Dominique Lavenier

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/.

Critical assessment of metagenome interpretation − a benchmark of computational metagenomics software

Methods for assembly, taxonomic profiling and binning are key to interpreting metagenome data, but a lack of consensus about benchmarking complicates performance assessment. The Critical Assessment of Metagenome Interpretation (CAMI) challenge has engaged the global developer community to benchmark their programs on highly complex and realistic data sets, generated from ∼700 newly sequenced microorganisms and ∼600 novel viruses and plasmids and representing common experimental setups. Assembly and genome binning programs performed well for species represented by individual genomes but were substantially affected by the presence of related strains. Taxonomic profiling and binning programs were proficient at high taxonomic ranks, with a notable performance decrease below family level. Parameter settings markedly affected performance, underscoring their importance for program reproducibility. The CAMI results highlight current challenges but also provide a roadmap for software selection to answer specific research questions.

SAMBA: hardware accelerator for biological sequence comparison

MOTIVATION SAMBA (Systolic Accelerator for Molecular Biological Applications) is a 128 processor hardware accelerator for speeding up the sequence comparison process. The short-term objective is to provide a low-cost board to boost PC or workstation performance on this class of applications. This paper places SAMBA amongst other existing systems and highlights the original features. RESULTS Real performance obtained from the prototype is demonstrated. For example, a sequence of 300 amino acids is scanned against SWISS-PROT-34 (21 210 389 residues) in 30 s using the Smith and Waterman algorithm. More time-consuming applications, like the bank-to-bank comparison, are computed in a few hours instead of days on standard workstations. Technology allows the prototype to fit onto a single PCI board for plugging into any PC or workstation. AVAILABILITY SAMBA can be tested on the WEB server at URL http://www.irisa.fr/SAMBA/.

Reference-free compression of high throughput sequencing data with a probabilistic de Bruijn graph

AbstractBackgroundData volumes generated by next-generation sequencing (NGS) technologies is now a major concern for both data storage and transmission. This triggered the need for more efficient methods than general purpose compression tools, such as the widely used gzip method.ResultsWe present a novel reference-free method meant to compress data issued from high throughput sequencing technologies. Our approach, implemented in the software Leon, employs techniques derived from existing assembly principles. The method is based on a reference probabilistic de Bruijn Graph, built de novo from the set of reads and stored in a Bloom filter. Each read is encoded as a path in this graph, by memorizing an anchoring kmer and a list of bifurcations. The same probabilistic de Bruijn Graph is used to perform a lossy transformation of the quality scores, which allows to obtain higher compression rates without losing pertinent information for downstream analyses.ConclusionsLeon was run on various real sequencing datasets (whole genome, exome, RNA-seq or metagenomics). In all cases, LEON showed higher overall compression ratios than state-of-the-art compression software. On a C. elegans whole genome sequencing dataset, LEON divided the original file size by more than 20. Leon is an open source software, distributed under GNU affero GPL License, available for download at http://gatb.inria.fr/software/leon/.

PLAST: parallel local alignment search tool for database comparison.

BackgroundSequence similarity searching is an important and challenging task in molecular biology and next-generation sequencing should further strengthen the need for faster algorithms to process such vast amounts of data. At the same time, the internal architecture of current microprocessors is tending towards more parallelism, leading to the use of chips with two, four and more cores integrated on the same die. The main purpose of this work was to design an effective algorithm to fit with the parallel capabilities of modern microprocessors.ResultsA parallel algorithm for comparing large genomic banks and targeting middle-range computers has been developed and implemented in PLAST software. The algorithm exploits two key parallel features of existing and future microprocessors: the SIMD programming model (SSE instruction set) and the multithreading concept (multicore). Compared to multithreaded BLAST software, tests performed on an 8-processor server have shown speedup ranging from 3 to 6 with a similar level of accuracy.ConclusionA parallel algorithmic approach driven by the knowledge of the internal microprocessor architecture allows significant speedup to be obtained while preserving standard sensitivity for similarity search problems.

