Understanding gene regulatory networks (GRNs) holds paramount importance for deciphering the intricate interplay among genes and their influence on biological processes and disease pathogenesis. The emergence of single-cell RNA sequencing (scRNA-seq) techniques has heralded a new era in GRN inference by capturing the nuanced heterogeneity and dynamic nature of gene expression at the single-cell level. However, extracting meaningful patterns from scRNA-seq measurements to infer GRNs poses significant challenges to existing methodologies due to the sheer scale and inherent complexity of the data. Here we propose a highly accurate and computationally efficient strategy for scRNA-seq-based GRN inference. Our approach leverages the underlying interactive relationships among the cells using state-of-the-art deep learning strategy. Specifically, a spatially semantic image representation, termed CelloGraph, is first introduced to portray the expressions of each gene across cells. The allocation of a cell to a spatial grid point of the CelloGraph is dictated by its interactions with other cells within the system, as determined by the maximization of system entropy of cell-cell interactions. Subsequently, the CelloGraphs of all pertinent genes are analyzed by using a customarily designed convolutional neural network (CNN) to discern discriminant patterns in the data and infer GRNs. The efficacy of the proposed approach is demonstrated through diverse real-world biomedical datasets. By harnessing the distinctive attributes of spatially semantic CelloGraphs and leveraging the unique pattern discovery capabilities of CNNs, our methodology paves the way for a deeper comprehension of the underlying mechanisms that govern gene expression and regulation. The proposed strategy not only overcomes challenges in scRNA-seq-based GRN inference but also promises to provide a more comprehensive understanding of intricate biological processes.

Test-time compute has empowered multimodal large language models to generate extended reasoning chains, yielding strong performance on tasks such as multimodal math reasoning. However, we observe that this improved reasoning ability often comes with increased hallucination: as generations become longer, models tend to drift away from image-grounded content and rely more on language priors. Attention analysis reveals that longer reasoning chains reduce focus on visual inputs, contributing to hallucination. To systematically study this phenomenon, we introduce RH-AUC, a metric that quantifies how a model's perception accuracy changes with reasoning length, enabling evaluation of whether the model preserves visual grounding while reasoning. We also release RH-Bench, a diagnostic benchmark covering diverse multimodal tasks, designed to jointly assess the balance of reasoning ability and hallucination. We find that (i) larger models generally exhibit a better balance between reasoning and perception; (ii) reasoning and perception balance depends more on the types and domains of the training data than its volume. Our findings highlight the need for evaluation frameworks that account for both reasoning quality and perceptual reliability.

The Segment Anything Model (SAM) has garnered significant attention for its versatile segmentation abilities and intuitive prompt-based interface. However, its application in medical imaging presents challenges, requiring either substantial training costs and extensive medical datasets for full model fine-tuning or high-quality prompts for optimal performance. This paper introduces H-SAM: a prompt-free adaptation of SAM tailored for efficient fine-tuning of medical images via a two-stage hierarchical decoding procedure. In the initial stage, H-SAM employs SAM's original decoder to generate a prior probabilistic mask, guiding a more intricate decoding process in the second stage. Specifically, we propose two key designs: 1) A class-balanced, mask-guided self-attention mechanism addressing the unbalanced label distribution, enhancing image embedding; 2) A learnable mask cross-attention mechanism spatially modulating the interplay among different image regions based on the prior mask. Moreover, the inclusion of a hierarchical pixel decoder in H-SAM enhances its proficiency in capturing fine-grained and localized details. This approach enables SAM to effectively integrate learned medical priors, facilitating enhanced adaptation for medical image segmentation with limited samples. Our H-SAM demonstrates a 4.78% improvement in average Dice compared to existing prompt-free SAM variants for multi-organ segmentation using only 10% of 2D slices. Notably, without using any unlabeled data, H-SAM even outperforms state-of-the-art semisupervised models relying on extensive unlabeled training data across various medical datasets. Our code is available at https://github.com/Cccccczh404/H-SAM.

