Daily Papers

Large language models (LLMs) have revolutionised many fields, with LLM-as-a-service (LLMSaaS) offering accessible, general-purpose solutions without costly task-specific training. In contrast to the widely studied prompt engineering for directly solving tasks (in vivo), this paper explores LLMs' potential for in-vitro applications: using LLM-generated labels to improve supervised training of mainstream models. We examine two strategies - (1) noisy label correction and (2) training data augmentation - in empathy computing, an emerging task to predict psychology-based questionnaire outcomes from inputs like textual narratives. Crowdsourced datasets in this domain often suffer from noisy labels that misrepresent underlying empathy. We show that replacing or supplementing these crowdsourced labels with LLM-generated labels, developed using psychology-based scale-aware prompts, achieves statistically significant accuracy improvements. Notably, the RoBERTa pre-trained language model (PLM) trained with noise-reduced labels yields a state-of-the-art Pearson correlation coefficient of 0.648 on the public NewsEmp benchmarks. This paper further analyses evaluation metric selection and demographic biases to help guide the future development of more equitable empathy computing models. Code and LLM-generated labels are available at https://github.com/hasan-rakibul/LLMPathy.

ImageNet has become a reputable resource for transfer learning, allowing the development of efficient ML models with reduced training time and data requirements. However, vibration analysis in predictive maintenance, structural health monitoring, and fault diagnosis, lacks a comparable large-scale, annotated dataset to facilitate similar advancements. To address this, a dataset framework is proposed that begins with bearing vibration data as an initial step towards creating a universal dataset for vibration-based spectrogram analysis for all machinery. The initial framework includes a collection of bearing vibration signals from various publicly available datasets. To demonstrate the advantages of this framework, experiments were conducted using a deep learning architecture, showing improvements in model performance when pre-trained on bearing vibration data and fine-tuned on a smaller, domain-specific dataset. These findings highlight the potential to parallel the success of ImageNet in visual computing but for vibration analysis. For future work, this research will include a broader range of vibration signals from multiple types of machinery, emphasizing spectrogram-based representations of the data. Each sample will be labeled according to machinery type, operational status, and the presence or type of faults, ensuring its utility for supervised and unsupervised learning tasks. Additionally, a framework for data preprocessing, feature extraction, and model training specific to vibration data will be developed. This framework will standardize methodologies across the research community, allowing for collaboration and accelerating progress in predictive maintenance, structural health monitoring, and related fields. By mirroring the success of ImageNet in visual computing, this dataset has the potential to improve the development of intelligent systems in industrial applications.

This work investigates a case study of using physical-based sonification of Quadratic Unconstrained Binary Optimization (QUBO) problems, optimized by the Variational Quantum Eigensolver (VQE) algorithm. The VQE approximates the solution of the problem by using an iterative loop between the quantum computer and a classical optimization routine. This work explores the intermediary statevectors found in each VQE iteration as the means of sonifying the optimization process itself. The implementation was realised in the form of a musical interface prototype named Variational Quantum Harmonizer (VQH), providing potential design strategies for musical applications, focusing on chords, chord progressions, and arpeggios. The VQH can be used both to enhance data visualization or to create artistic pieces. The methodology is also relevant in terms of how an artist would gain intuition towards achieving a desired musical sound by carefully designing QUBO cost functions. Flexible mapping strategies could supply a broad portfolio of sounds for QUBO and quantum-inspired musical compositions, as demonstrated in a case study composition, "Dependent Origination" by Peter Thomas and Paulo Itaborai.

Reconstructing articulated objects prevalent in daily environments is crucial for applications in augmented/virtual reality and robotics. However, existing methods face scalability limitations (requiring 3D supervision or costly annotations), robustness issues (being susceptible to local optima), and rendering shortcomings (lacking speed or photorealism). We introduce SplArt, a self-supervised, category-agnostic framework that leverages 3D Gaussian Splatting (3DGS) to reconstruct articulated objects and infer kinematics from two sets of posed RGB images captured at different articulation states, enabling real-time photorealistic rendering for novel viewpoints and articulations. SplArt augments 3DGS with a differentiable mobility parameter per Gaussian, achieving refined part segmentation. A multi-stage optimization strategy is employed to progressively handle reconstruction, part segmentation, and articulation estimation, significantly enhancing robustness and accuracy. SplArt exploits geometric self-supervision, effectively addressing challenging scenarios without requiring 3D annotations or category-specific priors. Evaluations on established and newly proposed benchmarks, along with applications to real-world scenarios using a handheld RGB camera, demonstrate SplArt's state-of-the-art performance and real-world practicality. Code is publicly available at https://github.com/ripl/splart.

