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In the statistical analysis of genome-wide association data, it is challenging to precisely localize the variants that affect complex traits, due to linkage disequilibrium, and to maximize power while limiting spurious findings. Here we report onKnockoffZoom: a flexible method that localizes causal variants at multiple resolutions by testing the conditional associations of genetic segments of decreasing width, while provably controlling the false discovery rate. Our method utilizes artificial genotypes as negative controls and is equally valid for quantitative and binary phenotypes, without requiring any assumptions about their genetic architectures. Instead, we rely on well-established genetic models of linkage disequilibrium.more »We demonstrate that our method can detect more associations than mixed effects models and achieve fine-mapping precision, at comparable computational cost. Lastly, we applyKnockoffZoomto data from 350k subjects in the UK Biobank and report many new findings.

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Abstract An unhealthy diet is a major risk factor for chronic diseases including cardiovascular disease, type 2 diabetes, and cancer 1–4 . Limited access to healthy food options may contribute to unhealthy diets 5,6 . Studying diets is challenging, typically restricted to small sample sizes, single locations, and non-uniform design across studies, and has led to mixed results on the impact of the food environment 7–23 . Here we leverage smartphones to track diet health, operationalized through the self-reported consumption of fresh fruits and vegetables, fast food and soda, as well as body-mass index status in a country-wide observational studymore »of 1,164,926 U.S. participants (MyFitnessPal app users) and 2.3 billion food entries to study the independent contributions of fast food and grocery store access, income and education to diet health outcomes. This study constitutes the largest nationwide study examining the relationship between the food environment and diet to date. We find that higher access to grocery stores, lower access to fast food, higher income and college education are independently associated with higher consumption of fresh fruits and vegetables, lower consumption of fast food and soda, and lower likelihood of being affected by overweight and obesity. However, these associations vary significantly across zip codes with predominantly Black, Hispanic or white populations. For instance, high grocery store access has a significantly larger association with higher fruit and vegetable consumption in zip codes with predominantly Hispanic populations (7.4% difference) and Black populations (10.2% difference) in contrast to zip codes with predominantly white populations (1.7% difference). Policy targeted at improving food access, income and education may increase healthy eating, but intervention allocation may need to be optimized for specific subpopulations and locations.« less

A key assumption in multi-task learning is that at the inference time the multi-task model only has access to a given data point but not to the data point’s labels from other tasks. This presents an opportunity to extend multi-task learning to utilize data point’s labels from other auxiliary tasks, and this way improves performance on the new task. Here we introduce a novel relational multi-task learning setting where we leverage data point labels from auxiliary tasks to make more accurate predictions on the new task. We develop MetaLink, where our key innovation is to build a knowledge graph thatmore »connects data points and tasks and thus allows us to leverage labels from auxiliary tasks. The knowledge graph consists of two types of nodes: (1) data nodes, where node features are data embeddings computed by the neural network, and (2) task nodes, with the last layer’s weights for each task as node features. The edges in this knowledge graph capture data-task relationships, and the edge label captures the label of a data point on a particular task. Under MetaLink, we reformulate the new task as a link label prediction problem between a data node and a task node. The MetaLink framework provides flexibility to model knowledge transfer from auxiliary task labels to the task of interest. We evaluate MetaLink on 6 benchmark datasets in both biochemical and vision domains. Experiments demonstrate that MetaLink can successfully utilize the relations among different tasks, outperforming the state-of-the-art methods under the proposed relational multi-task learning setting, with up to 27% improvement in ROC AUC.« less

