Biology subjects

Hayan Lee

Publications and source records attributed to Hayan Lee.

4 recordsLinked to original sources

bioRxiv2016

Third-generation sequencing and the future of genomics

Third-generation long-range DNA sequencing and mapping technologies are creating a renaissance in high-quality genome sequencing. Unlike second-generation sequencing, which produces short reads a few hundred base-pairs long, third-generation single-molecule technologies generate over 10,000 bp reads or map over 100,000 bp molecules. We analyze how increased read lengths can be used to address longstanding problems in de novo genome assembly, structural variation analysis and haplotype phasing.

Bioinformatics↗

bioRxiv2014

Error correction and assembly complexity of single molecule sequencing reads.

Third generation single molecule sequencing technology is poised to revolutionize genomics by enabling the sequencing of long, individual molecules of DNA and RNA. These technologies now routinely produce reads exceeding 5,000 basepairs, and can achieve reads as long as 50,000 basepairs. Here we evaluate the limits of single molecule sequencing by assessing the impact of long read sequencing in the assembly of the human genome and 25 other important genomes across the tree of life. From this, we develop a new data-driven model using support vector regression that can accurately predict assembly performance. We also present a novel hybrid error correction algorithm for long PacBio sequencing reads that uses pre-assembled Illumina sequences for the error correction. We apply it several prokaryotic and eukaryotic genomes, and show it can achieve near-perfect assemblies of small genomes (< 100Mbp) and substantially improved assemblies of larger ones. All source code and the assembly model are available open-source.

Bioinformatics↗

bioRxiv2014

SplitMEM: Graphical pan-genome analysis with suffix skips

Motivation: With the rise of improved sequencing technologies, genomics is expanding from a single reference per species paradigm into a more comprehensive pan-genome approach with multiple individuals represented and analyzed together. One of the most sophisticated data structures for representing an entire population of genomes is a compressed de Bruijn graph. The graph structure can robustly represent simple SNPs to complex structural variations far beyond what can be done from linear sequences alone. As such there is a strong need to develop algorithms that can efficiently construct and analyze these graphs. Results: In this paper we explore the deep topological relationships between the suffix tree and the compressed de Bruijn graph. We introduce a novel O(n log n) time and space algorithm called splitMEM, that directly constructs the compressed de Bruijn graph for a pan-genome of total length n. To achieve this time complexity, we augment the suffix tree with suffix skips, a new construct that allows us to traverse several suffix links in constant time, and use them to efficiently decompose maximal exact matches (MEMs) into the graph nodes. We demonstrate the utility of splitMEM by analyzing the pan- genomes of 9 strains of Bacillus anthracis and 9 strains of Escherichia coli to reveal the properties of their core genomes. Availability: The source code and documentation are available open- source at http://splitmem.sourceforge.net

Bioinformatics↗

bioRxiv2014

New whole genome de novo assemblies of three divergent strains of rice (O. sativa) documents novel gene space of aus and indica

The use of high throughput genome-sequencing technologies has uncovered a large extent of structural variation in eukaryotic genomes that makes important contributions to genomic diversity and phenotypic variation. Currently, when the genomes of different strains of a given organism are compared, whole genome resequencing data are aligned to an established reference sequence. However when the reference differs in significant structural ways from the individuals under study, the analysis is often incomplete or inaccurate. Here, we use rice as a model to explore the extent of structural variation among strains adapted to different ecologies and geographies, and show that this variation can be significant, often matching or exceeding the variation present in closely related human populations or other mammals. We demonstrate how improvements in sequencing and assembly technology allow rapid and inexpensive de novo assembly of next generation sequence data into high-quality assemblies that can be directly compared to provide an unbiased assessment. Using this approach, we are able to accurately assess the \"pan-genome\" of three divergent rice varieties and document several megabases of each genome absent in the other two. Many of the genome-specific loci are annotated to contain genes, reflecting the potential for new biological properties that would be missed by standard resequencing approaches. We further provide a detailed analysis of several loci associated with agriculturally important traits, illustrating the utility of our approach for biological discovery. All of the data and software are openly available to support further breeding and functional studies of rice and other species.

Genomics↗