Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease

in Alzheimer's and Dementia: the Journal of the Alzheimer's Association (2016), 12(6), 645-653

Novel drug target identification for the treatment of dementia using multi-relational association mining

in Scientific Reports (2015), 5

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia ... [more ▼]

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia. [less ▲]

Network analysis of neurodegenerative disease highlights a role of toll-like receptor signaling

in BioMed Research International (2014), 2014

Despite significant advances in the study of the molecular mechanisms altered in the development and progression of neurodegenerative diseases (NDs), the etiology is still enigmatic and the distinctions ... [more ▼]

Despite significant advances in the study of the molecular mechanisms altered in the development and progression of neurodegenerative diseases (NDs), the etiology is still enigmatic and the distinctions between diseases are not always entirely clear. We present an efficient computationalmethod based on protein-protein interaction network (PPI) tomodel the functional network of NDs. The aim of this work is fourfold: (i) reconstruction of a PPI network relating to the NDs, (ii) construction of an association network between diseases based on proximity in the disease PPI network, (iii) quantification of disease associations, and (iv) inference of potentialmolecularmechanisminvolved in the diseases.The functional links of diseases not only showed overlap with the traditional classification in clinical settings, but also offered new insight into connections between diseases with limited clinical overlap. To gain an expanded view of the molecular mechanisms involved in NDs, both direct and indirect connector proteins were investigated. The method uncovered molecular relationships that are in common apparently distinct diseases and provided important insight into the molecular networks implicated in disease pathogenesis. In particular, the current analysis highlighted the Toll-like receptor signaling pathway as a potential candidate pathway to be targeted by therapy in neurodegeneration. [less ▲]

Detecting Crosstalk Modules of Combined Networks: the Case for the NF-kappaB and p53

in Proceedings of IEEE International Conference on Bioscience, Biochemistry and Bioinformatics (2011)

Network Inference from Time-Dependent Omics Data

in Bioinformatics for Omics Data Methods in Molecular Biology (2011)