Answering complex questions about textual narratives requires reasoning over both stated context and the world knowledge that underlies it. However, pretrained language models (LM), the foundation of most modern QA systems, do not robustly represent latent relationships between concepts, which is necessary for reasoning. While knowledge graphs (KG) are often used to augment LMs with structured representations of world knowledge, it remains an open question how to effectively fuse and reason over the KG representations and the language context, which provides situational constraints and nuances. In this work, we propose GreaseLM, a new model that fuses encoded representations from pretrainedmore »LMs and graph neural networks over multiple layers of modality interaction operations. Information from both modalities propagates to the other, allowing language context representations to be grounded by structured world knowledge, and allowing linguistic nuances (e.g., negation, hedging) in the context to inform the graph representations of knowledge. Our results on three benchmarks in the commonsense reasoning (i.e., CommonsenseQA, OpenbookQA) and medical question answering (i.e., MedQA-USMLE) domains demonstrate that GreaseLM can more reliably answer questions that require reasoning over both situational constraints and structured knowledge, even outperforming models 8x larger.« less

The deployment of vaccines across the US provides significant defense against serious illness and death from COVID-19. Over 70% of vaccine-eligible Americans are at least partially vaccinated, but there are pockets of the population that are under-vaccinated, such as in rural areas and some demographic groups (e.g. age, race, ethnicity). These unvaccinated pockets are extremely susceptible to the Delta variant, exacerbating the healthcare crisis and increasing the risk of new variants. In this paper, we describe a data-driven model that provides real-time support to Virginia public health officials by recommending mobile vaccination site placement in order to target under-vaccinated populations.more »Our strategy uses fine-grained mobility data, along with US Census and vaccination uptake data, to identify locations that are most likely to be visited by unvaccinated individuals. We further extend our model to choose locations that maximize vaccine uptake among hesitant groups. We show that the top recommended sites vary substantially across some demographics, demonstrating the value of developing customized recommendation models that integrate fine-grained, heterogeneous data sources. In addition, we used a statistically equivalent Synthetic Population to study the effect of combined demographics (eg, people of a particular race and age), which is not possible using US Census data alone. We validate our recommendations by analyzing the success rates of deployed vaccine sites, and show that sites placed closer to our recommended areas administered higher numbers of doses. Our model is the first of its kind to consider evolving mobility patterns in real-time for suggesting placement strategies customized for different targeted demographic groups. Our results will be presented at IAAI-22, but given the critical nature of the pandemic, we offer this extended version of that paper for more timely consideration of our approach and to cover additional findings.« less

Identifying persuasive speakers in an adversarial environment is a critical task. In a national election, politicians would like to have persuasive speakers campaign on their behalf. When a company faces adverse publicity, they would like to engage persuasive advocates for their position in the presence of adversaries who are critical of them. Debates represent a common platform for these forms of adversarial persuasion. This paper solves two problems: the Debate Outcome Prediction (DOP) problem predicts who wins a debate while the Intensity of Persuasion Prediction (IPP) problem predicts the change in the number of votes before and after a speakermore »speaks. Though DOP has been previously studied, we are the first to study IPP. Past studies on DOP fail to leverage two important aspects of multimodal data: 1) multiple modalities are often semantically aligned, and 2) different modalities may provide diverse information for prediction. Our M2P2 (Multimodal Persuasion Prediction) framework is the first to use multimodal (acoustic, visual, language) data to solve the IPP problem. To leverage the alignment of different modalities while maintaining the diversity of the cues they provide, M2P2 devises a novel adaptive fusion learning framework which fuses embeddings obtained from two modules -- an alignment module that extracts shared information between modalities and a heterogeneity module that learns the weights of different modalities with guidance from three separately trained unimodal reference models. We test M2P2 on the popular IQ2US dataset designed for DOP. We also introduce a new dataset called QPS (from Qipashuo, a popular Chinese debate TV show) for IPP - we plan to release this dataset when the paper is published. M2P2 significantly outperforms 3 recent baselines on both datasets.« less

