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Langston, Michael A.

Publications and source records attributed to Langston, Michael A..

EHR-BERT: A BERT-based model for effective anomaly detection in electronic health records

Objective: Physicians and clinicians rely on data contained in electronic health records (EHRs), as recorded by health information technology (HIT), to make informed decisions about their patients. The reliability of HIT systems in this regard is critical to patient safety. Consequently, better tools are needed to monitor the performance of HIT systems for potential hazards that could compromise the collected EHRs, which in turn could affect patient safety. In this paper, we propose a new framework for detecting anomalies in EHRs using sequence of clinical events. This new framework, EHR-Bidirectional Encoder Representations from Transformers (BERT), is motivated by the gaps in the existing deep-learning related methods, including high false negatives, sub-optimal accuracy, higher computational cost, and the risk of information loss. EHR-BERT is an innovative framework rooted in the BERT architecture, meticulously tailored to navigate the hurdles in the contemporary BERT method; thus, enhancing anomaly detection in EHRs for healthcare applications.Methods: The EHR-BERT framework was designed using the Sequential Masked Token Prediction (SMTP) method. This approach treats EHRs as natural language sentences and iteratively masks input tokens during both training and prediction stages. This method facilitates the learning of EHR sequence patterns in both directions for each event and identifies anomalies based on deviations from the normal execution models trained on EHR sequences.Results: Extensive experiments on large EHR datasets across various medical domains demonstrate that EHR-BERT markedly improves upon existing models. It significantly reduces the number of false positives and enhances the detection rate, thus bolstering the reliability of anomaly detection in electronic health records. This improvement is attributed to the model’s ability to minimize information loss and maximize data utilization effectively.Conclusion: EHR-BERT showcases immense potential in decreasing medical errors related to anomalous clinical events, positioning itself as an indispensable asset for enhancing patient safety and the overall standard of healthcare services. The framework effectively overcomes the drawbacks of earlier models, making it a promising solution for healthcare professionals to ensure the reliability and quality of health data.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

Detecting anomalous sequences in electronic health records using higher-order tensor networks

Detecting anomalous sequences is an integral part of building and protecting modern large-scale health information technology (HIT) systems. These HIT systems generate a large volume of records of patients’ state and significant events, which provide a valuable resource to help improve clinical decisions, patient care processes, and other issues. However, detecting anomalous sequences in electronic health records (EHR) remains a challenge in healthcare applications for several reasons, including imbalances in the data, complexity of relationships between events in the sequence, and the curse of dimensionality. Conventional anomaly detection methods use the finite sequence of events to discriminate sequences. They fail to incorporate salient event details under variable higher-order dependencies (e.g., duration between events) that can provide better discrimination of sequences in their models. To address this problem, we propose event sequence and subsequence anomaly detection algorithms that (1) use network-based representations of interactions in the data, (2) account for variable higher-order dependencies in the data, and (3) incorporate events duration for adequate discrimination of the data. The proposed approach identifies anomalies by monitoring the change in the graph after the test sequence is removed from the network. The change is quantified using graph distance metrics so that dramatic changes in the network can be attributed to the removed sequence. Furthermore, the proposed subsequence algorithm recommends plausible paths and salient information for the detected anomalous subsequences. Our results show that the proposed event sequence anomaly detection algorithm outperforms the baseline methods for both synthetic data and real-world EHR data.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

Biclique: an R package for maximal biclique enumeration in bipartite graphs

Bipartite graphs are widely used to model relationships between pairs of heterogeneous data types. Maximal bicliques are foundational structures in such graphs, and their enumeration is an important task in systems biology, epidemiology and many other problem domains. Thus, there is a need for an efficient, general purpose, publicly available tool to enumerate maximal bicliques in bipartite graphs. The statistical programming language R is a logical choice for such a tool, but until now no R package has existed for this purpose. Our objective is to provide such a package, so that the research community can more easily perform this computationally demanding task. Biclique is an R package that takes as input a bipartite graph and produces a listing of all maximal bicliques in this graph. Input and output formats are straightforward, with examples provided both in this paper and in the package documentation. Biclique employs a state-of-the-art algorithm previously developed for basic research in functional genomics.

97 MATHEMATICS AND COMPUTING↗

Efficient prediction of human protein-protein interactions at a global scale

Background: Our knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods. Results: On the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network within 3 months. With a recall of 23% at a precision of 82.1%, we predicted 172,132 putative PPIs. We demonstrate the usefulness of these predictions through a range of experiments. Conclusions: The speed and accuracy associated with MP-PIPE can make this a potential tool to study individual human PPI networks (from genomic sequences alone) for personalized medicine.

