PT - JOURNAL ARTICLE AU - Chirag Jain AU - Alexander Dilthey AU - Sergey Koren AU - Srinivas Aluru AU - Adam M. Phillippy TI - A Fast Approximate Algorithm for Mapping Long Reads to Large Reference Databases AID - 10.1101/103812 DP - 2017 Jan 01 TA - bioRxiv PG - 103812 4099 - http://biorxiv.org/content/early/2017/03/24/103812.short 4100 - http://biorxiv.org/content/early/2017/03/24/103812.full AB - Emerging single-molecule sequencing technologies from Pacific Biosciences and Oxford Nanopore have revived interest in long read mapping algorithms. Alignment-based seed-and-extend methods demonstrate good accuracy, but face limited scalability, while faster alignment-free methods typically trade decreased precision for efficiency. In this paper, we combine a fast approximate read mapping algorithm based on minimizers with a novel MinHash identity estimation technique to achieve both scalability and precision. In contrast to prior methods, we develop a mathematical framework that defines the types of mapping targets we uncover, establish probabilistic estimates of p-value and sensitivity, and demonstrate tolerance for alignment error rates up to 20%. With this framework, our algorithm automatically adapts to different minimum length and identity requirements and provides both positional and identity estimates for each mapping reported. For mapping human PacBio reads to the hg38 reference, our method is 290x faster than BWA-MEM with a lower memory footprint and recall rate of 96%. We further demonstrate the scalability of our method by mapping noisy PacBio reads (each ≥ 5 kbp in length) to the complete NCBI RefSeq database containing 838 Gbp of sequence and > 60, 000 genomes.