Eric K. Oermann

Sully F. Chen, Robert J. Steele, Glen M. Hocky et al.

The transformer architecture has revolutionized bioinformatics and driven progress in the understanding and prediction of the properties of biomolecules. To date, most biosequence transformers have been trained on single-omic data - either proteins or nucleic acids - and have seen incredible success in downstream tasks in each domain, with particularly noteworthy breakthroughs in protein structural modeling. However, single-omic pretraining limits the ability of these models to capture cross-modal interactions. Here we present OmniBioTE, the largest open-source multi-omic model trained on over 250 billion tokens of mixed protein and nucleic acid data. We show that despite only being trained on unlabeled sequence data, OmniBioTE learns joint representations mapping genes to their corresponding protein sequences. We further demonstrate that OmniBioTE achieves state-of-the-art results predicting the change in Gibbs free energy ({ΔG}) of the binding interaction between a given nucleic acid and protein. Remarkably, we show that multi-omic biosequence transformers emergently learn useful structural information without any a priori structural training, allowing us to predict which protein residues are most involved in the protein-nucleic acid binding interaction. Compared to single-omic controls trained with identical compute, OmniBioTE also demonstrates superior performance-per-FLOP across both multi-omic and single-omic benchmarks. Together, these results highlight the power of a unified modeling approach for biological sequences and establish OmniBioTE as a foundation model for multi-omic discovery.

Grace Yang, Ming Cao, Lavender Y. Jiang et al.

Traditional evaluation metrics for classification in natural language processing such as accuracy and area under the curve fail to differentiate between models with different predictive behaviors despite their similar performance metrics. We introduce sensitivity score, a metric that scrutinizes models' behaviors at the vocabulary level to provide insights into disparities in their decision-making logic. We assess the sensitivity score on a set of representative words in the test set using two classifiers trained for hospital readmission classification with similar performance statistics. Our experiments compare the decision-making logic of clinicians and classifiers based on rank correlations of sensitivity scores. The results indicate that the language model's sensitivity score aligns better with the professionals than the xgboost classifier on tf-idf embeddings, which suggests that xgboost uses some spurious features. Overall, this metric offers a novel perspective on assessing models' robustness by quantifying their discrepancy with professional opinions. Our code is available on GitHub (https://github.com/nyuolab/Model_Sensitivity).

Julián N. Acosta, Xiaoman Zhang, Siddhant Dogra et al.

We present Head CT Ontology Normalized Evaluation (HeadCT-ONE), a metric for evaluating head CT report generation through ontology-normalized entity and relation extraction. HeadCT-ONE enhances current information extraction derived metrics (such as RadGraph F1) by implementing entity normalization through domain-specific ontologies, addressing radiological language variability. HeadCT-ONE compares normalized entities and relations, allowing for controllable weighting of different entity types or specific entities. Through experiments on head CT reports from three health systems, we show that HeadCT-ONE's normalization and weighting approach improves the capture of semantically equivalent reports, better distinguishes between normal and abnormal reports, and aligns with radiologists' assessment of clinically significant errors, while offering flexibility to prioritize specific aspects of report content. Our results demonstrate how HeadCT-ONE enables more flexible, controllable, and granular automated evaluation of head CT reports.

Yu-Hsiang Lan, Eric K. Oermann

There has been a recent surge of interest in time series modeling using the Transformer architecture. However, forecasting multivariate time series with Transformer presents a unique challenge as it requires modeling both temporal (cross-time) and variate (cross-variate) dependencies. While Transformer-based models have gained popularity for their flexibility in capturing both sequential and cross-variate relationships, it is unclear how to best integrate these two sources of information in the context of the Transformer architecture while optimizing for both performance and efficiency. We re-purpose the Transformer architecture to effectively model both cross-time and cross-variate dependencies. Our approach begins by embedding each variate independently into a variate-wise representation that captures its cross-time dynamics, and then models cross-variate dependencies through attention mechanisms on these learned embeddings. Gating operations in both cross-time and cross-variate modeling phases regulate information flow, allowing the model to focus on the most relevant features for accurate predictions. Our method achieves state-of-the-art performance across 13 real-world datasets and can be seamlessly integrated into other Transformer-based and LLM-based forecasters, delivering performance improvements up to 20.7\% over original models. Code is available at this repository: https://github.com/nyuolab/Gateformer.

Lavender Y. Jiang, Xujin Chris Liu, Kyunghyun Cho et al.

Privacy is a human right that sustains patient-provider trust. Clinical notes capture a patient's private vulnerability and individuality, which are used for care coordination and research. Under HIPAA Safe Harbor, these notes are de-identified to protect patient privacy. However, Safe Harbor was designed for an era of categorical tabular data, focusing on the removal of explicit identifiers while ignoring the latent information found in correlations between identity and quasi-identifiers, which can be captured by modern LLMs. We first formalize these correlations using a causal graph, then validate it empirically through individual re-identification of patients from scrubbed notes. The paradox of de-identification is further shown through a diagnosis ablation: even when all other information is removed, the model can predict the patient's neighborhood based on diagnosis alone. This position paper raises the question of how we can act as a community to uphold patient-provider trust when de-identification is inherently imperfect. We aim to raise awareness and discuss actionable recommendations.

Aahlad Puli, Lily H. Zhang, Eric K. Oermann et al.

In many prediction problems, spurious correlations are induced by a changing relationship between the label and a nuisance variable that is also correlated with the covariates. For example, in classifying animals in natural images, the background, which is a nuisance, can predict the type of animal. This nuisance-label relationship does not always hold, and the performance of a model trained under one such relationship may be poor on data with a different nuisance-label relationship. To build predictive models that perform well regardless of the nuisance-label relationship, we develop Nuisance-Randomized Distillation (NURD). We introduce the nuisance-randomized distribution, a distribution where the nuisance and the label are independent. Under this distribution, we define the set of representations such that conditioning on any member, the nuisance and the label remain independent. We prove that the representations in this set always perform better than chance, while representations outside of this set may not. NURD finds a representation from this set that is most informative of the label under the nuisance-randomized distribution, and we prove that this representation achieves the highest performance regardless of the nuisance-label relationship. We evaluate NURD on several tasks including chest X-ray classification where, using non-lung patches as the nuisance, NURD produces models that predict pneumonia under strong spurious correlations.

John R. Zech, Marcus A. Badgeley, Manway Liu et al.

Early results in using convolutional neural networks (CNNs) on x-rays to diagnose disease have been promising, but it has not yet been shown that models trained on x-rays from one hospital or one group of hospitals will work equally well at different hospitals. Before these tools are used for computer-aided diagnosis in real-world clinical settings, we must verify their ability to generalize across a variety of hospital systems. A cross-sectional design was used to train and evaluate pneumonia screening CNNs on 158,323 chest x-rays from NIH (n=112,120 from 30,805 patients), Mount Sinai (42,396 from 12,904 patients), and Indiana (n=3,807 from 3,683 patients). In 3 / 5 natural comparisons, performance on chest x-rays from outside hospitals was significantly lower than on held-out x-rays from the original hospital systems. CNNs were able to detect where an x-ray was acquired (hospital system, hospital department) with extremely high accuracy and calibrate predictions accordingly. The performance of CNNs in diagnosing diseases on x-rays may reflect not only their ability to identify disease-specific imaging findings on x-rays, but also their ability to exploit confounding information. Estimates of CNN performance based on test data from hospital systems used for model training may overstate their likely real-world performance.