title: Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method.
abstract: 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.
authors.affiliation: Program in Biochemistry, Cellular and Molecular Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Baugher
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Baugher
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Shirley
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pevsner
mesh_terms: D000465:Algorithms; D002869:Chromosome Aberrations; D019295:Computational Biology / Q000379:methods*; D020407:Internet; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012984:Software