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Public Health Public Health

Interpretable Meta-learning of Multi-omics Data for Survival Analysis and Pathway Enrichment.

In Bioinformatics (Oxford, England)

MOTIVATION : Despite the success of recent machine learning algorithms' applications to survival analysis, their black-box nature hinders interpretability, which is arguably the most important aspect. Similarly, multi-omics data integration for survival analysis is often constrained by the underlying relationships and correlations that are rarely well understood. The goal of this work is to alleviate the interpretability problem in machine learning approaches for survival analysis and also demonstrate how multi-omics data integration improves survival analysis and pathway enrichment. We use meta-learning, a machine learning algorithm that is trained on a variety of related datasets and allows quick adaptations to new tasks, to perform survival analysis and pathway enrichment on pan-cancer datasets. In recent machine learning research, meta-learning has been effectively used for knowledge transfer among multiple related datasets.

RESULTS : We use meta-learning with cox hazard loss to show that the integration of TCGA pan-cancer data increases the performance of survival analysis. We also apply advanced model interpretability method called DeepLIFT (Deep Learning Important FeaTures) to show different sets of enriched pathways for multi-omics and transcriptomics data. Our results show that multi-omics cancer survival analysis enhances performance compared with using transcriptomics or clinical data alone. Additionally, we show a correlation between variable importance assignment from DeepLIFT and gene co-enrichment, suggesting that genes with higher and similar contribution scores are more likely to be enriched together in the same enrichment sets.

AVAILABILITY : https://github.com/berkuva/TCGA-omics-integration.

SUPPLEMENTARY INFORMATION : Supplementary data are available at Bioinformatics online.

Cho Hyun Jae, Shu Mia, Bekiranov Stefan, Zang Chongzhi, Zhang Aidong

2023-Mar-02

General General

The future of automated infection detection: Innovation to transform practice (Part III/III).

In Antimicrobial stewardship & healthcare epidemiology : ASHE

Current methods of emergency-room-based syndromic surveillance were insufficient to detect early community spread of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in the United States, which slowed the infection prevention and control response to the novel pathogen. Emerging technologies and automated infection surveillance have the potential to improve upon current practice standards and to revolutionize the practice of infection detection, prevention and control both inside and outside of healthcare settings. Genomics, natural language processing, and machine learning can be leveraged to improve identification of transmission events and aid and evaluate outbreak response. In the near future, automated infection detection strategies can be used to advance a true "Learning Healthcare System" that will support near-real-time quality improvement efforts and advance the scientific basis for the practice of infection control.

Branch-Elliman Westyn, Sundermann Alexander J, Wiens Jenna, Shenoy Erica S

2023

General General

Assessing the Value of ChatGPT for Clinical Decision Support Optimization.

In medRxiv : the preprint server for health sciences

OBJECTIVE : To determine if ChatGPT can generate useful suggestions for improving clinical decision support (CDS) logic and to assess noninferiority compared to human-generated suggestions.

METHODS : We supplied summaries of CDS logic to ChatGPT, an artificial intelligence (AI) tool for question answering that uses a large language model, and asked it to generate suggestions. We asked human clinician reviewers to review the AI-generated suggestions as well as human-generated suggestions for improving the same CDS alerts, and rate the suggestions for their usefulness, acceptance, relevance, understanding, workflow, bias, inversion, and redundancy.

RESULTS : Five clinicians analyzed 36 AI-generated suggestions and 29 human-generated suggestions for 7 alerts. Of the 20 suggestions that scored highest in the survey, 9 were generated by ChatGPT. The suggestions generated by AI were found to offer unique perspectives and were evaluated as highly understandable and relevant, with moderate usefulness, low acceptance, bias, inversion, redundancy.

CONCLUSION : AI-generated suggestions could be an important complementary part of optimizing CDS alerts, can identify potential improvements to alert logic and support their implementation, and may even be able to assist experts in formulating their own suggestions for CDS improvement. ChatGPT shows great potential for using large language models and reinforcement learning from human feedback to improve CDS alert logic and potentially other medical areas involving complex, clinical logic, a key step in the development of an advanced learning health system.

Liu Siru, Wright Aileen P, Patterson Barron L, Wanderer Jonathan P, Turer Robert W, Nelson Scott D, McCoy Allison B, Sittig Dean F, Wright Adam

2023-Feb-23

General General

IntroUNET: identifying introgressed alleles via semantic segmentation.

