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We propose Cooperative Component Analysis (CoCA), a new method for unsupervised multi-view analysis: it identifies the component that simultaneously captures significant within-view variance and exhibits strong cross-view correlation. The challenge of integrating multi-view data is particularly important in biology and medicine, where various types of "-omic" data, ranging from genomics to proteomics, are measured on the same set of samples. The goal is to uncover important, shared signals that represent underlying biological mechanisms. CoCA combines an approximation error loss to preserve information within data views and an "agreement penalty" to encourage alignment across data views. By balancing the trade-off between these two key components in the objective, CoCA has the property of interpolating between the commonly-used principal component analysis (PCA) and canonical correlation analysis (CCA) as special cases at the two ends of the solution path. CoCA chooses the degree of agreement in a data-adaptive manner, using a validation set or cross-validation to estimate test error. Furthermore, we propose a sparse variant of CoCA that incorporates the Lasso penalty to yield feature sparsity, facilitating the identification of key features driving the observed patterns. We demonstrate the effectiveness of CoCA on simulated data and two real multiomics studies of COVID-19 and ductal carcinoma in situ of breast. In both real data applications, CoCA successfully integrates multiomics data, extracting components that are not only consistently present across different data views but also more informative and predictive of disease progression. CoCA offers a powerful framework for discovering important shared signals in multi-view data, with the potential to uncover novel insights in an increasingly multi-view data world.

Multiomics data fusion integrates diverse data modalities, ranging from transcriptomics to proteomics, to gain a comprehensive understanding of biological systems and enhance predictions on outcomes of interest related to disease phenotypes and treatment responses. Cooperative learning, a recently proposed method, unifies the commonly-used fusion approaches, including early and late fusion, and offers a systematic framework for leveraging the shared underlying relationships across omics to strengthen signals. However, the challenge of acquiring large-scale labeled data remains, and there are cases where multiomics data are available but in the absence of annotated labels. To harness the potential of unlabeled multiomcis data, we introduce semi-supervised cooperative learning. By utilizing an "agreement penalty", our method incorporates the additional unlabeled data in the learning process and achieves consistently superior predictive performance on simulated data and a real multiomics study of aging. It offers an effective solution to multiomics data fusion in settings with both labeled and unlabeled data and maximizes the utility of available data resources, with the potential of significantly improving predictive models for diagnostics and therapeutics in an increasingly multiomics world., Comment: The 2023 ICML Workshop on Machine Learning for Multimodal Healthcare Data. arXiv admin note: text overlap with arXiv:2112.12337

While RNA technologies hold immense therapeutic potential in a range of applications from vaccination to gene editing, the broad implementation of these technologies is hindered by the challenge of delivering these agents effectively. Lipid nanoparticles have emerged as one of the most widely used delivery agents, but their design optimization relies on laborious and costly experimental methods. We propose to in silico optimize LNP design with machine learning models. On a curated dataset of 622 LNPs from published studies, we demonstrate the effectiveness of our model in predicting the transfection efficiency of unseen LNPs, with the multilayer perceptron achieving a classification accuracy of 98% on the test set. Our work represents a pioneering effort in combining ML and LNP design, offering significant potential for improving screening efficiency by computationally prioritizing LNP candidates for experimental validation and accelerating the development of effective mRNA delivery systems., Comment: The 2023 ICML Workshop on Computational Biology

We propose a new method for supervised learning with multiple sets of features ("views"). The multiview problem is especially important in biology and medicine, where "-omics" data such as genomics, proteomics and radiomics are measured on a common set of samples. Cooperative learning combines the usual squared error loss of predictions with an "agreement" penalty to encourage the predictions from different data views to agree. By varying the weight of the agreement penalty, we get a continuum of solutions that include the well-known early and late fusion approaches. Cooperative learning chooses the degree of agreement (or fusion) in an adaptive manner, using a validation set or cross-validation to estimate test set prediction error. One version of our fitting procedure is modular, where one can choose different fitting mechanisms (e.g. lasso, random forests, boosting, neural networks) appropriate for different data views. In the setting of cooperative regularized linear regression, the method combines the lasso penalty with the agreement penalty, yielding feature sparsity. The method can be especially powerful when the different data views share some underlying relationship in their signals that can be exploited to boost the signals. We show that cooperative learning achieves higher predictive accuracy on simulated data and a real multiomics example of labor onset prediction. Leveraging aligned signals and allowing flexible fitting mechanisms for different modalities, cooperative learning offers a powerful approach to multiomics data fusion.

