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Joshua Pan

Publications and source records attributed to Joshua Pan.

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Modality-AGnostic Image Cascade (MAGIC) for Multi-Modality Cardiac Substructure Segmentation

Cardiac substructure delineation is emerging in treatment planning to minimize the risk of radiation-induced heart disease. Deep learning offers efficient methods to reduce contouring burden but currently lacks generalizability across different modalities and overlapping structures. This work introduces and validates a Modality-AGnostic Image Cascade (MAGIC) deep-learning pipeline for comprehensive and multi-modal cardiac substructure segmentation. MAGIC is implemented through replicated encoding and decoding branches of an nnU-Net backbone to handle multi-modality inputs and overlapping labels. First benchmarked on the multi-modality whole-heart segmentation (MMWHS) dataset including cardiac CT-angiography (CCTA) and MR modalities, twenty cardiac substructures (heart, chambers, great vessels (GVs), valves, coronary arteries (CAs), and conduction nodes) from clinical simulation CT (Sim-CT), low-field MR-Linac, and cardiac CT-angiography (CCTA) modalities were delineated to train semi-supervised (n=151), validate (n=15), and test (n=30) MAGIC. For comparison, fourteen single-modality comparison models (two MMWHS modalities and four subgroups across three clinical modalities) were trained. Methods were evaluated for efficiency and against reference contours through the Dice similarity coefficient (DSC) and two-tailed Wilcoxon Signed-Rank test (p<0.05). Average MMWHS DSC scores across CCTA and MR inputs were 0.88(0.08) and 0.87(0.04) respectively with significant improvement over unimodal baselines. Average 20-structure DSC scores were 0.75(0.16) for Sim-CT, 0.68(0.21) for MR-Linac, and 0.80(0.16) for CCTA. Furthermore, >80% and >70% reductions in training time and parameters were achieved, respectively. MAGIC offers an efficient, lightweight solution capable of segmenting multiple image modalities and overlapping structures in a single model without compromising segmentation accuracy.

physics.med-ph

Sparse dictionary learning recovers pleiotropy from human cell fitness screens

In high-throughput functional genomic screens, each gene product is commonly assumed to exhibit a singular biological function within a defined protein complex or pathway. In practice, a single gene perturbation may induce multiple cascading functional outcomes, a genetic principle known as pleiotropy. Here, we model pleiotropy in fitness screen collections by representing each gene perturbation as the sum of multiple perturbations of biological functions, each harboring independent fitness effects inferred empirically from the data. Our approach ('Webster') recovered pleiotropic functions for DNA damage proteins from genotoxic fitness screens, untangled distinct signaling pathways upstream of shared effector proteins from cancer cell fitness screens, and learned aspects of the cellular hierarchy in an unsupervised manner. Modeling compound sensitivity profiles in terms of genetically defined functions recovered compound mechanisms of action. Our approach establishes a sparse approximation mechanism for unraveling complex genetic architectures underlying high-dimensional gene perturbation readouts.

q-bio.QM