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Dufresne, Y.

Publications and source records attributed to Dufresne, Y..

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Binary search and and set operations on compacted k-mer lists

Sorted lists of elements are particularly good for computing set operations. A single scan of two lists is sufficient to materialize or count the results of the union, intersection, difference, and xor operators. In bioinformatics, only a few tools are designed to perform these operations on k-mers. A fast tool like KMC allows set operations at the cost of storing individual k-mers. In this paper, we introduce a novel way to represent sorted k-mers as a collection of recomposed super-k-mer sorted lists. We introduce the concept of virtual super-k-mer and show how to construct, query and perform set operations on sorted lists of virtual super-k-mers. In the implementation sklib, we demonstrate high throughput of the data structure for construction and set operations, while remaining competitive in query capabilities, within a controlled memory footprint (3.5-4.1x decrease in bits/element compared to KMC).

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Brisk: Exact resource-efficient dictionary for k-mers

The rapid advancements in DNA sequencing technology have led to an unprecedented increase in the generation of genomic datasets, with modern sequencers now capable of producing up to ten terabases per run. However, the effective indexing and analysis of this vast amount of data pose significant challenges to the scientific community. K-mer indexing has proven crucial in managing extensive datasets across a wide range of applications, including alignment, compression, dataset comparison, error correction, assembly, and quantification. As a result, developing efficient and scalable k-mer indexing methods has become an increasingly important area of research. Despite the progress made, current state-of-the-art indexing structures are predominantly static, necessitating resource-intensive index reconstruction when integrating new data. Recently, the need for dynamic indexing structures has been recognized. However, many proposed solutions are only pseudo-dynamic, requiring substantial updates to justify the costs of adding new datasets. In practice, applications often rely on standard hash tables to associate data with their k-mers, leading to high k-mer encoding rates exceeding 64 bits per k-mer. In this work, we introduce Brisk, a drop-in replacement for most k-mer dictionary applications. This novel hashmap-like data structure provides high throughput while significantly reducing memory usage compared to existing dynamic associative indexes, particularly for large k-mer sizes. Brisk achieves this by leveraging hierarchical minimizer indexing and memory-efficient super-k-mer representation. We also introduce novel techniques for efficiently probing k-mers within a set of super-k-mers and managing duplicated minimizers. We believe that the methodologies developed in this work represent a significant advancement in the creation of efficient and scalable k-mer dictionaries, greatly facilitating their routine use in genomic data analysis.

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The Backpack Quotient Filter: a dynamic and space-efficient data structure for querying k-mers with abundance.

Genomic data sequencing has become indispensable for elucidating the complexities of biological systems. As databases storing genomic information, such as the European Nucleotide Archive, continue to grow exponentially, efficient solutions for data manipulation are imperative. One funda-mental operation that remains challenging is querying these databases to determine the presence or absence of specific sequences and their abundance within datasets. This paper introduces a novel data structure indexing k-mers (substrings of length k), the Back-pack Quotient Filter (BQF), which serves as an alternative to the Counting Quotient Filter (CQF). The BQF offers enhanced space efficiency compared to the CQF while retaining key properties, including abundance information and dynamicity, with a negligible false positive rate, below 10-5%. The approach involves a redefinition of how abundance information is handled within the structure, alongside with an independent strategy for space efficiency. We show that the BQF uses 4x less space than the CQF on some of the most complex data to index: sea-water metagenomics sequences. Furthermore, we show that space efficiency increases as the amount of data to be indexed increases, which is in line with the original objective of scaling to ever-larger datasets. Availabilityhttps://github.com/vicLeva/bqf

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Construction and representation of human pangenome graphs

As a single reference genome cannot possibly represent all the variation present across human individuals, pangenome graphs have been introduced to incorporate population diversity within a wide range of genomic analyses. Several data structures have been proposed for representing collections of genomes as pangenomes, in particular graphs. In this work we collect all publicly available high-quality human haplotypes and constructed the largest human pangenome graphs to date, incorporating 52 individuals in addition to two synthetic references (CHM13 and GRCh38). We build variation graphs and de Bruijn graphs of this collection using five of the state-of-the-art tools: Bifrost, mdbg, Minigraph, Minigraph-Cactus and pggb. We examine differences in the way each of these tools represents variations between input sequences, both in terms of overall graph structure and representation of specific genetic loci. This work sheds light on key differences between pangenome graph representations, informing end-users on how to select the most appropriate graph type for their application.