Differentiable volumetric rendering is a powerful paradigm for 3D reconstruction and novel view synthesis. However, standard volume rendering approaches struggle with degenerate geometries in the case of limited viewpoint diversity, a common scenario in robotics applications. In this work, we propose to use the multi-view photometric objective from the self-supervised depth estimation literature as a geometric regularizer for volumetric rendering, significantly improving novel view synthesis without requiring additional information. Building upon this insight, we explore the explicit modeling of scene geometry using a generalist Transformer, jointly learning a radiance field as well as depth and light fields with a set of shared latent codes. We demonstrate that sharing geometric information across tasks is mutually beneficial, leading to improvements over single-task learning without an increase in network complexity. Our DeLiRa architecture achieves state-of-the-art results on the ScanNet benchmark, enabling high quality volumetric rendering as well as real-time novel view and depth synthesis in the limited viewpoint diversity setting.

Recent popularity surrounds large AI language models due to their impressive natural language capabilities. They contribute significantly to language-related tasks, including prompt-based learning, making them valuable for various specific tasks. This approach unlocks their full potential, enhancing precision and generalization. Research communities are actively exploring their applications, with ChatGPT receiving recognition. Despite extensive research on large language models, their potential in recommendation scenarios still needs to be explored. This study aims to fill this gap by investigating ChatGPT's capabilities as a zero-shot recommender system. Our goals include evaluating its ability to use user preferences for recommendations, reordering existing recommendation lists, leveraging information from similar users, and handling cold-start situations. We assess ChatGPT's performance through comprehensive experiments using three datasets (MovieLens Small, Last.FM, and Facebook Book). We compare ChatGPT's performance against standard recommendation algorithms and other large language models, such as GPT-3.5 and PaLM-2. To measure recommendation effectiveness, we employ widely-used evaluation metrics like Mean Average Precision (MAP), Recall, Precision, F1, normalized Discounted Cumulative Gain (nDCG), Item Coverage, Expected Popularity Complement (EPC), Average Coverage of Long Tail (ACLT), Average Recommendation Popularity (ARP), and Popularity-based Ranking-based Equal Opportunity (PopREO). Through thoroughly exploring ChatGPT's abilities in recommender systems, our study aims to contribute to the growing body of research on the versatility and potential applications of large language models. Our experiment code is available on the GitHub repository: https://github.com/sisinflab/Recommender-ChatGPT

Scalable learning of humanoid robots is crucial for their deployment in real-world applications. While traditional approaches primarily rely on reinforcement learning or teleoperation to achieve whole-body control, they are often limited by the diversity of simulated environments and the high costs of demonstration collection. In contrast, human videos are ubiquitous and present an untapped source of semantic and motion information that could significantly enhance the generalization capabilities of humanoid robots. This paper introduces Humanoid-X, a large-scale dataset of over 20 million humanoid robot poses with corresponding text-based motion descriptions, designed to leverage this abundant data. Humanoid-X is curated through a comprehensive pipeline: data mining from the Internet, video caption generation, motion retargeting of humans to humanoid robots, and policy learning for real-world deployment. With Humanoid-X, we further train a large humanoid model, UH-1, which takes text instructions as input and outputs corresponding actions to control a humanoid robot. Extensive simulated and real-world experiments validate that our scalable training approach leads to superior generalization in text-based humanoid control, marking a significant step toward adaptable, real-world-ready humanoid robots.

