Model-agnostic Knowledge Augmented Machine Learning for Weakly Annotated Bioimaging Data
Authors: Jayanie Bogahawatte, Sachith Seneviratne, Simon Maksour, Dzung Do-Ha, Elizabeth Qian, Samuel Brennan, Matthew Keon, Lezanne Ooi, Saman Halgamuge
Organizations: AI, Optimization and Pattern Recognition Research Group, Faculty of Engineering and Information Technology, The University of Melbourne, Melbourne, Victoria, Australia · School of Science and Molecular Horizons, University of Wollongong, Northfields Avenue, New South Wales, Australia · Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia · The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia · GenieUs Genomics Pty Ltd, Sydney, NSW, Australia · Xstendyl, Sydney, NSW, Australia
Machine learning models are increasingly used for automated feature extraction from weakly annotated bioimaging data, such as microscopy and cytomorphology images. Due to the sole dependency of automated feature extraction, existing methods yield inconsistent classification performance across weakly annotated datasets. Here, we propose a model-agnostic knowledge augmentation method that enables ML models to exploit domain knowledge beyond what automated feature extraction can capture. The proposed approach improves classification performance across seven ML architectures. When integrated with masked autoencoder-based self-supervised learning, our method achieves the strongest overall performance, improving precision by 2.9% over the next-best method on three in-house microscopy datasets and by an average of 6.8% across three public cytomorphology benchmarks. We perform nucleus-level classification based on mislocalization of TAR DNA-binding protein 43 (TDP-43) from the nucleus to the cytoplasm, a phenotype linked to Amyotrophic Lateral Sclerosis (ALS), using three independent microscopy datasets of motor neurons derived from human induced pluripotent stem cells. Accurate quantification of this phenotype at scale remains challenging and may contribute to inconsistencies across studies. Application of the best-performing model to these microscopy datasets reveals biological interpretations related to ALS, including dose-dependent effects of the proteasomal stressor, MG132, and the oxidative stressor, sodium arsenite (SA), on TDP-43 mislocalization, variable pathology in motor neurons from sporadic and familial ALS donors, and a lack of protection of the pharmacological compounds, edaravone and niclosamide, against SA-induced TDP-43 mislocalization. Together, our pipeline enables in-vitro cellular image analysis to advance understanding of ALS-associated pathology and potential treatments.
Vision transformers (ViT) have been shown to allow for more flexible feature detection and can outperform convolutional neural network (CNN) when pre-trained on sufficient data. Due to their promising feature detection capabilities, we deployed ViTs for morphological classification of anaplastic large cell lymphoma (ALCL) versus classic Hodgkin lymphoma (cHL). We had previously designed a ViT model which was trained on a small dataset of 1,200 image patches in fully supervised training. That model achieved a diagnostic accuracy of 100% and an F1 score of 1.0 on the independent test set. Since fully supervised training is not a practical method due to lack of expertise resources in both the training and testing phases, we conducted a recent study on a modified approach to training data (weakly supervised training) and show that labeling training image patch automatically at the slide level of each whole-slide-image is a more practical solution for clinical use of Vision Transformer. Our ViT model, trained on a larger dataset of 100,000 image patches, yields evaluation metrics with significant accuracy, F1 score, and area under the curve (AUC) at 91.85%, 0.92, and 0.98, respectively. These are respectable values that qualify this ViT model, with weakly supervised training, as a suitable tool for a deep learning module in clinical model development using automated image patch extraction.
Nghia, Nguyen, Amer Wahed +9
Andy · Department of Pathology and Laboratory Medicine, The University of Texas McGovern Medical School, Houston, Texas · Department of Hematopathology, The University of Texas MD Anderson Cancer, Houston, Texas
Deep learning has become the default tool for medical image analysis, driven by the open-source movement. However, achieving the best performance on a given task remains difficult, with architecture selection and hyperparameter optimization (HPO) still considered "more of an art than a science". Automated machine learning (AutoML) automates parts of model training, yet helps little in medical imaging: general-purpose approaches lack medical architectures and preprocessing, and medical-focused ones demand engineering expertise and remain confined to narrow tasks such as 3D segmentation. We introduce MedicalMLOmni, a multi-agent AutoML framework that automates model training for diverse single- and multi-modal medical tasks through a natural language interface. Specifically, MedicalMLOmni performs evidence-based planning by retrieving published results to guide model selection and configuration, and employs parallel HPO where multiple agents explore adjustment strategies concurrently. MedicalMLOmni achieves the best score on 19 of 20 benchmarks; PMC-VQA is the exception, where a vision-language model with broader pre-training leads. Backbone-matched controls attribute the gains to the framework, not the backbone. By removing coding requirements, MedicalMLOmni lowers the barrier for domain experts with rich datasets but limited engineering expertise.
Yiqing Shen, Mathias Unberath
Department of Computer Science, Johns Hopkins University
Background: Task-specific microscopy datasets are often small, making it difficult to train deep learning models that learn robust features. While self-supervised learning (SSL) has shown promise through pretraining on large, domain-specific datasets, generalizability across datasets with differing staining protocols and channel configurations remains underexplored. We investigated the generalizability of SSL models pretrained on ImageNet-1k and HPA FOV, evaluating their embeddings on OpenCell with and without fine-tuning, two channel-mismatch strategies, and varying fine-tuning data fractions. We additionally analyzed single-cell embeddings on a labeled OpenCell subset. Result: DINO-based ViT backbones pretrained on HPA FOV or ImageNet-1k transfer well to OpenCell even without fine-tuning. Fine-tuning further improved performance to 0.704 ± 0.027 (17 classes, multi-class labels). At the single-cell level, the HPA single-cell-pretrained model achieved the highest k-nearest neighbor performance across all neighborhood sizes (macro F1≥ 0.515). Conclusion: SSL methods like DINO, pretrained on large domain-relevant datasets, enable effective use of deep learning features for fine-tuning on small, task-specific microscopy datasets.
Ben Isselmann, Dilara Göksu, Heinz Neumann +1
Department of Mathematics and Natural Sciences, Hochschule Darmstadt, Schoefferstraße 3, Darmstadt, 64295, Hessen, Germany. · Department of Chemical Engineering and Biotechnology, Hochschule Darmstadt, Stephanstrasse 7, Darmstadt, 64295, Hessen, Germany. · European University of Technology, European Union. +1