Deep neural networks have shown great success in representation learning. However, when learning with noisy labels (LNL), they can easily overfit and fail to generalize to new data. This paper introduces a simple and effective method, named Learning to Bootstrap (L2B), which enables models to bootstrap themselves using their own predictions without being adversely affected by erroneous pseudo-labels. It achieves this by dynamically adjusting the importance weight between real observed and generated labels, as well as between different samples through metalearning. Unlike existing instance reweighting methods, the key to our method lies in a new, versatile objective that enables implicit relabeling concurrently, leading to significant improvements without incurring additional costs. L2B offers several benefits over the baseline methods. It yields more robust models that are less susceptible to the impact of noisy labels by guiding the bootstrapping procedure more effectively. It better exploits the valuable information contained in corrupted instances by adapting the weights of both instances and labels. Furthermore, L2B is compatible with existing LNL methods and delivers competitive results spanning natural and medical imaging tasks including classification and segmentation under both synthetic and real-world noise. Extensive experiments demonstrate that our method effectively mitigates the challenges of noisy labels, often necessitating few to no validation samples, and is well generalized to other tasks such as image segmentation. This not only positions it as a robust complement to existing LNL techniques but also underscores its practical applicability. The code and models are available at https://github.com/yuyinzhou/12b.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool to gain biological insights at the cellular level. However, due to technical limitations of the existing sequencing technologies, low gene expression values are often omitted, leading to inaccurate gene counts. Existing methods, including advanced deep learning techniques, struggle to reliably impute gene expressions due to a lack of mechanisms that explicitly consider the underlying biological knowledge of the system. In reality, it has long been recognized that gene-gene interactions may serve as reflective indicators of underlying biology processes, presenting discriminative signatures of the cells. A genomic data analysis framework that is capable of leveraging the underlying gene-gene interactions is thus highly desirable and could allow for more reliable identification of distinctive patterns of the genomic data through extraction and integration of intricate biological characteristics of the genomic data. Here we tackle the problem in two steps to exploit the gene-gene interactions of the system. We first reposition the genes into a 2D grid such that their spatial configuration reflects their interactive relationships. To alleviate the need for labeled ground truth gene expression datasets, a self-supervised 2D convolutional neural network is employed to extract the contextual features of the interactions from the spatially configured genes and impute the omitted values. Extensive experiments with both simulated and experimental scRNA-seq datasets are carried out to demonstrate the superior performance of the proposed strategy against the existing imputation methods.

Medical image segmentation is crucial for healthcare, yet convolution-based methods like U-Net face limitations in modeling long-range dependencies. To address this, Transformers designed for sequence-to-sequence predictions have been integrated into medical image segmentation. However, a comprehensive understanding of Transformers' self-attention in U-Net components is lacking. TransUNet, first introduced in 2021, is widely recognized as one of the first models to integrate Transformer into medical image analysis. In this study, we present the versatile framework of TransUNet that encapsulates Transformers' self-attention into two key modules: (1) a Transformer encoder tokenizing image patches from a convolution neural network (CNN) feature map, facilitating global context extraction, and (2) a Transformer decoder refining candidate regions through cross-attention between proposals and U-Net features. These modules can be flexibly inserted into the U-Net backbone, resulting in three configurations: Encoder-only, Decoder-only, and Encoder+Decoder. TransUNet provides a library encompassing both 2D and 3D implementations, enabling users to easily tailor the chosen architecture. Our findings highlight the encoder's efficacy in modeling interactions among multiple abdominal organs and the decoder's strength in handling small targets like tumors. It excels in diverse medical applications, such as multi-organ segmentation, pancreatic tumor segmentation, and hepatic vessel segmentation. Notably, our TransUNet achieves a significant average Dice improvement of 1.06% and 4.30% for multi-organ segmentation and pancreatic tumor segmentation, respectively, when compared to the highly competitive nn-UNet, and surpasses the top-1 solution in the BrasTS2021 challenge. 2D/3D Code and models are available at https://github.com/Beckschen/TransUNet and https://github.com/Beckschen/TransUNet-3D, respectively.

The collection and curation of large-scale medical datasets from multiple institutions is essential for training accurate deep learning models, but privacy concerns often hinder data sharing. Federated learning (FL) is a promising solution that enables privacy-preserving collaborative learning among different institutions, but it generally suffers from performance deterioration due to heterogeneous data distributions and a lack of quality labeled data. In this paper, we present a robust and label-efficient self-supervised FL framework for medical image analysis. Our method introduces a novel Transformer-based self-supervised pre-training paradigm that pre-trains models directly on decentralized target task datasets using masked image modeling, to facilitate more robust representation learning on heterogeneous data and effective knowledge transfer to downstream models. Extensive empirical results on simulated and real-world medical imaging non-IID federated datasets show that masked image modeling with Transformers significantly improves the robustness of models against various degrees of data heterogeneity. Notably, under severe data heterogeneity, our method, without relying on any additional pre-training data, achieves an improvement of 5.06%, 1.53% and 4.58% in test accuracy on retinal, dermatology and chest X-ray classification compared to the supervised baseline with ImageNet pre-training. In addition, we show that our federated self-supervised pre-training methods yield models that generalize better to out-of-distribution data and perform more effectively when fine-tuning with limited labeled data, compared to existing FL algorithms. The code is available at https://github.com/rui-yan/SSL-FL.