Journal article
Investigating and correcting plasma DNA sequencing coverage bias to enhance aneuploidy discovery
D Chandrananda, NP Thorne, D Ganesamoorthy, DL Bruno, Y Benjamini, TP Speed, HR Slater, M Bahlo
Plos One | Published : 2014
Open access
Abstract
Pregnant women carry a mixture of cell-free DNA fragments from self and fetus (non-self) in their circulation. In recent years multiple independent studies have demonstrated the ability to detect fetal trisomies such as trisomy 21, the cause of Down syndrome, by Next-Generation Sequencing of maternal plasma. The current clinical tests based on this approach show very high sensitivity and specificity, although as yet they have not become the standard diagnostic test. Here we describe improvements to the analysis of the sequencing data by reducing GC bias and better handling of the genomic repeats. We show substantial improvements in the sensitivity of the standard trisomy 21 statistical tests..
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Awarded by National Science Foundation
Funding Acknowledgements
This work was supported by the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. Additional support provided by Australian Postgraduate Awards (to DC and DG); The John and Patricia Farrant Scholarship (to DC); National Science Foundation VIGRE Graduate Fellowship (to YB); National Health and Medical Research Council Australia Fellowship (grant number 575503 to TPS); National Institutes of Health (grant number 5R01 GM083084-03 to TPS.) and an Australian Research Council Future Fellowship (grant number FT100100764 to MB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.