Systolic filter for fast DNA similarity search

This paper presents a systolic filter for speeding up the scan of DNA databases. The filter acts as a co-processor which performs the more intensive computations occurring during the process. Our validation, based on a FPGA prototype board tightly connected to a workstation, has shown that the filter may boost the performance of the machine by a factor ranging from 50 to 400 over current workstations.

Critical Assessment of Metagenome Interpretation — a benchmark of metagenomics software

Methods for assembly, taxonomic profiling and binning are key to interpreting metagenome data, but a lack of consensus about benchmarking complicates performance assessment. The Critical Assessment of Metagenome Interpretation (CAMI) challenge has engaged the global developer community to benchmark their programs on highly complex and realistic data sets, generated from ∼700 newly sequenced microorganisms and ∼600 novel viruses and plasmids and representing common experimental setups. Assembly and genome binning programs performed well for species represented by individual genomes but were substantially affected by the presence of related strains. Taxonomic profiling and binning programs were proficient at high taxonomic ranks, with a notable performance decrease below family level. Parameter settings markedly affected performance, underscoring their importance for program reproducibility. The CAMI results highlight current challenges but also provide a roadmap for software selection to answer specific research questions.

Rapid transcriptional plasticity of duplicated gene clusters enables a clonally reproducing aphid to colonise diverse plant species

BackgroundThe prevailing paradigm of host-parasite evolution is that arms races lead to increasing specialisation via genetic adaptation. Insect herbivores are no exception and the majority have evolved to colonise a small number of closely related host species. Remarkably, the green peach aphid, Myzus persicae, colonises plant species across 40 families and single M. persicae clonal lineages can colonise distantly related plants. This remarkable ability makes M. persicae a highly destructive pest of many important crop species.ResultsTo investigate the exceptional phenotypic plasticity of M. persicae, we sequenced the M. persicae genome and assessed how one clonal lineage responds to host plant species of different families. We show that genetically identical individuals are able to colonise distantly related host species through the differential regulation of genes belonging to aphid-expanded gene families. Multigene clusters collectively upregulate in single aphids within two days upon host switch. Furthermore, we demonstrate the functional significance of this rapid transcriptional change using RNA interference (RNAi)-mediated knock-down of genes belonging to the cathepsin B gene family. Knock-down of cathepsin B genes reduced aphid fitness, but only on the host that induced upregulation of these genes.ConclusionsPrevious research has focused on the role of genetic adaptation of parasites to their hosts. Here we show that the generalist aphid pest M. persicae is able to colonise diverse host plant species in the absence of genetic specialisation. This is achieved through rapid transcriptional plasticity of genes that have duplicated during aphid evolution.

GATB: Genome Assembly & Analysis Tool Box

Motivation: Efficient and fast next-generation sequencing (NGS) algorithms are essential to analyze the terabytes of data generated by the NGS machines. A serious bottleneck can be the design of such algorithms, as they require sophisticated data structures and advanced hardware implementation. Results: We propose an open-source library dedicated to genome assembly and analysis to fasten the process of developing efficient software. The library is based on a recent optimized de-Bruijn graph implementation allowing complex genomes to be processed on desktop computers using fast algorithms with low memory footprints. Availability and implementation: The GATB library is written in C++ and is available at the following Web site http://gatb.inria.fr under the A-GPL license. Contact: lavenier@irisa.fr Supplementary information: Supplementary data are available at Bioinformatics online.

Designing specific systolic arrays with the API15C chip

The API15C processor, a building block for different systolic structures, is designed exclusively for single-instruction-multiple data (SIMD) execution mode. To support this mode, the instruction set includes special control instructions. Three parallel I/O ports are available for different interconnection schemes. The API15C chip is designed in a CMOS 2- mu m technology. It contains 45000 transistors on a 6-mm