Motivation: The adoption of current single-cell DNA methylation sequencing protocols is hindered by incomplete coverage, outlining the need for effective imputation techniques. The task of imputing single-cell (methylation) data requires models to build an understanding of underlying biological processes.
Results: We adapt the transformer neural network architecture to operate on methylation matrices through combining axial attention with sliding window self-attention. The obtained CpG Transformer displays state-of-the-art performances on a wide range of scBS-seq and scRRBS-seq datasets. Furthermore, we demonstrate the interpretability of CpG Transformer and illustrate its rapid transfer learning properties, allowing practitioners to train models on new datasets with a limited computational and time budget.
Availability And Implementation: CpG Transformer is freely available at https://github.com/gdewael/cpg-transformer.
Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab746 | DOI Listing |
Sci Adv
January 2025
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21287, USA.
DNA methylation (DNAm) is essential for brain development and function and potentially mediates the effects of genetic risk variants underlying brain disorders. We present INTERACT, a transformer-based deep learning model to predict regulatory variants affecting DNAm levels in specific brain cell types, leveraging existing single-nucleus DNAm data from the human brain. We show that INTERACT accurately predicts cell type-specific DNAm profiles, achieving an average area under the receiver operating characteristic curve of 0.
View Article and Find Full Text PDFbioRxiv
November 2024
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
DNA methylation serves as a powerful biomarker for disease diagnosis and biological age assessment. However, current analytical approaches often rely on linear models that cannot capture the complex, context-dependent nature of methylation regulation. Here we present MethylGPT, a transformer-based foundation model trained on 226,555 (154,063 after QC and deduplication) human methylation profiles spanning diverse tissue types from 5,281 datasets, curated 49,156 CpG sites, and 7.
View Article and Find Full Text PDFIEEE J Biomed Health Inform
October 2024
The lack of explainability in using relevant clinical knowledge hinders the adoption of artificial intelligence-powered analysis of unstructured clinical dialogue. A wealth of relevant, untapped Mental Health (MH) data is available in online communities, providing the opportunity to address the explainability problem with substantial potential impact as a screening tool for both online and offline applications. Inspired by how clinicians rely on their expertise when interacting with patients, we leverage relevant clinical knowledge to classify and explain depression-related data, reducing manual review time and engendering trust.
View Article and Find Full Text PDFCell Rep Med
August 2024
Zhuhai International Eye Center and Precision Medicine Center, Zhuhai People's Hospital and The First Affiliated Hospital of Faculty of Medicine, Macau University of Technology, Zhuhai, China; Institute for Advanced Study on Eye Health and Diseases, Institute for Clinical Big Data, Wenzhou Eye Hospital, Wenzhou Medical University, Wenzhou, China; Guangzhou National Laboratory, Guangzhou, China. Electronic address:
Epithelial ovarian cancer (EOC) is the deadliest women's cancer and has a poor prognosis. Early detection is the key for improving survival (a 5-year survival rate in stage I/II is over 70% compared to that of 25% in stage III/IV) and can be achieved through methylation markers from circulating cell-free DNA (cfDNA) using a liquid biopsy. In this study, we first identify top 500 EOC markers differentiating EOC from healthy female controls from 3.
View Article and Find Full Text PDFObjective: Evaluate the quality of responses from Chat Generative Pre-Trained Transformer (ChatGPT) models compared to the answers for "Frequently Asked Questions" (FAQs) from the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Clinical Practice Guidelines (CPG) for Ménière's disease (MD).
Study Design: Comparative analysis.
Setting: The AAO-HNS CPG for MD includes FAQs that clinicians can give to patients for MD-related questions.
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