Disease progression models infer group-level temporal trajectories of change in patients' features as a chronic degenerative condition plays out. They provide unique insight into disease biology and staging systems with individual-level clinical utility. Discrete models consider disease progression as a latent permutation of events, where each event corresponds to a feature becoming measurably abnormal. However, permutation inference using traditional maximum likelihood approaches becomes prohibitive due to combinatoric explosion, severely limiting model dimensionality and utility. Here we leverage ideas from optimal transport to model disease progression as a latent permutation matrix of events belonging to the Birkhoff polytope, facilitating fast inference via optimisation of the variational lower bound. This enables a factor of 1000 times faster inference than the current state of the art and, correspondingly, supports models with several orders of magnitude more features than the current state of the art can consider. Experiments demonstrate the increase in speed, accuracy and robustness to noise in simulation.

In the past decade, deep conditional generative models have revolutionized the generation of realistic images, extending their application from entertainment to scientific domains. Single-particle cryo-electron microscopy (cryo-EM) is crucial in resolving near-atomic resolution 3D structures of proteins, such as the SARS-COV-2 spike protein. To achieve high-resolution reconstruction, a comprehensive data processing pipeline has been adopted. However, its performance is still limited as it lacks high-quality annotated datasets for training. To address this, we introduce physics-informed generative cryo-electron microscopy (CryoGEM), which for the first time integrates physics-based cryo-EM simulation with a generative unpaired noise translation to generate physically correct synthetic cryo-EM datasets with realistic noises. Initially, CryoGEM simulates the cryo-EM imaging process based on a virtual specimen. To generate realistic noises, we leverage an unpaired noise translation via contrastive learning with a novel mask-guided sampling scheme. Extensive experiments show that CryoGEM is capable of generating authentic cryo-EM images. The generated dataset can be used as training data for particle picking and pose estimation models, eventually improving the reconstruction resolution.

The empirical success of distributional reinforcement learning (RL) highly relies on the choice of distribution divergence equipped with an appropriate distribution representation. In this paper, we propose \textit{Sinkhorn distributional RL (SinkhornDRL)}, which leverages Sinkhorn divergence--a regularized Wasserstein loss--to minimize the difference between current and target Bellman return distributions. Theoretically, we prove the contraction properties of SinkhornDRL, aligning with the interpolation nature of Sinkhorn divergence between Wasserstein distance and Maximum Mean Discrepancy (MMD). The introduced SinkhornDRL enriches the family of distributional RL algorithms, contributing to interpreting the algorithm behaviors compared with existing approaches by our investigation into their relationships. Empirically, we show that SinkhornDRL consistently outperforms or matches existing algorithms on the Atari games suite and particularly stands out in the multi-dimensional reward setting.

Autonomous trucking is a promising technology that can greatly impact modern logistics and the environment. Ensuring its safety on public roads is one of the main duties that requires an accurate perception of the environment. To achieve this, machine learning methods rely on large datasets, but to this day, no such datasets are available for autonomous trucks.

Recent advances in self-supervised models for natural language, vision, and protein sequences have inspired the development of large genomic DNA language models (DNALMs). These models aim to learn generalizable representations of diverse DNA elements, potentially enabling various genomic prediction, interpretation and design tasks. Despite their potential, existing benchmarks do not adequately assess the capabilities of DNALMs on key downstream applications involving an important class of non-coding DNA elements critical for regulating gene activity. In this study, we introduce DART-Eval, a suite of representative benchmarks specifically focused on regulatory DNA to evaluate model performance across zero-shot, probed, and fine-tuned scenarios against contemporary ab initio models as baselines. Our benchmarks target biologically meaningful downstream tasks such as functional sequence feature discovery, predicting cell-type specific regulatory activity, and counterfactual prediction of the impacts of genetic variants. We find that current DNALMs exhibit inconsistent performance and do not offer compelling gains over alternative baseline models for most tasks, while requiring significantly more computational resources. We discuss potentially promising modeling, data curation, and evaluation strategies for the next generation of DNALMs.

Antibodies have become an important class of therapeutic agents to treat human diseases.To accelerate therapeutic antibody discovery, computational methods, especially machine learning, have attracted considerable interest for predicting specific interactions between antibody candidates and target antigens such as viruses and bacteria.However, the publicly available datasets in existing works have notable limitations, such as small sizes and the lack of non-binding samples and exact amino acid sequences.To overcome these limitations, we have developed AVIDa-hIL6, a large-scale dataset for predicting antigen-antibody interactions in the variable domain of heavy chain of heavy chain antibodies (VHHs), produced from an alpaca immunized with the human interleukin-6 (IL-6) protein, as antigens.By leveraging the simple structure of VHHs, which facilitates identification of full-length amino acid sequences by DNA sequencing technology, AVIDa-hIL6 contains 573,891 antigen-VHH pairs with amino acid sequences.All the antigen-VHH pairs have reliable labels for binding or non-binding, as generated by a novel labeling method.Furthermore, via introduction of artificial mutations, AVIDa-hIL6 contains 30 different mutants in addition to wild-type IL-6 protein.This characteristic provides opportunities to develop machine learning models for predicting changes in antibody binding by antigen mutations.We report experimental benchmark results on AVIDa-hIL6 by using machine learning models.The results indicate that the existing models have potential, but further research is needed to generalize them to predict effective antibodies against unknown mutants.The dataset is available at https://avida-hil6.cognanous.com.

