Step-by-Step Guidance to Differential Anemia Diagnosis with Real-World Data and Deep Reinforcement Learning

Clinical diagnostic guidelines outline the key questions to answer to reach a diagnosis. Inspired by guidelines, we aim to develop a model that learns from electronic health records to determine the optimal sequence of actions for accurate diagnosis. Focusing on anemia and its sub-types, we employ deep reinforcement learning (DRL) algorithms and evaluate their performance on both a synthetic dataset, which is based on expert-defined diagnostic pathways, and a real-world dataset. We investigate the performance of these algorithms across various scenarios. Our experimental results demonstrate that DRL algorithms perform competitively with state-of-the-art methods while offering the significant advantage of progressively generating pathways to the suggested diagnosis, providing a transparent decision-making process that can guide and explain diagnostic reasoning.

Facilitating phenotyping from clinical texts: the medkit library

Phenotyping consists in applying algorithms to identify individuals associated with a specific, potentially complex, trait or condition, typically out of a collection of Electronic Health Records (EHRs). Because a lot of the clinical information of EHRs are lying in texts, phenotyping from text takes an important role in studies that rely on the secondary use of EHRs. However, the heterogeneity and highly specialized aspect of both the content and form of clinical texts makes this task particularly tedious, and is the source of time and cost constraints in observational studies. To facilitate the development, evaluation and reproductibility of phenotyping pipelines, we developed an open-source Python library named medkit. It enables composing data processing pipelines made of easy-to-reuse software bricks, named medkit operations. In addition to the core of the library, we share the operations and pipelines we already developed and invite the phenotyping community for their reuse and enrichment. medkit is available at https://github.com/medkit-lib/medkit

Deep Reinforcement Learning for Personalized Diagnostic Decision Pathways Using Electronic Health Records: A Comparative Study on Anemia and Systemic Lupus Erythematosus

Background: Clinical diagnosis is typically reached by following a series of steps recommended by guidelines authored by colleges of experts. Accordingly, guidelines play a crucial role in rationalizing clinical decisions but suffer from limitations as they are built to cover the majority of the population and fail at covering patients with uncommon conditions. Moreover, their updates are long and expensive, making them unsuitable for emerging diseases and practices. Methods: Inspired by guidelines, we formulate the task of diagnosis as a sequential decision-making problem and study the use of Deep Reinforcement Learning (DRL) algorithms to learn the optimal sequence of actions to perform in order to obtain a correct diagnosis from Electronic Health Records (EHRs). We apply DRL on synthetic, but realistic EHRs and develop two clinical use cases: Anemia diagnosis, where the decision pathways follow the schema of a decision tree; and Systemic Lupus Erythematosus (SLE) diagnosis, which follows a weighted criteria score. We particularly evaluate the robustness of our approaches to noisy and missing data since these frequently occur in EHRs. Results: In both use cases, and in the presence of imperfect data, our best DRL algorithms exhibit competitive performance when compared to the traditional classifiers, with the added advantage that they enable the progressive generation of a pathway to the suggested diagnosis which can both guide and explain the decision-making process. Conclusion: DRL offers the opportunity to learn personalized decision pathways to diagnosis. We illustrate with our two use cases their advantages: they generate step-by-step pathways that are self-explanatory; and their correctness is competitive when compared to state-of-the-art approaches.

Extracting Diagnosis Pathways from Electronic Health Records Using Deep Reinforcement Learning

Clinical diagnosis guidelines aim at specifying the steps that may lead to a diagnosis. Guidelines enable rationalizing and normalizing clinical decisions but suffer drawbacks as they are built to cover the majority of the population and may fail in guiding to the right diagnosis for patients with uncommon conditions or multiple pathologies. Moreover, their updates are long and expensive, making them unsuitable to emerging practices. Inspired by guidelines, we formulate the task of diagnosis as a sequential decision-making problem and study the use of Deep Reinforcement Learning (DRL) algorithms trained on Electronic Health Records (EHRs) to learn the optimal sequence of observations to perform in order to obtain a correct diagnosis. Because of the variety of DRL algorithms and of their sensitivity to the context, we considered several approaches and settings that we compared to each other, and to classical classifiers. We experimented on a synthetic but realistic dataset to differentially diagnose anemia and its subtypes and particularly evaluated the robustness of various approaches to noise and missing data as those are frequent in EHRs. Within the DRL algorithms, Dueling DQN with Prioritized Experience Replay, and Dueling Double DQN with Prioritized Experience Replay show the best and most stable performances. In the presence of imperfect data, the DRL algorithms show competitive, but less stable performances when compared to the classifiers (Random Forest and XGBoost); although they enable the progressive generation of a pathway to the suggested diagnosis, which can both guide or explain the decision process.

