4.7 Article

Machine learning prediction and tau-based screening identifies potential Alzheimer's disease genes relevant to immunity

Journal

COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s42003-022-03068-7

Keywords

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Funding

  1. NIH [U24 CA224370-01S1, U24 TR002278]
  2. UNM Health Sciences Center
  3. UNM Department of Molecular Genetics and Microbiology
  4. Alzheimer's Disease Core Center from the National Institute on Aging to Northwestern University, Chicago Illinois [P30 AG013854]
  5. IDG KMC application from the University of New Mexico [NIH CA224370]
  6. [RF1NS083704-05A1]
  7. [R01NS083704]
  8. [R21NS077089]
  9. [R21NS093442]

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With increased research funding for Alzheimer's disease (AD) and related disorders across the globe, machine learning methods have been employed to understand the ever-growing data, enhancing early diagnosis and uncovering potential drug targets. The study identified potential AD risk genes and validated the top 20 candidates through experimental screening.
With increased research funding for Alzheimer's disease (AD) and related disorders across the globe, large amounts of data are being generated. Several studies employed machine learning methods to understand the ever-growing omics data to enhance early diagnosis, map complex disease networks, or uncover potential drug targets. We describe results based on a Target Central Resource Database protein knowledge graph and evidence paths transformed into vectors by metapath matching. We extracted features between specific genes and diseases, then trained and optimized our model using XGBoost, termed MPxgb(AD). To determine our MPxgb(AD) prediction performance, we examined the top twenty predicted genes through an experimental screening pipeline. Our analysis identified potential AD risk genes: FRRS1, CTRAM, SCGB3A1, FAM92B/CIBAR2, and TMEFF2. FRRS1 and FAM92B are considered dark genes, while CTRAM, SCGB3A1, and TMEFF2 are connected to TREM2-TYROBP, IL-1 beta-TNF alpha, and MTOR-APP AD-risk nodes, suggesting relevance to the pathogenesis of AD. Jessica Binder et al. developed a machine learning model to discover potential drug targets for Alzheimer's disease. They validated their 20 top candidates in several in vitro models, and highlight FRRS1, CTRAM, SCGB3A1, FAM92B/CIBAR2, and TMEFF2 as potential AD risk genes.

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