Recent work has shown that small distilled language models are strong competitors to models that are orders of magnitude larger and slower in a wide range of information retrieval tasks. This has made distilled and dense models, due to latency constraints, the go-to choice for deployment in real-world retrieval applications. In this work, we question this practice by showing that the number of parameters and early query-document interaction play a significant role in the generalization ability of retrieval models. Our experiments show that increasing model size results in marginal gains on in-domain test sets, but much larger gains in new domains never seen during fine-tuning. Furthermore, we show that rerankers largely outperform dense ones of similar size in several tasks. Our largest reranker reaches the state of the art in 12 of the 18 datasets of the Benchmark-IR (BEIR) and surpasses the previous state of the art by 3 average points. Finally, we confirm that in-domain effectiveness is not a good indicator of zero-shot effectiveness. Code is available at https://github.com/guilhermemr04/scaling-zero-shot-retrieval.git

Vision-language models (VLMs) are essential for contextual understanding of both visual and textual information. However, their vulnerability to adversarially manipulated inputs presents significant risks, leading to compromised outputs and raising concerns about the reliability in VLM-integrated applications. Detecting these malicious prompts is thus crucial for maintaining trust in VLM generations. A major challenge in developing a safeguarding prompt classifier is the lack of a large amount of labeled benign and malicious data. To address the issue, we introduce VLMGuard, a novel learning framework that leverages the unlabeled user prompts in the wild for malicious prompt detection. These unlabeled prompts, which naturally arise when VLMs are deployed in the open world, consist of both benign and malicious information. To harness the unlabeled data, we present an automated maliciousness estimation score for distinguishing between benign and malicious samples within this unlabeled mixture, thereby enabling the training of a binary prompt classifier on top. Notably, our framework does not require extra human annotations, offering strong flexibility and practicality for real-world applications. Extensive experiment shows VLMGuard achieves superior detection results, significantly outperforming state-of-the-art methods. Disclaimer: This paper may contain offensive examples; reader discretion is advised.

Time-lapse fluorescent microscopy (TLFM) combined with predictive mathematical modelling is a powerful tool to study the inherently dynamic processes of life on the single-cell level. Such experiments are costly, complex and labour intensive. A complimentary approach and a step towards in silico experimentation, is to synthesise the imagery itself. Here, we propose Multi-StyleGAN as a descriptive approach to simulate time-lapse fluorescence microscopy imagery of living cells, based on a past experiment. This novel generative adversarial network synthesises a multi-domain sequence of consecutive timesteps. We showcase Multi-StyleGAN on imagery of multiple live yeast cells in microstructured environments and train on a dataset recorded in our laboratory. The simulation captures underlying biophysical factors and time dependencies, such as cell morphology, growth, physical interactions, as well as the intensity of a fluorescent reporter protein. An immediate application is to generate additional training and validation data for feature extraction algorithms or to aid and expedite development of advanced experimental techniques such as online monitoring or control of cells. Code and dataset is available at https://git.rwth-aachen.de/bcs/projects/tp/multi-stylegan.

Discovering novel drug candidate molecules is one of the most fundamental and critical steps in drug development. Generative deep learning models, which create synthetic data given a probability distribution, offer a high potential for designing de novo molecules. However, to be utilisable in real life drug development pipelines, these models should be able to design drug like and target centric molecules. In this study, we propose an end to end generative system, DrugGEN, for the de novo design of drug candidate molecules that interact with intended target proteins. The proposed method represents molecules as graphs and processes them via a generative adversarial network comprising graph transformer layers. The system is trained using a large dataset of drug like compounds and target specific bioactive molecules to design effective inhibitory molecules against the AKT1 protein, which is critically important in developing treatments for various types of cancer. We conducted molecular docking and dynamics to assess the target centric generation performance of the model, as well as attention score visualisation to examine model interpretability. In parallel, selected compounds were chemically synthesised and evaluated in the context of in vitro enzymatic assays, which identified two bioactive molecules that inhibited AKT1 at low micromolar concentrations. These results indicate that DrugGEN's de novo molecules have a high potential for interacting with the AKT1 protein at the level of its native ligands. Using the open access DrugGEN codebase, it is possible to easily train models for other druggable proteins, given a dataset of experimentally known bioactive molecules.

