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In Frontiers in neuroscience ; h5-index 72.0

Agglomerative hierarchical clustering analysis (HCA) is a commonly used unsupervised machine learning approach for identifying informative natural clusters of observations. HCA is performed by calculating a pairwise dissimilarity matrix and then clustering similar observations until all observations are grouped within a cluster. Verifying the empirical clusters produced by HCA is complex and not well studied in biomedical applications. Here, we demonstrate the comparability of a novel HCA technique with one that was used in previous biomedical applications while applying both techniques to plasma angiogenic (FGF, FLT, PIGF, Tie-2, VEGF, VEGF-D) and inflammatory (MMP1, MMP3, MMP9, IL8, TNFα) protein data to identify informative subsets of individuals. Study subjects were diagnosed with mild cognitive impairment due to cerebrovascular disease (MCI-CVD). Through comparison of the two HCA techniques, we were able to identify subsets of individuals, based on differences in VEGF (p < 0.001), MMP1 (p < 0.001), and IL8 (p < 0.001) levels. These profiles provide novel insights into angiogenic and inflammatory pathologies that may contribute to VCID.

Winder Zachary, Sudduth Tiffany L, Fardo David, Cheng Qiang, Goldstein Larry B, Nelson Peter T, Schmitt Frederick A, Jicha Gregory A, Wilcock Donna M


IL8, MMP1, VEGF, hierarchical clustering analysis, mild cognitive impairment, vascular cognitive impairment and dementia