CONSERTING: integrating copy-number analysis with structural-variation detection.
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ABSTRACT:
SUBMITTER: Chen X
PROVIDER: S-EPMC4591043 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Publications
CONSERTING: integrating copy-number analysis with structural-variation detection.
Chen Xiang X Gupta Pankaj P Wang Jianmin J Nakitandwe Joy J Roberts Kathryn K Dalton James D JD Parker Matthew M Patel Samir S Holmfeldt Linda L Payne Debbie D Easton John J Ma Jing J Rusch Michael M Wu Gang G Patel Aman A Baker Suzanne J SJ Dyer Michael A MA Shurtleff Sheila S Espy Stephen S Pounds Stanley S Downing James R JR Ellison David W DW Mullighan Charles G CG Zhang Jinghui J
Nature methods 20150504 6
We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex re ...[more]
Similar Datasets
Project description:We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), a novel algorithm for detecting somatic copy number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation by read depth change and localized structural variation detection to achieve high accuracy and sensitivity. Analysis of 43 pediatric and adult cancer genomes revealed novel oncogenic CNAs, complex re-arrangements and subclonal CNAs missed by alternative approaches. This study contains all data for "CONSERTING: an accurate method for detecting somatic DNA copy number alterations in whole genome sequencing data", which was previously split between EGAS00001001202 and EGAS00001001050.
| EGAS00001001202 | EGA
Project description:Next-generation sequencing (NGS) technologies offer new opportunities for precise and accurate identification of genomic aberrations, including copy number variations (CNVs). For high-throughput NGS data, using depth of coverage has become a major approach to identify CNVs, especially for whole exome sequencing (WES) data. Due to the high level of noise and biases of read-count data and complexity of the WES data, existing CNV detection tools identify many false CNV segments. Besides, NGS generates a huge amount of data, requiring to use effective and efficient methods. In this work, we propose a novel segmentation algorithm based on the total variation approach to detect CNVs more precisely and efficiently using WES data. The proposed method also filters out outlier read-counts and identifies significant change points to reduce false positives. We used real and simulated data to evaluate the performance of the proposed method and compare its performance with those of other commonly used CNV detection methods. Using simulated and real data, we show that the proposed method outperforms the existing CNV detection methods in terms of accuracy and false discovery rate and has a faster runtime compared to the circular binary segmentation method.
| S-EPMC7278034 | biostudies-literature
Project description:Detection of chromosomal aberrations from a single cell by array comparative genomic hybridization (single-cell array CGH), instead of from a population of cells, is an emerging technique. However, such detection is challenging because of the genome artifacts and the DNA amplification process inherent to the single cell approach. Current normalization algorithms result in inaccurate aberration detection for single-cell data. We propose a normalization method based on channel, genome composition and recurrent genome artifact corrections. We demonstrate that the proposed channel clone normalization significantly improves the copy number variation detection in both simulated and real single-cell array CGH data.
| S-EPMC3245619 | biostudies-literature
Project description:BackgroundArray-based detection of copy number variations (CNVs) is widely used for identifying disease-specific genetic variations. However, the accuracy of CNV detection is not sufficient and results differ depending on the detection programs used and their parameters. In this study, we evaluated five widely used CNV detection programs, Birdsuite (mainly consisting of the Birdseye and Canary modules), Birdseye (part of Birdsuite), PennCNV, CGHseg, and DNAcopy from the viewpoint of performance on the Affymetrix platform using HapMap data and other experimental data. Furthermore, we identified CNVs of 180 healthy Japanese individuals using parameters that showed the best performance in the HapMap data and investigated their characteristics.ResultsThe results indicate that Hidden Markov model-based programs PennCNV and Birdseye (part of Birdsuite), or Birdsuite show better detection performance than other programs when the high reproducibility rates of the same individuals and the low Mendelian inconsistencies are considered. Furthermore, when rates of overlap with other experimental results were taken into account, Birdsuite showed the best performance from the view point of sensitivity but was expected to include many false negatives and some false positives. The results of 180 healthy Japanese demonstrate that the ratio containing repeat sequences, not only segmental repeats but also long interspersed nuclear element (LINE) sequences both in the start and end regions of the CNVs, is higher in CNVs that are commonly detected among multiple individuals than that in randomly selected regions, and the conservation score based on primates is lower in these regions than in randomly selected regions. Similar tendencies were observed in HapMap data and other experimental data.ConclusionsOur results suggest that not only segmental repeats but also interspersed repeats, especially LINE sequences, are deeply involved in CNVs, particularly in common CNV formations.The detected CNVs are stored in the CNV repository database newly constructed by the "Japanese integrated database project" for sharing data among researchers. http://gwas.lifesciencedb.jp/cgi-bin/cnvdb/cnv_top.cgi.
