On genomic repeats and reproducibility

Can Firtina, Can Alkan


Here, we present a comprehensive analysis on the reproducibility of computational characterization of genomic variants using high throughput sequencing data. We reanalyzed the same datasets twice, using the same tools with the same parameters, where we only altered the order of reads in the input (i.e. FASTQ file). Reshuffling caused the reads from repetitive regions being mapped to different locations in the second alignment, and we observed similar results when we only applied a scatter/gather approach for read mapping-without prior shuffling. Our results show that, some of the most common variation discovery algorithms do not handle the ambiguous read mappings accurately when random locations are selected. In addition, we also observed that even when the exact same alignment is used, the GATK HaplotypeCaller generates slightly different call sets, which we pinpoint to the variant filtration step. We conclude that, algorithms at each step of genomic variation discovery and characterization need to treat ambiguous mappings in a deterministic fashion to ensure full replication of results. Code, scripts and the generated VCF files are available at DOI:10.5281/zenodo.32611. calkan@cs.bilkent.edu.tr Supplementary data are availabl...Continue Reading


Jun 5, 2002·Genome Research·W James KentDavid Haussler
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
May 19, 2009·Genome Research·Fereydoun HormozdiariS Cenk Sahinalp
Jun 10, 2009·Bioinformatics·Heng Li1000 Genome Project Data Processing Subgroup
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Jun 10, 2010·Bioinformatics·Fereydoun HormozdiariS Cenk Sahinalp
Nov 4, 2011·Genome Research·Fereydoun HormozdiariS Cenk Sahinalp
Nov 30, 2011·Nature Reviews. Genetics·Todd J Treangen, Steven L Salzberg
Aug 28, 2012·Bioinformatics·David WeeseKnut Reinert
Jun 28, 2014·Genome Biology·Ryan M LayerIra M Hall
Jan 27, 2015·Nature Genetics·Robert E HandsakerSteven A McCarroll
Sep 19, 2015·PloS One·Pınar KavakMahmut Şamil Sağıroğlu
Oct 4, 2015·Nature·1000 Genomes Project ConsortiumGonçalo R Abecasis
Nov 6, 2015·BioMed Research International·Adam Cornish, Chittibabu Guda


Apr 5, 2018·Bioinformatics·Lukasz RoguskiSebastian Deorowicz
Jan 31, 2018·G3 : Genes - Genomes - Genetics·Charles Addo-QuayeBrian P Dilkes
Dec 14, 2019·Genes & Genomics·Da-Hye SonYong-Min Kim
Apr 27, 2018·BMC Medical Genomics·Tony KuoPaul Horton
Jan 20, 2017·BMC Genomics·Ole K TørresenAlexander J Nederbragt
Nov 14, 2018·Bioinformatics·Ibrahim NumanagicFaraz Hach

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