Book ChapterDOI
Framework for identifying common aberrations in DNA copy number data
Amir Ben-Dor,Doron Lipson,Anya Tsalenko,Mark Reimers,Lars Oliver Baumbusch,Michael T. Barrett,John N. Weinstein,A.L. Børresen-Dale,Zohar Yakhini +8 more
- pp 122-136
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TLDR
An efficient computational framework for identification and statistical characterization of genomic aberrations that are common to multiple cancer samples in a CGH data set is presented and three different algorithmic approaches within the context of that framework are presented.Abstract:
High-resolution array comparative genomic hybridization (aCGH) provides exon-level mapping of DNA aberrations in cells or tissues. Such aberrations are central to carcinogenesis and, in many cases, central to targeted therapy of the cancers. Some of the aberrations are sporadic, one-of-a-kind changes in particular tumor samples; others occur frequently and reflect common themes in cancer biology that have interpretable, causal ramifications. Hence, the difficult task of identifying and mapping common, overlapping genomic aberrations (including amplifications and deletions) across a sample set is an important one; it can provide insight for the discovery of oncogenes, tumor suppressors, and the mechanisms by which they drive cancer development.
In this paper we present an efficient computational framework for identification and statistical characterization of genomic aberrations that are common to multiple cancer samples in a CGH data set. We present and compare three different algorithmic approaches within the context of that framework. Finally, we apply our methods to two datasets - a collection of 20 breast cancer samples and a panel of 60 diverse human tumor cell lines (the NCI-60). Those analyses identified both known and novel common aberrations containing cancer-related genes. The potential impact of the analytical methods is well demonstrated by new insights into the patterns of deletion of CDKN2A (p16), a tumor suppressor gene crucial for the genesis of many types of cancer.read more
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Journal ArticleDOI
Array CGH analysis of copy number variation identifies 1284 new genes variant in healthy white males: implications for association studies of complex diseases
Adam J. de Smith,Anya Tsalenko,Nick Sampas,Alicia F. Scheffer,N. Alice Yamada,Peter Tsang,Amir Ben-Dor,Zohar Yakhini,Richard J. Ellis,Laurakay Bruhn,Stephen Laderman,Philippe Froguel,Philippe Froguel,Alexandra I. F. Blakemore +13 more
TL;DR: Genes involved in differentiation and development were significantly over-represented and approximately half of the genes identified feature in the Online Mendelian Inheritance in Man database, suggesting that they could have important implications for phenotype and, thus, be useful for association studies of complex diseases.
Journal ArticleDOI
Novel Rank-Based Statistical Methods Reveal MicroRNAs with Differential Expression in Multiple Cancer Types
Roy Navon,Hui Wang,Israel Steinfeld,Israel Steinfeld,Anya Tsalenko,Amir Ben-Dor,Zohar Yakhini +6 more
TL;DR: This study aims to identify miRNAs with consistent differential expression in multiple tumor types using a novel data analysis approach and develops scores for comparing miRNA expression in matched sample data based on a rigorous characterization of the distribution of order statistics over a discrete state set.
Journal ArticleDOI
Finding Recurrent Copy Number Alteration Regions: A Review of Methods
TL;DR: It is suggested that finding recurrent CNAs would benefit from clearly specifying the types of pattern to be detected and the intended usage of the regions found, and suggestions for further methodological research are suggested.
Journal ArticleDOI
Computational methods for identification of recurrent copy number alteration patterns by array CGH
TL;DR: Qualitatively evaluate methods designed to detect recurrent copy number alterations from array comparative genomic hybridization (aCGH) data based on their analytical strengths and limitations, and discuss expected future directions in this important area of cancer research.
Journal ArticleDOI
Detection of recurrent rearrangement breakpoints from copy number data
TL;DR: Neighborhood Breakpoint Conservation (NBC), an algorithm for identifying rearrangement breakpoints that are highly conserved at the same locus in multiple individuals, is demonstrated to be useful for detection of recurrent breakpoints resulting from copy number variants or other structural variants, and in particular identifies recurrent break points that result in gene truncations or fusion genes.
References
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Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
Therese Sørlie,Charles M. Perou,Robert Tibshirani,Turid Aas,Stephanie Geisler,Hilde Johnsen,Trevor Hastie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,T. Thorsen,Hanne Quist,John C. Matese,Patrick O. Brown,David Botstein,Per Eystein Lønning,Anne Lise Børresen-Dale +16 more
TL;DR: Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.
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Feasibility of a High-Flux Anticancer Drug Screen Using a Diverse Panel of Cultured Human Tumor Cell Lines
Anne Monks,Dominic A. Scudiero,Philip Skehan,Robert H. Shoemaker,Kenneth D. Paull,David T. Vistica,Curtis Hose,John Langley,Paul Cronise,Anne Vaigro-Wolff,Marcia Gray-Goodrich,H. D. Campbell,Joseph G. Mayo,Michael R. Boyd +13 more
TL;DR: A pilot-scale, in vitro, anticancer drug screen utilizing a panel of 60 human tumor cell lines organized into subpanels representing leukemia, melanoma, and cancers of the lung, colon, kidney, ovary, and central nervous system is described.
Journal ArticleDOI
Large-Scale Copy Number Polymorphism in the Human Genome
Jonathan Sebat,B. Lakshmi,Jennifer Troge,Joan Alexander,Janet M. Young,Pär Lundin,Susanne Månér,Hillary Massa,Megan Walker,Maoyen Chi,Nicholas Navin,Robert Lucito,John Healy,James W. Hicks,Kenny Q. Ye,Andrew Reiner,T. Conrad Gilliam,Barbara J. Trask,Nick Patterson,Anders Zetterberg,Michael Wigler +20 more
TL;DR: It is shown that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans.
Journal ArticleDOI
High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays
Daniel Pinkel,Daniel Pinkel,Richard Segraves,Damir Sudar,Steven M. Clark,Ian Poole,David Kowbel,Colin Collins,Wen Lin Kuo,Chira Chen,Ye Zhai,Shanaz H. Dairkee,Britt-Marie Ljung,Joe W. Gray,Joe W. Gray,Donna G. Albertson,Donna G. Albertson,Donna G. Albertson +17 more
TL;DR: The implementation of array CGH is demonstrated to be able to measure copy number with high precision in the human genome, and to analyse clinical specimens by obtaining new information on chromosome 20 aberrations in breast cancer.
Journal ArticleDOI
Circular binary segmentation for the analysis of array-based DNA copy number data.
TL;DR: A modification ofbinary segmentation is developed, which is called circular binary segmentation, to translate noisy intensity measurements into regions of equal copy number in DNA sequence copy number.
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