| S-EPMC3058066 | biostudies-literature
Project description:Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by an abnormal copy number variation (CNV) with a trisomy of chromosome 17p12. The increase of the DNA-segment copy number is expected to alter the allele frequency of single nucleotide polymorphism (SNP) within the duplicated region. We tested whether SNP allele frequency determined by a Sequenom MassArray can be used to detect the CMT1A mutation. Our results revealed distinct patterns of SNP allele frequency distribution, which reliably differentiated CMT1A patients from controls. This finding suggests that this technique may serve as an alternative approach to identifying CNV in certain diseases, including CMT1A.
| S-EPMC4254366 | biostudies-literature
Project description:Copy number variations (CNVs) are gain and loss of DNA sequence of a genome. High throughput platforms such as microarrays and next generation sequencing technologies (NGS) have been applied for genome wide copy number losses. Although progress has been made in both approaches, the accuracy and consistency of CNV calling from the two platforms remain in dispute. In this study, we perform a deep analysis on copy number losses on 254 human DNA samples, which have both SNP microarray data and NGS data publicly available from Hapmap Project and 1000 Genomes Project respectively. We show that the copy number losses reported from Hapmap Project and 1000 Genome Project only have < 30% overlap, while these reports are required to have cross-platform (e.g. PCR, microarray and high-throughput sequencing) experimental supporting by their corresponding projects, even though state-of-art calling methods were employed. On the other hand, copy number losses are found directly from HapMap microarray data by an accurate algorithm, i.e. CNVhac, almost all of which have lower read mapping depth in NGS data; furthermore, 88% of which can be supported by the sequences with breakpoint in NGS data. Our results suggest the ability of microarray calling CNVs and the possible introduction of false negatives from the unessential requirement of the additional cross-platform supporting. The inconsistency of CNV reports from Hapmap Project and 1000 Genomes Project might result from the inadequate information containing in microarray data, the inconsistent detection criteria, or the filtration effect of cross-platform supporting. The statistical test on CNVs called from CNVhac show that the microarray data can offer reliable CNV reports, and majority of CNV candidates can be confirmed by raw sequences. Therefore, the CNV candidates given by a good caller could be highly reliable without cross-platform supporting, so additional experimental information should be applied in need instead of necessarily.
| S-EPMC5922522 | biostudies-literature
Project description:Complex somatic genomic rearrangements and copy number alterations are hallmarks of nearly all cancers. We have developed an algorithm, LINX, to aid interpretation of structural variant and copy number data derived from short-read, whole-genome sequencing. LINX classifies raw structural variant calls into distinct events and predicts their effect on the local structure of the derivative chromosome and the functional impact on affected genes. Visualizations facilitate further investigation of complex rearrangements. LINX allows insights into a diverse range of structural variation events and can reliably detect pathogenic rearrangements, including gene fusions, immunoglobulin enhancer rearrangements, intragenic deletions, and duplications. Uniquely, LINX also predicts chained fusions that we demonstrate account for 13% of clinically relevant oncogenic fusions. LINX also reports a class of inactivation events that we term homozygous disruptions that may be a driver mutation in up to 9% of tumors and may frequently affect PTEN, TP53, and RB1.
