Biology subjects

Ko, B. J.

Publications and source records attributed to Ko, B. J..

3 recordsLinked to original sources

bioRxiv2021

False gene and chromosome losses affected by assembly and sequence errors

Many genome assemblies have been found to be incomplete and contain misassemblies. The Vertebrate Genomes Project (VGP) has been producing assemblies with an emphasis on being as complete and error-free as possible, utilizing long reads, long-range scaffolding data, new assembly algorithms, and manual curation. Here we evaluate these new vertebrate genome assemblies relative to the previous references for the same species, including a mammal (platypus), two birds (zebra finch, Annas hummingbird), and a fish (climbing perch). We found that 3 to 11% of genomic sequence was entirely missing in the previous reference assemblies, which included nearly entire GC-rich and repeat-rich microchromosomes with high gene density. Genome-wide, between 25 to 60% of the genes were either completely or partially missing in the previous assemblies, and this was in part due to a bias in GC-rich 5-proximal promoters and 5 exon regions. Our findings reveal novel regulatory landscapes and protein coding sequences that have been greatly underestimated in previous assemblies and are now present in the VGP assemblies.

genomics↗

bioRxiv2021

Widespread false gene gains caused by duplication errors in genome assemblies

False duplications in genome assemblies lead to false biological conclusions. We quantified false duplications in previous genome assemblies and their new counterparts of the same species (platypus, zebra finch, Annas hummingbird) generated by the Vertebrate Genomes Project (VGP). Whole genome alignments revealed that 4 to 16% of the sequences were falsely duplicated in the previous assemblies, impacting hundreds to thousands of genes. These led to overestimated gene family expansions. The main source of the false duplications was heterotype duplications, where the haplotype sequences were more divergent than other parts of the genome leading the assembly algorithms to classify them as separate genes or genomic regions. A minor source was sequencing errors. Although present in a smaller proportion, we observed false duplications remaining in the VGP assemblies that can be identified and purged. This study highlights the need for more advanced assembly methods that better separates haplotypes and sequence errors, and the need for cautious analyses on gene gains.

genomics↗

bioRxiv2020

Towards complete and error-free genome assemblies of all vertebrate species

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are only available for a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling the most accurate and complete reference genomes to date. Here we summarize these developments, introduce a set of quality standards, and present lessons learned from sequencing and assembling 16 species representing major vertebrate lineages (mammals, birds, reptiles, amphibians, teleost fishes and cartilaginous fishes). We confirm that long-read sequencing technologies are essential for maximizing genome quality and that unresolved complex repeats and haplotype heterozygosity are major sources of error in assemblies. Our new assemblies identify and correct substantial errors in some of the best historical reference genomes. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an effort to generate high-quality, complete reference genomes for all ~70,000 extant vertebrate species and help enable a new era of discovery across the life sciences.

genomics↗