Ivo D. Dinov

Alexandr A. Kalinin, Paula Llanos, Theresa Maria Sommer et al.

Microscopy enables direct observation of cellular morphology in 3D, with transmitted-light methods offering low-cost, minimally invasive imaging and fluorescence microscopy providing specificity and contrast. Virtual staining combines these strengths by using machine learning to predict fluorescence images from label-free inputs. However, training of existing methods typically relies on loss functions that treat all pixels equally, thus reproducing background noise and artifacts instead of focusing on biologically meaningful signals. We introduce Spotlight, a simple yet powerful virtual staining approach that guides the model to focus on relevant cellular structures. Spotlight uses histogram-based foreground estimation to mask pixel-wise loss and to calculate a Dice loss on soft-thresholded predictions for shape-aware learning. Applied to a 3D benchmark dataset, Spotlight improves morphological representation while preserving pixel-level accuracy, resulting in virtual stains better suited for downstream tasks such as segmentation and profiling.

Alexandr A. Kalinin, Gerald A. Higgins, Narathip Reamaroon et al.

This Perspective provides examples of current and future applications of deep learning in pharmacogenomics, including: (1) identification of novel regulatory variants located in noncoding domains and their function as applied to pharmacoepigenomics; (2) patient stratification from medical records; and (3) prediction of drugs, targets, and their interactions. Deep learning encapsulates a family of machine learning algorithms that over the last decade has transformed many important subfields of artificial intelligence (AI) and has demonstrated breakthrough performance improvements on a wide range of tasks in biomedicine. We anticipate that in the future deep learning will be widely used to predict personalized drug response and optimize medication selection and dosing, using knowledge extracted from large and complex molecular, epidemiological, clinical, and demographic datasets.