Arachne linked-read aligner

Arachne is a fork intended to be a revival and [hopefully] continuation of Lariat, the linked-read aware aligner created by 10X Genomics and bundled in their LongRanger pipeline.

The lariat developers made the case that linked-read data improved alignment, especially over highly repetitive regions. This was shown to work quite well in Aedes aegypti link and other works. Lariat relied on input FASTQ files with a rather peculiar variant: interleaved with 9 lines per record pair. Additionally, the Chromium 10X design did not preprocess the linked-read barcodes out of the sequence, hence the use of barcode "whitelists".

10X Genomics discontinued their linked-read technology in 2019 and Lariat was abandoned then as well. Since then, new linked-read methods emerged, namely haplotagging, stLFR, and TELLseq. These new techniques use different chemistries, but most importantly, all of them remove the linked-read barcode from the sequence and use conventional FASTQ formats. Lariat still has tons of value, so the goal was to update it for current technologies. To prevent platform lock-in and promote unified data standards, Arachne does not directly support any specific linked-read FASTQ format. Instead, it expects the 'standard' linked-read data format, which is a consistent future-proof format following the internationally recognized FASTQ and SAM specifications. Arachne provides a lossless converter that accepts haplotagging, stLFR, and TELLseq FASTQ data to faciliate these conversions. Our hope and intention is the ubiquitous adoption of this data format across all current and future linked-read chemistries.

1.0 release checklist:

  • Awesome new logo
  • Modernize Go idioms
  • Replace custom FASTQ reader with fastx (used by seqkit)
  • Rewrite internals to match Standard FASTQ format
  • Create preprocess subcommand
  • Expose bwa index for convenience
  • Output SAM to stdout instead of to many files
  • Create test data
  • Get everything to compile and run
  • Add build and run tests
  • Restore BWA as a submodule to get latest upstream fixes
  • Add jemalloc as a submodule to get latest upstream fixes
  • validate output

About Lariat

Lariat was designed to align all reads sharing the same barcode simultaneously, assuming that those reads came from the same molecule. Lariat is based on the original RFA method developed by the Batzoglou lab at Stanford: Genome Res. 2015. 25:1570-1580.