Correction: NGS read classification using AI.

[This corrects the article DOI: 10.1371/journal.pone.0261548.].

Domain generalization across tumor types, laboratories, and species - Insights from the 2022 edition of the Mitosis Domain Generalization Challenge.

Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert majority vote and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an F1 score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today's deep learning-based recognition pipelines. However, we also found that domain characteristics not present in the training set (feline as new species, spindle cell shape as new morphology and a new scanner) led to small but significant decreases in performance. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, with only minor changes in the order of participants in the ranking.

Investigation of semi- and self-supervised learning methods in the histopathological domain.

Training models with semi- or self-supervised learning methods is one way to reduce annotation effort since they rely on unlabeled or sparsely labeled datasets. Such approaches are particularly promising for domains with a time-consuming annotation process requiring specialized expertise and where high-quality labeled machine learning datasets are scarce, like in computational pathology. Even though some of these methods have been used in the histopathological domain, there is, so far, no comprehensive study comparing different approaches. Therefore, this work compares feature extractors models trained with state-of-the-art semi- or self-supervised learning methods PAWS, SimCLR, and SimSiam within a unified framework. We show that such models, across different architectures and network configurations, have a positive performance impact on histopathological classification tasks, even in low data regimes. Moreover, our observations suggest that features learned from a particular dataset, i.e., tissue type, are only in-domain transferable to a certain extent. Finally, we share our experience using each method in computational pathology and provide recommendations for its use.

NGS read classification using AI.

Clinical metagenomics is a powerful diagnostic tool, as it offers an open view into all DNA in a patient's sample. This allows the detection of pathogens that would slip through the cracks of classical specific assays. However, due to this unspecific nature of metagenomic sequencing, a huge amount of unspecific data is generated during the sequencing itself and the diagnosis only takes place at the data analysis stage where relevant sequences are filtered out. Typically, this is done by comparison to reference databases. While this approach has been optimized over the past years and works well to detect pathogens that are represented in the used databases, a common challenge in analysing a metagenomic patient sample arises when no pathogen sequences are found: How to determine whether truly no evidence of a pathogen is present in the data or whether the pathogen's genome is simply absent from the database and the sequences in the dataset could thus not be classified? Here, we present a novel approach to this problem of detecting novel pathogens in metagenomic datasets by classifying the (segments of) proteins encoded by the sequences in the datasets. We train a neural network on the sequences of coding sequences, labeled by taxonomic domain, and use this neural network to predict the taxonomic classification of sequences that can not be classified by comparison to a reference database, thus facilitating the detection of potential novel pathogens.