Cardiac Imaging of Aortic Valve Area From 34 287 UK Biobank Participants Reveals Novel Genetic Associations and Shared Genetic Comorbidity With Multiple Disease Phenotypes.

BACKGROUND: The aortic valve is an important determinant of cardiovascular physiology and anatomic location of common human diseases. METHODS: From a sample of 34 287 white British ancestry participants, we estimated functional aortic valve area by planimetry from prospectively obtained cardiac magnetic resonance imaging sequences of the aortic valve. Aortic valve area measurements were submitted to genome-wide association testing, followed by polygenic risk scoring and phenome-wide screening, to identify genetic comorbidities. RESULTS: A genome-wide association study of aortic valve area in these UK Biobank participants showed 3 significant associations, indexed by rs71190365 (chr13:50764607, DLEU1, P=1.8×10-9), rs35991305 (chr12:94191968, CRADD, P=3.4×10-8), and chr17:45013271:C:T (GOSR2, P=5.6×10-8). Replication on an independent set of 8145 unrelated European ancestry participants showed consistent effect sizes in all 3 loci, although rs35991305 did not meet nominal significance. We constructed a polygenic risk score for aortic valve area, which in a separate cohort of 311 728 individuals without imaging demonstrated that smaller aortic valve area is predictive of increased risk for aortic valve disease (odds ratio, 1.14; P=2.3×10-6). After excluding subjects with a medical diagnosis of aortic valve stenosis (remaining n=308 683 individuals), phenome-wide association of >10 000 traits showed multiple links between the polygenic score for aortic valve disease and key health-related comorbidities involving the cardiovascular system and autoimmune disease. Genetic correlation analysis supports a shared genetic etiology with between aortic valve area and birth weight along with other cardiovascular conditions. CONCLUSIONS: These results illustrate the use of automated phenotyping of cardiac imaging data from the general population to investigate the genetic etiology of aortic valve disease, perform clinical prediction, and uncover new clinical and genetic correlates of cardiac anatomy.

Slice-based Learning: A Programming Model for Residual Learning in Critical Data Slices.

In real-world machine learning applications, data subsets correspond to especially critical outcomes: vulnerable cyclist detections are safety-critical in an autonomous driving task, and "question" sentences might be important to a dialogue agent's language understanding for product purposes. While machine learning models can achieve high quality performance on coarse-grained metrics like F1-score and overall accuracy, they may underperform on critical subsets-we define these as slices, the key abstraction in our approach. To address slice-level performance, practitioners often train separate "expert" models on slice subsets or use multi-task hard parameter sharing. We propose Slice-based Learning, a new programming model in which the slicing function (SF), a programming interface, specifies critical data subsets for which the model should commit additional capacity. Any model can leverage SFs to learn slice expert representations, which are combined with an attention mechanism to make slice-aware predictions. We show that our approach maintains a parameter-efficient representation while improving over baselines by up to 19.0 F1 on slices and 4.6 F1 overall on datasets spanning language understanding (e.g. SuperGLUE), computer vision, and production-scale industrial systems.

Weakly supervised classification of aortic valve malformations using unlabeled cardiac MRI sequences.

Biomedical repositories such as the UK Biobank provide increasing access to prospectively collected cardiac imaging, however these data are unlabeled, which creates barriers to their use in supervised machine learning. We develop a weakly supervised deep learning model for classification of aortic valve malformations using up to 4,000 unlabeled cardiac MRI sequences. Instead of requiring highly curated training data, weak supervision relies on noisy heuristics defined by domain experts to programmatically generate large-scale, imperfect training labels. For aortic valve classification, models trained with imperfect labels substantially outperform a supervised model trained on hand-labeled MRIs. In an orthogonal validation experiment using health outcomes data, our model identifies individuals with a 1.8-fold increase in risk of a major adverse cardiac event. This work formalizes a deep learning baseline for aortic valve classification and outlines a general strategy for using weak supervision to train machine learning models using unlabeled medical images at scale.

Scene Graph Prediction with Limited Labels.

Visual knowledge bases such as Visual Genome power numerous applications in computer vision, including visual question answering and captioning, but suffer from sparse, incomplete relationships. All scene graph models to date are limited to training on a small set of visual relationships that have thousands of training labels each. Hiring human annotators is expensive, and using textual knowledge base completion methods are incompatible with visual data. In this paper, we introduce a semi-supervised method that assigns probabilistic relationship labels to a large number of unlabeled images using few' labeled examples. We analyze visual relationships to suggest two types of image-agnostic features that are used to generate noisy heuristics, whose outputs are aggregated using a factor graph-based generative model. With as few as 10 labeled examples per relationship, the generative model creates enough training data to train any existing state-of-the-art scene graph model. We demonstrate that our method outperforms all baseline approaches on scene graph prediction by 5.16 recall@ 100 for PREDCLS. In our limited label setting, we define a complexity metric for relationships that serves as an indicator (R2 = 0.778) for conditions under which our method succeeds over transfer learning, the de-facto approach for training with limited labels.