Progress Toward a Low Budget Reference Grade Genome Assembly

Reference quality de novo genome assemblies were once solely the domain of large, well-funded genome projects.  While next-generation short read technology removed some of the cost barriers, accurate chromosome-scale assembly remains a real challenge.  Here we present efforts to de novo assemble the goat (Capra hircus) genome.  Through the combination of single-molecule technologies from Pacific Biosciences (sequencing) and BioNano Genomics (optical mapping) coupled with high-throughput chromosome conformation capture sequencing (Hi-C), an inbred San Clemente goat genome has been sequenced and assembled to a high degree of completeness at a relatively modest cost.  Starting with 38 million PacBio reads, we integrated the MinHash Alignment Process (MHAP) with the Celera Assembler (CA) to produce an assembly composed of 3110 contigs with a contig N50 size of 4.7 Mb.  This assembly was scaffolded with BioNano genome maps derived from a single IrysChip into 333 scaffolds with an N50 of 23.1 Mb including the complete scaffolding of chromosome 20.  Finally, cis-chromosome associations were determined by Hi-C, yielding complete reconstruction of all autosomes into single scaffolds with a final N50 of 91.7 Mb.  We hope to demonstrate that our methods are not only cost effective, but improve our ability to annotate challenging genomic regions such as highly repetitive immune gene clusters.