Cargando…
Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method
BACKGROUND: Mosaic somatic alterations are present in all multi-cellular organisms, but the physiological effects of low-level mosaicism are largely unknown. Most mosaic alterations remain undetectable with current analytical approaches, although the presence of such alterations is increasingly impl...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680018/ https://www.ncbi.nlm.nih.gov/pubmed/23724825 http://dx.doi.org/10.1186/1471-2164-14-367 |
_version_ | 1782273058532229120 |
---|---|
author | Baugher, Joseph D Baugher, Benjamin D Shirley, Matthew D Pevsner, Jonathan |
author_facet | Baugher, Joseph D Baugher, Benjamin D Shirley, Matthew D Pevsner, Jonathan |
author_sort | Baugher, Joseph D |
collection | PubMed |
description | BACKGROUND: Mosaic somatic alterations are present in all multi-cellular organisms, but the physiological effects of low-level mosaicism are largely unknown. Most mosaic alterations remain undetectable with current analytical approaches, although the presence of such alterations is increasingly implicated as causative for disease. RESULTS: Here, we present the Parent-of-Origin-based Detection (POD) method for chromosomal abnormality detection in trio-based SNP microarray data. Our software implementation, triPOD, was benchmarked using a simulated dataset, outperformed comparable software for sensitivity of abnormality detection, and displayed substantial improvement in the detection of low-level mosaicism while maintaining comparable specificity. Examples of low-level mosaic abnormalities from a large autism dataset demonstrate the benefits of the increased sensitivity provided by triPOD. The triPOD analyses showed robustness across multiple types of Illumina microarray chips. Two large, clinically-relevant datasets were characterized and compared. CONCLUSIONS: Our method and software provide a significant advancement in the ability to detect low-level mosaic abnormalities, thereby opening new avenues for research into the implications of mosaicism in pathogenic and non-pathogenic processes. |
format | Online Article Text |
id | pubmed-3680018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36800182013-06-25 Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method Baugher, Joseph D Baugher, Benjamin D Shirley, Matthew D Pevsner, Jonathan BMC Genomics Methodology Article BACKGROUND: Mosaic somatic alterations are present in all multi-cellular organisms, but the physiological effects of low-level mosaicism are largely unknown. Most mosaic alterations remain undetectable with current analytical approaches, although the presence of such alterations is increasingly implicated as causative for disease. RESULTS: Here, we present the Parent-of-Origin-based Detection (POD) method for chromosomal abnormality detection in trio-based SNP microarray data. Our software implementation, triPOD, was benchmarked using a simulated dataset, outperformed comparable software for sensitivity of abnormality detection, and displayed substantial improvement in the detection of low-level mosaicism while maintaining comparable specificity. Examples of low-level mosaic abnormalities from a large autism dataset demonstrate the benefits of the increased sensitivity provided by triPOD. The triPOD analyses showed robustness across multiple types of Illumina microarray chips. Two large, clinically-relevant datasets were characterized and compared. CONCLUSIONS: Our method and software provide a significant advancement in the ability to detect low-level mosaic abnormalities, thereby opening new avenues for research into the implications of mosaicism in pathogenic and non-pathogenic processes. BioMed Central 2013-05-31 /pmc/articles/PMC3680018/ /pubmed/23724825 http://dx.doi.org/10.1186/1471-2164-14-367 Text en Copyright © 2013 Baugher et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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. |
spellingShingle | Methodology Article Baugher, Joseph D Baugher, Benjamin D Shirley, Matthew D Pevsner, Jonathan Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method |
title | Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method |
title_full | Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method |
title_fullStr | Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method |
title_full_unstemmed | Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method |
title_short | Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method |
title_sort | sensitive and specific detection of mosaic chromosomal abnormalities using the parent-of-origin-based detection (pod) method |
topic | Methodology Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680018/ https://www.ncbi.nlm.nih.gov/pubmed/23724825 http://dx.doi.org/10.1186/1471-2164-14-367 |
work_keys_str_mv | AT baugherjosephd sensitiveandspecificdetectionofmosaicchromosomalabnormalitiesusingtheparentoforiginbaseddetectionpodmethod AT baugherbenjamind sensitiveandspecificdetectionofmosaicchromosomalabnormalitiesusingtheparentoforiginbaseddetectionpodmethod AT shirleymatthewd sensitiveandspecificdetectionofmosaicchromosomalabnormalitiesusingtheparentoforiginbaseddetectionpodmethod AT pevsnerjonathan sensitiveandspecificdetectionofmosaicchromosomalabnormalitiesusingtheparentoforiginbaseddetectionpodmethod |