Assemblathon 1: a competitive assessment of de novo short read assembly methods.

Low-cost short read sequencing technology has revolutionized genomics, though it is only just becoming practical for the high-quality de novo assembly of a novel large genome. We describe the Assemblathon 1 competition, which aimed to comprehensively assess the state of the art in de novo assembly methods when applied to current sequencing technologies. In a collaborative effort, teams were asked to assemble a simulated Illumina HiSeq data set of an unknown, simulated diploid genome. A total of 41 assemblies from 17 different groups were received. Novel haplotype aware assessments of coverage, contiguity, structure, base calling, and copy number were made. We establish that within this benchmark: (1) It is possible to assemble the genome to a high level of coverage and accuracy, and that (2) large differences exist between the assemblies, suggesting room for further improvements in current methods. The simulated benchmark, including the correct answer, the assemblies, and the code that was used to evaluate the assemblies is now public and freely available from http://www.assemblathon.org/.

Transcriptional consequences of genomic structural aberrations in breast cancer.

Using a long-span, paired-end deep sequencing strategy, we have comprehensively identified cancer genome rearrangements in eight breast cancer genomes. Herein, we show that 40%-54% of these structural genomic rearrangements result in different forms of fusion transcripts and that 44% are potentially translated. We find that single segmental tandem duplication spanning several genes is a major source of the fusion gene transcripts in both cell lines and primary tumors involving adjacent genes placed in the reverse-order position by the duplication event. Certain other structural mutations, however, tend to attenuate gene expression. From these candidate gene fusions, we have found a fusion transcript (RPS6KB1-VMP1) recurrently expressed in ∼30% of breast cancers associated with potential clinical consequences. This gene fusion is caused by tandem duplication on 17q23 and appears to be an indicator of local genomic instability altering the expression of oncogenic components such as MIR21 and RPS6KB1.

PE-Assembler: de novo assembler using short paired-end reads.

MOTIVATION: Many de novo genome assemblers have been proposed recently. The basis for most existing methods relies on the de bruijn graph: a complex graph structure that attempts to encompass the entire genome. Such graphs can be prohibitively large, may fail to capture subtle information and is difficult to be parallelized. RESULT: We present a method that eschews the traditional graph-based approach in favor of a simple 3' extension approach that has potential to be massively parallelized. Our results show that it is able to obtain assemblies that are more contiguous, complete and less error prone compared with existing methods. AVAILABILITY: The software package can be found at http://www.comp.nus.edu.sg/~bioinfo/peasm/. Alternatively it is available from authors upon request.

ChIA-PET tool for comprehensive chromatin interaction analysis with paired-end tag sequencing.

Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. Here we present ChIA-PET Tool, a software package for automatic processing of ChIA-PET sequence data, including linker filtering, mapping tags to reference genomes, identifying protein binding sites and chromatin interactions, and displaying the results on a graphical genome browser. ChIA-PET Tool is fast, accurate, comprehensive, user-friendly, and open source (available at http://chiapet.gis.a-star.edu.sg).