title: Utilizing mapping targets of sequences underrepresented in the reference assembly to reduce false positive alignments.
abstract: The human reference assembly remains incomplete due to the underrepresentation of repeat-rich sequences that are found within centromeric regions and acrocentric short arms. Although these sequences are marginally represented in the assembly, they are often fully represented in whole-genome short-read datasets and contribute to inappropriate alignments and high read-depth signals that localize to a small number of assembled homologous regions. As a consequence, these regions often provide artifactual peak calls that confound hypothesis testing and large-scale genomic studies. To address this problem, we have constructed mapping targets that represent roughly 8% of the human genome generally omitted from the human reference assembly. By integrating these data into standard mapping and peak-calling pipelines we demonstrate a 10-fold reduction in signals in regions common to the blacklisted region and identify a comprehensive set of regions that exhibit mapping sensitivity with the presence of the repeat-rich targets.
authors.affiliation: Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA khmiga@soe.ucsc.edu.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Miga
authors.affiliation: Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Eisenhart
authors.affiliation: Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA.
authors.forename: W James
authors.initials: WJ
authors.lastname: Kent
mesh_terms: D016477:Artifacts; D004247:DNA / Q000737:chemistry; D030561:Databases, Nucleic Acid; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment / Q000379:methods*
chemical_list: D004247:DNA