License: Creative Commons Attribution 3.0 Unported license (CC BY 3.0)
When quoting this document, please refer to the following
DOI: 10.4230/LIPIcs.WABI.2020.4
URN: urn:nbn:de:0030-drops-127933
URL: http://dagstuhl.sunsite.rwth-aachen.de/volltexte/2020/12793/
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Zentgraf, Jens ; Rahmann, Sven

Fast Lightweight Accurate Xenograft Sorting

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LIPIcs-WABI-2020-4.pdf (0.5 MB)

Abstract

Motivation: With an increasing number of patient-derived xenograft (PDX) models being created and subsequently sequenced to study tumor heterogeneity and to guide therapy decisions, there is a similarly increasing need for methods to separate reads originating from the graft (human) tumor and reads originating from the host species' (mouse) surrounding tissue. Two kinds of methods are in use: On the one hand, alignment-based tools require that reads are mapped and aligned (by an external mapper/aligner) to the host and graft genomes separately first; the tool itself then processes the resulting alignments and quality metrics (typically BAM files) to assign each read or read pair. On the other hand, alignment-free tools work directly on the raw read data (typically FASTQ files). Recent studies compare different approaches and tools, with varying results.

Results: We show that alignment-free methods for xenograft sorting are superior concerning CPU time usage and equivalent in accuracy. We improve upon the state of the art by presenting a fast lightweight approach based on three-way bucketed quotiented Cuckoo hashing. Our hash table requires memory comparable to an FM index typically used for read alignment and less than other alignment-free approaches. It allows extremely fast lookups and uses less CPU time than other alignment-free methods and alignment-based methods at similar accuracy.

BibTeX - Entry

@InProceedings{zentgraf_et_al:LIPIcs:2020:12793,
  author =	{Jens Zentgraf and Sven Rahmann},
  title =	{{Fast Lightweight Accurate Xenograft Sorting}},
  booktitle =	{20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
  pages =	{4:1--4:16},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-161-0},
  ISSN =	{1868-8969},
  year =	{2020},
  volume =	{172},
  editor =	{Carl Kingsford and Nadia Pisanti},
  publisher =	{Schloss Dagstuhl--Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/opus/volltexte/2020/12793},
  URN =		{urn:nbn:de:0030-drops-127933},
  doi =		{10.4230/LIPIcs.WABI.2020.4},
  annote =	{Keywords: xenograft sorting, alignment-free method, Cuckoo hashing, k-mer}
}

Keywords: xenograft sorting, alignment-free method, Cuckoo hashing, k-mer
Collection: 20th International Workshop on Algorithms in Bioinformatics (WABI 2020)
Issue Date: 2020
Date of publication: 25.08.2020
Supplementary Material: Our software xengsort is available under the MIT license at http://gitlab.com/genomeinformatics/xengsort. It is written in numba-compiled Python and comes with Snakemake workflows for hash table construction and dataset processing.

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