Nearest hyperplane distance neighbor clustering algorithm applied to gene co-expression analysis in Alzheimer's disease

Microarray analysis can contribute considerably to the understanding of biologically significant cellular mechanisms that yield novel information regarding co-regulated sets of gene patterns. Clustering is one of the most popular tools for analyzing DNA microarray data. In this paper, we present an unsupervised clustering algorithm based on the K-local hyperplane distance nearest-neighbor classifier (HKNN). We adapted the well-known nearest neighbor clustering algorithm for use with hyperplane distance. The result is a simple and computationally inexpensive unsupervised clustering algorithm that can be applied to high-dimensional data. It has been reported that the NFkB1 gene is progressively over-expressed in moderate-to-severe Alzheimer's disease (AD) cases, and that the NF-kB complex plays a key role in neuroinflammatory responses in AD pathogenesis. In this study, we apply the proposed clustering algorithm to identify co-expression patterns with the NFkB1 in gene expression data from hippocampal tissue samples. Finally, we validate our experiments with biomedical literature search.

[1]  Aidong Zhang,et al.  Cluster analysis for gene expression data: a survey , 2004, IEEE Transactions on Knowledge and Data Engineering.

[2]  J. Thierry-Mieg,et al.  AceView: a comprehensive cDNA-supported gene and transcripts annotation , 2006, Genome Biology.

[3]  A. Schapira,et al.  Human complex I defects in neurodegenerative diseases. , 1998, Biochimica et biophysica acta.

[4]  M. Tabaton,et al.  Adrenergic Receptors in Aging and Alzheimer's Disease: Increased β2‐Receptors in Prefrontal Cortex and Hippocampus , 1989, Journal of neurochemistry.

[5]  M. Beal,et al.  Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases , 2006, Nature.

[6]  T. Tatusova,et al.  Entrez Gene: gene-centered information at NCBI , 2006, Nucleic Acids Res..

[7]  Hong Yan,et al.  Cluster validity for DNA microarray data using a geometrical index , 2005, 2005 International Conference on Machine Learning and Cybernetics.

[8]  Henrik S Huitfeldt,et al.  Identification and characterization of two putative nuclear localization signals (NLS) in the DNA-binding protein NUCKS. , 2007, Biochimica et biophysica acta.

[9]  Walter J. Lukiw,et al.  Isolation of High Spectral Quality RNA Using Run-on Gene Transcription; Application to Gene Expression Profiling of Human Brain , 2005, Cellular and Molecular Neurobiology.

[10]  Zhengzhi Wang,et al.  Kernel K-Local Hyperplanes for Predicting Protein-Protein Interactions , 2008, 2008 Fourth International Conference on Natural Computation.

[11]  Wolfgang Wurst,et al.  Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer's Disease-Related Genes by In Silico Promoter Analysis and Microarrays , 2011, International journal of Alzheimer's disease.

[12]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[13]  Walter J. Lukiw,et al.  Micro-RNA abundance and stability in human brain: Specific alterations in Alzheimer's disease temporal lobe neocortex , 2009, Neuroscience Letters.

[14]  W. Markesbery,et al.  Incipient Alzheimer's disease: Microarray correlation analyses reveal major transcriptional and tumor suppressor responses , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Yuhai Zhao,et al.  Characterization of an NF-kappaB-regulated, miRNA-146a-mediated down-regulation of complement factor H (CFH) in metal-sulfate-stressed human brain cells. , 2009, Journal of inorganic biochemistry.

[16]  Loris Nanni,et al.  An ensemble of K-local hyperplanes for predicting protein-protein interactions , 2006, Bioinform..

[17]  David A Bennett,et al.  Parkinsonianlike signs and risk of incident Alzheimer disease in older persons. , 2003, Archives of neurology.

[18]  O. G. Okun K-local hyperplane distance nearest-neighbor algorithm and protein fold recognition , 2006, Pattern Recognition and Image Analysis.

[19]  A. Leiter,et al.  Novel Transcriptional Potentiation of BETA2/NeuroD on the Secretin Gene Promoter by the DNA-Binding Protein Finb/RREB-1 , 2003, Molecular and Cellular Biology.

[20]  L. Sazanov,et al.  Respiratory complex I: mechanistic and structural insights provided by the crystal structure of the hydrophilic domain. , 2007, Biochemistry.

[21]  N. Bazan,et al.  Strong nuclear factor‐κB‐DNA binding parallels cyclooxygenase‐2 gene transcription in aging and in sporadic alzheimer's disease superior temporal lobe neocortex , 1998, Journal of neuroscience research.

[22]  Alex E. Lash,et al.  Gene Expression Omnibus: NCBI gene expression and hybridization array data repository , 2002, Nucleic Acids Res..

[23]  Yuhai Zhao,et al.  Differential Regulation of Interleukin-1 Receptor-associated Kinase-1 (IRAK-1) and IRAK-2 by MicroRNA-146a and NF-κB in Stressed Human Astroglial Cells and in Alzheimer Disease* , 2010, The Journal of Biological Chemistry.

[24]  Pascal Vincent,et al.  K-Local Hyperplane and Convex Distance Nearest Neighbor Algorithms , 2001, NIPS.

[25]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[26]  Yusuke Nakamura,et al.  Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease , 2009, Nature Genetics.

[27]  Walter J. Lukiw,et al.  An NF-κB-sensitive Micro RNA-146a-mediated Inflammatory Circuit in Alzheimer Disease and in Stressed Human Brain Cells* , 2008, Journal of Biological Chemistry.

[28]  W. Lukiw,et al.  Micro-RNA speciation in fetal, adult and Alzheimer's disease hippocampus , 2007, Neuroreport.