A computational procedure for functional characterization of potential marker genes from molecular data: Alzheimer's as a case study

For each dataset we identified a signature that was successively evaluated both from the computational and functional characterization viewpoints, estimating the classification error and retrieving the most relevant biological knowledge from different repositories. Each signature includes genes already known to be related to AD and genes that are likely to be involved in the pathogenesis or in the disease progression. The integrated analysis revealed a meaningful overlap at the functional level.The identification of three gene signatures showing a relevant overlap of pathways and ontologies, increases the likelihood of finding potential marker genes for AD.Alzheimer's Disease (AD) is a common progressive brain disease generally diagnosed in individuals over 65 years of age and it is mostly characterized by cognition deterioration that causes dementia [1]. Within 3 to 9 years after diagnosis, it usually leads to death.From the molecular point of view, AD is characterized by many different lesions: the most evident are deposits of beta amyloid and tangles of hyperphosphorylated tau proteins, together with a marked loss of neurons in the neocortex and hippocampus [2,3]. In the early stages, the most common symptom is memory loss, followed by mood swings, difficult in speech, long-memory loss and confusion. Several characteristics of AD are common to normal aging or to other neurological diseases, making its diagnosis very difficult. Usually, psycho-logical tests are used to indicate the presence of the disease, but only a post-mortem exam can confirm it. The diagnostic process is time-consuming and, by the time AD is detected, the disease has been progressing for many years, causing increased brain damages along with the deterioration of cognitive capacities. For these reasons, AD patients need constant care from their relatives or from specialized structures. Clearly, this phenomenon has a relevant economical impact on the national health systems.Although many scienti