bioRxiv Science⌕ Search

bioRxiv · 10.64898/2025.12.19.694650

Assessing Knowledge Distillation of a Multi-Emitter Localizing Neural Network for Applications in Stochastic Optical Reconstruction Microscopy

Abstract

BackgroundSuper Resolution Microscopy (SRM) is a powerful method in quantitative bioscience that allows interrogation of nanoscale details. These methods require extensive imaging times on the microscope resulting in data sets on the scale of gigabytes. In order to reduce imaging times, the concentration of emitters can be increased, however that results in overlapping emitters rendering the isolation of single emitters extremely difficult. Statistical methods have been developed to deconvolute overlapping emitters, however they require parameter optimization and user expertise. Recently, Machine Learning (ML) has been developed to automate this analysis but often require larger Convolutional Neural Networks (CNN). While powerful, such models require compute and storage that would make pushing these models to compute limited devices difficult. To address this, we investigate if the dense multi-emitter localization capacity of a larger model, Deep Residual Stochastic Optical Reconstruction Microscopy (DRL-STORM), can be transferred to a smaller model, Super Resolution Convolutional Neural Network (SRCNN). ResultsKnowledge transfer from DRL-STORM to SRCNN did not result in an improvement of multi-emitter localization performance of SRCNN. Hint Learning (HL) was performed to facilitate knowledge transfer in a more deliberate manner. SRCNN demonstrated a limited capacity to learn an intermediate representation of the input image in the same manner as DRL-STORM and resultantly did not perform any better in its task. ConclusionsKnowledge transfer was not successful between DRL-STORM and SRCNN, but evidence suggests that it is possible and may require another model besides SRCNN. A future work will investigate if hyper-parameter optimization results in greater knowledge distillation between DRL-STORM and SRCNN. SRCNN may not be ideal for multi-emitter localizations, but it can still prove effective for SRM data analysis at emitter concentrations typical of SRM experiments and is uniquely suited as a neural network model that can be deployed in compute limited settings.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Reed, M. B., Zadegan, R.. 2025-12-22. Assessing Knowledge Distillation of a Multi-Emitter Localizing Neural Network for Applications in Stochastic Optical Reconstruction Microscopy. https://doi.org/10.64898/2025.12.19.694650

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A meta-interaction basis for cell-cell communication in tissues

Tissue function depends on signals exchanged between cells and the responses they elicit. Yet whether diverse cell-cell interactions in situ form recurrent sender-receiver programs remains unclear. We present SpiderNet, an interpretable representation-learning framework that discovers such directed programs as a compact basis of cell-cell meta-interactions (MIs) from spatial transcriptomics. SpiderNet jointly learns which sender regulators, ligand-receptor pairs, and receiver targets define each MI and where each program is active across neighboring cell pairs. The resulting representation traces multicellular relays and links communication to cell states, perturbation responses, and phenotypes. SpiderNet recovers ground-truth MIs and their molecular components in simulations and, in real tissues, shows stronger direction-specific agreement with independently curated regulatory programs in senders and receivers than alternative methods. Across more than 5.8 million spatially profiled cells, SpiderNet resolves an SPP1-THBS relay linking monocytes, fibroblasts, and tumor cells within an immune-suppressive ovarian cancer niche, predicts T-cell responses to held-out melanoma-cell perturbations, and identifies a T-cell-associated brain-aging program and age-predictive signals that transfer across regions and platforms. It reveals a recurrent pan-cancer COLLAGEN-linked fibroblast-tumor program whose projected abundance in independent cohorts is associated with poorer survival and non-response to immunotherapy. SpiderNet thus establishes MIs as a reusable organizational layer between molecular interactions and tissue phenotypes, providing a framework to resolve, compare, trace, and perturb multicellular regulation in situ.

bioinformatics↗

Heterogeneous Graph Contrastive Learning for Drug-Gene-Disease Motif Prediction

Drug repurposing and target discovery offer critical strategies for advancing therapeutic development by uncovering the potential biological pathways and novel associations among drugs, genes, and diseases. However, experimental discovery remains expensive and time-consuming, which limits the scalability of large-scale studies. In addition, existing computational approaches often struggle to effectively integrate heterogeneous biomedical data, capture the complex higher-order topological signatures of biological interactomes, and generalize to unseen entities. Here, we present HANAMI (Heterogeneous grAph coNtrastive leArning for drug-gene-disease Motif predIction), a multi-view deep graph learning framework designed to model complex interactions among drugs, genes, and diseases. HANAMI integrates diverse heterogeneous biomedical knowledge, including chemical structures, genomic sequences, and clinical phenotypes, and leverages relation-aware topology encoding, structure-aware aggregation, and contrastive learning to enable accurate motif prediction with biological context from the network. Systematic evaluation on benchmark datasets shows that HANAMI achieves up to 6% improvements over existing state-of-the-art methods in predicting drug-gene-disease motifs. The framework further demonstrates strong inductive generalization, maintaining an [~]18% performance advantage in zero-shot settings involving previously unseen entities. Beyond predictive performance, HANAMI effectively prioritizes drug-disease relationships investigated in Phase II or III trials while identifying candidate genes that suggest plausible mechanistic links. Together, HANAMI provides a computational framework for interpreting complex biomedical interactions, offering a scalable foundation to accelerate drug repurposing and therapeutic innovation.

bioinformatics↗

PTMExplorer: A Multi-Dimensional Integrative Visualization Platform for Protein Post-Translational Modification Function and Structure

Deciphering the functions of post-translational modifications (PTMs) is a critical bridge connecting large-scale modification proteomics data to mechanistic studies. However, most existing tools for visualizing PTM omics data are limited to site catalogs or single-dimensional feature displays. They lack the capability to simultaneously map user-derived differential modification sites onto multi-dimensional contexts, including protein three-dimensional (3D) structure, evolutionary conservation, functional sites, and disease associations. This limitation makes it difficult for researchers to rapidly assess the biological importance of candidate sites from among a vast number of differentially modified sites. Here, we present PTMExplorer, an interactive platform for the multi-dimensional visualization of protein PTMs. PTMExplorer comprises three core modules: PTM Inspector, built upon ProtVista, provides a multi-track, sequence-feature integrated view incorporating intrinsically disordered region (IDR) prediction (via flDPnn), surface accessibility calculation (via FreeSASA), and UniProt functional annotations; PTM 3D Locator, leveraging the Nightingale/Mol* engine, anchors modification sites onto AlphaFold/Protein Data Bank (PDB) 3D structures through residue mapping via PDBe-SIFTS; and PTM Overview, utilizing the R circlize package, presents a panoramic polar circos plot illustrating modification distribution and inter-group differential regulation. Additionally, three major disease-associated modification databases (PTMD, qPTM, and PhosCancer) are integrated as PTM-Disease Nexus, enabling co-localization comparison between user-defined differential sites and reported disease-related sites. PTMExplorer currently supports eight model organisms, accepts user-uploaded differential analysis results, and provides multi-dimensional annotations and various visualization options (https://www.bioladder.cn/PTMExplorer/). Using a multi-omics dataset from hepatocellular carcinoma (18 patients, 9 modification types) as a case study, we demonstrate the practical utility of PTMExplorer in screening potential biomarkers, revealing multi-modification coordination mechanisms, and distinguishing between absolute and relative quantification patterns.

bioinformatics↗