Drug-target affinity (DTA) prediction is a critical aspect of drug discovery. The meaningful representation of drugs and targets is crucial for accurate prediction. Using 1D string-based representations for drugs and targets is a common approach that has demonstrated good results in drug-target affinity prediction. However, these approach lacks information on the relative position of the atoms and bonds. To address this limitation, graph-based representations have been used to some extent. However, solely considering the structural aspect of drugs and targets may be insufficient for accurate DTA prediction. Integrating the functional aspect of these drugs at the genetic level can enhance the prediction capability of the models. To fill this gap, we propose GramSeq-DTA, which integrates chemical perturbation information with the structural information of drugs and targets. We applied a Grammar Variational Autoencoder (GVAE) for drug feature extraction and utilized two different approaches for protein feature extraction: Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). The chemical perturbation data is obtained from the L1000 project, which provides information
Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential
Advances in computational modeling, neuroimaging, and artificial intelligence are revolutionizing the modeling of neurological disorders for improved diagnostics, prognosis, and treatment planning. Mechanistic models provide valuable scientific insight into the disorders, but in practice they are often simplified with assumptions or computationally expensive and slow to solve. However, while purely data driven approaches provide speed and scalability, they require large, high quality data to train and generally suffer from interpretability and generalization issues. This perspective paper presents a structured overview of hybrid modeling strategies, which combine deep learning models with physics based solvers, and are categorized into parallel, series, and parallel-series architectures. Three main approaches that have been emphasized are residual modeling for missing or incomplete physics, Neural Ordinary Differential Equations (NODEs) for continuous time dynamics approximation, and solver in the loop that accelerates traditional solvers with neural approximations. These hybrid models integrate the governing differential equation based formulations and deep learning to characteriz
Drug-target interaction (DTI) prediction is a critical component of the drug discovery process. In the drug development engineering field, predicting novel drug-target interactions is extremely crucial.However, although existing methods have achieved high accuracy levels in predicting known drugs and drug targets, they fail to utilize global protein information during DTI prediction. This leads to an inability to effectively predict interaction the interactions between novel drugs and their targets. As a result, the cross-field information fusion strategy is employed to acquire local and global protein information. Thus, we propose the siamese drug-target interaction SiamDTI prediction method, which utilizes a double channel network structure for cross-field supervised learning.Experimental results on three benchmark datasets demonstrate that SiamDTI achieves higher accuracy levels than other state-of-the-art (SOTA) methods on novel drugs and targets.Additionally, SiamDTI's performance with known drugs and targets is comparable to that of SOTA approachs. The code is available at https://anonymous.4open.science/r/DDDTI-434D.
Automated facial expression quality assessment (FEQA) in neurological disorders is critical for enhancing diagnostic accuracy and improving patient care, yet effectively capturing the subtle motions and nuances of facial muscle movements remains a challenge. We propose to analyse facial landmark trajectories, a compact yet informative representation, that encodes these subtle motions from a high-level structural perspective. Hence, we introduce Trajectory-guided Motion Perception Transformer (TraMP-Former), a novel FEQA framework that fuses landmark trajectory features for fine-grained motion capture with visual semantic cues from RGB frames, ultimately regressing the combined features into a quality score. Extensive experiments demonstrate that TraMP-Former achieves new state-of-the-art performance on benchmark datasets with neurological disorders, including PFED5 (up by 6.51%) and an augmented Toronto NeuroFace (up by 7.62%). Our ablation studies further validate the efficiency and effectiveness of landmark trajectories in FEQA. Our code is available at https://github.com/shuchaoduan/TraMP-Former.
