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Leveraging Mutual Information for Functional Annotation Analysis of Microglia in Alzheimer's Disease

Published: 16 December 2024 Publication History

Abstract

Single-cell sequencing technologies have been advancing rapidly, enabling scientists to identify cell subtypes in tissues and study their interrelationships at the single-cell level. Current algorithms can effectively differentiate cell subgroups when gene expression values of known markers vary greatly, yet they are inadequate for classifying cells based on functionality because functionality analysis cannot be achieved by examining a handful number of marker genes. To overcome this limitation, we propose a novel clustering method specifically designed to identify functional subtypes. This method employs mutual information to dissect interrelationships among gene expression patterns of functionally aggregated groups of genes, known as Biological Processes. We applied our clustering method to 12 publicly available Alzheimer's Disease (AD) related single-cell mRNA datasets and evaluated if our method can identify additional functional roles of various subtypes of cells such as resting microglia, transitional microglia, disease associated microglia type 1 and type 2---a key research topics in current AD studies. Our method not only confirms previously known functional relationships among these subtypes but also discovers new and more specific ones. This method offers a new way of subgrouping cells, and it can aid scientists in labeling cell subtypes with functional nomenclature.

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Leveraging Mutual Information for Functional Annotation Analysis of Microglia in Alzheimer's Disease

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  • (2024)FuncNet: A Machine Learning Framework Capable of Enhancing Neural Cell Type Classification via Functional Subtype Clustering2024 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)10.1109/BIBM62325.2024.10821858(1758-1762)Online publication date: 3-Dec-2024

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    cover image ACM Conferences
    BCB '24: Proceedings of the 15th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics
    November 2024
    614 pages
    ISBN:9798400713026
    DOI:10.1145/3698587
    Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than the author(s) must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected].

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    Published: 16 December 2024

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    Author Tags

    1. Alzheimer's Disease
    2. Machine Learning
    3. Microglia
    4. Mutual information
    5. Optimization
    6. Single cell clustering

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    • (2024)FuncNet: A Machine Learning Framework Capable of Enhancing Neural Cell Type Classification via Functional Subtype Clustering2024 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)10.1109/BIBM62325.2024.10821858(1758-1762)Online publication date: 3-Dec-2024

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