CGHPRO – A comprehensive data analysis tool for array CGH

BackgroundArray CGH (Comparative Genomic Hybridisation) is a molecular cytogenetic technique for the genome wide detection of chromosomal imbalances. It is based on the co-hybridisation of differentially labelled test and reference DNA onto arrays of genomic BAC clones, cDNAs or oligonucleotides, and after correction for various intervening variables, loss or gain in the test DNA can be indicated from spots showing aberrant signal intensity ratios.Now that this technique is no longer confined to highly specialized laboratories and is entering the realm of clinical application, there is a need for a user-friendly software package that facilitates estimates of DNA dosage from raw signal intensities obtained by array CGH experiments, and which does not depend on a sophisticated computational environment.ResultsWe have developed a user-friendly and versatile tool for the normalization, visualization, breakpoint detection and comparative analysis of array-CGH data. CGHPRO is a stand-alone JAVA application that guides the user through the whole process of data analysis. The import option for image analysis data covers several data formats, but users can also customize their own data formats. Several graphical representation tools assist in the selection of the appropriate normalization method. Intensity ratios of each clone can be plotted in a size-dependent manner along the chromosome ideograms. The interactive graphical interface offers the chance to explore the characteristics of each clone, such as the involvement of the clones sequence in segmental duplications. Circular Binary Segmentation and unsupervised Hidden Markov Model algorithms facilitate objective detection of chromosomal breakpoints. The storage of all essential data in a back-end database allows the simultaneously comparative analysis of different cases. The various display options facilitate also the definition of shortest regions of overlap and simplify the identification of odd clones.ConclusionCGHPRO is a comprehensive and easy-to-use data analysis tool for array CGH. Since all of its features are available offline, CGHPRO may be especially suitable in situations where protection of sensitive patient data is an issue. It is distributed under GNU GPL licence and runs on Linux and Windows.

[1]  M. Adams,et al.  Recent Segmental Duplications in the Human Genome , 2002, Science.

[2]  Jason E. Stewart,et al.  Minimum information about a microarray experiment (MIAME)—toward standards for microarray data , 2001, Nature Genetics.

[3]  P. Stankiewicz,et al.  Genome architecture, rearrangements and genomic disorders. , 2002, Trends in genetics : TIG.

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

[5]  Sarah Barber,et al.  A set of BAC clones spanning the human genome. , 2004, Nucleic acids research.

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

[7]  W. Cleveland.  Robust Locally Weighted Regression and Smoothing Scatterplots , 1979 .

[8]  P. D. de Jong,et al.  A bacterial artificial chromosome library for sequencing the complete human genome. , 2001, Genome research.

[9]  E. Eichler,et al.  BAC microarray analysis of 15q11–q13 rearrangements and the impact of segmental duplications , 2004, Journal of Medical Genetics.

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

[11]  N. Carter,et al.  DNA microarrays for comparative genomic hybridization based on DOP‐PCR amplification of BAC and PAC clones , 2003, Genes, chromosomes & cancer.

[12]  W. Kuo,et al.  High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays , 1998, Nature Genetics.

[13]  H. Döhner,et al.  Matrix‐based comparative genomic hybridization: Biochips to screen for genomic imbalances , 1997, Genes, chromosomes & cancer.

[14]  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 .

[15]  김삼묘,et al.  “Bioinformatics” 특집을 내면서 , 2000 .

[16]  Bradley P. Coe,et al.  A tiling resolution DNA microarray with complete coverage of the human genome , 2004, Nature Genetics.

[17]  Calum MacAulay,et al.  SeeGH – A software tool for visualization of whole genome array comparative genomic hybridization data , 2004, BMC Bioinformatics.

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

[19]  S. Dudoit,et al.  Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. , 2002, Nucleic acids research.