Neurological disorders involve diverse pathologies of the brain and nervous system, making early and accurate detection essential. While many deep CNNs have been developed for MRI-based classification of neurological disorders, most are optimized for binary tasks and often fail to capture the multi-class features needed to distinguish subtle anatomical differences across conditions. This study proposes the Enhanced Neurological Disorder Detection Network (End-Net) for multi-class MRI classification of neurological disorders. End-Net includes 24 convolutional layers, beginning with convolutional blocks followed by 21 optimized inception modules. These modules extract multiscale features via parallel 1 x 1, 3 x 3, and factorized 5 x 5 convolutional branches, along with max pooling, enabling the model to capture complementary texture, edge, shape, and contextual information. A global average pooling head, compact fully connected classifier, and dropout reduce parameters, limit overfitting, and improve robustness. End-Net was evaluated on the Multi-Class Neurological Disorder dataset, comprising MRI scans from patients with Alzheimer's disease, brain tumors, multiple sclerosis, and hea
Accurately predicting drug-target interactions (DTIs) is pivotal for advancing drug discovery and target validation techniques. While machine learning approaches including those that are based on Graph Neural Networks (GNN) have achieved notable success in DTI prediction, many of them have difficulties in effectively integrating the diverse features of drugs, targets and their interactions. To address this limitation, we introduce a novel framework to take advantage of the power of both transductive learning and inductive learning so that features at molecular level and drug-target interaction network level can be exploited. Within this framework is a GNN-based model called Graph-in-Graph (GiG) that represents graphs of drug and target molecular structures as meta-nodes in a drug-target interaction graph, enabling a detailed exploration of their intricate relationships. To evaluate the proposed model, we have compiled a special benchmark comprising drug SMILES, protein sequences, and their interaction data, which is interesting in its own right. Our experimental results demonstrate that the GiG model significantly outperforms existing approaches across all evaluation metrics, highl
Current research in machine learning and artificial intelligence is largely centered on modeling and performance evaluation, less so on data collection. However, recent research demonstrated that limitations and biases in data may negatively impact trustworthiness and reliability. These aspects are particularly impactful on sensitive domains such as mental health and neurological disorders, where speech data are used to develop AI applications for patients and healthcare providers. In this paper, we chart the landscape of available speech datasets for this domain, to highlight possible pitfalls and opportunities for improvement and promote fairness and diversity. We present a comprehensive list of desiderata for building speech datasets for mental health and neurological disorders and distill it into an actionable checklist focused on ethical concerns to foster more responsible research.
Development of new medications is a very lengthy and costly process. Finding novel indications for existing drugs, or drug repositioning, can serve as a useful strategy to shorten the development cycle. In this study, we present an approach to drug discovery or repositioning by predicting indication for a particular disease based on expression profiles of drugs, with a focus on applications in psychiatry. Drugs that are not originally indicated for the disease but with high predicted probabilities serve as good candidates for repurposing. This framework is widely applicable to any chemicals or drugs with expression profiles measured, even if the drug targets are unknown. It is also highly flexible as virtually any supervised learning algorithms can be used. We applied this approach to identify repositioning opportunities for schizophrenia as well as depression and anxiety disorders. We applied various state-of-the-art machine learning (ML) approaches for prediction, including deep neural networks, support vector machines (SVM), elastic net, random forest and gradient boosted machines. The performance of the five approaches did not differ substantially, with SVM slightly outperforme
The drug discovery and development process is a long and expensive one, costing over 1 billion USD on average per drug and taking 10-15 years. To reduce the high levels of attrition throughout the process, there has been a growing interest in applying machine learning methodologies to various stages of drug discovery and development in the recent decade, especially at the earliest stage identification of druggable disease genes. In this paper, we have developed a new tensor factorisation model to predict potential drug targets (genes or proteins) for treating diseases. We created a three dimensional data tensor consisting of 1,048 gene targets, 860 diseases and 230,011 evidence attributes and clinical outcomes connecting them, using data extracted from the Open Targets and PharmaProjects databases. We enriched the data with gene target representations learned from a drug discovery oriented knowledge graph and applied our proposed method to predict the clinical outcomes for unseen gene target and disease pairs. We designed three evaluation strategies to measure the prediction performance and benchmarked several commonly used machine learning classifiers together with Bayesian matrix
The first step in drug discovery is finding drug molecule moieties with medicinal activity against specific targets. Therefore, it is crucial to investigate the interaction between drug-target proteins and small chemical molecules. However, traditional experimental methods for discovering potential small drug molecules are labor-intensive and time-consuming. There is currently a lot of interest in building computational models to screen small drug molecules using drug molecule-related databases. In this paper, we propose a method for predicting drug-target binding affinity using deep learning models. This method uses a modified GRU and GNN to extract features from the drug-target protein sequences and the drug molecule map, respectively, to obtain their feature vectors. The combined vectors are used as vector representations of drug-target molecule pairs and then fed into a fully connected network to predict drug-target binding affinity. This proposed model demonstrates its accuracy and effectiveness in predicting drug-target binding affinity on the DAVIS and KIBA datasets.
