Abstract

BackgroundCopy number alterations (CNAs) in genomic DNA have been associated with complex human diseases, including cancer. One of the most common techniques to detect CNAs is array-based comparative genomic hybridization (aCGH). The availability of aCGH platforms and the need for identification of CNAs has resulted in a wealth of methodological studies.Methodology/Principal FindingsADaCGH is an R package and a web-based application for the analysis of aCGH data. It implements eight methods for detection of CNAs, gains and losses of genomic DNA, including all of the best performing ones from two recent reviews (CBS, GLAD, CGHseg, HMM). For improved speed, we use parallel computing (via MPI). Additional information (GO terms, PubMed citations, KEGG and Reactome pathways) is available for individual genes, and for sets of genes with altered copy numbers.Conclusions/SignificanceADaCGH represents a qualitative increase in the standards of these types of applications: a) all of the best performing algorithms are included, not just one or two; b) we do not limit ourselves to providing a thin layer of CGI on top of existing BioConductor packages, but instead carefully use parallelization, examining different schemes, and are able to achieve significant decreases in user waiting time (factors up to 45×); c) we have added functionality not currently available in some methods, to adapt to recent recommendations (e.g., merging of segmentation results in wavelet-based and CGHseg algorithms); d) we incorporate redundancy, fault-tolerance and checkpointing, which are unique among web-based, parallelized applications; e) all of the code is available under open source licenses, allowing to build upon, copy, and adapt our code for other software projects.

Highlights

  • Copy number alterations (CNAs) in genomic DNA have been associated with complex human diseases, including cancer [1,2,3,4,5,6,7]

  • The web-based application is available at http:// adacgh2.bioinfo.cnio.es

  • We have implemented all of the best performing methods for the analysis of array-based comparative genomic hybridization (aCGH) data, based on [12,13], plus several others that can be of interest

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Summary

Introduction

Copy number alterations (CNAs) in genomic DNA have been associated with complex human diseases, including cancer [1,2,3,4,5,6,7]. ADaCGH is an R package and a web-based application for the analysis of aCGH data It implements eight methods for detection of CNAs, gains and losses of genomic DNA, including all of the best performing ones from two recent reviews (CBS, GLAD, CGHseg, HMM). ADaCGH represents a qualitative increase in the standards of these types of applications: a) all of the best performing algorithms are included, not just one or two; b) we do not limit ourselves to providing a thin layer of CGI on top of existing BioConductor packages, but instead carefully use parallelization, examining different schemes, and are able to achieve significant decreases in user waiting time (factors up to 456); c) we have added functionality not currently available in some methods, to adapt to recent recommendations (e.g., merging of segmentation results in wavelet-based and CGHseg algorithms); d) we incorporate redundancy, fault-tolerance and checkpointing, which are unique among web-based, parallelized applications; e) all of the code is available under open source licenses, allowing to build upon, copy, and adapt our code for other software projects

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