title: Innovations and challenges in detecting long read overlaps: an evaluation of the state-of-the-art.
abstract: Identifying overlaps between error-prone long reads, specifically those from Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PB), is essential for certain downstream applications, including error correction and de novo assembly. Though akin to the read-to-reference alignment problem, read-to-read overlap detection is a distinct problem that can benefit from specialized algorithms that perform efficiently and robustly on high error rate long reads. Here, we review the current state-of-the-art read-to-read overlap tools for error-prone long reads, including BLASR, DALIGNER, MHAP, GraphMap and Minimap. These specialized bioinformatics tools differ not just in their algorithmic designs and methodology, but also in their robustness of performance on a variety of datasets, time and memory efficiency and scalability. We highlight the algorithmic features of these tools, as well as their potential issues and biases when utilizing any particular method. To supplement our review of the algorithms, we benchmarked these tools, tracking their resource needs and computational performance, and assessed the specificity and precision of each. In the versions of the tools tested, we observed that Minimap is the most computationally efficient, specific and sensitive method on the ONT datasets tested; whereas GraphMap and DALIGNER are the most specific and sensitive methods on the tested PB datasets. The concepts surveyed may apply to future sequencing technologies, as scalability is becoming more relevant with increased sequencing throughput.
  
  
  BACKGROUND
  cjustin@bcgsc.ca , ibirol@bcgsc.ca.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: University of British Columbia, Vancouver, BC V6T 1Z4, Canada.|Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Chu
authors.affiliation: University of British Columbia, Vancouver, BC V6T 1Z4, Canada.|Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Hamid
authors.initials: H
authors.lastname: Mohamadi
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors.forename: René L
authors.initials: RL
authors.lastname: Warren
authors.affiliation: University of British Columbia, Vancouver, BC V6T 1Z4, Canada.|Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: University of British Columbia, Vancouver, BC V6T 1Z4, Canada.|Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4S6, Canada.|Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
authors.forename: Inanç
authors.initials: I
authors.lastname: Birol
mesh_terms: D000465:Algorithms; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software