Anomaly Detection and Biomarkers Localization in Retinal Images.

Background: To design a novel anomaly detection and localization approach using artificial intelligence methods using optical coherence tomography (OCT) scans for retinal diseases. Methods: High-resolution OCT scans from the publicly available Kaggle dataset and a local dataset were used by four state-of-the-art self-supervised frameworks. The backbone model of all the frameworks was a pre-trained convolutional neural network (CNN), which enabled the extraction of meaningful features from OCT images. Anomalous images included choroidal neovascularization (CNV), diabetic macular edema (DME), and the presence of drusen. Anomaly detectors were evaluated by commonly accepted performance metrics, including area under the receiver operating characteristic curve, F1 score, and accuracy. Results: A total of 25,315 high-resolution retinal OCT slabs were used for training. Test and validation sets consisted of 968 and 4000 slabs, respectively. The best performing across all anomaly detectors had an area under the receiver operating characteristic of 0.99. All frameworks were shown to achieve high performance and generalize well for the different retinal diseases. Heat maps were generated to visualize the quality of the frameworks' ability to localize anomalous areas of the image. Conclusions: This study shows that with the use of pre-trained feature extractors, the frameworks tested can generalize to the domain of retinal OCT scans and achieve high image-level ROC-AUC scores. The localization results of these frameworks are promising and successfully capture areas that indicate the presence of retinal pathology. Moreover, such frameworks have the potential to uncover new biomarkers that are difficult for the human eye to detect. Frameworks for anomaly detection and localization can potentially be integrated into clinical decision support and automatic screening systems that will aid ophthalmologists in patient diagnosis, follow-up, and treatment design. This work establishes a solid basis for further development of automated anomaly detection frameworks for clinical use.

Detecting anomalous proteins using deep representations.

Many advances in biomedicine can be attributed to identifying unusual proteins and genes. Many of these proteins' unique properties were discovered by manual inspection, which is becoming infeasible at the scale of modern protein datasets. Here, we propose to tackle this challenge using anomaly detection methods that automatically identify unexpected properties. We adopt a state-of-the-art anomaly detection paradigm from computer vision, to highlight unusual proteins. We generate meaningful representations without labeled inputs, using pretrained deep neural network models. We apply these protein language models (pLM) to detect anomalies in function, phylogenetic families, and segmentation tasks. We compute protein anomaly scores to highlight human prion-like proteins, distinguish viral proteins from their host proteome, and mark non-classical ion/metal binding proteins and enzymes. Other tasks concern segmentation of protein sequences into folded and unstructured regions. We provide candidates for rare functionality (e.g. prion proteins). Additionally, we show the anomaly score is useful in 3D folding-related segmentation. Our novel method shows improved performance over strong baselines and has objectively high performance across a variety of tasks. We conclude that the combination of pLM and anomaly detection techniques is a valid method for discovering a range of global and local protein characteristics.

Disentanglement of single-cell data with biolord.

Biolord is a deep generative method for disentangling single-cell multi-omic data to known and unknown attributes, including spatial, temporal and disease states, used to reveal the decoupled biological signatures over diverse single-cell modalities and biological systems. By virtually shifting cells across states, biolord generates experimentally inaccessible samples, outperforming state-of-the-art methods in predictions of cellular response to unseen drugs and genetic perturbations. Biolord is available at https://github.com/nitzanlab/biolord .