Hierarchical relations are prevalent and indispensable for organizing human knowledge captured by a knowledge graph (KG). The key property of hierarchical relations is that they induce a partial ordering over the entities, which needs to be modeled in order to allow for hierarchical reasoning. However, current KG embeddings can model only a single global hierarchy (single global partial ordering) and fail to model multiple heterogeneous hierarchies that exist in a single KG. Here we present ConE (Cone Embedding), a KG embedding model that is able to simultaneously model multiple hierarchical as well as non-hierarchical relations in a knowledge graph. ConEmore »embeds entities into hyperbolic cones and models relations as transformations between the cones. In particular, ConE uses cone containment constraints in different subspaces of the hyperbolic embedding space to capture multiple heterogeneous hierarchies. Experiments on standard knowledge graph benchmarks show that ConE obtains state-of-the-art performance on hierarchical reasoning tasks as well as knowledge graph completion task on hierarchical graphs. In particular, our approach yields new state-of-the-art Hits@1 of 45.3% on WN18RR and 16.1% on DDB14 (0.231 MRR). As for hierarchical reasoning task, our approach outperforms previous best results by an average of 20% across the three datasets.« less

The development of data-dependent heuristics and representations for biological sequences that reflect their evolutionary distance is critical for large-scale biological research. However, popular machine learning approaches, based on continuous Euclidean spaces, have struggled with the discrete combinatorial formulation of the edit distance that models evolution and the hierarchical relationship that characterises real-world datasets. We present Neural Distance Embeddings (NeuroSEED), a general framework to embed sequences in geometric vector spaces, and illustrate the effectiveness of the hyperbolic space that captures the hierarchical structure and provides an average 38% reduction in embedding RMSE against the best competing geometry. The capacity of themore »framework and the significance of these improvements are then demonstrated devising supervised and unsupervised NeuroSEED approaches to multiple core tasks in bioinformatics. Benchmarked with common baselines, the proposed approaches display significant accuracy and/or runtime improvements on real-world datasets. As an example for hierarchical clustering, the proposed pretrained and from-scratch methods match the quality of competing baselines with 30x and 15x runtime reduction, respectively.« less

Abstract Most diseases disrupt multiple proteins, and drugs treat such diseases by restoring the functions of the disrupted proteins. How drugs restore these functions, however, is often unknown as a drug’s therapeutic effects are not limited to the proteins that the drug directly targets. Here, we develop the multiscale interactome, a powerful approach to explain disease treatment. We integrate disease-perturbed proteins, drug targets, and biological functions into a multiscale interactome network. We then develop a random walk-based method that captures how drug effects propagate through a hierarchy of biological functions and physical protein-protein interactions. On three key pharmacological tasks, themore »multiscale interactome predicts drug-disease treatment, identifies proteins and biological functions related to treatment, and predicts genes that alter a treatment’s efficacy and adverse reactions. Our results indicate that physical interactions between proteins alone cannot explain treatment since many drugs treat diseases by affecting the biological functions disrupted by the disease rather than directly targeting disease proteins or their regulators. We provide a general framework for explaining treatment, even when drugs seem unrelated to the diseases they are recommended for.« less

Transformers provide a class of expressive architectures that are extremely effective for sequence modeling. However, the key limitation of transformers is their quadratic memory and time complexity O(L2) with respect to the sequence length in attention layers, which restricts application in extremely long sequences. Most existing approaches leverage sparsity or low-rank assumptions in the attention matrix to reduce cost, but sacrifice expressiveness. Instead, we propose Combiner, which provides full attention capability in each attention head while maintaining low computation and memory complexity. The key idea is to treat the self-attention mechanism as a conditional expectation over embeddings at each location,more »and approximate the conditional distribution with a structured factorization. Each location can attend to all other locations, either via direct attention, or through indirect attention to abstractions, which are again conditional expectations of embeddings from corresponding local regions. We show that most sparse attention patterns used in existing sparse transformers are able to inspire the design of such factorization for full attention, resulting in the same sub-quadratic cost (O(L log(L)) or O(L√L)). Combiner is a drop-in replacement for attention layers in existing transformers and can be easily implemented in common frameworks. An experimental evaluation on both autoregressive and bidirectional sequence tasks demonstrates the effectiveness of this approach, yielding state-of-the-art results on several image and text modeling tasks.« less