Enriched Annotations for Tumor Attribute Classification from Pathology Reports with Limited Labeled Data

Precision medicine has the potential to revolutionize healthcare, but much of the data for patients is locked away in unstructured free-text, limiting research and delivery of effective personalized treatments. Generating large annotated datasets for information extraction from clinical notes is often challenging and expensive due to the high level of expertise needed for high quality annotations. To enable natural language processing for small dataset sizes, we develop a novel enriched hierarchical annotation scheme and algorithm, Supervised Line Attention (SLA), and apply this algorithm to predicting categorical tumor attributes from kidney and colon cancer pathology reports from the University of California San Francisco (UCSF). Whereas previous work only annotated document level labels, we in addition ask the annotators to enrich the traditional label by asking them to also highlight the relevant line or potentially lines for the final label, which leads to a 20% increase of annotation time required per document. With the enriched annotations, we develop a simple and interpretable machine learning algorithm that first predicts the relevant lines in the document and then predicts the tumor attribute. Our results show across the small dataset sizes of 32, 64, 128, and 186 labeled documents per cancer, SLA only requires half the number of labeled documents as state-of-the-art methods to achieve similar or better micro-f1 and macro-f1 scores for the vast majority of comparisons that we made. Accounting for the increased annotation time, this leads to a 40% reduction in total annotation time over the state of the art.

Stable discovery of interpretable subgroups via calibration in causal studies

Building on Yu and Kumbier's PCS framework and for randomized experiments, we introduce a novel methodology for Stable Discovery of Interpretable Subgroups via Calibration (StaDISC), with large heterogeneous treatment effects. StaDISC was developed during our re-analysis of the 1999-2000 VIGOR study, an 8076 patient randomized controlled trial (RCT), that compared the risk of adverse events from a then newly approved drug, Rofecoxib (Vioxx), to that from an older drug Naproxen. Vioxx was found to, on average and in comparison to Naproxen, reduce the risk of gastrointestinal (GI) events but increase the risk of thrombotic cardiovascular (CVT) events. Applying StaDISC, we fit 18 popular conditional average treatment effect (CATE) estimators for both outcomes and use calibration to demonstrate their poor global performance. However, they are locally well-calibrated and stable, enabling the identification of patient groups with larger than (estimated) average treatment effects. In fact, StaDISC discovers three clinically interpretable subgroups each for the GI outcome (totaling 29.4% of the study size) and the CVT outcome (totaling 11.0%). Complementary analyses of the found subgroups using the 2001-2004 APPROVe study, a separate independently conducted RCT with 2587 patients, provides further supporting evidence for the promise of StaDISC.

Revisiting complexity and the bias-variance tradeoff

The recent success of high-dimensional models, such as deep neural networks (DNNs), has led many to question the validity of the bias-variance tradeoff principle in high dimensions. We reexamine it with respect to two key choices: the model class and the complexity measure. We argue that failing to suitably specify either one can falsely suggest that the tradeoff does not hold. This observation motivates us to seek a valid complexity measure, defined with respect to a reasonably good class of models. Building on Rissanen's principle of minimum description length (MDL), we propose a novel MDL-based complexity (MDL-COMP). We focus on the context of linear models, which have been recently used as a stylized tractable approximation to DNNs in high-dimensions. MDL-COMP is defined via an optimality criterion over the encodings induced by a good Ridge estimator class. We derive closed-form expressions for MDL-COMP and show that for a dataset with $n$ observations and $d$ parameters it is \emph{not always} equal to $d/n$, and is a function of the singular values of the design matrix and the signal-to-noise ratio. For random Gaussian design, we find that while MDL-COMP scales linearly with $d$ in low-dimensions ($d<n$), for high-dimensions ($d>n$) the scaling is exponentially smaller, scaling as $\log d$. We hope that such a slow growth of complexity in high-dimensions can help shed light on the good generalization performance of several well-tuned high-dimensional models. Moreover, via an array of simulations and real-data experiments, we show that a data-driven Prac-MDL-COMP can inform hyper-parameter tuning for ridge regression in limited data settings, sometimes improving upon cross-validation.

Instability, Computational Efficiency and Statistical Accuracy

Many statistical estimators are defined as the fixed point of a data-dependent operator, with estimators based on minimizing a cost function being an important special case. The limiting performance of such estimators depends on the properties of the population-level operator in the idealized limit of infinitely many samples. We develop a general framework that yields bounds on statistical accuracy based on the interplay between the deterministic convergence rate of the algorithm at the population level, and its degree of (in)stability when applied to an empirical object based on $n$ samples. Using this framework, we analyze both stable forms of gradient descent and some higher-order and unstable algorithms, including Newton's method and its cubic-regularized variant, as well as the EM algorithm. We provide applications of our general results to several concrete classes of models, including Gaussian mixture estimation, single-index models, and informative non-response models. We exhibit cases in which an unstable algorithm can achieve the same statistical accuracy as a stable algorithm in exponentially fewer steps---namely, with the number of iterations being reduced from polynomial to logarithmic in sample size $n$.

