Advances in deep generative models shed light on de novo molecule generation with desired properties. However, molecule generation targeted for dual protein targets still faces formidable challenges including protein 3D structure data requisition for model training, auto-regressive sampling, and model generalization for unseen targets. Here, we proposed DiffDTM, a novel conditional structure-free deep generative model based on a diffusion model for dual targets based molecule generation to address the above issues. Specifically, DiffDTM receives protein sequences and molecular graphs as inputs instead of protein and molecular conformations and incorporates an information fusion module to achieve conditional generation in a one-shot manner. We have conducted comprehensive multi-view experiments to demonstrate that DiffDTM can generate drug-like, synthesis-accessible, novel, and high-binding affinity molecules targeting specific dual proteins, outperforming the state-of-the-art (SOTA) models in terms of multiple evaluation metrics. Furthermore, we utilized DiffDTM to generate molecules towards dopamine receptor D2 and 5-hydroxytryptamine receptor 1A as new antipsychotics. The experimental results indicate that DiffDTM can be easily plugged into unseen dual targets to generate bioactive molecules, addressing the issues of requiring insufficient active molecule data for training as well as the need to retrain when encountering new targets.

Drug-target interaction (DTI) prediction, which aims at predicting whether a drug will be bounded to a target, have received wide attention recently, with the goal to automate and accelerate the costly process of drug design. Most of the recently proposed methods use single drug-drug similarity and target-target similarity information for DTI prediction, which are unable to take advantage of the abundant information regarding various types of similarities between them. Very recently, some methods are proposed to leverage multi-similarity information, however, they still lack the ability to take into consideration the rich topological information of all sorts of knowledge bases where the drugs and targets reside in. More importantly, the time consumption of these approaches is very high, which prevents the usage of large-scale network information. We thus propose a network-based drug-target interaction prediction approach, which applies probabilistic soft logic (PSL) to meta-paths on a heterogeneous network that contains multiple sources of information, including drug-drug similarities, target-target similarities, drug-target interactions, and other potential information. Our approach is based on the PSL graphical model and uses meta-path counts instead of path instances to reduce the number of rule instances of PSL. We compare our model against five methods, on three open-source datasets. The experimental results show that our approach outperforms all the five baselines in terms of AUPR score and AUC score.

The primary aim of this research was to address the limitations observed in the medical knowledge of prevalent large language models (LLMs) such as ChatGPT, by creating a specialized language model with enhanced accuracy in medical advice. We achieved this by adapting and refining the large language model meta-AI (LLaMA) using a large dataset of 100,000 patient-doctor dialogues sourced from a widely used online medical consultation platform. These conversations were cleaned and anonymized to respect privacy concerns. In addition to the model refinement, we incorporated a self-directed information retrieval mechanism, allowing the model to access and utilize real-time information from online sources like Wikipedia and data from curated offline medical databases. The fine-tuning of the model with real-world patient-doctor interactions significantly improved the model's ability to understand patient needs and provide informed advice. By equipping the model with self-directed information retrieval from reliable online and offline sources, we observed substantial improvements in the accuracy of its responses. Our proposed ChatDoctor, represents a significant advancement in medical LLMs, demonstrating a significant improvement in understanding patient inquiries and providing accurate advice. Given the high stakes and low error tolerance in the medical field, such enhancements in providing accurate and reliable information are not only beneficial but essential.

The library scikit-fda is a Python package for Functional Data Analysis (FDA). It provides a comprehensive set of tools for representation, preprocessing, and exploratory analysis of functional data. The library is built upon and integrated in Python's scientific ecosystem. In particular, it conforms to the scikit-learn application programming interface so as to take advantage of the functionality for machine learning provided by this package: pipelines, model selection, and hyperparameter tuning, among others. The scikit-fda package has been released as free and open-source software under a 3-Clause BSD license and is open to contributions from the FDA community. The library's extensive documentation includes step-by-step tutorials and detailed examples of use.

Scientists at the University of Bristol have shown that reinforcement learning, a type of machine learning in which a computer program learns to make decisions by trying different actions, significantly outperforms commercial blood glucose controllers in terms of safety and effectiveness. By using offline reinforcement learning, where the algorithm learns from patient records, the researchers improve on prior work, showing that good blood glucose control can be achieved by learning from the decisions of the patient rather than by trial and error. Type 1 diabetes is one of the most prevalent auto-immune conditions in the UK and is characterised by an insufficiency of the hormone insulin, which is responsible for blood glucose regulation. Many factors affect a person's blood glucose and therefore it can be a challenging and burdensome task to select the correct insulin dose for a given scenario. Current artificial pancreas devices provide automated insulin dosing but are limited by their simplistic decision-making algorithms.