We introduce InVirtuoGen, a discrete flow generative model for fragmented SMILES for de novo and fragment-constrained generation, and target-property/lead optimization of small molecules. The model learns to transform a uniform source over all possible tokens into the data distribution. Unlike masked models, its training loss accounts for predictions on all sequence positions at every denoising step, shifting the generation paradigm from completion to refinement, and decoupling the number of sampling steps from the sequence length. For de novo generation, InVirtuoGen achieves a stronger quality-diversity pareto frontier than prior fragment-based models and competitive performance on fragment-constrained tasks. For property and lead optimization, we propose a hybrid scheme that combines a genetic algorithm with a Proximal Property Optimization fine-tuning strategy adapted to discrete flows. Our approach sets a new state-of-the-art on the Practical Molecular Optimization benchmark, measured by top-10 AUC across tasks, and yields higher docking scores in lead optimization than previous baselines. InVirtuoGen thus establishes a versatile generative foundation for drug discovery, from early hit finding to multi-objective lead optimization. We further contribute to open science by releasing pretrained checkpoints and code, making our results fully reproduciblehttps://github.com/invirtuolabs/InVirtuoGen_results.

Single-cell transcriptomics enabled the study of cellular heterogeneity in response to perturbations at the resolution of individual cells. However, scaling high-throughput screens (HTSs) to measure cellular responses for many drugs remains a challenge due to technical limitations and, more importantly, the cost of such multiplexed experiments. Thus, transferring information from routinely performed bulk RNA HTS is required to enrich single-cell data meaningfully. We introduce chemCPA, a new encoder-decoder architecture to study the perturbational effects of unseen drugs. We combine the model with an architecture surgery for transfer learning and demonstrate how training on existing bulk RNA HTS datasets can improve generalisation performance. Better generalisation reduces the need for extensive and costly screens at single-cell resolution. We envision that our proposed method will facilitate more efficient experiment designs through its ability to generate in-silico hypotheses, ultimately accelerating drug discovery.

Genetic engineering of cells has a range of applications in treating incurable diseases. Plasmid DNA is a popular choice of nucleic acid for cell engineering due to its low cost and stability. However, plasmid DNA must survive the protective mechanisms present in the cell's cytoplasm to enter the nucleus for translation. Many of the existing methods for nucleic acid delivery, such as chemical-based and virus-based delivery, suffer from drawbacks induced by the nucleic acid carrier itself. Mechanical methods present an alternative to nucleic acid carriers by physically producing openings in the cell to deliver cargos. However, in most systems, the cell membrane openings are too small to deliver large cargos, or the poration process leads to low cell viability. In this study, we present a microfluidic device with integrated high aspect ratio nanostructures that repeatably rupture the cell membrane and nuclear envelope. These sharp-tipped nanolancets penetrate the cell deep enough to allow direct delivery of cargos into the nucleus, but still allow for cell recovery after treatment. We show the device's ability to deliver cargo to a variety of cell types while maintaining high viability. Then, we demonstrate the rapid onset of plasmid DNA expression that results from direct nuclear delivery of naked DNA, showing expression speeds comparable to microinjection, but with significantly greater throughput. We envision the use of this device as a tool to quickly produce high quantities of genetically engineered cells to treat a myriad of diseases.

Deep neural networks have been extensively applied in the medical domain for various tasks, including image classification, segmentation, and landmark detection. However, their application is often hindered by data scarcity, both in terms of available annotations and images. This study introduces a novel application of denoising diffusion probabilistic models (DDPMs) to the landmark detection task, specifically addressing the challenge of limited annotated data in x-ray imaging. Our key innovation lies in leveraging DDPMs for self-supervised pre-training in landmark detection, a previously unexplored approach in this domain. This method enables accurate landmark detection with minimal annotated training data (as few as 50 images), surpassing both ImageNet supervised pre-training and traditional self-supervised techniques across three popular x-ray benchmark datasets. To our knowledge, this work represents the first application of diffusion models for self-supervised learning in landmark detection, which may offer a valuable pre-training approach in few-shot regimes, for mitigating data scarcity.

Understanding and designing biomolecules, such as proteins and small molecules, is central to advancing drug discovery, synthetic biology, and enzyme engineering. Recent breakthroughs in Artificial Intelligence (AI) have revolutionized biomolecular research, achieving remarkable accuracy in biomolecular prediction and design. However, a critical gap remains between AI's computational power and researchers' intuition, using natural language to align molecular complexity with human intentions. Large Language Models (LLMs) have shown potential to interpret human intentions, yet their application to biomolecular research remains nascent due to challenges including specialized knowledge requirements, multimodal data integration, and semantic alignment between natural language and biomolecules. To address these limitations, we present InstructBioMol, a novel LLM designed to bridge natural language and biomolecules through a comprehensive any-to-any alignment of natural language, molecules, and proteins. This model can integrate multimodal biomolecules as input, and enable researchers to articulate design goals in natural language, providing biomolecular outputs that meet precise biological needs. Experimental results demonstrate InstructBioMol can understand and design biomolecules following human instructions. Notably, it can generate drug molecules with a 10% improvement in binding affinity and design enzymes that achieve an ESP Score of 70.4, making it the only method to surpass the enzyme-substrate interaction threshold of 60.0 recommended by the ESP developer. This highlights its potential to transform real-world biomolecular research.

