Publications

Abstract not available (Letter to the Editor)

Background: Amyotrophic lateral sclerosis (ALS) is a rare progressive neurodegenerative disease that affects upper and lower motor neurons. As the molecular basis of the disease is still elusive, the development of high-throughput sequencing technologies, combined with data mining techniques and machine learning methods, could provide remarkable results in identifying pathogenetic mechanisms. High dimensionality is a major problem when applying machine learning techniques in biomedical data analysis, since a huge number of features is available for a limited number of samples. The aim of this study was to develop a methodology for training interpretable machine learning models in the classification of ALS and ALS-subtypes samples, using gene expression datasets.

Bacterial lipopolysaccharide (LPS) induces a multi-organ, Toll-like receptor 4 (TLR4)-dependent acute inflammatory response. Using network analysis, the spatiotemporal dynamics of 20 LPS-induced protein-level inflammatory mediators over 0-48 hours were defined in the heart, gut, lung, liver, spleen, kidney, and systemic circulation in both wild-type and TLR4-null mice. Dynamic Network Analysis suggested that inflammation in the heart is most dependent on TLR4, followed by the liver, kidney, plasma, gut, lung, and spleen. Insights from computational analyses suggest an early role for TLR4-dependent tumor necrosis factor in coordinating multiple signaling pathways in the heart, giving way to later interleukin-17A (possibly derived from pathogenic Th17 cells and effector/memory T cells) in the spleen and blood.