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Compression algorithms for colored de Bruijn graphs

A colored de Bruijn graph (also called a set of k-mer sets), is a set of k-mers with every k-mer assigned a set of colors. Colored de Bruijn graphs are used in a variety of applications, including variant calling, genome assembly, and database search. However, their size has posed a scalability challenge to algorithm developers and users. There have been numerous indexing data structures proposed that allow to store the graph compactly while supporting fast query operations. However, disk compression algorithms, which do not need to support queries on the compressed data and can thus be more space-efficient, have received little attention. The dearth of specialized compression tools has been a detriment to tool developers, tool users, and reproducibility efforts. In this paper, we develop a new tool that compresses colored de Bruijn graphs to disk, building on previous ideas for compression of k-mer sets and indexing colored de Bruijn graphs. We test our tool, called ESS-color, on various datasets, including both sequencing data and whole genomes. ESS-color achieves better compression than all evaluated tools and all datasets, with no other tool able to consistently achieve less than 44% space overhead. The software is available at http://github.com/medvedevgroup/ESSColor.

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BioConvert: a comprehensive format converter for life sciences

AO_SCPLOWBSTRACTC_SCPLOWBioinformatics is a field known for the numerous standards and formats that have been developed over the years. This plethora of formats, sometimes complementary, and often redundant, poses many challenges to bioinformatics data analysts. They constantly need to find the best tool to convert their data into the suitable format, which is often a complex, technical and time consuming task. Moreover, these small yet important tasks are often difficult to make reproducible. To over-come these difficulties, we initiated BioConvert, a collaborative project to facilitate the conversion of life science data from one format to another. BioConvert aggregates existing software within a single framework and complemented them with original code when needed. It provides a common interface to make the user experience more streamlined instead of having to learn tens of them. Currently, BioConvert supports about 50 formats and 100 direct conversions in areas such as alignment, sequencing, phylogeny, and variant calling. In addition to being useful for end-users, BioConvert can also be utilized by developers as a universal benchmarking framework for evaluating and comparing numerous conversion tools. Additionally, we provide a web server implementing an online user-friendly interface to BioConvert, hence allowing direct use for the community.

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Read correction for non-uniform coverages

Next generation sequencing produces large volumes of short sequences with broad applications. The noise due to sequencing errors led to the development of several correction methods. The main correction paradigm expects a high (from 30-40X) uniform coverage to correctly infer a reference set of subsequences from the reads, that are used for correction. In practice, most accurate methods use k-mer spectrum techniques to obtain a set of reference k-mers. However, when correcting NGS datasets that present an uneven coverage, such as RNA-seq data, this paradigm tends to mistake rare variants for errors. It may therefore discard or alter them using highly covered sequences, which leads to an information loss and may introduce bias. In this paper we present two new contributions in order to cope with this situation.\n\nFirst, we show that starting from non-uniform sequencing coverages, a De Bruijn graph can be cleaned from most errors while preserving biological variability. Second, we demonstrate that reads can be efficiently corrected via local alignment on the cleaned De Bruijn graph paths. We implemented the described method in a tool dubbed BCT and evaluated its results on RNA-seq and metagenomic data. We show that the graph cleaning strategy combined with the mapping strategy leads to save more rare k-mers, resulting in a more conservative correction than previous methods. BCT is also capable to better take advantage of the signal of high depth datasets. We suggest that BCT, being scalable to large metagenomic datasets as well as correcting shallow single cell RNA-seq data, can be a general corrector for non-uniform data. Availability: BCT is open source and available at github.com/Malfoy/BCT under the Affero GPL License.

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MATAM: Reconstruction Of Phylogenetic Marker Genes From Short Sequencing Reads In Metagenomes

MotivationAdvances in the sequencing of uncultured environmental samples, dubbed metagenomics, raise a growing need for accurate taxonomic assignment. Accurate identification of organisms present within a community is essential to understanding even the most elementary ecosystems. However, current high-throughput sequencing technologies generate short reads which partially cover full-length marker genes and this poses difficult bioinformatic challenges for taxonomy identification at high resolution\n\nResultsWe designed MATAM, a software dedicated to the fast and accurate targeted assembly of short reads sequenced from a genomic marker of interest. The method implements a stepwise process based on construction and analysis of a read overlap graph. It is applied to the assembly of 16S rRNA markers and is validated on simulated, synthetic and genuine metagenomes. We show that MATAM outperforms other available methods in terms of low error rates and recovered genome fractions and is suitable to provide improved assemblies for precise taxonomic assignments.\n\nAvailabilityhttps://github.com/bonsai-team/matam\n\nContactpierre.pericard@gmail.com, helene.touzet@univ-lille1.fr

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