Genetic disorders such as Rubinstein-Taybi syndrome (RTS) and Coffin-Lowry syndrome (CLS) cause lifelong cognitive disability, including deficits in learning and memory. Can pharmacological therapies be suggested to improve learning and memory in these disorders? To address this question, we simulated drug effects within a computational model describing induction of late long-term potentiation (L-LTP). Biochemical pathways impaired in these and other disorders converge on a common target, histone acetylation by acetyltransferases such as CREB binding protein (CBP), which facilitates gene induction necessary for L-LTP. We focused on four drug classes: tropomyosin receptor kinase B (TrkB) agonists, cAMP phosphodiesterase inhibitors, histone deacetylase inhibitors, and ampakines. Simulations suggested each drug type alone may rescue deficits in L-LTP. A potential disadvantage, however, was the necessity of simulating strong drug effects (high doses), which could produce adverse side effects. Thus, we investigated the effects of six drug pairs among the four classes described above. These combination treatments normalized impaired L-LTP with substantially smaller drug doses. In additio
We introduce a novel state-space model (SSM)-based framework for skeleton-based human action recognition, with an anatomically-guided architecture that improves state-of-the-art performance in both clinical diagnostics and general action recognition tasks. Our approach decomposes skeletal motion analysis into spatial, temporal, and spatio-temporal streams, using channel partitioning to capture distinct movement characteristics efficiently. By implementing a structured, multi-directional scanning strategy within SSMs, our model captures local joint interactions and global motion patterns across multiple anatomical body parts. This anatomically-aware decomposition enhances the ability to identify subtle motion patterns critical in medical diagnosis, such as gait anomalies associated with neurological conditions. On public action recognition benchmarks, i.e., NTU RGB+D, NTU RGB+D 120, and NW-UCLA, our model outperforms current state-of-the-art methods, achieving accuracy improvements up to $3.2\%$ with lower computational complexity than previous leading transformer-based models. We also introduce a novel medical dataset for motion-based patient neurological disorder analysis to valid
The role of Artificial Intelligence (AI) is growing in every stage of drug development. Nevertheless, a major challenge in drug discovery AI remains: Drug pharmacokinetic (PK) and Drug-Target Interaction (DTI) datasets collected in different studies often exhibit limited overlap, creating data overlap sparsity. Thus, data curation becomes difficult, negatively impacting downstream research investigations in high-throughput screening, polypharmacy, and drug combination. We propose xImagand-DKI, a novel SMILES/Protein-to-Pharmacokinetic/DTI (SP2PKDTI) diffusion model capable of generating an array of PK and DTI target properties conditioned on SMILES and protein inputs that exhibit data overlap sparsity. We infuse additional molecular and genomic domain knowledge from the Gene Ontology (GO) and molecular fingerprints to further improve our model performance. We show that xImagand-DKI-generated synthetic PK data closely resemble real data univariate and bivariate distributions, and can adequately fill in gaps among PK and DTI datasets. As such, xImagand-DKI is a promising solution for data overlap sparsity and may improve performance for downstream drug discovery research tasks. Code
This paper presents a comprehensive study focused on disentangling hippocampal shape variations from diffusion tensor imaging (DTI) datasets within the context of neurological disorders. Leveraging a Mesh Variational Autoencoder (VAE) enhanced with Supervised Contrastive Learning, our approach aims to improve interpretability by disentangling two distinct latent variables corresponding to age and the presence of diseases. In our ablation study, we investigate a range of VAE architectures and contrastive loss functions, showcasing the enhanced disentanglement capabilities of our approach. This evaluation uses synthetic 3D torus mesh data and real 3D hippocampal mesh datasets derived from the DTI hippocampal dataset. Our supervised disentanglement model outperforms several state-of-the-art (SOTA) methods like attribute and guided VAEs in terms of disentanglement scores. Our model distinguishes between age groups and disease status in patients with Multiple Sclerosis (MS) using the hippocampus data. Our Mesh VAE with Supervised Contrastive Learning shows the volume changes of the hippocampus of MS populations at different ages, and the result is consistent with the current neuroimagin
Cancer is a disease involving many genes, consequently it has been difficult to design anticancer drugs that are efficacious over a broad range of cancers. The robustness of cellular responses to gene knockout and the need to reduce undesirable side effects also contribute to the problem of effective anti-cancer drug design. To promote the successful selection of drug targets, each potential target should be subjected to a systems biology scrutiny to locate effective and specific targets while minimizing undesirable side effects. The gene p53 is considered a good candidate for such a target because it has been implicated in 50% of all cancers and is considered to encode a hub protein that is highly connected to other proteins. Using P53 as a test case, this paper explores the capacity of the systems biology tool, CellDesigner, to aid in the selection of anticancer drug targets and to serve as a teaching resource for human resource development.
