Advanced analysis and visualization of gene copy number and expression data

BackgroundGene copy number and gene expression values play important roles in cancer initiation and progression. Both can be measured with high-throughput microarrays and some methodologies to integrate and analyze these data exist. However, varying gene sets within different gene expression and copy number microarrays present significant challenges.ResultsWe report an advanced version of earlier published CGH-Plotter that rapidly can identify amplified and deleted areas using gene copy number data. With CGH-Plotter v2, the copy number values can be filtered based on the genomic location in basepair units. After filtering, the values for the missing genes can be interpolated. Moreover, the effect of non-informative areas in the genome can be systematically removed by smoothing and interpolating. Further, we developed a tool (ECN) to illustrate the CGH-data values annotated based on the gene expression. The ECN-tool is a MATLAB toolbox enabling straightforward illustration of copy numbers annotated based on the gene expression levels.ConclusionCGH-Plotter v2 provides two methods for analyzing copy number data; dynamic programming and genomic location based smoothing. With ECN-tool the data analyzed with CGH-Plotter v2 can easily be illustrated along the chromosomes individually or along the whole genome. ECN-tool plots the copy number data annotated based on the gene expression data, and it is easy to find the genes that are both over-expressed and amplified or under-expressed and deleted in the samples. From the resulting figures it is straightforward to select interesting genes.

[1]  M. Ringnér,et al.  Impact of DNA amplification on gene expression patterns in breast cancer. , 2002, Cancer research.

[2]  Jane Fridlyand,et al.  Erratum: "Hidden Markov models approach to the analysis of array CGH data" (Journal of Multivariate Analysis (2004) vol. 90 (132-153) 10.1016/j.jmva.2004.02.008) , 2005 .

[3]  D. Pinkel,et al.  Comparative Genomic Hybridization for Molecular Cytogenetic Analysis of Solid Tumors , 2022 .

[4]  Jaakko Astola,et al.  CGH-Plotter: MATLAB toolbox for CGH-data analysis , 2003, Bioinform..

[5]  Damian Smedley,et al.  Ensembl 2005 , 2004, Nucleic Acids Res..

[6]  Junbai Wang,et al.  M-CGH: Analysing microarray-based CGH experiments , 2004, BMC Bioinformatics.

[7]  Ash A. Alizadeh,et al.  Genome-wide analysis of DNA copy-number changes using cDNA microarrays , 1999, Nature Genetics.

[8]  Wei Chen,et al.  CGHPRO – A comprehensive data analysis tool for array CGH , 2005, BMC Bioinformatics.

[9]  Ajay N. Jain,et al.  Hidden Markov models approach to the analysis of array CGH data , 2004 .

[10]  Sampsa Hautaniemi,et al.  High-resolution genomic and expression profiling reveals 105 putative amplification target genes in pancreatic cancer. , 2004, Neoplasia.

[11]  Ingrid K. Glad,et al.  CGH-Explorer: a program for analysis of array-CGH data , 2005, Bioinform..

[12]  O. Kallioniemi,et al.  Identification of target genes in laryngeal squamous cell carcinoma by high-resolution copy number and gene expression microarray analyses , 2006, Oncogene.

[13]  J. Gray,et al.  Genome changes and gene expression in human solid tumors. , 2000, Carcinogenesis.

[14]  M. Wigler,et al.  Circular binary segmentation for the analysis of array-based DNA copy number data. , 2004, Biostatistics.

[15]  Ash A. Alizadeh,et al.  Genome-wide analysis of DNA copy number variation in breast cancer using DNA microarrays , 1999, Nature Genetics.

[16]  Joaquín Dopazo,et al.  ISACGH: a web-based environment for the analysis of Array CGH and gene expression which includes functional profiling , 2007, Nucleic Acids Res..

[17]  Sami Kilpinen,et al.  High‐resolution copy number and gene expression microarray analyses of head and neck squamous cell carcinoma cell lines of tongue and larynx , 2008, Genes, chromosomes & cancer.

[18]  Elena Marchiori,et al.  Breakpoint identification and smoothing of array comparative genomic hybridization data , 2004, Bioinform..

[19]  Yidong Chen,et al.  High-resolution analysis of gene copy number alterations in human prostate cancer using CGH on cDNA microarrays: impact of copy number on gene expression. , 2004, Neoplasia.