Abstract
BackgroundMosaic 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.ResultsHere, 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.ConclusionsOur 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.
Highlights
Mosaic somatic alterations are present in all multi-cellular organisms, but the physiological effects of low-level mosaicism are largely unknown
We describe an implementation of this algorithm in triPOD (Parent-of-Origin-based Detection in trios), which includes additional parental contribution-based approaches for abnormality detection. triPOD outperforms current state of the art detection methods, shows greatly improved sensitivity for detection of low-level mosaicism, and uniquely provides the parental origin for each detected abnormality. triPOD software is made available as a command line program and as a web application
The resulting value is an expression of the intensity ratio in terms of the B allele and is referred to as the B allele frequency (BAF)
Summary
Mosaic somatic alterations are present in all multi-cellular organisms, but the physiological effects of low-level mosaicism are largely unknown. Chromosomal abnormalities, including deletions, amplifications, and uniparental disomy (UPD) events, are a significant cause of Mendelian and complex disorders, as well as a source of benign variation within a population. Technological advancements such as SNP microarrays and next-generation sequencing have dramatically enhanced disease research and diagnosis by improving the ability to detect genomic variation. Other HMM-based approaches, including PSCN, genoCN, MixHMM, and GPHMM, can detect CNVs and UPD events in tumor/normal mixtures and are capable of detecting mosaic changes at a certain level of resolution [12,13,14,15]. While many algorithms can detect a subset of mosaic abnormalities, the resolution for low-level mosaicism can be greatly improved
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