Food polysaccharides have emerged as suitable carriers of active substances and as additives to food and nutraceutical formulations, showing potential to stabilize bioactive compounds during the storage of microencapsulate preparations, even in the gastrointestinal tract following the intake of bioactive compounds, thereby improving their bioaccessibility and bioavailability. This review provides a comprehensive overview of the main polysaccharides employed as wall materials, including starch, maltodextrin, alginate, pectin, inulin, chitosan, and gum arabic, and discusses how structural interactions and physicochemical properties can benefit the microencapsulation of polyphenols and pigments. The main findings and principles of the major encapsulation techniques, including spray drying, freeze drying, extrusion, emulsification, and coacervation, related to the production of microparticles, were briefly described. Polysaccharides can entrap hydrophilic and hydrophobic compounds by physical interactions, forming a barrier around the nucleus or binding to the bioactive compound. Intermolecular binding between polysaccharides in the wall matrix, polyphenols, and pigments in the nucleus can confer up to 90% of encapsulation efficiency, governed mainly by hydrogen bonds and electrostatic interactions. The mixture of wall polysaccharides in the microparticles synthesis favors the encapsulation solubility, storage stability, bioaccessibility, and bioactivity of the microencapsulate compounds. Clinical trials on the bioefficacy of polyphenols and pigments loaded in polysaccharide microparticles are scarce and require further evidence to reinforce the use of this technology.

Human medical data can be challenging to obtain due to data privacy concerns, difficulties conducting certain types of experiments, or prohibitive associated costs. In many settings, data from animal models or in-vitro cell lines are available to help augment our understanding of human data. However, this data is known for having low etiological validity in comparison to human data. In this work, we augment small human medical datasets with in-vitro data and animal models. We use Invariant Risk Minimisation (IRM) to elucidate invariant features by considering cross-organism data as belonging to different data-generating environments. Our models identify genes of relevance to human cancer development. We observe a degree of consistency between varying the amounts of human and mouse data used, however, further work is required to obtain conclusive insights. As a secondary contribution, we enhance existing open source datasets and provide two uniformly processed, cross-organism, homologue gene-matched datasets to the community.

High-throughput screening techniques, such as microscopy imaging of cellular responses to genetic and chemical perturbations, play a crucial role in drug discovery and biomedical research. However, robust perturbation screening for de novo cell lines remains challenging due to the significant morphological and biological heterogeneity across cell lines. To address this, we propose a novel framework that integrates external biological knowledge into existing pretraining strategies to enhance microscopy image profiling models. Our approach explicitly disentangles perturbation-specific and cell line-specific representations using external biological information. Specifically, we construct a knowledge graph leveraging protein interaction data from STRING and Hetionet databases to guide models toward perturbation-specific features during pretraining. Additionally, we incorporate transcriptomic features from single-cell foundation models to capture cell line-specific representations. By learning these disentangled features, our method improves the generalization of imaging models to de novo cell lines. We evaluate our framework on the RxRx database through one-shot fine-tuning on an RxRx1 cell line and few-shot fine-tuning on cell lines from the RxRx19a dataset. Experimental results demonstrate that our method enhances microscopy image profiling for de novo cell lines, highlighting its effectiveness in real-world phenotype-based drug discovery applications.

In Vitro Fertilization is among the most widespread treatments for infertility. One of its main challenges is the evaluation and selection of embryo for implantation, a process with large inter- and intra-clinician variability. Deep learning based methods are gaining attention, but their opaque nature compromises their acceptance in the clinical context, where transparency in the decision making is key. In this paper we analyze the current work in the explainability of AI-assisted embryo analysis models, identifying the limitations. We also discuss how these models could be integrated in the clinical context as decision support systems, considering the needs of clinicians and patients. Finally, we propose guidelines for the sake of increasing interpretability and trustworthiness, pushing this technology forward towards established clinical practice.

