title: Beta-Binomial Model for the Detection of Rare Mutations in Pooled Next-Generation Sequencing Experiments.
abstract: Against diminishing costs, next-generation sequencing (NGS) still remains expensive for studies with a large number of individuals. As cost saving, sequencing genome of pools containing multiple samples might be used. Currently, there are many software available for the detection of single-nucleotide polymorphisms (SNPs). Sensitivity and specificity depend on the model used and data analyzed, indicating that all software have space for improvement. We use beta-binomial model to detect rare mutations in untagged pooled NGS experiments. We propose a multireference framework for pooled data with ability being specific up to two patients affected by neuromuscular disorders (NMD). We assessed the results comparing with The Genome Analysis Toolkit (GATK), CRISP, SNVer, and FreeBayes. Our results show that the multireference approach applying beta-binomial model is accurate in predicting rare mutations at 0.01 fraction. Finally, we explored the concordance of mutations between the model and software, checking their involvement in any NMD-related gene. We detected seven novel SNPs, for which the functional analysis produced enriched terms related to locomotion and musculature.
authors.affiliation: 1 Bioinformatics and Biostatistics Center, Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University , Vilnius, Lithuania .
authors.forename: Audrone
authors.initials: A
authors.lastname: Jakaitiene
authors.affiliation: 2 High Performance Computing and Networking Institute , National Research Council, Naples, Italy .
authors.forename: Mariano
authors.initials: M
authors.lastname: Avino
authors.affiliation: 2 High Performance Computing and Networking Institute , National Research Council, Naples, Italy .
authors.forename: Mario Rosario
authors.initials: MR
authors.lastname: Guarracino
mesh_terms: D000465:Algorithms; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D015233:Models, Statistical; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software
keywords: NGS; beta-binomial; pooling; rare mutations