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Deep learning techniques have significantly enhanced the convenience and precision of ultrasound image diagnosis, particularly in the crucial step of lesion segmentation. However, recent studies reveal that both train-from-scratch models and pre-trained models often exhibit performance disparities across sex and age attributes, leading to biased diagnoses for different subgroups. In this paper, we propose APPLE, a novel approach designed to mitigate unfairness without altering the parameters of the base model. APPLE achieves this by learning fair perturbations in the latent space through a generative adversarial network. Extensive experiments on both a publicly available dataset and an in-house ultrasound image dataset demonstrate that our method improves segmentation and diagnostic fairness across all sensitive attributes and various backbone architectures compared to the base models. Through this study, we aim to highlight the critical importance of fairness in medical segmentation and contribute to the development of a more equitable healthcare system.
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http://dx.doi.org/10.1038/s41746-025-01641-y | DOI Listing |
Nat Biomed Eng
September 2025
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Phenotype-driven approaches identify disease-counteracting compounds by analysing the phenotypic signatures that distinguish diseased from healthy states. Here we introduce PDGrapher, a causally inspired graph neural network model that predicts combinatorial perturbagens (sets of therapeutic targets) capable of reversing disease phenotypes. Unlike methods that learn how perturbations alter phenotypes, PDGrapher solves the inverse problem and predicts the perturbagens needed to achieve a desired response by embedding disease cell states into networks, learning a latent representation of these states, and identifying optimal combinatorial perturbations.
View Article and Find Full Text PDFNat Commun
September 2025
BioMap Research, Palo Alto, CA, USA.
Investigating cell morphology changes after perturbations using high-throughput image-based profiling is increasingly important for phenotypic drug discovery, including predicting mechanisms of action (MOA) and compound bioactivity. The vast space of chemical and genetic perturbations makes it impractical to explore all possibilities using conventional methods. Here we propose MorphDiff, a transcriptome-guided latent diffusion model that simulates high-fidelity cell morphological responses to perturbations.
View Article and Find Full Text PDFArXiv
August 2025
Paul G. Allen School of Computer Science & Engineering, University of Washington.
Neural recording technologies now enable simultaneous recording of population activity across many brain regions, motivating the development of data-driven models of communication between brain regions. However, existing models can struggle to disentangle the sources that influence recorded neural populations, leading to inaccurate portraits of inter-regional communication. Here, we introduce Multi-Region Latent Factor Analysis via Dynamical Systems (MR-LFADS), a sequential variational autoencoder designed to disentangle inter-regional communication, inputs from unobserved regions, and local neural population dynamics.
View Article and Find Full Text PDFmedRxiv
August 2025
Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
Myocardial infarction (MI) often leads to ischemic cardiomyopathy, which is characterized by extensive cardiac remodeling and pathological fibrosis accompanied by inflammatory cell accumulation. Although inflammatory responses elicited by cardiac macrophages are instrumental in post-MI cardiac remodeling, macrophage microniche-mediated fibroblast activation in MI are not understood. Analyses of the spatial transcriptomics data of the hearts of patients with ischemic cardiomyopathy and a history of MI using a novel workflow combining Significant Latent Factor Interaction Discovery (SLIDE), which is an interpretable machine learning approach recently developed by us, regulatory network inference, and in-silico perturbations unveiled unique context-specific cellular programs and corresponding transcription factors driving these programs (that would have been missed by traditional analyses) in macrophages, and resting and activated cardiac fibroblasts.
View Article and Find Full Text PDFBioengineering (Basel)
August 2025
Department of Computer Science, City University of Hong Kong, Kowloon Tong, Hong Kong SAR 999077, China.
Modeling drug-induced transcriptional responses at the single-cell level is essential for advancing human healthcare, particularly in understanding disease mechanisms, assessing therapeutic efficacy, and anticipating adverse effects. However, existing approaches often impose a rigid constraint by enforcing pointwise alignment of latent representations to a standard normal prior, which limits expressiveness and results in biologically uninformative embeddings, especially in complex biological systems. Additionally, many methods inadequately address the challenges of unpaired data, typically relying on naive averaging strategies that ignore cell-type specificity and intercellular heterogeneity.
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