Traditional drug design faces significant challenges due to inherent chemical and biological complexities, often resulting in high failure rates in clinical trials. Deep learning advancements, particularly generative models, offer potential solutions to these challenges. One promising algorithm is DrugGPT, a transformer-based model, that generates small molecules for input protein sequences. Although promising, it generates both chemically valid and invalid structures and does not incorporate the features of approved drugs, resulting in time-consuming and inefficient drug discovery. To address these issues, we introduce DrugGen, an enhanced model based on the DrugGPT structure. DrugGen is fine-tuned on approved drug-target interactions and optimized with proximal policy optimization. By giving reward feedback from protein-ligand binding affinity prediction using pre-trained transformers (PLAPT) and a customized invalid structure assessor, DrugGen significantly improves performance. Evaluation across multiple targets demonstrated that DrugGen achieves 100% valid structure generation compared to 95.5% with DrugGPT and produced molecules with higher predicted binding affinities (7.22 [6.30-8.07]) compared to DrugGPT (5.81 [4.97-6.63]) while maintaining diversity and novelty. Docking simulations further validate its ability to generate molecules targeting binding sites effectively. For example, in the case of fatty acid-binding protein 5 (FABP5), DrugGen generated molecules with superior docking scores (FABP5/11, -9.537 and FABP5/5, -8.399) compared to the reference molecule (Palmitic acid, -6.177). Beyond lead compound generation, DrugGen also shows potential for drug repositioning and creating novel pharmacophores for existing targets. By producing high-quality small molecules, DrugGen provides a high-performance medium for advancing pharmaceutical research and drug discovery.

Intracellular lasers are emerging as powerful biosensors for multiplexed tracking and precision sensing of cells and their microenvironment. This sensing capacity is enabled by quantifying their narrow-linewidth emission spectra, which is presently challenging to do at high speeds. In this work, we demonstrate rapid snapshot hyperspectral imaging of intracellular lasers. Using integral field mapping with a microlens array and a diffraction grating, we obtain images of the spatial and spectral intensity distribution from a single camera acquisition. We demonstrate widefield hyperspectral imaging over a 3times3 mm^2 field of view and volumetric imaging over 250times250times800 mum^3 volumes with a spatial resolution of 5 mum and a spectral resolution of less than 0.8 nm. We evaluate the performance and outline the challenges and strengths of snapshot methods in the context of characterising the emission from intracellular lasers. This method offers new opportunities for a diverse range of applications, including high-throughput and long-term biosensing with intracellular lasers.

An important limitation to the development of Artificial Intelligence (AI)-based solutions for In Vitro Fertilization (IVF) is the absence of a public reference benchmark to train and evaluate deep learning (DL) models. In this work, we describe a fully annotated dataset of 704 videos of developing embryos, for a total of 337k images. We applied ResNet, LSTM, and ResNet-3D architectures to our dataset and demonstrate that they overperform algorithmic approaches to automatically annotate stage development phases. Altogether, we propose the first public benchmark that will allow the community to evaluate morphokinetic models. This is the first step towards deep learning-powered IVF. Of note, we propose highly detailed annotations with 16 different development phases, including early cell division phases, but also late cell divisions, phases after morulation, and very early phases, which have never been used before. We postulate that this original approach will help improve the overall performance of deep learning approaches on time-lapse videos of embryo development, ultimately benefiting infertile patients with improved clinical success rates (Code and data are available at https://gitlab.univ-nantes.fr/E144069X/bench_mk_pred.git).