Machine learning with missing data has been approached in two different ways, including feature imputation where missing feature values are estimated based on observed values, and label prediction where downstream labels are learned directly from incomplete data. However, existing imputation models tend to have strong prior assumptions and cannot learn from downstream tasks, while models targeting label prediction often involve heuristics and can encounter scalability issues. Here we propose GRAPE, a graph-based framework for feature imputation as well as label prediction. GRAPE tackles the missing data problem using a graph representation, where the observations and features are viewed as two types of nodes in a bipartite graph, and the observed feature values as edges. Under the GRAPE framework, the feature imputation is formulated as an edge-level prediction task and the label prediction as a node-level prediction task. These tasks are then solved with Graph Neural Networks. Experimental results on nine benchmark datasets show that GRAPE yields 20% lower mean absolute error for imputation tasks and 10% lower for label prediction tasks, compared with existing state-of-the-art methods., Comment: NeurIPS 2020

We present Natural Gradient Boosting (NGBoost), an algorithm for generic probabilistic prediction via gradient boosting. Typical regression models return a point estimate, conditional on covariates, but probabilistic regression models output a full probability distribution over the outcome space, conditional on the covariates. This allows for predictive uncertainty estimation -- crucial in applications like healthcare and weather forecasting. NGBoost generalizes gradient boosting to probabilistic regression by treating the parameters of the conditional distribution as targets for a multiparameter boosting algorithm. Furthermore, we show how the Natural Gradient is required to correct the training dynamics of our multiparameter boosting approach. NGBoost can be used with any base learner, any family of distributions with continuous parameters, and any scoring rule. NGBoost matches or exceeds the performance of existing methods for probabilistic prediction while offering additional benefits in flexibility, scalability, and usability. An open-source implementation is available at github.com/stanfordmlgroup/ngboost., Comment: Accepted for ICML 2020

The use of machine learning systems to support decision making in healthcare raises questions as to what extent these systems may introduce or exacerbate disparities in care for historically underrepresented and mistreated groups, due to biases implicitly embedded in observational data in electronic health records. To address this problem in the context of clinical risk prediction models, we develop an augmented counterfactual fairness criteria to extend the group fairness criteria of equalized odds to an individual level. We do so by requiring that the same prediction be made for a patient, and a counterfactual patient resulting from changing a sensitive attribute, if the factual and counterfactual outcomes do not differ. We investigate the extent to which the augmented counterfactual fairness criteria may be applied to develop fair models for prolonged inpatient length of stay and mortality with observational electronic health records data. As the fairness criteria is ill-defined without knowledge of the data generating process, we use a variational autoencoder to perform counterfactual inference in the context of an assumed causal graph. While our technique provides a means to trade off maintenance of fairness with reduction in predictive performance in the context of a learned generative model, further work is needed to assess the generality of this approach., Comment: Machine Learning for Healthcare 2019

The Impression section of a radiology report summarizes crucial radiology findings in natural language and plays a central role in communicating these findings to physicians. However, the process of generating impressions by summarizing findings is time-consuming for radiologists and prone to errors. We propose to automate the generation of radiology impressions with neural sequence-to-sequence learning. We further propose a customized neural model for this task which learns to encode the study background information and use this information to guide the decoding process. On a large dataset of radiology reports collected from actual hospital studies, our model outperforms existing non-neural and neural baselines under the ROUGE metrics. In a blind experiment, a board-certified radiologist indicated that 67% of sampled system summaries are at least as good as the corresponding human-written summaries, suggesting significant clinical validity. To our knowledge our work represents the first attempt in this direction., Comment: EMNLP 2018 Workshop on Health Text Mining and Information Analysis (EMNLP-LOUHI). Code and pretrained model available at: https://github.com/yuhaozhang/summarize-radiology-findings

Electronic phenotyping is the task of ascertaining whether an individual has a medical condition of interest by analyzing their medical record and is foundational in clinical informatics. Increasingly, electronic phenotyping is performed via supervised learning. We investigate the effectiveness of multitask learning for phenotyping using electronic health records (EHR) data. Multitask learning aims to improve model performance on a target task by jointly learning additional auxiliary tasks and has been used in disparate areas of machine learning. However, its utility when applied to EHR data has not been established, and prior work suggests that its benefits are inconsistent. We present experiments that elucidate when multitask learning with neural nets improves performance for phenotyping using EHR data relative to neural nets trained for a single phenotype and to well-tuned logistic regression baselines. We find that multitask neural nets consistently outperform single-task neural nets for rare phenotypes but underperform for relatively more common phenotypes. The effect size increases as more auxiliary tasks are added. Moreover, multitask learning reduces the sensitivity of neural nets to hyperparameter settings for rare phenotypes. Last, we quantify phenotype complexity and find that neural nets trained with or without multitask learning do not improve on simple baselines unless the phenotypes are sufficiently complex., Comment: Pacific Symposium on Biocomputing (PSB) 2019, Hawaii, https://psb.stanford.edu/psb-online/; 13 pages, 7 figures