Structural Variation Detection with Read Pair Information—An Improved Null-Hypothesis Reduces Bias

  • Kristoffer Sahlin
  • Mattias Frånberg
  • Lars Arvestad
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 9649)


Reads from paired-end and mate-pair libraries are often utilized to find structural variation in genomes, and one common approach is to use their fragment length for detection. After aligning read-pairs to the reference, read-pair distances are analyzed for statistically significant deviations. However, previously proposed methods are based on a simplified model of observed fragment lengths that does not agree with data. We show how this model limits statistical analysis of identifying variants and propose a new model, by adapting a model we have previously introduced for contig scaffolding, which agrees with data. From this model we derive an improved null hypothesis that, when applied in the variant caller CLEVER, reduces the number of false positives and corrects a bias that contributes to more deletion calls than insertion calls. A reference implementation is freely available at


Fragment Length Fragment Size Read Pair Mate Pair Library Donor Sequence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Kristoffer Sahlin
    • 1
  • Mattias Frånberg
    • 2
    • 3
  • Lars Arvestad
    • 3
    • 4
  1. 1.KTH Royal Institute of TechnologyScience for Life Laboratory, School of Computer Science and CommunicationStockholmSweden
  2. 2.Atherosclerosis Research Unit, Department of Medicine, SolnaKarolinska InstitutetStockholmSweden
  3. 3.Department of Numerical Analysis and Computer ScienceStockholm UniversityStockholmSweden
  4. 4.Swedish e-Science Research Centre (SeRC)StockholmSweden

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