Deep Learning Predicts Biomarker Status and Discovers Related Histomorphology Characteristics for Low-Grade Glioma

Biomarker detection is an indispensable part in the diagnosis and treatment of low-grade glioma (LGG). However, current LGG biomarker detection methods rely on expensive and complex molecular genetic testing, for which professionals are required to analyze the results, and intra-rater variability is often reported. To overcome these challenges, we propose an interpretable deep learning pipeline, a Multi-Biomarker Histomorphology Discoverer (Multi-Beholder) model based on the multiple instance learning (MIL) framework, to predict the status of five biomarkers in LGG using only hematoxylin and eosin-stained whole slide images and slide-level biomarker status labels. Specifically, by incorporating the one-class classification into the MIL framework, accurate instance pseudo-labeling is realized for instance-level supervision, which greatly complements the slide-level labels and improves the biomarker prediction performance. Multi-Beholder demonstrates superior prediction performance and generalizability for five LGG biomarkers (AUROC=0.6469-0.9735) in two cohorts (n=607) with diverse races and scanning protocols. Moreover, the excellent interpretability of Multi-Beholder allows for discovering the quantitative and qualitative correlations between biomarker status and histomorphology characteristics. Our pipeline not only provides a novel approach for biomarker prediction, enhancing the applicability of molecular treatments for LGG patients but also facilitates the discovery of new mechanisms in molecular functionality and LGG progression.

An Operational Perspective to Fairness Interventions: Where and How to Intervene

As AI-based decision systems proliferate, their successful operationalization requires balancing multiple desiderata: predictive performance, disparity across groups, safeguarding sensitive group attributes (e.g., race), and engineering cost. We present a holistic framework for evaluating and contextualizing fairness interventions with respect to the above desiderata. The two key points of practical consideration are where (pre-, in-, post-processing) and how (in what way the sensitive group data is used) the intervention is introduced. We demonstrate our framework using a thorough benchmarking study on predictive parity; we study close to 400 methodological variations across two major model types (XGBoost vs. Neural Net) and ten datasets. Methodological insights derived from our empirical study inform the practical design of ML workflow with fairness as a central concern. We find predictive parity is difficult to achieve without using group data, and despite requiring group data during model training (but not inference), distributionally robust methods provide significant Pareto improvement. Moreover, a plain XGBoost model often Pareto-dominates neural networks with fairness interventions, highlighting the importance of model inductive bias.