Investigating ADR mechanisms with knowledge graph mining and explainable AI

Adverse Drug Reactions (ADRs) are characterized within randomized clinical trials and postmarketing pharmacovigilance, but their molecular mechanism remains unknown in most cases. Aside from clinical trials, many elements of knowledge about drug ingredients are available in open-access knowledge graphs. In addition, drug classifications that label drugs as either causative or not for several ADRs, have been established. We propose to mine knowledge graphs for identifying biomolecular features that may enable reproducing automatically expert classifications that distinguish drug causative or not for a given type of ADR. In an explainable AI perspective, we explore simple classification techniques such as Decision Trees and Classification Rules because they provide human-readable models, which explain the classification itself, but may also provide elements of explanation for molecular mechanisms behind ADRs. In summary, we mine a knowledge graph for features; we train classifiers at distinguishing, drugs associated or not with ADRs; we isolate features that are both efficient in reproducing expert classifications and interpretable by experts (i.e., Gene Ontology terms, drug targets, or pathway names); and we manually evaluate how they may be explanatory. Extracted features reproduce with a good fidelity classifications of drugs causative or not for DILI and SCAR. Experts fully agreed that 73% and 38% of the most discriminative features are possibly explanatory for DILI and SCAR, respectively; and partially agreed (2/3) for 90% and 77% of them. Knowledge graphs provide diverse features to enable simple and explainable models to distinguish between drugs that are causative or not for ADRs. In addition to explaining classifications, most discriminative features appear to be good candidates for investigating ADR mechanisms further.

Experiments on transfer learning architectures for biomedical relation extraction

Relation extraction (RE) consists in identifying and structuring automatically relations of interest from texts. Recently, BERT improved the top performances for several NLP tasks, including RE. However, the best way to use BERT, within a machine learning architecture, and within a transfer learning strategy is still an open question since it is highly dependent on each specific task and domain. Here, we explore various BERT-based architectures and transfer learning strategies (i.e., frozen or fine-tuned) for the task of biomedical RE on two corpora. Among tested architectures and strategies, our *BERT-segMCNN with finetuning reaches performances higher than the state-of-the-art on the two corpora (1.73 % and 32.77 % absolute improvement on ChemProt and PGxCorpus corpora respectively). More generally, our experiments illustrate the expected interest of fine-tuning with BERT, but also the unexplored advantage of using structural information (with sentence segmentation), in addition to the context classically leveraged by BERT.

Rediscovering alignment relations with Graph Convolutional Networks

Knowledge graphs are concurrently published and edited in the Web of data. Hence they may overlap, which makes key the task that consists in matching their content. This task encompasses the identification, within and across knowledge graphs, of nodes that are equivalent, more specific, or weakly related. In this article, we propose to match nodes of a knowledge graph by (i) learning node embeddings with Graph Convolutional Networks such that similar nodes have low distances in the embedding space, and (ii) clustering nodes based on their embeddings. We experimented this approach on a biomedical knowledge graph and particularly investigated the interplay between formal semantics and GCN models with the two following main focuses. Firstly, we applied various inference rules associated with domain knowledge, independently or combined, before learning node embeddings, and we measured the improvements in matching results. Secondly, while our GCN model is agnostic to the exact alignment relations (e.g., equivalence, weak similarity), we observed that distances in the embedding space are coherent with the "strength" of these different relations (e.g., smaller distances for equivalences), somehow corresponding to their rediscovery by the model.

Tackling scalability issues in mining path patterns from knowledge graphs: a preliminary study

Features mined from knowledge graphs are widely used within multiple knowledge discovery tasks such as classification or fact-checking. Here, we consider a given set of vertices, called seed vertices, and focus on mining their associated neighboring vertices, paths, and, more generally, path patterns that involve classes of ontologies linked with knowledge graphs. Due to the combinatorial nature and the increasing size of real-world knowledge graphs, the task of mining these patterns immediately entails scalability issues. In this paper, we address these issues by proposing a pattern mining approach that relies on a set of constraints (e.g., support or degree thresholds) and the monotonicity property. As our motivation comes from the mining of real-world knowledge graphs, we illustrate our approach with PGxLOD, a biomedical knowledge graph.

Knowledge Reconciliation of $n$-ary Relations

In the expanding Semantic Web, an increasing number of sources of data and knowledge are accessible by human and software agents. Sources may differ in granularity or completeness, and thus be complementary. Consequently, unlocking the full potential of the available knowledge requires combining them. To this aim, we define the task of knowledge reconciliation, which consists in identifying, within and across sources, equivalent, more specific, or similar units. This task can be challenging since knowledge units are heterogeneously represented in sources (e.g., in terms of vocabularies). In this paper, we propose a rule-based methodology for the reconciliation of $n$-ary relations. To alleviate the heterogeneity in representation, we rely on domain knowledge expressed by ontologies. We tested our method on the biomedical domain of pharmacogenomics by reconciling 50,435 $n$-ary relations from four different real-world sources, which highlighted noteworthy agreements and discrepancies within and across sources.

Creating Fair Models of Atherosclerotic Cardiovascular Disease Risk

Guidelines for the management of atherosclerotic cardiovascular disease (ASCVD) recommend the use of risk stratification models to identify patients most likely to benefit from cholesterol-lowering and other therapies. These models have differential performance across race and gender groups with inconsistent behavior across studies, potentially resulting in an inequitable distribution of beneficial therapy. In this work, we leverage adversarial learning and a large observational cohort extracted from electronic health records (EHRs) to develop a "fair" ASCVD risk prediction model with reduced variability in error rates across groups. We empirically demonstrate that our approach is capable of aligning the distribution of risk predictions conditioned on the outcome across several groups simultaneously for models built from high-dimensional EHR data. We also discuss the relevance of these results in the context of the empirical trade-off between fairness and model performance.