Effective gene expression prediction from sequence by integrating long-range interactions.

How noncoding DNA determines gene expression in different cell types is a major unsolved problem, and critical downstream applications in human genetics depend on improved solutions. Here, we report substantially improved gene expression prediction accuracy from DNA sequences through the use of a deep learning architecture, called Enformer, that is able to integrate information from long-range interactions (up to 100 kb away) in the genome. This improvement yielded more accurate variant effect predictions on gene expression for both natural genetic variants and saturation mutagenesis measured by massively parallel reporter assays. Furthermore, Enformer learned to predict enhancer-promoter interactions directly from the DNA sequence competitively with methods that take direct experimental data as input. We expect that these advances will enable more effective fine-mapping of human disease associations and provide a framework to interpret cis-regulatory evolution.

Clinically applicable deep learning for diagnosis and referral in retinal disease.

The volume and complexity of diagnostic imaging is increasing at a pace faster than the availability of human expertise to interpret it. Artificial intelligence has shown great promise in classifying two-dimensional photographs of some common diseases and typically relies on databases of millions of annotated images. Until now, the challenge of reaching the performance of expert clinicians in a real-world clinical pathway with three-dimensional diagnostic scans has remained unsolved. Here, we apply a novel deep learning architecture to a clinically heterogeneous set of three-dimensional optical coherence tomography scans from patients referred to a major eye hospital. We demonstrate performance in making a referral recommendation that reaches or exceeds that of experts on a range of sight-threatening retinal diseases after training on only 14,884 scans. Moreover, we demonstrate that the tissue segmentations produced by our architecture act as a device-independent representation; referral accuracy is maintained when using tissue segmentations from a different type of device. Our work removes previous barriers to wider clinical use without prohibitive training data requirements across multiple pathologies in a real-world setting.

Automated analysis of retinal imaging using machine learning techniques for computer vision.

There are almost two million people in the United Kingdom living with sight loss, including around 360,000 people who are registered as blind or partially sighted. Sight threatening diseases, such as diabetic retinopathy and age related macular degeneration have contributed to the 40% increase in outpatient attendances in the last decade but are amenable to early detection and monitoring. With early and appropriate intervention, blindness may be prevented in many cases. Ophthalmic imaging provides a way to diagnose and objectively assess the progression of a number of pathologies including neovascular ("wet") age-related macular degeneration (wet AMD) and diabetic retinopathy. Two methods of imaging are commonly used: digital photographs of the fundus (the 'back' of the eye) and Optical Coherence Tomography (OCT, a modality that uses light waves in a similar way to how ultrasound uses sound waves). Changes in population demographics and expectations and the changing pattern of chronic diseases creates a rising demand for such imaging. Meanwhile, interrogation of such images is time consuming, costly, and prone to human error. The application of novel analysis methods may provide a solution to these challenges. This research will focus on applying novel machine learning algorithms to automatic analysis of both digital fundus photographs and OCT in Moorfields Eye Hospital NHS Foundation Trust patients. Through analysis of the images used in ophthalmology, along with relevant clinical and demographic information, DeepMind Health will investigate the feasibility of automated grading of digital fundus photographs and OCT and provide novel quantitative measures for specific disease features and for monitoring the therapeutic success.