Platanus-allee is a de novo haplotype assembler enabling a comprehensive access to divergent heterozygous regions

Abstract

The ultimate goal for diploid genome determination is to completely decode homologous chromosomes independently, and several phasing programs from consensus sequences have been developed. These methods work well for lowly heterozygous genomes, but the manifold species have high heterozygosity. Additionally, there are highly divergent regions (HDRs), where the haplotype sequences differ considerably. Because HDRs are likely to direct various interesting biological phenomena, many genomic analysis targets fall within these regions. However, they cannot be accessed by existing phasing methods, and we have to adopt costly traditional methods. Here, we develop a de novo haplotype assembler, Platanus-allee ( http://platanus.bio.titech.ac.jp/platanus2 ), which initially constructs each haplotype sequence and then untangles the assembly graphs utilizing sequence links and synteny information. A comprehensive benchmark analysis reveals that Platanus-allee exhibits high recall and precision, particularly for HDRs. Using this approach, previously unknown HDRs are detected in the human genome, which may uncover novel aspects of genome variability.

A single polyploidization event at the origin of the tetraploid genome of Coffea arabica is responsible for the extremely low genetic variation in wild and cultivated germplasm

“…The accuracy of genome sequencing and assembly of complex genomes is affected by different factors ranging from plant material availability to genome size, GC content, repeat content, ploidy level, sequencing technology, and bioinformatic software [19][20][21][22] . Long-read sequencing technologies, such as those of Pacific Biosciences or Oxford Nanopore Technologies, are currently used for reconstructing Mb-long chromosome sequences or both haplotypes of highly heterozygous genomes [23][24][25][26][27] . Short-read sequencing is less expensive, provides more coverage with the same investment and thus more sequence accuracy, but it leads to more fragmented assemblies.…”

A universal subcuticular bacterial symbiont of a coral predator, the crown-of-thorns starfish, in the Indo-Pacific

“…The average coverage depth for all scaffolds was ×130. The longest scaffold, which was identified as the COTS27 chromosome, was closed by Sanger sequencing, and an alternative assembly was obtained using Platanus-allee v. 2.0.0 [47]. A circular view of the COTS27 chromosome was created using CGView Server [48] and manual processing.…”

Recovering individual haplotypes and a contiguous genome assembly from pooled long read sequencing of the diamondback moth (Lepidoptera: Plutellidae)

“…Nevertheless, the reconstruction of these data into accurate haploid (or phased diploid) genome representations still poses a challenge. In particular, current algorithms are not fully robust to differences in heterozygosity between loci and across clades (2). Importantly, the differences in type and structure of heterozygosity are the consequences of unique evolutionary histories.…”

“…A particularly challenging aspect of genome assembly is the detection of highly divergent regions (HDRs) (2), which often cannot be determined as allelic within the assembly process and requires supervised analysis (3). HDRs are likely to be biologically important and may indicate regions experiencing diversifying selection, for example the MHC locus in humans (4).…”

“…These simple occurrences can be partitioned and subsequently collapsed or phased (2,5,7). Alternatively, pedigree information, such as trios, can be leveraged by either partitioning F1 read data a priori (8,9) or integrating the pedigree information into the assembly graph itself (10).…”