| S-EPMC9903802 | biostudies-literature
Project description:Copy number variants (CNVs) are increasingly acknowledged as an important source of evolutionary novelties in the human lineage. However, our understanding of their significance is still hindered by the lack of primate CNV data. We performed intraspecific comparative genomic hybridizations to identify loci harboring copy number variants in each of the four great apes: bonobos, chimpanzees, gorillas, and orangutans. For the first time, we could analyze differences in CNV location and frequency in these four species, and compare them with human CNVs and primate segmental duplication (SD) maps. In addition, for bonobo and gorilla, patterns of CNV and nucleotide diversity were studied in the same individuals. We show that CNVs have been subject to different selective pressures in different lineages. Evidence for purifying selection is stronger in gorilla CNVs overlapping genes, while positive selection appears to have driven the fixation of structural variants in the orangutan lineage. In contrast, chimpanzees and bonobos present high levels of common structural polymorphism, which is indicative of relaxed purifying selection together with the higher mutation rates induced by the known burst of segmental duplication in the ancestor of the African apes. Indeed, the impact of the duplication burst is noticeable by the fact that bonobo and chimpanzee share more CNVs with gorilla than expected. Finally, we identified a number of interesting genomic regions that present high-frequency CNVs in all great apes, while containing only very rare or even pathogenic structural variants in humans.
| S-EPMC3202280 | biostudies-literature
Project description:The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We provide a bioinformatic analysis of copy number variation and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We individually examined the copy number variation and DNA methylation for 44 primary ovarian cancer samples and 7 ovarian normal samples using our MOMA-ROMA technology and Affymetrix expression data as well as 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with significantly altered copy number and correlated changes in expression. We identify changes in DNA methylation and expression for all amplified and deleted genes. We predicted 615 potential oncogenes and tumor suppressors candidates by integrating these multiple genomic and epigenetic data types. This ROMA experiment was performed on Ovarian Tumor samples using the same platform as previously reported by Navin, N. et. al. Genome Res. 2010 Jan;20(1):68-80 (PMID: 19903760). Analysis of the array data was performed as previously reported in Chen, S. et. al. Cancer Biol Ther. 2008 Nov;7(11):1793-802. (PMID: 18836286 ).
2011-10-17 | GSE28013 | GEO
Project description:The analysis of structural variants, in particular of copy-number variations (CNVs), has proven valuable in unraveling the genetic basis of human diseases. Hence, a large number of algorithms have been developed for the detection of CNVs in SNP array signal intensity data. Using the European and African HapMap trio data, we undertook a comparative evaluation of six commonly used CNV detection software tools, namely Affymetrix Power Tools (APT), QuantiSNP, PennCNV, GLAD, R-gada and VEGA, and assessed their level of pair-wise prediction concordance. The tool-specific CNV prediction accuracy was assessed in silico by way of intra-familial validation. Software tools differed greatly in terms of the number and length of the CNVs predicted as well as the number of markers included in a CNV. All software tools predicted substantially more deletions than duplications. Intra-familial validation revealed consistently low levels of prediction accuracy as measured by the proportion of validated CNVs (34-60%). Moreover, up to 20% of apparent family-based validations were found to be due to chance alone. Software using Hidden Markov models (HMM) showed a trend to predict fewer CNVs than segmentation-based algorithms albeit with greater validity. PennCNV yielded the highest prediction accuracy (60.9%). Finally, the pairwise concordance of CNV prediction was found to vary widely with the software tools involved. We recommend HMM-based software, in particular PennCNV, rather than segmentation-based algorithms when validity is the primary concern of CNV detection. QuantiSNP may be used as an additional tool to detect sets of CNVs not detectable by the other tools. Our study also reemphasizes the need for laboratory-based validation, such as qPCR, of CNVs predicted in silico.
| S-EPMC4510559 | biostudies-literature