Modeling electronic health record data using an end-to-end knowledge-graph-informed topic model.

The rapid growth of electronic health record (EHR) datasets opens up promising opportunities to understand human diseases in a systematic way. However, effective extraction of clinical knowledge from EHR data has been hindered by the sparse and noisy information. We present Graph ATtention-Embedded Topic Model (GAT-ETM), an end-to-end taxonomy-knowledge-graph-based multimodal embedded topic model. GAT-ETM distills latent disease topics from EHR data by learning the embedding from a constructed medical knowledge graph. We applied GAT-ETM to a large-scale EHR dataset consisting of over 1 million patients. We evaluated its performance based on topic quality, drug imputation, and disease diagnosis prediction. GAT-ETM demonstrated superior performance over the alternative methods on all tasks. Moreover, GAT-ETM learned clinically meaningful graph-informed embedding of the EHR codes and discovered interpretable and accurate patient representations for patient stratification and drug recommendations. GAT-ETM code is available at https://github.com/li-lab-mcgill/GAT-ETM .

deepSimDEF: deep neural embeddings of gene products and gene ontology terms for functional analysis of genes.

MOTIVATION: There is a plethora of measures to evaluate functional similarity (FS) of genes based on their co-expression, protein-protein interactions and sequence similarity. These measures are typically derived from hand-engineered and application-specific metrics to quantify the degree of shared information between two genes using their Gene Ontology (GO) annotations. RESULTS: We introduce deepSimDEF, a deep learning method to automatically learn FS estimation of gene pairs given a set of genes and their GO annotations. deepSimDEF's key novelty is its ability to learn low-dimensional embedding vector representations of GO terms and gene products and then calculate FS using these learned vectors. We show that deepSimDEF can predict the FS of new genes using their annotations: it outperformed all other FS measures by >5-10% on yeast and human reference datasets on protein-protein interactions, gene co-expression and sequence homology tasks. Thus, deepSimDEF offers a powerful and adaptable deep neural architecture that can benefit a wide range of problems in genomics and proteomics, and its architecture is flexible enough to support its extension to any organism. AVAILABILITY AND IMPLEMENTATION: Source code and data are available at https://github.com/ahmadpgh/deepSimDEF. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Population Genomics Approaches for Genetic Characterization of SARS-CoV-2 Lineages.

The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), has been sequenced at an unprecedented scale leading to a tremendous amount of viral genome sequencing data. To assist in tracing infection pathways and design preventive strategies, a deep understanding of the viral genetic diversity landscape is needed. We present here a set of genomic surveillance tools from population genetics which can be used to better understand the evolution of this virus in humans. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic. We analyzed 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets. This approach enables real-time lineage identification, a clear description of the relationship between variants of concern, and efficient detection of recurrent mutations. Furthermore, time series change of Tajima's D by haplotype provides a powerful metric of lineage expansion. Finally, principal component analysis (PCA) highlights key steps in variant emergence and facilitates the visualization of genomic variation in the context of SARS-CoV-2 diversity. The computational framework presented here is simple to implement and insightful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of populations of humans and other organisms.

Implementing Machine Learning in Interventional Cardiology: The Benefits Are Worth the Trouble.

Driven by recent innovations and technological progress, the increasing quality and amount of biomedical data coupled with the advances in computing power allowed for much progress in artificial intelligence (AI) approaches for health and biomedical research. In interventional cardiology, the hope is for AI to provide automated analysis and deeper interpretation of data from electrocardiography, computed tomography, magnetic resonance imaging, and electronic health records, among others. Furthermore, high-performance predictive models supporting decision-making hold the potential to improve safety, diagnostic and prognostic prediction in patients undergoing interventional cardiology procedures. These applications include robotic-assisted percutaneous coronary intervention procedures and automatic assessment of coronary stenosis during diagnostic coronary angiograms. Machine learning (ML) has been used in these innovations that have improved the field of interventional cardiology, and more recently, deep Learning (DL) has emerged as one of the most successful branches of ML in many applications. It remains to be seen if DL approaches will have a major impact on current and future practice. DL-based predictive systems also have several limitations, including lack of interpretability and lack of generalizability due to cohort heterogeneity and low sample sizes. There are also challenges for the clinical implementation of these systems, such as ethical limits and data privacy. This review is intended to bring the attention of health practitioners and interventional cardiologists to the broad and helpful applications of ML and DL algorithms to date in the field. Their implementation challenges in daily practice and future applications in the field of interventional cardiology are also discussed.

deepBioWSD: effective deep neural word sense disambiguation of biomedical text data.

OBJECTIVE: In biomedicine, there is a wealth of information hidden in unstructured narratives such as research articles and clinical reports. To exploit these data properly, a word sense disambiguation (WSD) algorithm prevents downstream difficulties in the natural language processing applications pipeline. Supervised WSD algorithms largely outperform un- or semisupervised and knowledge-based methods; however, they train 1 separate classifier for each ambiguous term, necessitating a large number of expert-labeled training data, an unattainable goal in medical informatics. To alleviate this need, a single model that shares statistical strength across all instances and scales well with the vocabulary size is desirable. MATERIALS AND METHODS: Built on recent advances in deep learning, our deepBioWSD model leverages 1 single bidirectional long short-term memory network that makes sense prediction for any ambiguous term. In the model, first, the Unified Medical Language System sense embeddings will be computed using their text definitions; and then, after initializing the network with these embeddings, it will be trained on all (available) training data collectively. This method also considers a novel technique for automatic collection of training data from PubMed to (pre)train the network in an unsupervised manner. RESULTS: We use the MSH WSD dataset to compare WSD algorithms, with macro and micro accuracies employed as evaluation metrics. deepBioWSD outperforms existing models in biomedical text WSD by achieving the state-of-the-art performance of 96.82% for macro accuracy. CONCLUSIONS: Apart from the disambiguation improvement and unsupervised training, deepBioWSD depends on considerably less number of expert-labeled data as it learns the target and the context terms jointly. These merit deepBioWSD to be conveniently deployable in real-time biomedical applications.

simDEF: definition-based semantic similarity measure of gene ontology terms for functional similarity analysis of genes.

MOTIVATION: Measures of protein functional similarity are essential tools for function prediction, evaluation of protein-protein interactions (PPIs) and other applications. Several existing methods perform comparisons between proteins based on the semantic similarity of their GO terms; however, these measures are highly sensitive to modifications in the topological structure of GO, tend to be focused on specific analytical tasks and concentrate on the GO terms themselves rather than considering their textual definitions. RESULTS: We introduce simDEF, an efficient method for measuring semantic similarity of GO terms using their GO definitions, which is based on the Gloss Vector measure commonly used in natural language processing. The simDEF approach builds optimized definition vectors for all relevant GO terms, and expresses the similarity of a pair of proteins as the cosine of the angle between their definition vectors. Relative to existing similarity measures, when validated on a yeast reference database, simDEF improves correlation with sequence homology by up to 50%, shows a correlation improvement >4% with gene expression in the biological process hierarchy of GO and increases PPI predictability by > 2.5% in F1 score for molecular function hierarchy. AVAILABILITY AND IMPLEMENTATION: Datasets, results and source code are available at http://kiwi.cs.dal.ca/Software/simDEF CONTACT: ahmad.pgh@dal.ca or beiko@cs.dal.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.