An understanding how neurological disorders lead to mechanical dysfunction of the esophagus requires knowledge of the neural circuit of the enteric nervous system. Historically, this has been elusive. Here, we present an empirically guided neural circuit for the esophagus. It has a chain of unidirectionally coupled relaxation oscillators, receiving excitatory signals from stretch receptors along the esophagus. The resulting neuromechanical model reveals complex patterns and behaviors that emerge from interacting components in the system. A wide variety of clinically observed normal and abnormal esophageal responses to distension are successfully predicted. Specifically, repetitive antegrade contractions (RACs) are conclusively shown to emerge from the coupled neuromechanical dynamics in response to sustained volumetric distension. Normal RACs are shown to have a robust balance between excitatory and inhibitory neuronal populations, and the mechanical input through stretch receptors. When this balance is affected, contraction patterns akin to motility disorders are observed. For example, clinically observed repetitive retrograde contractions emerge due to a hyper stretch sensitive w
Accurate drug target affinity prediction can improve drug candidate selection, accelerate the drug discovery process, and reduce drug production costs. Previous work focused on traditional fingerprints or used features extracted based on the amino acid sequence in the protein, ignoring its 3D structure which affects its binding affinity. In this work, we propose GraphPrint: a framework for incorporating 3D protein structure features for drug target affinity prediction. We generate graph representations for protein 3D structures using amino acid residue location coordinates and combine them with drug graph representation and traditional features to jointly learn drug target affinity. Our model achieves a mean square error of 0.1378 and a concordance index of 0.8929 on the KIBA dataset and improves over using traditional protein features alone. Our ablation study shows that the 3D protein structure-based features provide information complementary to traditional features.
Drug-target binding affinity prediction plays an important role in the early stages of drug discovery, which can infer the strength of interactions between new drugs and new targets. However, the performance of previous computational models is limited by the following drawbacks. The learning of drug representation relies only on supervised data, without taking into account the information contained in the molecular graph itself. Moreover, most previous studies tended to design complicated representation learning module, while uniformity, which is used to measure representation quality, is ignored. In this study, we propose GraphCL-DTA, a graph contrastive learning with molecular semantics for drug-target binding affinity prediction. In GraphCL-DTA, we design a graph contrastive learning framework for molecular graphs to learn drug representations, so that the semantics of molecular graphs are preserved. Through this graph contrastive framework, a more essential and effective drug representation can be learned without additional supervised data. Next, we design a new loss function that can be directly used to smoothly adjust the uniformity of drug and target representations. By dire
Accurate diagnosis of neurological disorders is contingent upon advanced imaging modalities such as Magnetic Resonance Imaging (MRI), which commonly utilize sparse imaging techniques to reconstruct images from limited data, thus reducing storage and acquisition time. However, challenges remain in managing noise and preserving critical diagnostic features for effective analysis. In this study, an ensemble classifier is enriched with PARAFAC CP tensor decompositions, drawing mathematical inspiration from quantum neural network architectures but implemented entirely classically. The model was evaluated on a large, balanced clinical dataset comprising 55,160 images across 8 diagnostic categories, employing both higher and lower PARAFAC rank configurations. Evaluated through 5-fold nested stratified cross-validation, both configurations achieved strong validation performance, demonstrating robustness to tensor network expressivity. Additionally, the proposed model achieved competitive performance relative to recent classical approaches, further underscoring the potential of quantum-inspired classical frameworks to enhance medical image analysis and support reliable clinical diagnosis. F