Scientific discovery relies on scientists generating novel hypotheses that undergo rigorous experimental validation. To augment this process, we introduce an AI co-scientist, a multi-agent system built on Gemini 2.0. The AI co-scientist is intended to help uncover new, original knowledge and to formulate demonstrably novel research hypotheses and proposals, building upon prior evidence and aligned to scientist-provided research objectives and guidance. The system's design incorporates a generate, debate, and evolve approach to hypothesis generation, inspired by the scientific method and accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute, improving hypothesis quality. While general purpose, we focus development and validation in three biomedical areas: drug repurposing, novel target discovery, and explaining mechanisms of bacterial evolution and anti-microbial resistance. For drug repurposing, the system proposes candidates with promising validation findings, including candidates for acute myeloid leukemia that show tumor inhibition in vitro at clinically applicable concentrations. For novel target discovery, the AI co-scientist proposed new epigenetic targets for liver fibrosis, validated by anti-fibrotic activity and liver cell regeneration in human hepatic organoids. Finally, the AI co-scientist recapitulated unpublished experimental results via a parallel in silico discovery of a novel gene transfer mechanism in bacterial evolution. These results, detailed in separate, co-timed reports, demonstrate the potential to augment biomedical and scientific discovery and usher an era of AI empowered scientists.

Building a virtual cell capable of accurately simulating cellular behaviors in silico has long been a dream in computational biology. We introduce CellFlux, an image-generative model that simulates cellular morphology changes induced by chemical and genetic perturbations using flow matching. Unlike prior methods, CellFlux models distribution-wise transformations from unperturbed to perturbed cell states, effectively distinguishing actual perturbation effects from experimental artifacts such as batch effects -- a major challenge in biological data. Evaluated on chemical (BBBC021), genetic (RxRx1), and combined perturbation (JUMP) datasets, CellFlux generates biologically meaningful cell images that faithfully capture perturbation-specific morphological changes, achieving a 35% improvement in FID scores and a 12% increase in mode-of-action prediction accuracy over existing methods. Additionally, CellFlux enables continuous interpolation between cellular states, providing a potential tool for studying perturbation dynamics. These capabilities mark a significant step toward realizing virtual cell modeling for biomedical research. Project page: https://yuhui-zh15.github.io/CellFlux/.

To generate evidence regarding the safety and efficacy of artificial intelligence (AI) enabled medical devices, AI models need to be evaluated on a diverse population of patient cases, some of which may not be readily available. We propose an evaluation approach for testing medical imaging AI models that relies on in silico imaging pipelines in which stochastic digital models of human anatomy (in object space) with and without pathology are imaged using a digital replica imaging acquisition system to generate realistic synthetic image datasets. Here, we release M-SYNTH, a dataset of cohorts with four breast fibroglandular density distributions imaged at different exposure levels using Monte Carlo x-ray simulations with the publicly available Virtual Imaging Clinical Trial for Regulatory Evaluation (VICTRE) toolkit. We utilize the synthetic dataset to analyze AI model performance and find that model performance decreases with increasing breast density and increases with higher mass density, as expected. As exposure levels decrease, AI model performance drops with the highest performance achieved at exposure levels lower than the nominal recommended dose for the breast type.

AI-driven discovery can greatly reduce design time and enhance new therapeutics' effectiveness. Models using simulators explore broad design spaces but risk violating implicit constraints due to a lack of experimental priors. For example, in a new analysis we performed on a diverse set of models on the GuacaMol benchmark using supervised classifiers, over 60\% of molecules proposed had high probability of being mutagenic. In this work, we introduce \ourdataset, a dataset of priors for design problems extracted from literature describing compounds used in lab settings. It is constructed with LLM pipelines for discovering therapeutic entities in relevant paragraphs and summarizing information in concise fair-use facts. \ourdataset~ consists of 32.3 million pairs of natural language facts, and appropriate entity representations (i.e. SMILES or refseq IDs). To demonstrate the potential of the data, we train LLM, CLIP, and LLava architectures to reason jointly about text and design targets and evaluate on tasks from the Therapeutic Data Commons (TDC). \ourdataset~is highly effective for creating models with strong priors: in supervised prediction problems that use our data as pretraining, our best models with 15M learnable parameters outperform larger 2B TxGemma on both regression and classification TDC tasks, and perform comparably to 9B models on average. Models built with \ourdataset~can be used as constraints while optimizing for novel molecules in GuacaMol, resulting in proposals that are safer and nearly as effective. We release our dataset at https://huggingface.co/datasets/medexanon/Medex{huggingface.co/datasets/medexanon/Medex}, and will provide expanded versions as available literature grows.

