Daisy Yi Ding

Weixin Liang, Yuhui Zhang, Hancheng Cao et al. · stanford

Expert feedback lays the foundation of rigorous research. However, the rapid growth of scholarly production and intricate knowledge specialization challenge the conventional scientific feedback mechanisms. High-quality peer reviews are increasingly difficult to obtain. Researchers who are more junior or from under-resourced settings have especially hard times getting timely feedback. With the breakthrough of large language models (LLM) such as GPT-4, there is growing interest in using LLMs to generate scientific feedback on research manuscripts. However, the utility of LLM-generated feedback has not been systematically studied. To address this gap, we created an automated pipeline using GPT-4 to provide comments on the full PDFs of scientific papers. We evaluated the quality of GPT-4's feedback through two large-scale studies. We first quantitatively compared GPT-4's generated feedback with human peer reviewer feedback in 15 Nature family journals (3,096 papers in total) and the ICLR machine learning conference (1,709 papers). The overlap in the points raised by GPT-4 and by human reviewers (average overlap 30.85% for Nature journals, 39.23% for ICLR) is comparable to the overlap between two human reviewers (average overlap 28.58% for Nature journals, 35.25% for ICLR). The overlap between GPT-4 and human reviewers is larger for the weaker papers. We then conducted a prospective user study with 308 researchers from 110 US institutions in the field of AI and computational biology to understand how researchers perceive feedback generated by our GPT-4 system on their own papers. Overall, more than half (57.4%) of the users found GPT-4 generated feedback helpful/very helpful and 82.4% found it more beneficial than feedback from at least some human reviewers. While our findings show that LLM-generated feedback can help researchers, we also identify several limitations.

Tony Duan, Anand Avati, Daisy Yi Ding et al.

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.

Yuhui Zhang, Yuchang Su, Chenyu Wang et al. · stanford

Building a virtual cell capable of accurately simulating cellular behaviors in silico has long been a dream in computational biology. We introduce CellFlux, an image-generative model that simulates cellular morphology changes induced by chemical and genetic perturbations using flow matching. Unlike prior methods, CellFlux models distribution-wise transformations from unperturbed to perturbed cell states, effectively distinguishing actual perturbation effects from experimental artifacts such as batch effects -- a major challenge in biological data. Evaluated on chemical (BBBC021), genetic (RxRx1), and combined perturbation (JUMP) datasets, CellFlux generates biologically meaningful cell images that faithfully capture perturbation-specific morphological changes, achieving a 35% improvement in FID scores and a 12% increase in mode-of-action prediction accuracy over existing methods. Additionally, CellFlux enables continuous interpolation between cellular states, providing a potential tool for studying perturbation dynamics. These capabilities mark a significant step toward realizing virtual cell modeling for biomedical research. Project page: https://yuhui-zh15.github.io/CellFlux/.

Daisy Yi Ding, Shuangning Li, Balasubramanian Narasimhan et al.

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.

Jiaxuan You, Xiaobai Ma, Daisy Yi Ding et al.

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.

Scott L. Fleming, Kuhan Jeyapragasan, Tony Duan et al.

There is an emerging trend in the reinforcement learning for healthcare literature. In order to prepare longitudinal, irregularly sampled, clinical datasets for reinforcement learning algorithms, many researchers will resample the time series data to short, regular intervals and use last-observation-carried-forward (LOCF) imputation to fill in these gaps. Typically, they will not maintain any explicit information about which values were imputed. In this work, we (1) call attention to this practice and discuss its potential implications; (2) propose an alternative representation of the patient state that addresses some of these issues; and (3) demonstrate in a novel but representative clinical dataset that our alternative representation yields consistently better results for achieving optimal control, as measured by off-policy policy evaluation, compared to representations that do not incorporate missingness information.

Stephen Pfohl, Tony Duan, Daisy Yi Ding et al.

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.

Yuhao Zhang, Daisy Yi Ding, Tianpei Qian et al.

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.

Daisy Yi Ding, Chloé Simpson, Stephen Pfohl et al.

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.

Pranav Rajpurkar, Jeremy Irvin, Aarti Bagul et al.

We introduce MURA, a large dataset of musculoskeletal radiographs containing 40,561 images from 14,863 studies, where each study is manually labeled by radiologists as either normal or abnormal. To evaluate models robustly and to get an estimate of radiologist performance, we collect additional labels from six board-certified Stanford radiologists on the test set, consisting of 207 musculoskeletal studies. On this test set, the majority vote of a group of three radiologists serves as gold standard. We train a 169-layer DenseNet baseline model to detect and localize abnormalities. Our model achieves an AUROC of 0.929, with an operating point of 0.815 sensitivity and 0.887 specificity. We compare our model and radiologists on the Cohen's kappa statistic, which expresses the agreement of our model and of each radiologist with the gold standard. Model performance is comparable to the best radiologist performance in detecting abnormalities on finger and wrist studies. However, model performance is lower than best radiologist performance in detecting abnormalities on elbow, forearm, hand, humerus, and shoulder studies. We believe that the task is a good challenge for future research. To encourage advances, we have made our dataset freely available at https://stanfordmlgroup.github.io/competitions/mura .

Pranav Rajpurkar, Jeremy Irvin, Kaylie Zhu et al.

We develop an algorithm that can detect pneumonia from chest X-rays at a level exceeding practicing radiologists. Our algorithm, CheXNet, is a 121-layer convolutional neural network trained on ChestX-ray14, currently the largest publicly available chest X-ray dataset, containing over 100,000 frontal-view X-ray images with 14 diseases. Four practicing academic radiologists annotate a test set, on which we compare the performance of CheXNet to that of radiologists. We find that CheXNet exceeds average radiologist performance on the F1 metric. We extend CheXNet to detect all 14 diseases in ChestX-ray14 and achieve state of the art results on all 14 diseases.