynamic of DR progression.
We propose a method for obtaining parsimonious decompositions of networks into higher order interactions which can take the form of arbitrary motifs.The method is based on a class of analytically solvable generative models, where vertices are connected via explicit copies of motifs, which in combination with non-parametric priors allow us to infer higher order interactions from dyadic graph data without any prior knowledge on the types or frequencies of such interactions. Crucially, we also consider 'degree--corrected' models that correctly reflect the degree distribution of the network and consequently prove to be a better fit for many real world--networks compared to non-degree corrected models. We test the presented approach on simulated data for which we recover the set of underlying higher order interactions to a high degree of accuracy. For empirical networks the method identifies concise sets of atomic subgraphs from within thousands of candidates that cover a large fraction of edges and include higher order interactions of known structural and functional significance. The method not only produces an explicit higher order representation of the network but also a fit of the network to analytically tractable models opening new avenues for the systematic study of higher order network structures.
Arthroplasty is commonly performed to treat joint osteoarthritis, reducing pain and improving mobility. While arthroplasty has known several technical improvements, a significant share of patients are still unsatisfied with their surgery. Personalised arthroplasty improves surgical outcomes however current solutions require delays, making it difficult to integrate in clinical routine. We propose a fully automated workflow to design patient-specific implants, presented for total knee arthroplasty, the most widely performed arthroplasty in the world nowadays. The proposed pipeline first uses artificial neural networks to segment the proximal and distal extremities of the femur and tibia. Then the full bones are reconstructed using augmented statistical shape models, combining shape and landmarks information. Finally, 77 morphological parameters are computed to design patient-specific implants. The developed workflow has been trained using 91 CT scans of lower limb and evaluated on 41 CT scans manually segmented, in terms of accuracy and execution time. The workflow accuracy was $0.4\pm0.2mm$ for the segmentation, $1.2\pm0.4mm$ for the full bones reconstruction, and $2.8\pm2.2mm$ for the anatomical landmarks determination. The custom implants fitted the patients' anatomy with $0.6\pm0.2mm$ accuracy. The whole process from segmentation to implants' design lasted about 5 minutes. The proposed workflow allows for a fast and reliable personalisation of knee implants, directly from the patient CT image without requiring any manual intervention. It establishes a patient-specific pre-operative planning for TKA in a very short time making it easily available for all patients. Combined with efficient implant manufacturing techniques, this solution could help answer the growing number of arthroplasties while reducing complications and improving the patients' satisfaction.
Developing algorithms for accurate and comprehensive neural decoding of mental contents is one of the long-cherished goals in the field of neuroscience and brain-machine interfaces. Previous studies have demonstrated the feasibility of neural decoding by training machine learning models to map brain activity patterns into a semantic vector representation of stimuli. These vectors, hereafter referred as pretrained feature vectors, are usually derived from semantic spaces based solely on image and/or text features and therefore they might have a totally different characteristics than how visual stimuli is represented in the human brain, resulting in limiting the capability of brain decoders to learn this mapping. To address this issue, we propose a representation learning framework, termed brain-grounding of semantic vectors, which fine-tunes pretrained feature vectors to better align with the neural representation of visual stimuli in the human brain. We trained this model this model with functional magnetic resonance imaging (fMRI) of 150 different visual stimuli categories, and then performed zero-shot brain decoding and identification analyses on 1) fMRI and 2) magnetoencephalography (MEG). Interestingly, we observed that by using the brain-grounded vectors, the brain decoding and identification accuracy on brain data from different neuroimaging modalities increases. These findings underscore the potential of incorporating a richer array of brain-derived features to enhance performance of brain decoding algorithms.
Numerous Deep Learning (DL) models have been developed for a large spectrum of medical image analysis applications, which promises to reshape various facets of medical practice. Despite early advances in DL model validation and implementation, which encourage healthcare institutions to adopt them, some fundamental questions remain: are the DL models capable of generalizing? What causes a drop in DL model performances? How to overcome the DL model performance drop? Medical data are dynamic and prone to domain shift, due to multiple factors such as updates to medical equipment, new imaging workflow, and shifts in patient demographics or populations can induce this drift over time. In this paper, we review recent developments in generalization methods for DL-based classification models. We also discuss future challenges, including the need for improved evaluation protocols and benchmarks, and envisioned future developments to achieve robust, generalized models for medical image classification.
