MOTIVATION: Illumina DNA sequencing is now the predominant source of raw genomic data, and data volumes are growing rapidly. Bioinformatic analysis pipelines are having trouble keeping pace. A common bottleneck in such pipelines is the requirement to read, write, sort and compress large BAM files multiple times. RESULTS: We present SAMBLASTER, a tool that reduces the number of times such costly operations are performed. SAMBLASTER is designed to mark duplicates in read-sorted SAM files as a piped post-pass on DNA aligner output before it is compressed to BAM. In addition, it can simultaneously output into separate files the discordant read-pairs and/or split-read mappings used for structural variant calling. As an alignment post-pass, its own runtime overhead is negligible, while dramatically reducing overall pipeline complexity and runtime. As a stand-alone duplicate marking tool, it performs significantly better than PICARD or SAMBAMBA in terms of both speed and memory usage, while achieving nearly identical results. AVAILABILITY AND IMPLEMENTATION: SAMBLASTER is open-source C+ + code and freely available for download from https://github.com/GregoryFaust/samblaster.

MOTIVATION: With improved short-read assembly algorithms and the recent development of long-read sequencers, split mapping will soon be the preferred method for structural variant (SV) detection. Yet, current alignment tools are not well suited for this. RESULTS: We present YAHA, a fast and flexible hash-based aligner. YAHA is as fast and accurate as BWA-SW at finding the single best alignment per query and is dramatically faster and more sensitive than both SSAHA2 and MegaBLAST at finding all possible alignments. Unlike other aligners that report all, or one, alignment per query, or that use simple heuristics to select alignments, YAHA uses a directed acyclic graph to find the optimal set of alignments that cover a query using a biologically relevant breakpoint penalty. YAHA can also report multiple mappings per defined segment of the query. We show that YAHA detects more breakpoints in less time than BWA-SW across all SV classes, and especially excels at complex SVs comprising multiple breakpoints. AVAILABILITY: YAHA is currently supported on 64-bit Linux systems. Binaries and sample data are freely available for download from http://faculty.virginia.edu/irahall/YAHA. CONTACT: [email protected].