title: MiST: a new approach to variant detection in deep sequencing datasets.
abstract: MiST is a novel approach to variant calling from deep sequencing data, using the inverted mapping approach developed for Geoseq. Reads that can map to a targeted exonic region are identified using exact matches to tiles from the region. The reads are then aligned to the targets to discover variants. MiST carefully handles paralogous reads that map ambiguously to the genome and clonal reads arising from PCR bias, which are the two major sources of errors in variant calling. The reduced computational complexity of mapping selected reads to targeted regions of the genome improves speed, specificity and sensitivity of variant detection. Compared with variant calls from the GATK platform, MiST showed better concordance with SNPs from dbSNP and genotypes determined by an exonic-SNP array. Variant calls made only by MiST confirm at a high rate (>90%) by Sanger sequencing. Thus, MiST is a valuable alternative tool to analyse variants in deep sequencing data.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, NY 10029, USA, The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, NY 10029, USA and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, NY 10029, USA.
authors.forename: Sailakshmi
authors.initials: S
authors.lastname: Subramanian
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Pierro
authors.forename: Hardik
authors.initials: H
authors.lastname: Shah
authors.forename: Anitha D
authors.initials: AD
authors.lastname: Jayaprakash
authors.forename: Ian
authors.initials: I
authors.lastname: Weisberger
authors.forename: Jaehee
authors.initials: J
authors.lastname: Shim
authors.forename: Ajish
authors.initials: A
authors.lastname: George
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gelb
authors.forename: Ravi
authors.initials: R
authors.lastname: Sachidanandam
mesh_terms: D000465:Algorithms; D014644:Genetic Variation; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: D012333:RNA, Messenger