Built to Last? Reproducibility and Reusability of Deep Learning Algorithms in Computational Pathology.

Recent progress in computational pathology has been driven by deep learning. While code and data availability are essential to reproduce findings from preceding publications, ensuring a deep learning model's reusability is more challenging. For that, the codebase should be well-documented and easy to integrate into existing workflows and models should be robust toward noise and generalizable toward data from different sources. Strikingly, only a few computational pathology algorithms have been reused by other researchers so far, let alone employed in a clinical setting. To assess the current state of reproducibility and reusability of computational pathology algorithms, we evaluated peer-reviewed articles available in PubMed, published between January 2019 and March 2021, in 5 use cases: stain normalization; tissue type segmentation; evaluation of cell-level features; genetic alteration prediction; and inference of grading, staging, and prognostic information. We compiled criteria for data and code availability and statistical result analysis and assessed them in 160 publications. We found that only one-quarter (41 of 160 publications) made code publicly available. Among these 41 studies, three-quarters (30 of 41) analyzed their results statistically, half of them (20 of 41) released their trained model weights, and approximately a third (16 of 41) used an independent cohort for evaluation. Our review is intended for both pathologists interested in deep learning and researchers applying algorithms to computational pathology challenges. We provide a detailed overview of publications with published code in the field, list reusable data handling tools, and provide criteria for reproducibility and reusability.

The future landscape of large language models in medicine.

Large language models (LLMs) are artificial intelligence (AI) tools specifically trained to process and generate text. LLMs attracted substantial public attention after OpenAI's ChatGPT was made publicly available in November 2022. LLMs can often answer questions, summarize, paraphrase and translate text on a level that is nearly indistinguishable from human capabilities. The possibility to actively interact with models like ChatGPT makes LLMs attractive tools in various fields, including medicine. While these models have the potential to democratize medical knowledge and facilitate access to healthcare, they could equally distribute misinformation and exacerbate scientific misconduct due to a lack of accountability and transparency. In this article, we provide a systematic and comprehensive overview of the potentials and limitations of LLMs in clinical practice, medical research and medical education.

Transformer-based biomarker prediction from colorectal cancer histology: A large-scale multicentric study.

Deep learning (DL) can accelerate the prediction of prognostic biomarkers from routine pathology slides in colorectal cancer (CRC). However, current approaches rely on convolutional neural networks (CNNs) and have mostly been validated on small patient cohorts. Here, we develop a new transformer-based pipeline for end-to-end biomarker prediction from pathology slides by combining a pre-trained transformer encoder with a transformer network for patch aggregation. Our transformer-based approach substantially improves the performance, generalizability, data efficiency, and interpretability as compared with current state-of-the-art algorithms. After training and evaluating on a large multicenter cohort of over 13,000 patients from 16 colorectal cancer cohorts, we achieve a sensitivity of 0.99 with a negative predictive value of over 0.99 for prediction of microsatellite instability (MSI) on surgical resection specimens. We demonstrate that resection specimen-only training reaches clinical-grade performance on endoscopic biopsy tissue, solving a long-standing diagnostic problem.

Multi-Modality Microscopy Image Style Augmentation for Nuclei Segmentation.

Annotating microscopy images for nuclei segmentation by medical experts is laborious and time-consuming. To leverage the few existing annotations, also across multiple modalities, we propose a novel microscopy-style augmentation technique based on a generative adversarial network (GAN). Unlike other style transfer methods, it can not only deal with different cell assay types and lighting conditions, but also with different imaging modalities, such as bright-field and fluorescence microscopy. Using disentangled representations for content and style, we can preserve the structure of the original image while altering its style during augmentation. We evaluate our data augmentation on the 2018 Data Science Bowl dataset consisting of various cell assays, lighting conditions, and imaging modalities. With our style augmentation, the segmentation accuracy of the two top-ranked Mask R-CNN-based nuclei segmentation algorithms in the competition increases significantly. Thus, our augmentation technique renders the downstream task more robust to the test data heterogeneity and helps counteract class imbalance without resampling of minority classes.