Dynamical systems across the sciences, from electrical circuits to ecological networks, undergo qualitative and often catastrophic changes in behavior, called bifurcations, when their underlying parameters cross a threshold. Existing methods predict oncoming catastrophes in individual systems but are primarily time-series-based and struggle both to categorize qualitative dynamical regimes across diverse systems and to generalize to real data. To address this challenge, we propose a data-driven, physically-informed deep-learning framework for classifying dynamical regimes and characterizing bifurcation boundaries based on the extraction of topologically invariant features. We focus on the paradigmatic case of the supercritical Hopf bifurcation, which is used to model periodic dynamics across a wide range of applications. Our convolutional attention method is trained with data augmentations that encourage the learning of topological invariants which can be used to detect bifurcation boundaries in unseen systems and to design models of biological systems like oscillatory gene regulatory networks. We further demonstrate our method's use in analyzing real data by recovering distinct proliferation and differentiation dynamics along pancreatic endocrinogenesis trajectory in gene expression space based on single-cell data. Our method provides valuable insights into the qualitative, long-term behavior of a wide range of dynamical systems, and can detect bifurcations or catastrophic transitions in large-scale physical and biological systems.
The latency location routing problem integrates the facility location problem and the multi-depot cumulative capacitated vehicle routing problem. This problem involves making simultaneous decisions about depot locations and vehicle routes to serve customers while aiming to minimize the sum of waiting (arriving) times for all customers. To address this computationally challenging problem, we propose a reinforcement learning guided hybrid evolutionary algorithm following the framework of the memetic algorithm. The proposed algorithm relies on a diversity-enhanced multi-parent edge assembly crossover to build promising offspring and a reinforcement learning guided variable neighborhood descent to determine the exploration order of multiple neighborhoods. Additionally, strategic oscillation is used to achieve a balanced exploration of both feasible and infeasible solutions. The competitiveness of the algorithm against state-of-the-art methods is demonstrated by experimental results on the three sets of 76 popular instances, including 51 improved best solutions (new upper bounds) for the 59 instances with unknown optima and equal best results for the remaining instances. We also conduct additional experiments to shed light on the key components of the algorithm.
Recently, the increasing availability of repeated measurements in biomedical studies has motivated the development of several statistical methods for the dynamic prediction of survival in settings where a large (potentially high-dimensional) number of longitudinal covariates is available. These methods differ in both how they model the longitudinal covariates trajectories, and how they specify the relationship between the longitudinal covariates and the survival outcome. Because these methods are still quite new, little is known about their applicability, limitations and performance when applied to real-world data. To investigate these questions, we present a comparison of the predictive performance of the aforementioned methods and two simpler prediction approaches to three datasets that differ in terms of outcome type, sample size, number of longitudinal covariates and length of follow-up. We discuss how different modelling choices can have an impact on the possibility to accommodate unbalanced study designs and on computing time, and compare the predictive performance of the different approaches using a range of performance measures and landmark times.
In many communication contexts, the capabilities of the involved actors cannot be known beforehand, whether it is a cell, a plant, an insect, or even a life form unknown to Earth. Regardless of the recipient, the message space and time scale could be too fast, too slow, too large, or too small and may never be decoded. Therefore, it pays to devise a way to encode messages agnostic of space and time scales. We propose the use of fractal functions as self-executable infinite-frequency carriers for sending messages, given their properties of structural self-similarity and scale invariance. We call it `fractal messaging'. Starting from a spatial embedding, we introduce a framework for a space-time scale-free messaging approach to this challenge. When considering a space and time-agnostic framework for message transmission, it would be interesting to encode a message such that it could be decoded at several spatio-temporal scales. Hence, the core idea of the framework proposed herein is to encode a binary message as waves along infinitely many frequencies (in power-like distributions) and amplitudes, transmit such a message, and then decode and reproduce it. To do so, the components of the Weierstrass function, a known fractal, are used as carriers of the message. Each component will have its amplitude modulated to embed the binary stream, allowing for a space-time-agnostic approach to messaging.
Graph representation learning for hypergraphs can be used to extract patterns among higher-order interactions that are critically important in many real world problems. Current approaches designed for hypergraphs, however, are unable to handle different types of hypergraphs and are typically not generic for various learning tasks. Indeed, models that can predict variable-sized heterogeneous hyperedges have not been available. Here we develop a new self-attention based graph neural network called Hyper-SAGNN applicable to homogeneous and heterogeneous hypergraphs with variable hyperedge sizes. We perform extensive evaluations on multiple datasets, including four benchmark network datasets and two single-cell Hi-C datasets in genomics. We demonstrate that Hyper-SAGNN significantly outperforms the state-of-the-art methods on traditional tasks while also achieving great performance on a new task called outsider identification. Hyper-SAGNN will be useful for graph representation learning to uncover complex higher-order interactions in different applications.