Confocal fluorescence microscopy is one of the most accessible and widely used imaging techniques for the study of biological processes at the cellular and subcellular levels. Scanning confocal microscopy allows the capture of high-quality images from thick three-dimensional (3D) samples, yet suffers from well-known limitations such as photobleaching and phototoxicity of specimens caused by intense light exposure, which limits its use in some applications, especially for living cells. Cellular damage can be alleviated by changing imaging parameters to reduce light exposure, often at the expense of image quality.Machine/deep learning methods for single-image super-resolution (SISR) can be applied to restore image quality by upscaling lower-resolution (LR) images to produce high-resolution images (HR). These SISR methods have been successfully applied to photo-realistic images due partly to the abundance of publicly available datasets. In contrast, the lack of publicly available data partly limits their application and success in scanning confocal microscopy.In this paper, we introduce a large scanning confocal microscopy dataset named SR-CACO-2 that is comprised of low-and high-resolution image pairs marked for three different fluorescent markers. It allows to evaluate the performance of SISR methods on three different upscaling levels (X2, X4, X8).

In order to thrive in hostile and ever-changing natural environments, mammalian brains evolved to store large amounts of knowledge about the world and continually integrate new information while avoiding catastrophic forgetting. Despite the impressive accomplishments, large language models (LLMs), even with retrieval-augmented generation (RAG), still struggle to efficiently and effectively integrate a large amount of new experiences after pre-training. In this work, we introduce HippoRAG, a novel retrieval framework inspired by the hippocampal indexing theory of human long-term memory to enable deeper and more efficient knowledge integration over new experiences. HippoRAG synergistically orchestrates LLMs, knowledge graphs, and the Personalized PageRank algorithm to mimic the different roles of neocortex and hippocampus in human memory. We compare HippoRAG with existing RAG methods on multi-hop question answering (QA) and show that our method outperforms the state-of-the-art methods remarkably, by up to 20%. Single-step retrieval with HippoRAG achieves comparable or better performance than iterative retrieval like IRCoT while being 10-20 times cheaper and 6-13 times faster, and integrating HippoRAG into IRCoT brings further substantial gains. Finally, we show that our method can tackle new types of scenarios that are out of reach of existing methods.

Precision livestock farming (PLF) has been transformed by machine learning (ML), enabling more precise and timely interventions that enhance overall farm productivity, animal welfare, and environmental sustainability. However, despite the availability of various sensing technologies, few datasets leverage multiple modalities, which are crucial for developing more accurate and efficient monitoring devices and ML models. To address this gap, we present MmCows, a multimodal dataset for dairy cattle monitoring. This dataset comprises a large amount of synchronized, high-quality measurement data on behavioral, physiological, and environmental factors. It includes two weeks of data collected using wearable and implantable sensors deployed on ten milking Holstein cows, such as ultra-wideband (UWB) sensors, inertial sensors, and body temperature sensors.

Fact-checking is extensively studied in the context of misinformation and disinformation, addressing objective inaccuracies. However, a softer form of misinformation involves responses that are factually correct but lack certain features such as clarity and relevance. This challenge is prevalent in formal Question-Answer (QA) settings such as press conferences in finance, politics, sports, and other domains, where subjective answers can obscure transparency. Despite this, there is a lack of manually annotated datasets for subjective features across multiple dimensions. To address this gap, we introduce SubjECTive-QA, a human annotated dataset on Earnings Call Transcripts' (ECTs) QA sessions as the answers given by company representatives are often open to subjective interpretations and scrutiny. The dataset includes 49,446 annotations for long-form QA pairs across six features: Assertive, Cautious, Optimistic, Specific, Clear, and Relevant. These features are carefully selected to encompass the key attributes that reflect the tone of the answers provided during QA sessions across different domains. Our findings are that the best-performing Pre-trained Language Model (PLM), RoBERTa-base, has similar weighted F1 scores to Llama-3-70b-Chat on features with lower subjectivity, such as Relevant and Clear, with a mean difference of 2.17% in their weighted F1 scores. The models perform significantly better on features with higher subjectivity, such as Specific and Assertive, with a mean difference of 10.01% in their weighted F1 scores.