title: RNA2DNAlign: nucleotide resolution allele asymmetries through quantitative assessment of RNA and DNA paired sequencing data.
abstract: We introduce RNA2DNAlign, a computational framework for quantitative assessment of allele counts across paired RNA and DNA sequencing datasets. RNA2DNAlign is based on quantitation of the relative abundance of variant and reference read counts, followed by binomial tests for genotype and allelic status at SNV positions between compatible sequences. RNA2DNAlign detects positions with differential allele distribution, suggesting asymmetries due to regulatory/structural events. Based on the type of asymmetry, RNA2DNAlign outlines positions likely to be implicated in RNA editing, allele-specific expression or loss, somatic mutagenesis or loss-of-heterozygosity (the first three also in a tumor-specific setting). We applied RNA2DNAlign on 360 matching normal and tumor exomes and transcriptomes from 90 breast cancer patients from TCGA. Under high-confidence settings, RNA2DNAlign identified 2038 distinct SNV sites associated with one of the aforementioned asymetries, the majority of which have not been linked to functionality before. The performance assessment shows very high specificity and sensitivity, due to the corroboration of signals across multiple matching datasets. RNA2DNAlign is freely available from http://github.com/HorvathLab/NGS as a self-contained binary package for 64-bit Linux systems.
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA.|University of Massachusetts Medical School, Graduate School of Biomedical Sciences, Program in Bioinformatics and Integrative Biology, Worcester, MA 01605, USA.
authors: Mercedeh
authors: M
authors: Movassagh
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA.|Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USA.
authors: Nawaf
authors: N
authors: Alomran
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA.
authors: Prakriti
authors: P
authors: Mudvari
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA.
authors: Merve
authors: M
authors: Dede
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA.
authors: Cem
authors: C
authors: Dede
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA.|Department of Computer Science, School of Engineering and applied Science, The George Washington University, Washington, DC 20037, USA.
authors: Kamran
authors: K
authors: Kowsari
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA.
authors: Paula
authors: P
authors: Restrepo
authors: Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037, USA.
authors: Edmund
authors: E
authors: Cauley
authors: Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037, USA.
authors: Sonali
authors: S
authors: Bahl
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA.|Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USA.
authors: Muzi
authors: M
authors: Li
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA.
authors: Wesley
authors: W
authors: Waterhouse
authors: Department of Mathematics, College of Engineering, Mathematics and Physical Sciences & EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter, EX4 4QJ, UK.
authors: Krasimira
authors: K
authors: Tsaneva-Atanasova
authors: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USA.
authors: Nathan
authors: N
authors: Edwards
authors: McCormick Genomics and Proteomics Center, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037, USA horvatha@gwu.edu.|Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037, USA.
authors: Anelia
authors: A
authors: Horvath
mesh_terms: D000465:Algorithms; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D059472:Exome; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D019656:Loss of Heterozygosity; D020641:Polymorphism, Single Nucleotide; D017393:RNA Editing; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D012984:Software; D059467:Transcriptome