In bioRxiv : the preprint server for biology

A growing body of evidence suggests that gene flow between closely related species is a widespread phenomenon. Alleles that introgress from one species into a close relative are typically neutral or deleterious, but sometimes confer a significant fitness advantage. Given the potential relevance to speciation and adaptation, numerous methods have therefore been devised to identify regions of the genome that have experienced introgression. Recently, supervised machine learning approaches have been shown to be highly effective for detecting introgression. One especially promising approach is to treat population genetic inference as an image classification problem, and feed an image representation of a population genetic alignment as input to a deep neural network that distinguishes among evolutionary models (i.e. introgression or no introgression). However, if we wish to investigate the full extent and fitness effects of introgression, merely identifying genomic regions in a population genetic alignment that harbor introgressed loci is insufficient-ideally we would be able to infer precisely which individuals have introgressed material and at which positions in the genome. Here we adapt a deep learning algorithm for semantic segmentation, the task of correctly identifying the type of object to which each individual pixel in an image belongs, to the task of identifying introgressed alleles. Our trained neural network is thus able to infer, for each individual in a two-population alignment, which of those individual's alleles were introgressed from the other population. We use simulated data to show that this approach is highly accurate, and that it can be readily extended to identify alleles that are introgressed from an unsampled "ghost" population, performing comparably to a supervised learning method tailored specifically to that task. Finally, we apply this method to data from Drosophila, showing that it is able to accurately recover introgressed haplotypes from real data. This analysis reveals that introgressed alleles are typically confined to lower frequencies within genic regions, suggestive of purifying selection, but are found at much higher frequencies in a region previously shown to be affected by adaptive introgression. Our method's success in recovering introgressed haplotypes in challenging real-world scenarios underscores the utility of deep learning approaches for making richer evolutionary inferences from genomic data.

Ray Dylan D, Flagel Lex, Schrider Daniel R

2023-Feb-07

General General

Patients with fibrosis from non-alcoholic steatohepatitis have heterogeneous intrahepatic macrophages and therapeutic targets.

In medRxiv : the preprint server for health sciences

BACKGROUND AND AIMS : In clinical trials for reducing fibrosis in NASH patients, therapeutics that target macrophages have had variable results. We evaluated intrahepatic macrophages in patients with non-alcoholic steatohepatitis to determine if fibrosis influenced phenotypes and expression of CCR2 and Galectin-3.

APPROACH & RESULTS : We used nCounter to analyze liver biopsies from well-matched patients with minimal (n=12) or advanced (n=12) fibrosis to determine which macrophage-related genes would be significantly different. Known therapy targets (e.g., CCR2 and Galectin-3) were significantly increased in patients with cirrhosis.However, several genes (e.g., CD68, CD16, and CD14) did not show significant differences, and CD163, a marker of pro-fibrotic macrophages was significantly decreased with cirrhosis. Next, we analyzed patients with minimal (n=6) or advanced fibrosis (n=5) using approaches that preserved hepatic architecture by multiplex-staining with anti-CD68, Mac387, CD163, CD14, and CD16. Spectral data were analyzed using deep learning/artificial intelligence to determine percentages and spatial relationships. This approach showed patients with advanced fibrosis had increased CD68+, CD16+, Mac387+, CD163+, and CD16+CD163+ populations. Interaction of CD68+ and Mac387+ populations was significantly increased in patients with cirrhosis and enrichment of these same phenotypes in individuals with minimal fibrosis correlated with poor outcomes. Evaluation of a final set of patients (n=4) also showed heterogenous expression of CD163, CCR2, Galectin-3, and Mac387, and significant differences were not dependent on fibrosis stage or NAFLD activity.

CONCLUSIONS : Approaches that leave hepatic architecture intact, like multispectral imaging, may be paramount to developing effective treatments for NASH. In addition, understanding individual differences in patients may be required for optimal responses to macrophage-targeting therapies.

Saldarriaga Omar A, Krishnan Santhoshi, Wanninger Timothy G, Oneka Morgan, Rao Arvind, Bao Daniel, Arroyave Esteban, Gosnell Joseph, Kueht Michael, Moghe Akshata, Millian Daniel, Jiao Jingjing, Sanchez Jessica I, Spratt Heidi, Beretta Laura, Stevenson Heather L

2023-Feb-23

General General

Retracted: Effectiveness of Artificial Intelligence Multimedia Courseware in Classroom Teaching Application.

In Applied bionics and biomechanics

[This retracts the article DOI: 10.1155/2022/4543875.].

And Biomechanics Applied Bionics

2023