Approaching Small Molecule Prioritization as a Cross-Modal Information Retrieval Task through Coordinated Representation Learning

Modeling the relationship between chemical structure and molecular activity is a key task in drug development and precision medicine. In this paper, we utilize a novel deep learning architecture to jointly train coordinated embeddings of chemical structures and transcriptional signatures. We do so by training neural networks in a coordinated manner such that learned chemical representations correlate most highly with the encodings of the transcriptional patterns they induce. We then test this approach by using held-out gene expression signatures as queries into embedding space to recover their corresponding compounds. We evaluate these embeddings' utility for small molecule prioritization on this new benchmark task. Our method outperforms a series of baselines, successfully generalizing to unseen transcriptional experiments, but still struggles to generalize to entirely unseen chemical structures.

Feature Robustness in Non-stationary Health Records: Caveats to Deployable Model Performance in Common Clinical Machine Learning Tasks

When training clinical prediction models from electronic health records (EHRs), a key concern should be a model's ability to sustain performance over time when deployed, even as care practices, database systems, and population demographics evolve. Due to de-identification requirements, however, current experimental practices for public EHR benchmarks (such as the MIMIC-III critical care dataset) are time agnostic, assigning care records to train or test sets without regard for the actual dates of care. As a result, current benchmarks cannot assess how well models trained on one year generalise to another. In this work, we obtain a Limited Data Use Agreement to access year of care for each record in MIMIC and show that all tested state-of-the-art models decay in prediction quality when trained on historical data and tested on future data, particularly in response to a system-wide record-keeping change in 2008 (0.29 drop in AUROC for mortality prediction, 0.10 drop in AUROC for length-of-stay prediction with a random forest classifier). We further develop a simple yet effective mitigation strategy: by aggregating raw features into expert-defined clinical concepts, we see only a 0.06 drop in AUROC for mortality prediction and a 0.03 drop in AUROC for length-of-stay prediction. We demonstrate that this aggregation strategy outperforms other automatic feature preprocessing techniques aimed at increasing robustness to data drift. We release our aggregated representations and code to encourage more deployable clinical prediction models.

REflex: Flexible Framework for Relation Extraction in Multiple Domains

Systematic comparison of methods for relation extraction (RE) is difficult because many experiments in the field are not described precisely enough to be completely reproducible and many papers fail to report ablation studies that would highlight the relative contributions of their various combined techniques. In this work, we build a unifying framework for RE, applying this on three highly used datasets (from the general, biomedical and clinical domains) with the ability to be extendable to new datasets. By performing a systematic exploration of modeling, pre-processing and training methodologies, we find that choices of pre-processing are a large contributor performance and that omission of such information can further hinder fair comparison. Other insights from our exploration allow us to provide recommendations for future research in this area.

MIMIC-Extract: A Data Extraction, Preprocessing, and Representation Pipeline for MIMIC-III

Robust machine learning relies on access to data that can be used with standardized frameworks in important tasks and the ability to develop models whose performance can be reasonably reproduced. In machine learning for healthcare, the community faces reproducibility challenges due to a lack of publicly accessible data and a lack of standardized data processing frameworks. We present MIMIC-Extract, an open-source pipeline for transforming raw electronic health record (EHR) data for critical care patients contained in the publicly-available MIMIC-III database into dataframes that are directly usable in common machine learning pipelines. MIMIC-Extract addresses three primary challenges in making complex health records data accessible to the broader machine learning community. First, it provides standardized data processing functions, including unit conversion, outlier detection, and aggregating semantically equivalent features, thus accounting for duplication and reducing missingness. Second, it preserves the time series nature of clinical data and can be easily integrated into clinically actionable prediction tasks in machine learning for health. Finally, it is highly extensible so that other researchers with related questions can easily use the same pipeline. We demonstrate the utility of this pipeline by showcasing several benchmark tasks and baseline results.

Reproducibility in Machine Learning for Health

Machine learning algorithms designed to characterize, monitor, and intervene on human health (ML4H) are expected to perform safely and reliably when operating at scale, potentially outside strict human supervision. This requirement warrants a stricter attention to issues of reproducibility than other fields of machine learning. In this work, we conduct a systematic evaluation of over 100 recently published ML4H research papers along several dimensions related to reproducibility. We find that the field of ML4H compares poorly to more established machine learning fields, particularly concerning data and code accessibility. Finally, drawing from success in other fields of science, we propose recommendations to data providers, academic publishers, and the ML4H research community in order to promote reproducible research moving forward.

Reflex: Flexible Framework for Relation Extraction in Multiple Domains

Systematic comparison of methods for relation extraction (RE) is difficult because many experiments in the field are not described precisely enough to be completely reproducible and many papers fail to report ablation studies that would highlight the relative contributions of their various combined techniques. In this work, we build a unifying framework for RE, applying this on three highly used datasets (from the general, biomedical and clinical domains) with the ability to be extendable to new datasets. By performing a systematic exploration of modeling, pre-processing and training methodologies, we find that choices of pre-processing are a large contributor performance and that omission of such information can further hinder fair comparison. Other insights from our exploration allow us to provide recommendations for future research in this area.

Publicly Available Clinical BERT Embeddings

Contextual word embedding models such as ELMo (Peters et al., 2018) and BERT (Devlin et al., 2018) have dramatically improved performance for many natural language processing (NLP) tasks in recent months. However, these models have been minimally explored on specialty corpora, such as clinical text; moreover, in the clinical domain, no publicly-available pre-trained BERT models yet exist. In this work, we address this need by exploring and releasing BERT models for clinical text: one for generic clinical text and another for discharge summaries specifically. We demonstrate that using a domain-specific model yields performance improvements on three common clinical NLP tasks as compared to nonspecific embeddings. These domain-specific models are not as performant on two clinical de-identification tasks, and argue that this is a natural consequence of the differences between de-identified source text and synthetically non de-identified task text.

Rethinking clinical prediction: Why machine learning must consider year of care and feature aggregation

Machine learning for healthcare often trains models on de-identified datasets with randomly-shifted calendar dates, ignoring the fact that data were generated under hospital operation practices that change over time. These changing practices induce definitive changes in observed data which confound evaluations which do not account for dates and limit the generalisability of date-agnostic models. In this work, we establish the magnitude of this problem on MIMIC, a public hospital dataset, and showcase a simple solution. We augment MIMIC with the year in which care was provided and show that a model trained using standard feature representations will significantly degrade in quality over time. We find a deterioration of 0.3 AUC when evaluating mortality prediction on data from 10 years later. We find a similar deterioration of 0.15 AUC for length-of-stay. In contrast, we demonstrate that clinically-oriented aggregates of raw features significantly mitigate future deterioration. Our suggested aggregated representations, when retrained yearly, have prediction quality comparable to year-agnostic models.