Gene Expression Biomarkers in the Brain of a Mouse Model for Alzheimer's Disease: Mining of Microarray Data by Logic Classification and Feature Selection

Article type: Research Article

Authors: Arisi, Ivan^a | D'Onofrio, Mara^a | Brandi, Rossella^a | Felsani, Armando^{b; c} | Capsoni, Simona^{d; g} | Drovandi, Guido^{e; f} | Felici, Giovanni^e | Weitschek, Emanuel^{e; f} | Bertolazzi, Paola^e | Cattaneo, Antonino^{d; g; *}

Affiliations: [a] European Brain Research Institute (EBRI) “Rita Levi-Montalcini”, Italian Institute of Technology Neurogenomics Unit, Roma, Italy | [b] Istituto di Neurobiologia e Medicina Molecolare, CNR, Roma, Italy | [c] Genomnia, Lainate, Milano, Italy | [d] Scuola Normale Superiore, Piazza dei Cavalieri, Pisa, Italy | [e] Istituto di Analisi dei Sistemi ed Informatica “Antonio Ruberti”, Roma, Italy | [f] Università degli Studi Roma Tre, Roma, Italy | [g] European Brain Research Institute (EBRI) “Rita Levi-Montalcini”, Neurotrophic Factors and Neurodegenerative Diseases Unit, Roma, Italy

Correspondence: [*] Correspondence to: Prof. Antonino Cattaneo, European Brain Research Institute (EBRI) “Rita Levi-Montalcini”, Neurotrophic Factors and Neurodenerative Diseases Unit, Via del Fosso di Fiorano 64/65, 00143 Roma, Italy. Tel.: +39 06 501703110; Fax: +39 06 501703335; E-mail: [email protected].

Abstract: The identification of early and stage-specific biomarkers for Alzheimer's disease (AD) is critical, as the development of disease-modification therapies may depend on the discovery and validation of such markers. The identification of early reliable biomarkers depends on the development of new diagnostic algorithms to computationally exploit the information in large biological datasets. To identify potential biomarkers from mRNA expression profile data, we used the Logic Mining method for the unbiased analysis of a large microarray expression dataset from the anti-NGF AD11 transgenic mouse model. The gene expression profile of AD11 brain regions was investigated at different neurodegeneration stages by whole genome microarrays. A new implementation of the Logic Mining method was applied both to early (1–3 months) and late stage (6–15 months) expression data, coupled to standard statistical methods. A small number of “fingerprinting” formulas was isolated, encompassing mRNAs whose expression levels were able to discriminate between diseased and control mice. We selected three differential “signature” genes specific for the early stage (Nudt19, Arl16, Aph1b), five common to both groups (Slc15a2, Agpat5, Sox2ot, 2210015, D19Rik, Wdfy1), and seven specific for late stage (D14Ertd449, Tia1, Txnl4, 1810014B01Rik, Snhg3, Actl6a, Rnf25). We suggest these genes as potential biomarkers for the early and late stage of AD-like neurodegeneration in this model and conclude that Logic Mining is a powerful and reliable approach for large scale expression data analysis. Its application to large expression datasets from brain or peripheral human samples may facilitate the discovery of early and stage-specific AD biomarkers.

Keywords: Alzheimer's disease, biomarkers, data mining, gene expression, microarray, mouse models, nerve growth factor, statistical data interpretation

DOI: 10.3233/JAD-2011-101881

Journal: Journal of Alzheimer's Disease, vol. 24, no. 4, pp. 721-738, 2011