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SIGMA2: a system for the integrative genomic multi-dimensional analysis of cancer genomes, epigenomes, and transcriptomes.

Chari R, Coe BP, Wedseltoft C, Benetti M, Wilson IM, Vucic EA, MacAulay C, Ng RT, Lam WL - BMC Bioinformatics (2008)

Bottom Line: However, software packages to handle, analyze, and visualize data from these multiple 'omics disciplines have not been adequately developed.Multi-dimensional datasets can be simultaneously visualized and analyzed with respect to each dimension, allowing combinatorial integration of the different assays belonging to the different 'omics.The identification of genes altered at multiple levels such as copy number, loss of heterozygosity (LOH), DNA methylation and the detection of consequential changes in gene expression can be concertedly performed, establishing SIGMA2 as a novel tool to facilitate the high throughput systems biology analysis of cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cancer Genetics and Developmental Biology, BC Cancer Agency Research Centre, Vancouver, BC, Canada. rchari@bccrc.ca

ABSTRACT

Background: High throughput microarray technologies have afforded the investigation of genomes, epigenomes, and transcriptomes at unprecedented resolution. However, software packages to handle, analyze, and visualize data from these multiple 'omics disciplines have not been adequately developed.

Results: Here, we present SIGMA2, a system for the integrative genomic multi-dimensional analysis of cancer genomes, epigenomes, and transcriptomes. Multi-dimensional datasets can be simultaneously visualized and analyzed with respect to each dimension, allowing combinatorial integration of the different assays belonging to the different 'omics.

Conclusion: The identification of genes altered at multiple levels such as copy number, loss of heterozygosity (LOH), DNA methylation and the detection of consequential changes in gene expression can be concertedly performed, establishing SIGMA2 as a novel tool to facilitate the high throughput systems biology analysis of cancer.

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Related in: MedlinePlus

Parallel visualization and analysis of the copy number and genotype profiles of the breast cancer cell line HCC2218. Genotype profile of the matching normal blood lymphoblast line (HCC2218BL) is also provided to define regions of LOH. DNA copy number profile was generated on the BCCA whole genome tiling path BAC array and genotype profiles are from the Affymetrix SNP 10K array [28]. This region of chromosome arm 3q has a defined segmental copy number loss and the boundary of the change is evident from the LOH profile. In the genotype profile, the horizontal blue lines indicate a SNP transition from heterozygous in normal to homozygous in the tumor, indicating LOH.
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Figure 6: Parallel visualization and analysis of the copy number and genotype profiles of the breast cancer cell line HCC2218. Genotype profile of the matching normal blood lymphoblast line (HCC2218BL) is also provided to define regions of LOH. DNA copy number profile was generated on the BCCA whole genome tiling path BAC array and genotype profiles are from the Affymetrix SNP 10K array [28]. This region of chromosome arm 3q has a defined segmental copy number loss and the boundary of the change is evident from the LOH profile. In the genotype profile, the horizontal blue lines indicate a SNP transition from heterozygous in normal to homozygous in the tumor, indicating LOH.

Mentions: Within a given 'omics dimension, multiple assay types can be analyzed in combination. For example, it is useful to investigate copy number and LOH and the interplay between DNA methylation and different states of histone modification. Typically, in regions of copy number loss, LOH is also observed. However, LOH can also occur in regions which are copy number neutral, indicating a change in allelic status which is not interpretable by one dimension alone. Here, we show a sample for which copy number and LOH information exists, a region of copy number loss associated with LOH (Figure 6). In terms of epigenetics, DNA methylation and states of histone methylation and acetylation have been known to be biologically relevant. With high throughput technologies available to assay these dimensions, this type of analysis will become more prevalent.


SIGMA2: a system for the integrative genomic multi-dimensional analysis of cancer genomes, epigenomes, and transcriptomes.

Chari R, Coe BP, Wedseltoft C, Benetti M, Wilson IM, Vucic EA, MacAulay C, Ng RT, Lam WL - BMC Bioinformatics (2008)

Parallel visualization and analysis of the copy number and genotype profiles of the breast cancer cell line HCC2218. Genotype profile of the matching normal blood lymphoblast line (HCC2218BL) is also provided to define regions of LOH. DNA copy number profile was generated on the BCCA whole genome tiling path BAC array and genotype profiles are from the Affymetrix SNP 10K array [28]. This region of chromosome arm 3q has a defined segmental copy number loss and the boundary of the change is evident from the LOH profile. In the genotype profile, the horizontal blue lines indicate a SNP transition from heterozygous in normal to homozygous in the tumor, indicating LOH.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2571113&req=5

Figure 6: Parallel visualization and analysis of the copy number and genotype profiles of the breast cancer cell line HCC2218. Genotype profile of the matching normal blood lymphoblast line (HCC2218BL) is also provided to define regions of LOH. DNA copy number profile was generated on the BCCA whole genome tiling path BAC array and genotype profiles are from the Affymetrix SNP 10K array [28]. This region of chromosome arm 3q has a defined segmental copy number loss and the boundary of the change is evident from the LOH profile. In the genotype profile, the horizontal blue lines indicate a SNP transition from heterozygous in normal to homozygous in the tumor, indicating LOH.
Mentions: Within a given 'omics dimension, multiple assay types can be analyzed in combination. For example, it is useful to investigate copy number and LOH and the interplay between DNA methylation and different states of histone modification. Typically, in regions of copy number loss, LOH is also observed. However, LOH can also occur in regions which are copy number neutral, indicating a change in allelic status which is not interpretable by one dimension alone. Here, we show a sample for which copy number and LOH information exists, a region of copy number loss associated with LOH (Figure 6). In terms of epigenetics, DNA methylation and states of histone methylation and acetylation have been known to be biologically relevant. With high throughput technologies available to assay these dimensions, this type of analysis will become more prevalent.

Bottom Line: However, software packages to handle, analyze, and visualize data from these multiple 'omics disciplines have not been adequately developed.Multi-dimensional datasets can be simultaneously visualized and analyzed with respect to each dimension, allowing combinatorial integration of the different assays belonging to the different 'omics.The identification of genes altered at multiple levels such as copy number, loss of heterozygosity (LOH), DNA methylation and the detection of consequential changes in gene expression can be concertedly performed, establishing SIGMA2 as a novel tool to facilitate the high throughput systems biology analysis of cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cancer Genetics and Developmental Biology, BC Cancer Agency Research Centre, Vancouver, BC, Canada. rchari@bccrc.ca

ABSTRACT

Background: High throughput microarray technologies have afforded the investigation of genomes, epigenomes, and transcriptomes at unprecedented resolution. However, software packages to handle, analyze, and visualize data from these multiple 'omics disciplines have not been adequately developed.

Results: Here, we present SIGMA2, a system for the integrative genomic multi-dimensional analysis of cancer genomes, epigenomes, and transcriptomes. Multi-dimensional datasets can be simultaneously visualized and analyzed with respect to each dimension, allowing combinatorial integration of the different assays belonging to the different 'omics.

Conclusion: The identification of genes altered at multiple levels such as copy number, loss of heterozygosity (LOH), DNA methylation and the detection of consequential changes in gene expression can be concertedly performed, establishing SIGMA2 as a novel tool to facilitate the high throughput systems biology analysis of cancer.

Show MeSH
Related in: MedlinePlus