Curating a COVID-19 data repository and forecasting county-level death counts in the United States

As the COVID-19 outbreak continues to evolve, accurate forecasting continues to play an extremely important role in informing policy decisions. In this paper, we collate a large data repository containing COVID-19 information from a range of different sources. We use this data to develop several predictors and prediction intervals for forecasting the short-term (e.g., over the next week) trajectory of COVID-19-related recorded deaths at the county-level in the United States. Specifically, using data from January 22, 2020, to May 10, 2020, we produce several different predictors and combine their forecasts using ensembling techniques, resulting in an ensemble we refer to as Combined Linear and Exponential Predictors (CLEP). Our individual predictors include county-specific exponential and linear predictors, an exponential predictor that pools data together across counties, and a demographics-based exponential predictor. In addition, we use the largest prediction errors in the past five days to assess the uncertainty of our death predictions, resulting in prediction intervals that we refer to as Maximum (absolute) Error Prediction Intervals (MEPI). We show that MEPI is an effective method in practice with a 94.5\% coverage rate when averaged across counties. Our forecasts are already being used by the non-profit organization, Response4Life, to determine the medical supply need for individual hospitals and have directly contributed to the distribution of medical supplies across the country. We hope that our forecasts and data repository can help guide necessary county-specific decision-making and help counties prepare for their continued fight against COVID-19. All collected data, modeling code, forecasts, and visualizations are updated daily and available at \url{https://github.com/Yu-Group/covid19-severity-prediction}.

Transformation Importance with Applications to Cosmology

Machine learning lies at the heart of new possibilities for scientific discovery, knowledge generation, and artificial intelligence. Its potential benefits to these fields requires going beyond predictive accuracy and focusing on interpretability. In particular, many scientific problems require interpretations in a domain-specific interpretable feature space (e.g. the frequency domain) whereas attributions to the raw features (e.g. the pixel space) may be unintelligible or even misleading. To address this challenge, we propose TRIM (TRansformation IMportance), a novel approach which attributes importances to features in a transformed space and can be applied post-hoc to a fully trained model. TRIM is motivated by a cosmological parameter estimation problem using deep neural networks (DNNs) on simulated data, but it is generally applicable across domains/models and can be combined with any local interpretation method. In our cosmology example, combining TRIM with contextual decomposition shows promising results for identifying which frequencies a DNN uses, helping cosmologists to understand and validate that the model learns appropriate physical features rather than simulation artifacts.

Interpretations are useful: penalizing explanations to align neural networks with prior knowledge

For an explanation of a deep learning model to be effective, it must provide both insight into a model and suggest a corresponding action in order to achieve some objective. Too often, the litany of proposed explainable deep learning methods stop at the first step, providing practitioners with insight into a model, but no way to act on it. In this paper, we propose contextual decomposition explanation penalization (CDEP), a method which enables practitioners to leverage existing explanation methods in order to increase the predictive accuracy of deep learning models. In particular, when shown that a model has incorrectly assigned importance to some features, CDEP enables practitioners to correct these errors by directly regularizing the provided explanations. Using explanations provided by contextual decomposition (CD) (Murdoch et al., 2018), we demonstrate the ability of our method to increase performance on an array of toy and real datasets.

A Debiased MDI Feature Importance Measure for Random Forests

Tree ensembles such as Random Forests have achieved impressive empirical success across a wide variety of applications. To understand how these models make predictions, people routinely turn to feature importance measures calculated from tree ensembles. It has long been known that Mean Decrease Impurity (MDI), one of the most widely used measures of feature importance, incorrectly assigns high importance to noisy features, leading to systematic bias in feature selection. In this paper, we address the feature selection bias of MDI from both theoretical and methodological perspectives. Based on the original definition of MDI by Breiman et al. for a single tree, we derive a tight non-asymptotic bound on the expected bias of MDI importance of noisy features, showing that deep trees have higher (expected) feature selection bias than shallow ones. However, it is not clear how to reduce the bias of MDI using its existing analytical expression. We derive a new analytical expression for MDI, and based on this new expression, we are able to propose a debiased MDI feature importance measure using out-of-bag samples, called MDI-oob. For both the simulated data and a genomic ChIP dataset, MDI-oob achieves state-of-the-art performance in feature selection from Random Forests for both deep and shallow trees.