A probe-density-based analysis method for array CGH data: simulation, normalization and centralization

Chen, Hung-I Harry; Hsu, Fu-Chieh; Jiang, Yuan; Tsai, Mong-Hsun; Meltzer, Paul S.; Chuang, Eric Y.; Chen, Yidong

doi:10.1093/bioinformatics/btn321

Cited by 22 publications

(9 citation statements)

References 31 publications

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“…We considered whether this was due to the normalization protocol and subsequent segmentation analysis. Using technical replicates of LAU-Me275 DNA, we tested three independent normalization schemes, two of which were specifically developed for cancer genome analysis (see Materials and Methods ) and found that the methodology proposed by Chen and colleagues [15] was the most reproducible (Spearman correlation 0.96; see Fig. S2 ).…”

Section: Resultsmentioning

confidence: 99%

Network-Guided Analysis of Genes with Altered Somatic Copy Number and Gene Expression Reveals Pathways Commonly Perturbed in Metastatic Melanoma

et al. 2011

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Cancer genomes frequently contain somatic copy number alterations (SCNA) that can significantly perturb the expression level of affected genes and thus disrupt pathways controlling normal growth. In melanoma, many studies have focussed on the copy number and gene expression levels of the BRAF, PTEN and MITF genes, but little has been done to identify new genes using these parameters at the genome-wide scale. Using karyotyping, SNP and CGH arrays, and RNA-seq, we have identified SCNA affecting gene expression (‘SCNA-genes’) in seven human metastatic melanoma cell lines. We showed that the combination of these techniques is useful to identify candidate genes potentially involved in tumorigenesis. Since few of these alterations were recurrent across our samples, we used a protein network-guided approach to determine whether any pathways were enriched in SCNA-genes in one or more samples. From this unbiased genome-wide analysis, we identified 28 significantly enriched pathway modules. Comparison with two large, independent melanoma SCNA datasets showed less than 10% overlap at the individual gene level, but network-guided analysis revealed 66% shared pathways, including all but three of the pathways identified in our data. Frequently altered pathways included WNT, cadherin signalling, angiogenesis and melanogenesis. Additionally, our results emphasize the potential of the EPHA3 and FRS2 gene products, involved in angiogenesis and migration, as possible therapeutic targets in melanoma. Our study demonstrates the utility of network-guided approaches, for both large and small datasets, to identify pathways recurrently perturbed in cancer.

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Section: Resultsmentioning

confidence: 99%

Network-Guided Analysis of Genes with Altered Somatic Copy Number and Gene Expression Reveals Pathways Commonly Perturbed in Metastatic Melanoma

et al. 2011

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“…The log 2 ratio value of each averaged replicate probe was then modified in order to shift the main peak of each hybridization reaction to center around zero. The method, modified from Chen et al (11), was performed to further reduce the effects of hybridization efficiency variation on the data set.…”

Section: Methodsmentioning

confidence: 99%

Genomic Diversity of Lactobacillus salivarius

Raftis

Salvetti

Torriani

et al. 2011

Appl Environ Microbiol

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Strains of Lactobacillus salivarius are increasingly employed as probiotic agents for humans or animals. Despite the diversity of environmental sources from which they have been isolated, the genomic diversity of L. salivarius has been poorly characterized, and the implications of this diversity for strain selection have not been examined. To tackle this, we applied comparative genomic hybridization (CGH) and multilocus sequence typing (MLST) to 33 strains derived from humans, animals, or food. The CGH, based on total genome content, including small plasmids, identified 18 major regions of genomic variation, or hot spots for variation. Three major divisions were thus identified, with only a subset of the human isolates constituting an ecologically discernible group. Omission of the small plasmids from the CGH or analysis by MLST provided broadly concordant fine divisions and separated human-derived and animal-derived strains more clearly. The two gene clusters for exopolysaccharide (EPS) biosynthesis corresponded to regions of significant genomic diversity. The CGH-based groupings of these regions did not correlate with levels of production of bound or released EPS. Furthermore, EPS production was significantly modulated by available carbohydrate. In addition to proving difficult to predict from the gene content, EPS production levels correlated inversely with production of biofilms, a trait considered desirable in probiotic commensals. L. salivarius displays a high level of genomic diversity, and while selection of L. salivarius strains for probiotic use can be informed by CGH or MLST, it also requires pragmatic experimental validation of desired phenotypic traits.Lactobacillus spp. are lactic acid bacteria (LAB) that display phylogenetic, phenotypic, and ecological heterogeneity that is reflected in their taxonomic diversity (13). Lactobacilli have complex nutritional requirements that are reflected in the diverse, carbon-rich habitats in which they are found (59). Lactobacilli have been studied extensively because of their importance for the production of fermented foods and beverages (59). Some well-characterized lactobacilli are generally regarded as safe (GRAS), and in more recent times, they have been used as probiotics and vaccine carriers (30). Administration of probiotic cultures benefits the host through a wide variety of mechanisms that are increasingly recognized as being species and strain specific (34). Knowledge of the genetic basis for strain diversity in potentially probiotic species is thus called for. Comparative genomics has emerged as a powerful approach in this era of high-throughput sequencing technologies, and it provides a technological platform to identify strainspecific traits (13).Lactobacillus salivarius (38) is part of the indigenous microbiota of the gastrointestinal tract (GIT) and oral cavity of humans and hamsters (49). The species has also been isolated from human breast milk (41) and from the intestinal tracts of swine (10) and chickens (1). There has been a recent increase i...

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“…A previous study indicated that the correlation of neighboring genomic intervals should be considered in the structural analysis of aCGH datasets [17], and the neighboring probes correlated with each other [3]. These findings indicate that the significant region would be more reliable for classification of experimental groups, which includes the correlated neighboring probes.…”

Section: Discussionmentioning

confidence: 79%

A method for detecting significant genomic regions associated with oral squamous cell carcinoma using aCGH

Kim

et al. 2010

Med Biol Eng Comput

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Array comparative genomic hybridization (aCGH) provides a genome-wide technique for identifying chromosomal aberrations in human diseases, including cancer. Chromosomal aberrations in cancers are defined as regions that contain an increased or decreased DNA copy number, relative to normal samples. The identification of genomic regions associated with systematic aberrations provides insights into initiation and progression of cancer, and improves diagnosis, prognosis, and therapy strategies. The McNemar test can be used to detect differentially expressed genes after discretization of gene expressions in a microarray experiment for the matched dataset. In this study, we propose a method to detect significantly altered DNA regions, shifted McNemar test, which is based on the standard McNemar test and takes into account changes in copy number variations and the region size throughout the whole genome. In addition, this novel method can be used to detect genomic regions associated with the progress of oral squamous cell carcinoma (OSCC). The performance of the proposed method was evaluated based on the homogeneity within the selected regions and the classification accuracies of the selected regions. This method might be useful for identifying new candidate genes that neighbor known genes based on the whole-genomic variation because it detects significant chromosomal regions, not independent probes.

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A probe-density-based analysis method for array CGH data: simulation, normalization and centralization

Abstract: Source codes and.gures may be found at http://ntumaps.cgm.ntu.edu.tw/aCGH_supplementary.

Cited by 22 publications

References 31 publications

Network-Guided Analysis of Genes with Altered Somatic Copy Number and Gene Expression Reveals Pathways Commonly Perturbed in Metastatic Melanoma

Network-Guided Analysis of Genes with Altered Somatic Copy Number and Gene Expression Reveals Pathways Commonly Perturbed in Metastatic Melanoma

Genomic Diversity of Lactobacillus salivarius

A method for detecting significant genomic regions associated with oral squamous cell carcinoma using aCGH

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