title: Alpha-CENTAURI: assessing novel centromeric repeat sequence variation with long read sequencing.
abstract: Long arrays of near-identical tandem repeats are a common feature of centromeric and subtelomeric regions in complex genomes. These sequences present a source of repeat structure diversity that is commonly ignored by standard genomic tools. Unlike reads shorter than the underlying repeat structure that rely on indirect inference methods, e.g. assembly, long reads allow direct inference of satellite higher order repeat structure. To automate characterization of local centromeric tandem repeat sequence variation we have designed Alpha-CENTAURI (ALPHA satellite CENTromeric AUtomated Repeat Identification), that takes advantage of Pacific Bioscience long-reads from whole-genome sequencing datasets. By operating on reads prior to assembly, our approach provides a more comprehensive set of repeat-structure variants and is not impacted by rearrangements or sequence underrepresentation due to misassembly.
  
  
  
  We demonstrate the utility of Alpha-CENTAURI in characterizing repeat structure for alpha satellite containing reads in the hydatidiform mole (CHM1, haploid-like) genome. The pipeline is designed to report local repeat organization summaries for each read, thereby monitoring rearrangements in repeat units, shifts in repeat orientation and sites of array transition into non-satellite DNA, typically defined by transposable element insertion. We validate the method by showing consistency with existing centromere high order repeat references. Alpha-CENTAURI can, in principle, run on any sequence data, offering a method to generate a sequence repeat resolution that could be readily performed using consensus sequences available for other satellite families in genomes without high-quality reference assemblies.
  
  
  
  Documentation and source code for Alpha-CENTAURI are freely available at http://github.com/volkansevim/alpha-CENTAURI CONTACT: ali.bashir@mssm.edu
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Pacific Biosciences, Inc., Menlo Park, CA 94025, USA.
authors.forename: Volkan
authors.initials: V
authors.lastname: Sevim
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.|Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Bashir
authors.affiliation: Pacific Biosciences, Inc., Menlo Park, CA 94025, USA.
authors.forename: Chen-Shan
authors.initials: CS
authors.lastname: Chin
authors.affiliation: Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA 95064, USA.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Miga
mesh_terms: D000465:Algorithms; D002503:Centromere / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D016384:Consensus Sequence; D005260:Female; D023281:Genomics; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics; D011247:Pregnancy; D017422:Sequence Analysis, DNA / Q000379:methods*; D020080:Tandem Repeat Sequences