With the development of computer-assisted techniques, research communities including biochemistry and deep learning have been devoted into the drug discovery field for over a decade. Various applications of deep learning have drawn great attention in drug discovery, such as molecule generation, molecular property prediction, retrosynthesis prediction, and reaction prediction. While most existing surveys only focus on one of the applications, limiting the view of researchers in the community. In this paper, we present a comprehensive review on the aforementioned four aspects, and discuss the relationships among different applications. The latest literature and classical benchmarks are presented for better understanding the development of variety of approaches. We commence by summarizing the molecule representation format in these works, followed by an introduction of recent proposed approaches for each of the four tasks. Furthermore, we review a variety of commonly used datasets and evaluation metrics and compare the performance of deep learning-based models. Finally, we conclude by identifying remaining challenges and discussing the future trend for deep learning methods in drug discovery.

Achieving flexible and high-fidelity identity-preserved image generation remains formidable, particularly with advanced Diffusion Transformers (DiTs) like FLUX. We introduce InfiniteYou (InfU), one of the earliest robust frameworks leveraging DiTs for this task. InfU addresses significant issues of existing methods, such as insufficient identity similarity, poor text-image alignment, and low generation quality and aesthetics. Central to InfU is InfuseNet, a component that injects identity features into the DiT base model via residual connections, enhancing identity similarity while maintaining generation capabilities. A multi-stage training strategy, including pretraining and supervised fine-tuning (SFT) with synthetic single-person-multiple-sample (SPMS) data, further improves text-image alignment, ameliorates image quality, and alleviates face copy-pasting. Extensive experiments demonstrate that InfU achieves state-of-the-art performance, surpassing existing baselines. In addition, the plug-and-play design of InfU ensures compatibility with various existing methods, offering a valuable contribution to the broader community.

The discovery of novel materials and functional molecules can help to solve some of society's most urgent challenges, ranging from efficient energy harvesting and storage to uncovering novel pharmaceutical drug candidates. Traditionally matter engineering -- generally denoted as inverse design -- was based massively on human intuition and high-throughput virtual screening. The last few years have seen the emergence of significant interest in computer-inspired designs based on evolutionary or deep learning methods. The major challenge here is that the standard strings molecular representation SMILES shows substantial weaknesses in that task because large fractions of strings do not correspond to valid molecules. Here, we solve this problem at a fundamental level and introduce SELFIES (SELF-referencIng Embedded Strings), a string-based representation of molecules which is 100\% robust. Every SELFIES string corresponds to a valid molecule, and SELFIES can represent every molecule. SELFIES can be directly applied in arbitrary machine learning models without the adaptation of the models; each of the generated molecule candidates is valid. In our experiments, the model's internal memory stores two orders of magnitude more diverse molecules than a similar test with SMILES. Furthermore, as all molecules are valid, it allows for explanation and interpretation of the internal working of the generative models.

The efficient exploration of chemical space to design molecules with intended properties enables the accelerated discovery of drugs, materials, and catalysts, and is one of the most important outstanding challenges in chemistry. Encouraged by the recent surge in computer power and artificial intelligence development, many algorithms have been developed to tackle this problem. However, despite the emergence of many new approaches in recent years, comparatively little progress has been made in developing realistic benchmarks that reflect the complexity of molecular design for real-world applications. In this work, we develop a set of practical benchmark tasks relying on physical simulation of molecular systems mimicking real-life molecular design problems for materials, drugs, and chemical reactions. Additionally, we demonstrate the utility and ease of use of our new benchmark set by demonstrating how to compare the performance of several well-established families of algorithms. Surprisingly, we find that model performance can strongly depend on the benchmark domain. We believe that our benchmark suite will help move the field towards more realistic molecular design benchmarks, and move the development of inverse molecular design algorithms closer to designing molecules that solve existing problems in both academia and industry alike.

Computational design of protein-binding proteins is a fundamental capability with broad utility in biomedical research and biotechnology. Recent methods have made strides against some target proteins, but on-demand creation of high-affinity binders without multiple rounds of experimental testing remains an unsolved challenge. This technical report introduces AlphaProteo, a family of machine learning models for protein design, and details its performance on the de novo binder design problem. With AlphaProteo, we achieve 3- to 300-fold better binding affinities and higher experimental success rates than the best existing methods on seven target proteins. Our results suggest that AlphaProteo can generate binders "ready-to-use" for many research applications using only one round of medium-throughput screening and no further optimization.