OMGS: Optical Map-Based Genome Scaffolding.

Due to the current limitations of sequencing technologies, de novo genome assembly is typically carried out in two stages, namely contig (sequence) assembly and scaffolding. While scaffolding is computationally easier than sequence assembly, the scaffolding problem can be challenging due to the high repetitive content of eukaryotic genomes, possible mis-joins in assembled contigs, and inaccuracies in the linkage information. Genome scaffolding tools either use paired-end/mate-pair/linked/Hi-C reads or genome-wide maps (optical, physical, or genetic) as linkage information. Optical maps (in particular Bionano Genomics maps) have been extensively used in many recent large-scale genome assembly projects (e.g., goat, apple, barley, maize, quinoa, sea bass, among others). However, the most commonly used scaffolding tools have a serious limitation: they can only deal with one optical map at a time, forcing users to alternate or iterate over multiple maps. In this article, we introduce a novel scaffolding algorithm called OMGS (Optical Map-based Genome Scaffolding) that for the first time can take advantages of multiple optical maps. OMGS solves several optimization problems to generate scaffolds with optimal contiguity and correctness. Extensive experimental results demonstrate that our tool outperforms existing methods when multiple optical maps are available and produces comparable scaffolds using a single optical map.

Pan W ，Jiang T ，Lonardi S 《-》

Novo&Stitch: accurate reconciliation of genome assemblies via optical maps.

De novo genome assembly is a challenging computational problem due to the high repetitive content of eukaryotic genomes and the imperfections of sequencing technologies (i.e. sequencing errors, uneven sequencing coverage and chimeric reads). Several assembly tools are currently available, each of which has strengths and weaknesses in dealing with the trade-off between maximizing contiguity and minimizing assembly errors (e.g. mis-joins). To obtain the best possible assembly, it is common practice to generate multiple assemblies from several assemblers and/or parameter settings and try to identify the highest quality assembly. Unfortunately, often there is no assembly that both maximizes contiguity and minimizes assembly errors, so one has to compromise one for the other. The concept of assembly reconciliation has been proposed as a way to obtain a higher quality assembly by merging or reconciling all the available assemblies. While several reconciliation methods have been introduced in the literature, we have shown in one of our recent papers that none of them can consistently produce assemblies that are better than the assemblies provided in input. Here we introduce Novo&Stitch, a novel method that takes advantage of optical maps to accurately carry out assembly reconciliation (assuming that the assembled contigs are sufficiently long to be reliably aligned to the optical maps, e.g. 50 Kbp or longer). Experimental results demonstrate that Novo&Stitch can double the contiguity (N50) of the input assemblies without introducing mis-joins or reducing genome completeness. Novo&Stitch can be obtained from https://github.com/ucrbioinfo/Novo_Stitch.

Pan W ，Wanamaker SI ，Ah-Fong AMV ，Judelson HS ，Lonardi S ... -  《-》

Accurate detection of chimeric contigs via Bionano optical maps.

A chimeric contig is contig that has been incorrectly assembled, i.e. a contig that contains one or more mis-joins. The detection of chimeric contigs can be carried out either by aligning assembled contigs to genome-wide maps (e.g. genetic, physical or optical maps) or by mapping sequenced reads to the assembled contigs. Here, we introduce a software tool called Chimericognizer that takes advantage of one or more Bionano Genomics optical maps to accurately detect and correct chimeric contigs. Experimental results show that Chimericognizer is very accurate, and significantly better than the chimeric detection method offered by the Bionano Hybrid Scaffold pipeline. Chimericognizer can also detect and correct chimeric optical molecules. https://github.com/ucrbioinfo/Chimericognizer. Supplementary data are available at Bioinformatics online.

Pan W ，Lonardi S 《-》

Scaffolding pre-assembled contigs using SSPACE.

De novo assembly tools play a main role in reconstructing genomes from next-generation sequencing (NGS) data and usually yield a number of contigs. Using paired-read sequencing data it is possible to assess the order, distance and orientation of contigs and combine them into so-called scaffolds. Although the latter process is a crucial step in finishing genomes, scaffolding algorithms are often built-in functions in de novo assembly tools and cannot be independently controlled. We here present a new tool, called SSPACE, which is a stand-alone scaffolder of pre-assembled contigs using paired-read data. Main features are: a short runtime, multiple library input of paired-end and/or mate pair datasets and possible contig extension with unmapped sequence reads. SSPACE shows promising results on both prokaryote and eukaryote genomic testsets where the amount of initial contigs was reduced by at least 75%.

Boetzer M ，Henkel CV ，Jansen HJ ，Butler D ，Pirovano W ... -  《-》

Improvement of the Threespine Stickleback Genome Using a Hi-C-Based Proximity-Guided Assembly.

Scaffolding genomes into complete chromosome assemblies remains challenging even with the rapidly increasing sequence coverage generated by current next-generation sequence technologies. Even with scaffolding information, many genome assemblies remain incomplete. The genome of the threespine stickleback (Gasterosteus aculeatus), a fish model system in evolutionary genetics and genomics, is not completely assembled despite scaffolding with high-density linkage maps. Here, we first test the ability of a Hi-C based proximity-guided assembly (PGA) to perform a de novo genome assembly from relatively short contigs. Using Hi-C based PGA, we generated complete chromosome assemblies from a distribution of short contigs (20-100 kb). We found that 96.40% of contigs were correctly assigned to linkage groups (LGs), with ordering nearly identical to the previous genome assembly. Using available bacterial artificial chromosome (BAC) end sequences, we provide evidence that some of the few discrepancies between the Hi-C assembly and the existing assembly are due to structural variation between the populations used for the 2 assemblies or errors in the existing assembly. This Hi-C assembly also allowed us to improve the existing assembly, assigning over 60% (13.35 Mb) of the previously unassigned (~21.7 Mb) contigs to LGs. Together, our results highlight the potential of the Hi-C based PGA method to be used in combination with short read data to perform relatively inexpensive de novo genome assemblies. This approach will be particularly useful in organisms in which it is difficult to perform linkage mapping or to obtain high molecular weight DNA required for other scaffolding methods.

Peichel CL ，Sullivan ST ，Liachko I ，White MA ... -  《-》