Biology subjects

Heringer, P.

Publications and source records attributed to Heringer, P..

5 recordsLinked to original sources

bioRxiv2026

HPRC2: A human pangenome reference with near-complete coverage of common genetic variation

A pangenome reference overcomes the inherent limitation of any individual reference genome by integrating the variation present in a population. We present the Human Pangenome Reference Consortiums (HPRC) Release 2 (HPRC2), an openly available, second phase pangenome that is an approximately fivefold expansion in genome number over HPRC Release 1 (HPRC1) and measurable improvement in genome completeness, contiguity, and accuracy. Selecting samples with a principled algorithm prioritising common variant coverage, HPRC2 contributes 460 haplotypes that together capture over 99% of common variation observed in the All of Us Research Program v8 cohort. Combining high-coverage long and ultra-long reads with modern assemblers and polishers, we produce thousands of telomere-to-telomere (T2T) chromosomes, and relative to HPRC1 halve the number of structurally unreliable regions as well as individual base errors per haplotype. We complement the assemblies with whole genome multiple alignments and gene annotations, and derive formal pangenome coordinate systems for addressing off-reference variation, demonstrating that individual human genomes contain more than one hundred thousand variants not succinctly described with respect to existing reference genomes. We also present the first matched long-read backed pantranscriptome and panepigenome at this scale, provide continuous local-ancestry estimates spanning every genome, and outline a host of new tools and applications that leverage the pangenome resource for improved genomics analysis.

genomics↗

bioRxiv2025

Human readable compression of GFA paths using grammar-based code

Pangenome graphs offer a compact and comprehensive representation of genomic diversity, improving tasks such as variant calling, genotyping, and other downstream analyses. Although the underlying graph structures scale sublinearly with the number of haplotypes, the widely used GFA file format suffers from rapidly growing file sizes due to the explicit and repetitive encoding of haplotype paths. In this work, we introduce an extension to the GFA format that enables efficient grammar-based compression of haplotype paths while retaining human readability. In addition, grammar-based encoding provides an efficient in-memory data structure that does not require decompression, but conversely improves the runtime of many computational tasks that involve haplotype comparisons. We present sqz, a method that makes use of the proposed format extension to encode haplotype paths using byte pair encoding, a grammar-based compression scheme. We evaluate sqz on recent human pangenome graphs from Heumos et al. and the Human Pangenome Reference Consortium (HPRC), comparing it to existing compressors bgzip, gbz, and sequitur. sqz scales sublinearly with the number of haplotypes in a pangenome graph and consistently achieves higher compression ratios than sequitur and up to 5 times better compression than bgzip in HPRC graphs and up to 10 times in the graph from Heumos et al.. When combined with bgzip, sqz matches or excels the compression ratio of gbz across all our datasets. These results demonstrate the potential of our proposed extension of the GFA format in reducing haplotype path redundancy and improving storage efficiency for pangenome graphs.

bioinformatics↗

bioRxiv2024

Cluster efficient pangenome graph construction with nf-core/pangenome

MotivationPangenome graphs offer a comprehensive way of capturing genomic variability across multiple genomes. However, current construction methods often introduce biases, excluding complex sequences or relying on references. The PanGenome Graph Builder (PGGB) addresses these issues. To date, though, there is no state-of-the-art pipeline allowing for easy deployment, efficient and dynamic use of available resources, and scalable usage at the same time. ResultsTo overcome these limitations, we present nf-core/pangenome, a reference-unbiased approach implemented in Nextflow following nf-cores best practices. Leveraging biocontainers ensures portability and seamless deployment in HPC environments. Unlike PGGB, nf-core/pangenome distributes alignments across cluster nodes, enabling scalability. Demonstrating its efficiency, we constructed pangenome graphs for 1000 human chromosome 19 haplotypes and 2146 E. coli sequences, achieving a two to threefold speedup compared to PGGB without increasing greenhouse gas emissions. Availabilitynf-core/pangenome is released under the MIT open-source license, available on GitHub and Zenodo, with documentation accessible at https://nf-co.re/pangenome/1.1.2/docs/usage. Contactsimon.heumos@qbic.uni-tuebingen.de, sven.nahnsen@qbic.uni-tuebingen.de

bioinformatics↗

bioRxiv2019

De novo identification of satellite DNAs in the sequenced genomes of Drosophila virilis and D. americana using the RepeatExplorer and TAREAN pipelines

Satellite DNAs are among the most abundant repetitive DNAs found in eukaryote genomes, where they participate in a variety of biological roles, from being components of important chromosome structures to gene regulation. Experimental methodologies used before the genomic era were not sufficient despite being too laborious and time-consuming to recover the collection of all satDNAs from a genome. Today, the availability of whole sequenced genomes combined with the development of specific bioinformatic tools are expected to foster the identification of virtually all of the \"satellitome\" from a particular species. While whole genome assemblies are important to obtain a global view of genome organization, most assemblies are incomplete and lack repetitive regions. Here, we applied short-read sequencing and similarity clustering in order to perform a de novo identification of the most abundant satellite families in two Drosophila species from the virilis group: Drosophila virilis and D. americana. These species were chosen because they have been used as a model to understand satDNA biology since early 70s. We combined computational tandem repeat detection via similarity-based read clustering (implemented in Tandem Repeat Analyzer pipeline - \"TAREAN\") with data from the literature and chromosome mapping to obtain an overview of satDNAs in D. virilis and D. americana. The fact that all of the abundant tandem repeats we detected were previously identified in the literature allowed us to evaluate the efficiency of TAREAN in correctly identifying true satDNAs. Our results indicate that raw sequencing reads can be efficiently used to detect satDNAs, but that abundant tandem repeats present in dispersed arrays or associated with transposable elements are frequent false positives. We demonstrate that TAREAN with its parent method RepeatExplorer, may be used as resources to detect tandem repeats associated with transposable elements and also to reveal families of dispersed tandem repeats.

genomics↗

bioRxiv2017

A horizontally transferred autonomous Helitron became a full polydnavirus segment in Cotesia vestalis

Bracoviruses associate symbiotically with thousands of parasitoid wasp species in the family Braconidae, working as virulence gene vectors, and allowing the development of wasp larvae within hosts. These viruses are composed by multiple DNA circles that are packaged into infective particles and injected together with wasp's eggs during parasitization. One of the viral segments of Cotesia vestalis bracovirus contains a gene that has been previously described as a helicase of unknown origin. Here we demonstrate that this gene is a Rep/Helicase from an intact Helitron transposable element that covers the viral segment almost entirely. We also provide evidence that this element underwent at least two horizontal transfers, which appear to have occurred consecutively: first from a Drosophila host ancestor to the genome of the parasitoid wasp Cotesia vestalis and its bracovirus, and then from C. vestalis to a lepidopteran host (Bombyx mori). Our results reinforce the idea of parasitoid wasps as frequent agents of horizontal transfers in eukaryotes. Additionally, this Helitron-bracovirus segment is the first example of a transposable element that effectively became a whole viral circle.

genomics↗