San Francisco – Billionaire entrepreneur Elon Musk expects his brain-chip startup Neuralink to start its first human trial this year, he said on Friday in France. Speaking at the VivaTech event in Paris, co-founder Musk said Neuralink plans to implant a tetraplegic or paraplegic patient during a webcast. While Musk didn't specify how many patients his company would implant or for how long, "it's looking like the first case will be later this year," said Musk, who is also CEO of electric carmaker Tesla, social media platform Twitter and the SpaceX rocket launch company. Last month, Neuralink said it received U.S. Food and Drug Administration (FDA) clearance for its first-in-human clinical trial, a critical milestone for the startup as it faces U.S. probes over its handling of animal experiments. The FDA acknowledged in an earlier statement that the agency cleared Neuralink to use its brain implant and surgical robot for trials but declined to provide more details.

Activity and property prediction models are the central workhorses in drug discovery and materials sciences, but currently they have to be trained or fine-tuned for new tasks. Without training or fine-tuning, scientific language models could be used for such low-data tasks through their announced zero- and few-shot capabilities. However, their predictive quality at activity prediction is lacking. In this work, we envision a novel type of activity prediction model that is able to adapt to new prediction tasks at inference time, via understanding textual information describing the task. To this end, we propose a new architecture with separate modules for chemical and natural language inputs, and a contrastive pre-training objective on data from large biochemical databases. In extensive experiments, we show that our method CLAMP yields improved predictive performance on few-shot learning benchmarks and zero-shot problems in drug discovery. We attribute the advances of our method to the modularized architecture and to our pre-training objective.

The identification of compound-protein interactions (CPI) plays a critical role in drug screening, drug repurposing, and combination therapy studies. The effectiveness of CPI prediction relies heavily on the features extracted from both compounds and target proteins. While various prediction methods employ different feature combinations, both molecular-based and network-based models encounter the common obstacle of incomplete feature representations. Thus, a promising solution to this issue is to fully integrate all relevant CPI features. This study proposed a novel model named MCPI, which is designed to improve the prediction performance of CPI by integrating multiple sources of information, including the PPI network, CCI network, and structural features of CPI. The results of the study indicate that the MCPI model outperformed other existing methods for predicting CPI on public datasets. Furthermore, the study has practical implications for drug development, as the model was applied to search for potential inhibitors among FDA-approved drugs in response to the SARS-CoV-2 pandemic. The prediction results were then validated through the literature, suggesting that the MCPI model could be a useful tool for identifying potential drug candidates. Overall, this study has the potential to advance our understanding of CPI and guide drug development efforts.

Opioid Use Disorder (OUD) has emerged as a significant global public health issue, with complex multifaceted conditions. Due to the lack of effective treatment options for various conditions, there is a pressing need for the discovery of new medications. In this study, we propose a deep generative model that combines a stochastic differential equation (SDE)-based diffusion modeling with the latent space of a pretrained autoencoder model. The molecular generator enables efficient generation of molecules that are effective on multiple targets, specifically the mu, kappa, and delta opioid receptors. Furthermore, we assess the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the generated molecules to identify drug-like compounds. To enhance the pharmacokinetic properties of some lead compounds, we employ a molecular optimization approach. We obtain a diverse set of drug-like molecules. We construct binding affinity predictors by integrating molecular fingerprints derived from autoencoder embeddings, transformer embeddings, and topological Laplacians with advanced machine learning algorithms. Further experimental studies are needed to evaluate the pharmacological effects of these drug-like compounds for OUD treatment. Our machine learning platform serves as a valuable tool in designing and optimizing effective molecules for addressing OUD.

Elon Musk's SpaceX recently launched the biggest and most powerful rocket into flight, even though it did make it into orbit. But the world's richest man isn't content on expanding his sci-fi inspired technology into just the cosmos. Neuralink, the tech startup co-founded by Musk, also wants to embark on a fantastic voyage into the brain. Two weeks ago, the company announced it had gained approval from the Food and Drug Administration to begin trials to implant brain chips into humans. We don't know when trials will begin, but there's plenty of buzz around Neuralink's development of a brain-computer interface.