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An integrated Bayesian analysis of LOH and copy number data

Rancoita, Paola M. V.; Hutter, Marcus; Bertoni, Francesco; Kwee, Ivo

Description

BACKGROUND Cancer and other disorders are due to genomic lesions. SNP-microarrays are able to measure simultaneously both genotype and copy number (CN) at several Single Nucleotide Polymorphisms (SNPs) along the genome. CN is defined as the number of DNA copies, and the normal is two, since we have two copies of each chromosome. The genotype of a SNP is the status given by the nucleotides (alleles) which are present on the two copies of DNA. It is defined homozygous or heterozygous if the two...[Show more]

dc.contributor.authorRancoita, Paola M. V.
dc.contributor.authorHutter, Marcus
dc.contributor.authorBertoni, Francesco
dc.contributor.authorKwee, Ivo
dc.date.accessioned2015-08-24T05:59:49Z
dc.date.available2015-08-24T05:59:49Z
dc.identifier.issn1471-2105
dc.identifier.urihttp://hdl.handle.net/1885/14904
dc.description.abstractBACKGROUND Cancer and other disorders are due to genomic lesions. SNP-microarrays are able to measure simultaneously both genotype and copy number (CN) at several Single Nucleotide Polymorphisms (SNPs) along the genome. CN is defined as the number of DNA copies, and the normal is two, since we have two copies of each chromosome. The genotype of a SNP is the status given by the nucleotides (alleles) which are present on the two copies of DNA. It is defined homozygous or heterozygous if the two alleles are the same or if they differ, respectively. Loss of heterozygosity (LOH) is the loss of the heterozygous status due to genomic events. Combining CN and LOH data, it is possible to better identify different types of genomic aberrations. For example, a long sequence of homozygous SNPs might be caused by either the physical loss of one copy or a uniparental disomy event (UPD), i.e. each SNP has two identical nucleotides both derived from only one parent. In this situation, the knowledge of the CN can help in distinguishing between these two events. RESULTS To better identify genomic aberrations, we propose a method (called gBPCR) which infers the type of aberration occurred, taking into account all the possible influence in the microarray detection of the homozygosity status of the SNPs, resulting from an altered CN level. Namely, we model the distributions of the detected genotype, given a specific genomic alteration and we estimate the parameters involved on public reference datasets. The estimation is performed similarly to the modified Bayesian Piecewise Constant Regression, but with improved estimators for the detection of the breakpoints.Using artificial and real data, we evaluate the quality of the estimation of gBPCR and we also show that it outperforms other well-known methods for LOH estimation. CONCLUSIONS We propose a method (gBPCR) for the estimation of both LOH and CN aberrations, improving their estimation by integrating both types of data and accounting for their relationships. Moreover, gBPCR performed very well in comparison with other methods for LOH estimation and the estimated CN lesions on real data have been validated with another technique.
dc.description.sponsorshipThis work was supported by Swiss National Science Foundation (grants 205321-112430, 205320-121886/1); Oncosuisse grants OCS-1939-8-2006 and OCS - 02296-08-2008; Cantone Ticino ("Computational life science/Ticino in rete” program); Fondazione per la Ricerca e la Cura sui Linfomi (Lugano, Switzerland).
dc.publisherBioMed Central
dc.rights© 2010 Rancoita et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.sourceBMC Bioinformatics
dc.subjectalleles
dc.subjectbase sequence
dc.subjectbreast neoplasms
dc.subjectdna
dc.subjectgenome, human
dc.subjecthumans
dc.subjectleukemia, lymphocytic, chronic, b-cell
dc.subjectneoplasms
dc.subjectpolymorphism, single nucleotide
dc.subjectsequence analysis, dna
dc.subjectuniparental disomy
dc.subjectbayes theorem
dc.subjectgene dosage
dc.subjectloss of heterozygosity
dc.titleAn integrated Bayesian analysis of LOH and copy number data
dc.typeJournal article
local.identifier.citationvolume11
dc.date.issued2010-06-15
local.identifier.absfor080401 - Coding and Information Theory
local.identifier.ariespublicationu4963866xPUB66
local.publisher.urlhttp://www.biomedcentral.com/bmcbioinformatics/
local.type.statusPublished Version
local.contributor.affiliationHutter, M., Research School of Computer Science, The Australian National University
local.identifier.essn1471-2105
local.bibliographicCitation.issue1
local.bibliographicCitation.startpage321
local.identifier.doi10.1186/1471-2105-11-321
local.identifier.absseo970108 - Expanding Knowledge in the Information and Computing Sciences
dc.date.updated2016-02-24T11:30:53Z
local.identifier.scopusID2-s2.0-77955393548
CollectionsANU Research Publications

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