scholarly journals CINdex: A Bioconductor Package for Analysis of Chromosome Instability in DNA Copy Number Data

2017 ◽  
Vol 16 ◽  
pp. 117693511774663 ◽  
Author(s):  
Lei Song ◽  
Krithika Bhuvaneshwar ◽  
Yue Wang ◽  
Yuanjian Feng ◽  
Ie-Ming Shih ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosome Instability ◽  
Genomic Analysis ◽  
Copy Number Data ◽  
Bioconductor Package ◽  
Dna Copy Number ◽  
Integrative Study ◽  
Genomic Regions ◽  
And Control ◽  
The Impact

The CINdex Bioconductor package addresses an important area of high-throughput genomic analysis. It calculates the chromosome instability (CIN) index, a novel measurement that quantitatively characterizes genome-wide copy number alterations (CNAs) as a measure of CIN. The advantage of this package is an ability to compare CIN index values between several groups for patients (case and control groups), which is a typical use case in translational research. The differentially changed cytobands or chromosomes can then be linked to genes located in the affected genomic regions, as well as pathways. This enables in-depth systems biology–based network analysis and assessment of the impact of CNA on various biological processes or clinical outcomes. This package was successfully applied to analysis of DNA copy number data in colorectal cancer as a part of multi-omics integrative study as well as for analysis of several other cancer types. The source code, along with an end-to-end tutorial, and example data are freely available in Bioconductor at http://bioconductor.org/packages/CINdex/ .

scholarly journals Integrated Genomic Analysis of Sézary Syndrome

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Xin Mao ◽  
Tracy Chaplin ◽  
Bryan D. Young
Keyword(s):  
Copy Number ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genomic Analysis ◽  
Gene Clusters ◽  
Sézary Syndrome ◽  
Sezary Syndrome ◽  
Snp Microarray ◽  
The Impact ◽  
Chromosome Regions

Sézary syndrome (SS) is a rare variant of primary cutaneous T-cell lymphoma. Little is known about the underlying pathogenesis of S. To address this issue, we used Affymetrix 10K SNP microarray to analyse 13 DNA samples isolated from 8 SS patients and qPCR with ABI TaqMan SNP genotyping assays for the validation of the SNP microarray results. In addition, we tested the impact of SNP loss of heterozygosity (LOH) identified in SS cases on the gene expression profiles of SS cases detected with Affymetrix GeneChip U133A. The results showed: (1) frequent SNP copy number change and LOH involving 1, 2p, 3, 4q, 5q, 6, 7p, 8, 9, 10, 11, 12q, 13, 14, 16q, 17, and 20, (2) reduced SNP copy number at FAT gene (4q35) in 75% of SS cases, and (3) the separation of all SS cases from normal control samples by SNP LOH gene clusters at chromosome regions of 9q31q34, 10p11q26, and 13q11q12. These findings provide some intriguing information for our current understanding of the molecular pathogenesis of this tumour and suggest the possibility of presence of functional SNP LOH in SS tumour cells.

Correlation of DNA Copy Number, Gene Expression, Protein Expression and Clinical Outcome in a Group of Patients with Diffuse Large B Cell Lymphoma (DLBCL) Treated with CHOP Plus Rituximab (CHOP-R).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2027-2027
Author(s):  
N.A. Johnson ◽  
T. Relander ◽  
P. Farinha ◽  
T. Nayar ◽  
D.E. Horsman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Outcome ◽  
Protein Expression ◽  
B Cell ◽  
Human Genome ◽  
Copy Number ◽  
B Cell Lymphoma ◽  
Dna Copy Number ◽  
The Impact ◽  
Successes And Failures

Abstract Background: DLBCL is the most common subtype of Non-Hodgkin lymphoma and has a mortality rate of 40%. It is characterized by marked clinical and biological heterogeneity. Tumors with similar histology have different genetic abnormalities. The influence of many of these genetic changes on clinical outcome is unknown. Furthermore, treatment itself can influence the prognostic significance of certain biomarkers. Exploring the impact of genetic aberrations on gene expression, protein expression and clinical outcome is the focus of this investigation. Understanding the biology of DLBCL from patients treated with CHOP-R may lead to the discovery of novel biomarkers that are relevant in the CHOP-R era. Methods: RNA and DNA were extracted from frozen de novo DLBCL biopsies taken at the time of diagnosis from April 2001 to April 2005. Cases were selected based on their clinical outcome (11 patients with a >2 year remission with CHOP-R and 10 patients who progressed or relapsed after CHOP-R). We studied DNA amplifications and deletions using array comparative genomic hybridization (aCGH) comprising of >26,000 overlapping bacterial artificial chromosomes. This provides a >95% coverage of the human genome and the capability to reproducibly detect amplifications and deletions as small as 120 kb. We performed gene expression profiling (GEP) using the Affymetrix Human Genome U133 Plus 2 array. A tissue microarray was constructed to assess protein expression using paraffin active antibodies. BCL2, BCL6, P53 and MUM1 genes were assessed using all three platforms and results were correlated with clinical outcome. Results: DNA gains and losses were identified in all patients with an average of 19 alterations per tumor with amplifications being more frequent than deletions. GEP revealed a predominance (57%) of Activated B Cell (ABC) type. A supervised analysis identified a list of 471 genes that were differentially expressed (p<0.01) between treatment failures and successes, many of which are implicated in nucleic acid binding and cell cycle regulation. The correlation between DNA copy number and gene expression was poor especially in areas of DNA gain. The correlation between gene expression and copy number was greater for BCL2 and P53 than for BCL6 and MUM1 (r= 0.67 and 0.80 versus −0.02 and −0.08). The correlation between protein expression and gene expression were r = 0.22, 0.65, 0.66 and 0.53 for BCL2, P53, BCL6 and MUM1, respectively. In this small group of patients treated with CHOP-R, the international prognostic index (IPI) was higher in the patients “failing” CHOP-R (mean IPI 3.2 vs. 1.7). Deletions of 17p13.1 (P53) and high P53 protein expression were predominantly seen in the failures (7 vs 1). High BCL2 protein, low BCL6 protein and ABC signature were randomly distributed in both CHOP-R successes and failures. Conclusion: In this limited group of patients with DLBCL treated with CHOP-R, IPI had the strongest prognostic value. Candidate genes that could predict CHOP-R successes and failures will be validated by RT-PCR and TMA on a larger cohort of patients. The unpredictable correlation between gene expression and DNA copy number suggests that alternate mechanisms of gene regulation are involved in the pathogenesis of DLBCL.

scholarly journals Efficient Calculation of Interval Scores for DNA Copy Number Data Analysis

2006 ◽  
Vol 13 (2) ◽  
pp. 215-228 ◽  
Author(s):  
Doron Lipson ◽  
Yonatan Aumann ◽  
Amir Ben-Dor ◽  
Nathan Linial ◽  
Zohar Yakhini
Keyword(s):  
Data Analysis ◽  
Copy Number ◽  
Copy Number Data ◽  
Dna Copy Number ◽  
Efficient Calculation
Sign in / Sign up

Export Citation Format

Share Document