59 BASIC BIOLOGICAL SCIENCES↗

Scalable Computational Methods for the Analysis of High-Throughput Biological Data

This primary focus of this research project is elucidating genetic regulatory mechanisms that control an organism's responses to low-dose ionizing radiation. Although low doses (at most ten centigrays) are not lethal to humans, they elicit a highly complex physiological response, with the ultimate outcome in terms of risk to human health unknown. The tools of molecular biology and computational science will be harnessed to study coordinated changes in gene expression that orchestrate the mechanisms a cell uses to manage the radiation stimulus. High performance implementations of novel algorithms that exploit the principles of fixed-parameter tractability will be used to extract gene sets suggestive of co-regulation. Genomic mining will be performed to scrutinize, winnow and highlight the most promising gene sets for more detailed investigation. The overall goal is to increase our understanding of the health risks associated with exposures to low levels of radiation.

59 BASIC BIOLOGICAL SCIENCES↗

The maximum clique enumeration problem: algorithms, applications, and implementations

Background: The maximum clique enumeration (MCE) problem asks that we identify all maximum cliques in a finite, simple graph. MCE is closely related to two other well-known and widely-studied problems: the maximum clique optimization problem, which asks us to determine the size of a largest clique, and the maximal clique enumeration problem, which asks that we compile a listing of all maximal cliques. Naturally, these three problems are N P -hard, given that they subsume the classic version of the N P -complete clique decision problem. MCE can be solved in principle with standard enumeration methods due to Bron, Kerbosch, Kose and others. Unfortunately, these techniques are ill-suited to graphs encountered in our applications. We must solve MCE on instances deeply seeded in data mining and computational biology, where high-throughput data capture often creates graphs of extreme size and density. MCE can also be solved in principle using more modern algorithms based in part on vertex cover and the theory of fixed-parameter tractability (FPT). While FPT is an improvement, these algorithms too can fail to scale sufficiently well as the sizes and densities of our datasets grow. Results: An extensive testbed of benchmark graphs are created using publicly available transcriptomic datasets from the Gene Expression Omnibus (GEO). Empirical testing reveals crucial but latent features of such high-throughput biological data. In turn, it is shown that these features distinguish real data from random data intended to reproduce salient topological features. In particular, with real data there tends to be an unusually high degree of maximum clique overlap. Armed with this knowledge, novel decomposition strategies are tuned to the data and coupled with the best FPT MCE implementations. Conclusions: Several algorithmic improvements to MCE are made which progressively decrease the run time on graphs in the testbed. Frequently the final runtime improvement is several orders of magnitude. As a result, instances which were once prohibitively time-consuming to solve are brought into the domain of realistic feasibility.

59 BASIC BIOLOGICAL SCIENCES↗

A systematic comparison of genome-scale clustering algorithms

Background: A wealth of clustering algorithms has been applied to gene co-expression experiments. These algorithms cover a broad range of approaches, from conventional techniques such as k-means and hierarchical clustering, to graphical approaches such as k-clique communities, weighted gene co-expression networks (WGCNA) and paraclique. Comparison of these methods to evaluate their relative effectiveness provides guidance to algorithm selection, development and implementation. Most prior work on comparative clustering evaluation has focused on parametric methods. Graph theoretical methods are recent additions to the tool set for the global analysis and decomposition of microarray co-expression matrices that have not generally been included in earlier methodological comparisons. In the present study, a variety of parametric and graph theoretical clustering algorithms are compared using well-characterized transcriptomic data at a genome scale from Saccharomyces cerevisiae. Methods: For each clustering method under study, a variety of parameters were tested. Jaccard similarity was used to measure each cluster’s agreement with every GO and KEGG annotation set, and the highest Jaccard score was assigned to the cluster. Clusters were grouped into small, medium, and large bins, and the Jaccard score of the top five scoring clusters in each bin were averaged and reported as the best average top 5 (BAT5) score for the particular method. Results: Clusters produced by each method were evaluated based upon the positive match to known pathways. This produces a readily interpretable ranking of the relative effectiveness of clustering on the genes. Methods were also tested to determine whether they were able to identify clusters consistent with those identified by other clustering methods. Conclusions: Validation of clusters against known gene classifications demonstrate that for this data, graph-based techniques outperform conventional clustering approaches, suggesting that further development and application of combinatorial strategies is warranted.

59 BASIC BIOLOGICAL SCIENCES↗

Small diameter symmetric networks from linear groups

In this note is reported a collection of constructions of symmetric networks that provide the largest known values for the number of nodes that can be placed in a network of a given degree and diameter. Some of the constructions are in the range of current potential engineering significance. The constructions are Cayley graphs of linear groups obtained by experimental computation.

Campbell, Lowell↗