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A high-throughput computational framework for identifying significant copy number aberrations from array comparative genomic hybridisation data.

ABSTRACT: Reliable identification of copy number aberrations (CNA) from comparative genomic hybridization data would be improved by the availability of a generalised method for processing large datasets. To this end, we developed swatCGH, a data analysis framework and region detection heuristic for computational grids. swatCGH analyses sequentially displaced (sliding) windows of neighbouring probes and applies adaptive thresholds of varying stringency to identify the 10% of each chromosome that contains the most frequently occurring CNAs. We used the method to analyse a published dataset, comparing data preprocessed using four different DNA segmentation algorithms, and two methods for prioritising the detected CNAs. The consolidated list of the most commonly detected aberrations confirmed the value of swatCGH as a simplified high-throughput method for identifying biologically significant CNA regions of interest.

SUBMITTER: Roberts I

PROVIDER: S-EPMC3449101 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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A high-throughput computational framework for identifying significant copy number aberrations from array comparative genomic hybridisation data.

Roberts Ian I Carter Stephanie A SA Scarpini Cinzia G CG Karagavriilidou Konstantina K Barna Jenny C J JC Calleja Mark M Coleman Nicholas N

Advances in bioinformatics 20120913

Reliable identification of copy number aberrations (CNA) from comparative genomic hybridization data would be improved by the availability of a generalised method for processing large datasets. To this end, we developed swatCGH, a data analysis framework and region detection heuristic for computational grids. swatCGH analyses sequentially displaced (sliding) windows of neighbouring probes and applies adaptive thresholds of varying stringency to identify the 10% of each chromosome that contains t ...[more]

PMID: 23008709

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Project description:Structural variants which cause changes in copy numbers constitute an important component of genomic variability. They account for 0.7% of genomic differences in two individual genomes, of which copy number variants (CNVs) are the largest component. A recent population-based CNV study revealed the need of better characterization of CNVs, especially the small ones (<500 bp).We propose a three step computational framework (Identification of germline Changes in Copy Number or IgC2N) to discover and genotype germline CNVs. First, we detect candidate CNV loci by combining information across multiple samples without imposing restrictions to the number of coverage markers or to the variant size. Secondly, we fine tune the detection of rare variants and infer the putative copy number classes for each locus. Last, for each variant we combine the relative distance between consecutive copy number classes with genetic information in a novel attempt to estimate the reference model bias. This computational approach is applied to genome-wide data from 1250 HapMap individuals. Novel variants were discovered and characterized in terms of size, minor allele frequency, type of polymorphism (gains, losses or both), and mechanism of formation. Using data generated for a subset of individuals by a 42 million marker platform, we validated the majority of the variants with the highest validation rate (66.7%) was for variants of size larger than 1 kb. Finally, we queried transcriptomic data from 129 individuals determined by RNA-sequencing as further validation and to assess the functional role of the new variants. We investigated the possible enrichment for variant's regulatory effect and found that smaller variants (<1 Kb) are more likely to regulate gene transcript than larger variants (p-value = 2.04e-08). Our results support the validity of the computational framework to detect novel variants relevant to disease susceptibility studies and provide evidence of the importance of genetic variants in regulatory network studies.

Dataset Information

A high-throughput computational framework for identifying significant copy number aberrations from array comparative genomic hybridisation data.

Publications

A high-throughput computational framework for identifying significant copy number aberrations from array comparative genomic hybridisation data.

Similar Datasets

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