Precision machine learning to understand micro-RNA regulation in neurodegenerative diseases

Abstract

Micro-RNAs (miRNAs) are short (∼21 nt) non-coding RNAs that regulate gene expression through the degradation or translational repression of mRNAs. Accumulating evidence points to a role of miRNA regulation in the pathogenesis of a wide range of neurodegenerative (ND) diseases such as, for example, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and Huntington disease (HD). Several systems level studies aimed to explore the role of miRNA regulation in NDs, but these studies remain challenging. Part of the problem may be related to the lack of sufficiently rich or homogeneous data, such as time series or cell-type-specific data obtained in model systems or human biosamples, to account for context dependency. Part of the problem may also be related to the methodological challenges associated with the accurate system-level modeling of miRNA and mRNA data. Here, we critically review the main families of machine learning methods used to analyze expression data, highlighting the added value of using shape-analysis concepts as a solution for precisely modeling highly dimensional miRNA and mRNA data such as the ones obtained in the study of the HD process, and elaborating on the potential of these concepts and methods for modeling complex omics data.

Patient-derived neuron model: Capturing age-dependent adult-onset degenerative pathology in Huntington’s disease

“…The dysregulation of genes governed by miRNAs and changes in miRNA expression have been associated with various neurodegenerative diseases, including Huntington’s disease (HD), Alzheimer’s disease, and Parkinson’s disease. In Alzheimer’s and Parkinson’s diseases, investigations using blood samples and postmortem brain tissue have identified distinct expression patterns of miRNAs, such as mir-1, mir-22p, mir-26b-3p, and mir-28-3p ( Garcia-Fonseca et al, 2021 , Hu et al, 2016 , Kumar et al, 2017 , Megret et al, 2022 , Pritchard et al, 2012 ). HD pathogenesis is also associated with miRNA regulation ( Ghose et al, 2011 , Jin et al, 2012 , Marti et al, 2010 ).…”