Daily Papers

Imitation learning from human demonstrations is an effective means to teach robots manipulation skills. But data acquisition is a major bottleneck in applying this paradigm more broadly, due to the amount of cost and human effort involved. There has been significant interest in imitation learning for bimanual dexterous robots, like humanoids. Unfortunately, data collection is even more challenging here due to the challenges of simultaneously controlling multiple arms and multi-fingered hands. Automated data generation in simulation is a compelling, scalable alternative to fuel this need for data. To this end, we introduce DexMimicGen, a large-scale automated data generation system that synthesizes trajectories from a handful of human demonstrations for humanoid robots with dexterous hands. We present a collection of simulation environments in the setting of bimanual dexterous manipulation, spanning a range of manipulation behaviors and different requirements for coordination among the two arms. We generate 21K demos across these tasks from just 60 source human demos and study the effect of several data generation and policy learning decisions on agent performance. Finally, we present a real-to-sim-to-real pipeline and deploy it on a real-world humanoid can sorting task. Videos and more are at https://dexmimicgen.github.io/

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, have been developed with the purpose of picking completely new samples from a partially known space. Generative models offer high potential for designing de novo molecules; however, in order for them to be useful in real-life drug development pipelines, these models should be able to design target-specific molecules, which is the next step in this field. In this study, we propose DrugGEN, for the de novo design of drug candidate molecules that interact with selected target proteins. The proposed system represents compounds and protein structures as graphs and processes them via serially connected two generative adversarial networks comprising graph transformers. DrugGEN is trained using a large dataset of compounds from ChEMBL and target-specific bioactive molecules, to design effective and specific inhibitory molecules against the AKT1 protein, which has critical importance for developing treatments against various types of cancer. On fundamental benchmarks, DrugGEN models have either competitive or better performance against other methods. To assess the target-specific generation performance, we conducted further in silico analysis with molecular docking and deep learning-based bioactivity prediction. Results indicate that de novo molecules have high potential for interacting with the AKT1 protein structure in the level of its native ligand. DrugGEN can be used to design completely novel and effective target-specific drug candidate molecules for any druggable protein, given target features and a dataset of experimental bioactivities. Code base, datasets, results and trained models of DrugGEN are available at https://github.com/HUBioDataLab/DrugGEN

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.

Drug discovery is a complex process that involves multiple scenarios and stages, such as fragment-constrained molecule generation, hit generation and lead optimization. However, existing molecular generative models can only tackle one or two of these scenarios and lack the flexibility to address various aspects of the drug discovery pipeline. In this paper, we present Generalist Molecular generative model (GenMol), a versatile framework that addresses these limitations by applying discrete diffusion to the Sequential Attachment-based Fragment Embedding (SAFE) molecular representation. GenMol generates SAFE sequences through non-autoregressive bidirectional parallel decoding, thereby allowing utilization of a molecular context that does not rely on the specific token ordering and enhanced computational efficiency. Moreover, under the discrete diffusion framework, we introduce fragment remasking, a strategy that optimizes molecules by replacing fragments with masked tokens and regenerating them, enabling effective exploration of chemical space. GenMol significantly outperforms the previous GPT-based model trained on SAFE representations in de novo generation and fragment-constrained generation, and achieves state-of-the-art performance in goal-directed hit generation and lead optimization. These experimental results demonstrate that GenMol can tackle a wide range of drug discovery tasks, providing a unified and versatile approach for molecular design.

This report introduces xGen-MM (also known as BLIP-3), a framework for developing Large Multimodal Models (LMMs). The framework comprises meticulously curated datasets, a training recipe, model architectures, and a resulting suite of LMMs. xGen-MM, short for xGen-MultiModal, expands the Salesforce xGen initiative on foundation AI models. Our models undergo rigorous evaluation across a range of tasks, including both single and multi-image benchmarks. Our pre-trained base model exhibits strong in-context learning capabilities and the instruction-tuned model demonstrates competitive performance among open-source LMMs with similar model sizes. In addition, we introduce a safety-tuned model with DPO, aiming to mitigate harmful behaviors such as hallucinations and improve safety. We open-source our models, curated large-scale datasets, and our fine-tuning codebase to facilitate further advancements in LMM research. Associated resources will be available on our project page above.

While various models and computational tools have been proposed for structure and property analysis of molecules, generating molecules that conform to all desired structures and properties remains a challenge. Here, we introduce a multi-constraint molecular generation large language model, TSMMG, which, akin to a student, incorporates knowledge from various small models and tools, namely, the 'teachers'. To train TSMMG, we construct a large set of text-molecule pairs by extracting molecular knowledge from these 'teachers', enabling it to generate novel molecules that conform to the descriptions through various text prompts. We experimentally show that TSMMG remarkably performs in generating molecules meeting complex, natural language-described property requirements across two-, three-, and four-constraint tasks, with an average molecular validity of over 99% and success ratio of 82.58%, 68.03%, and 67.48%, respectively. The model also exhibits adaptability through zero-shot testing, creating molecules that satisfy combinations of properties that have not been encountered. It can comprehend text inputs with various language styles, extending beyond the confines of outlined prompts, as confirmed through empirical validation. Additionally, the knowledge distillation feature of TSMMG contributes to the continuous enhancement of small models, while the innovative approach to dataset construction effectively addresses the issues of data scarcity and quality, which positions TSMMG as a promising tool in the domains of drug discovery and materials science.

In an era of increasing pressure to achieve sustainable agriculture, the optimization of livestock feed for enhancing yield and minimizing environmental impact is a paramount objective. This study presents a pioneering approach towards this goal, using rumen microbiome data to predict the efficacy of feed additives in dairy cattle. We collected an extensive dataset that includes methane emissions from 2,190 Holstein cows distributed across 34 distinct sites. The cows were divided into control and experimental groups in a double-blind, unbiased manner, accounting for variables such as age, days in lactation, and average milk yield. The experimental groups were administered one of four leading commercial feed additives: Agolin, Kexxtone, Allimax, and Relyon. Methane emissions were measured individually both before the administration of additives and over a subsequent 12-week period. To develop our predictive model for additive efficacy, rumen microbiome samples were collected from 510 cows from the same herds prior to the study's onset. These samples underwent deep metagenomic shotgun sequencing, yielding an average of 15.7 million reads per sample. Utilizing innovative artificial intelligence techniques we successfully estimated the efficacy of these feed additives across different farms. The model's robustness was further confirmed through validation with independent cohorts, affirming its generalizability and reliability. Our results underscore the transformative capability of using targeted feed additive strategies to both optimize dairy yield and milk composition, and to significantly reduce methane emissions. Specifically, our predictive model demonstrates a scenario where its application could guide the assignment of additives to farms where they are most effective. In doing so, we could achieve an average potential reduction of over 27\% in overall emissions.

Despite recent advances in natural language generation, it remains challenging to control attributes of generated text. We propose DExperts: Decoding-time Experts, a decoding-time method for controlled text generation that combines a pretrained language model with "expert" LMs and/or "anti-expert" LMs in a product of experts. Intuitively, under the ensemble, tokens only get high probability if they are considered likely by the experts, and unlikely by the anti-experts. We apply DExperts to language detoxification and sentiment-controlled generation, where we outperform existing controllable generation methods on both automatic and human evaluations. Moreover, because DExperts operates only on the output of the pretrained LM, it is effective with (anti-)experts of smaller size, including when operating on GPT-3. Our work highlights the promise of tuning small LMs on text with (un)desirable attributes for efficient decoding-time steering.