ArticlePloS one2014
Outlier-based identification of copy number variations using targeted resequencing in a small cohort of patients with Tetralogy of Fallot.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Human Genetics of Tetralogy of Fallot and Double-Outlet Right Ventricle.Advances in experimental medicine and biology · 2024Review
- Genetic Variants ofBiomolecules · 2023Article
- The Needle in the Haystack-Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot.Journal of cardiovascular development and disease · 2020Article
- From Clinic to Computer and Back Again: Practical Considerations When Designing and Implementing Machine Learning Solutions for Pediatrics.Current treatment options in pediatrics · 2020Review
- Altered microRNA and target gene expression related to Tetralogy of Fallot.Scientific reports · 2019Article
- ONCOGENE PANEL SEQUENCING ANALYSIS IDENTIFIES CANDIDATE ACTIONABLE GENES IN ADVANCED WELL-DIFFERENTIATED GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2019Article
- Detection of de novo copy number deletions from targeted sequencing of trios.Bioinformatics (Oxford, England) · 2019Article
- Evaluation of three read-depth based CNV detection tools using whole-exome sequencing data.Molecular cytogenetics · 2017Article
- A Biobank for Long-term and Sustainable Research in the Field of Congenital Heart Disease in Germany.Genomics, proteomics & bioinformatics · 2016Review
- Article
- De novo 9q gain in an infant with tetralogy of Fallot with absent pulmonary valve: Patient report and review of congenital heart disease in 9q duplication syndrome.American journal of medical genetics. Part A · 2015Review
- Detection of Genomic Structural Variants from Next-Generation Sequencing Data.Frontiers in bioengineering and biotechnology · 2015Review
- PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome.PloS one · 2015Article
- Haploinsufficiency of insulin gene enhancer protein 1 (ISL1) is associated with d-transposition of the great arteries.Molecular genetics & genomic medicine · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Copy number variations (CNVs) are one of the main sources of variability in the human genome. Many CNVs are associated with various diseases including cardiovascular disease. In addition to hybridization-based methods, next-generation sequencing (NGS) technologies are increasingly used for CNV discovery. However, respective computational methods applicable to NGS data are still limited. We developed a novel CNV calling method based on outlier detection applicable to small cohorts, which is of particular interest for the discovery of individual CNVs within families, de novo CNVs in trios and/or small cohorts of specific phenotypes like rare diseases. Approximately 7,000 rare diseases are currently known, which collectively affect ∼6% of the population. For our method, we applied the Dixon's Q test to detect outliers and used a Hidden Markov Model for their assessment. The method can be used for data obtained by exome and targeted resequencing. We evaluated our outlier-based method in comparison to the CNV calling tool CoNIFER using eight HapMap exome samples and subsequently applied both methods to targeted resequencing data of patients with Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease. In both the HapMap samples and the TOF cases, our method is superior to CoNIFER, such that it identifies more true positive CNVs. Called CNVs in TOF cases were validated by qPCR and HapMap CNVs were confirmed with available array-CGH data. In the TOF patients, we found four copy number gains affecting three genes, of which two are important regulators of heart development (NOTCH1, ISL1) and one is located in a region associated with cardiac malformations (PRODH at 22q11). In summary, we present a novel CNV calling method based on outlier detection, which will be of particular interest for the analysis of de novo or individual CNVs in trios or cohorts up to 30 individuals, respectively.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.