Jana Ebler
A5077819335- Genomics and Phylogenetic Studies
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Chromosomal and Genetic Variations
- Gene expression and cancer classification
- Machine Learning in Bioinformatics
- Medical Imaging and Pathology Studies
- RNA and protein synthesis mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Bioinformatics and Genomic Networks
- Medical Imaging Techniques and Applications
- Interactive and Immersive Displays
- Genetic Mapping and Diversity in Plants and Animals
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Genetic Associations and Epidemiology
- Genetic diversity and population structure
- Cancer Genomics and Diagnostics
- Physics and Engineering Research Articles
- Radiation Dose and Imaging
- Plant Pathogens and Resistance
- Genome Rearrangement Algorithms
- Lymphoma Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Prenatal Screening and Diagnostics
Heinrich Heine University Düsseldorf
2020-2024
Max Planck Institute for Informatics
2018-2021
Jackson Laboratory
2021
Saarland University
2016-2020
Abstract Here the Human Pangenome Reference Consortium presents a first draft of human pangenome reference. The contains 47 phased, diploid assemblies from cohort genetically diverse individuals 1 . These cover more than 99% expected sequence in each genome and are accurate at structural base pair levels. Based on alignments assemblies, we generate that captures known variants haplotypes reveals new alleles structurally complex loci. We also add 119 million pairs euchromatic polymorphic...
Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent-child trio data. We present 64 assembled haplotypes from 32 diverse genomes. These highly contiguous haplotype assemblies (average minimum contig length needed to cover 50% genome: 26 million base pairs) integrate all forms genetic variation, even across complex loci. identified 107,590 structural variants (SVs), which 68% were not...
Abstract Human genomes are typically assembled as consensus sequences that lack information on parental haplotypes. Here we describe a reference-free workflow for diploid de novo genome assembly combines the chromosome-wide phasing and scaffolding capabilities of single-cell strand sequencing 1,2 with continuous long-read or high-fidelity 3 data. Employing this strategy, produced completely phased each haplotype an individual Puerto Rican descent (HG00733) in absence The assemblies accurate...
Abstract Typical genotyping workflows map reads to a reference genome before identifying genetic variants. Generating such alignments introduces biases and comes with substantial computational burden. Furthermore, short-read lengths limit the ability characterize repetitive genomic regions, which are particularly challenging for fast k -mer-based genotypers. In present study, we propose new algorithm, PanGenie, that leverages haplotype-resolved pangenome together -mer counts from sequencing...
Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 in 41 human genomes. Approximately 85% of <2 kbp form by twin-priming during L1 retrotransposition; 80% the larger are balanced and affect twice as many nucleotides CNVs. Balanced show excess common variants, 72% flanked segmental duplications (SDs) or retrotransposons. Since flanking repeats promote non-allelic homologous...
Abstract The short arms of the human acrocentric chromosomes 13, 14, 15, 21 and 22 (SAACs) share large homologous regions, including ribosomal DNA repeats extended segmental duplications 1,2 . Although resolution these regions in first complete assembly a genome—the Telomere-to-Telomere Consortium’s CHM13 (T2T-CHM13)—provided model their homology 3 , it remained unclear whether patterns were ancestral or maintained by ongoing recombination exchange. Here we show that contain...
Abstract The Human Pangenome Reference Consortium (HPRC) presents a first draft human pangenome reference. contains 47 phased, diploid assemblies from cohort of genetically diverse individuals. These cover more than 99% the expected sequence and are accurate at structural base-pair levels. Based on alignments assemblies, we generated that captures known variants haplotypes, reveals novel alleles structurally complex loci, adds 119 million base pairs euchromatic polymorphic 1,529 gene...
Abstract Single-nucleotide variants (SNVs) in segmental duplications (SDs) have not been systematically assessed because of the limitations mapping short-read sequencing data 1,2 . Here we constructed 1:1 unambiguous alignments spanning high-identity SDs across 102 human haplotypes and compared pattern SNVs between unique duplicated regions 3,4 We find that are elevated 60% to estimate at least 23% this increase is due interlocus gene conversion (IGC) with up 4.3 megabase pairs SD sequence...
The telomere-to-telomere (T2T) complete human reference has significantly improved our ability to characterize genome structural variation. To understand its impact on inversion polymorphisms, we remapped data from 41 genomes against the T2T and compared it GRCh38 reference. We find a ~ 21% increase in sensitivity improving mapping of 63 inversions identify 26 misorientations within show that is three times more likely represent correct orientation major allele. Analysis 10 additional...
Structural variants (SVs) contribute significantly to human genetic diversity and disease
Diverse sets of complete human genomes are required to construct a pangenome reference and understand the extent complex structural variation. Here, we sequence 65 diverse build 130 haplotype-resolved assemblies (130 Mbp median continuity), closing 92% all previous assembly gaps reaching telomere-to-telomere (T2T) status for 39% chromosomes. We highlight continuity loci, including major histocompatibility (MHC), SMN1/SMN2, NBPF8, AMY1/AMY2, fully resolve 1,852 variants (SVs). In addition,...
Abstract Resolving genomes at haplotype level is crucial for understanding the evolutionary history of polyploid species and designing advanced breeding strategies. Polyploid phasing still presents considerable challenges, especially in regions collapsing haplotypes.We present WhatsHap polyphase , a novel two-stage approach that addresses these challenges by (i) clustering reads (ii) threading haplotypes through clusters. Our method outperforms state-of-the-art terms quality. Using real...
Current genotyping approaches for single-nucleotide variations rely on short, accurate reads from second-generation sequencing devices. Presently, third-generation platforms are rapidly becoming more widespread, yet leveraging their long but error-prone lacking. Here, we introduce a novel statistical framework the joint inference of haplotypes and genotypes noisy reads, which term diplotyping. Our technique takes full advantage linkage information provided by reads. We validate hundreds...
Accurate detection of somatic structural variation (SV) in cancer genomes remains a challenging problem. This is part due to the lack high-quality, gold-standard datasets that enable benchmarking experimental approaches and bioinformatic analysis pipelines. Here, we performed SV paired melanoma normal lymphoblastoid COLO829 cell lines using four different sequencing technologies. Based on evidence from multiple technologies combined with extensive validation, compiled comprehensive set...
Abstract Reference genomes provide mapping targets and coordinate systems but introduce biases when samples under study diverge sufficiently from them. Pangenome references seek to address this by storing a representative set of diverse haplotypes their alignment, usually as graph. Alternate alleles determined variant callers can be used construct pangenome graphs, thanks advances in long-read sequencing, high-quality phased assemblies are becoming widely available. Constructing graph...
Brief summary: The Human Pangenome Reference Consortium reports a first draft of the human pangenome reference due to replace existing GRCh38 (1, 2). It is an updated, high-quality, graph-based, telomere-to-telomere representation global genomic diversity including common variants (single-nucleotide variants, structural and functional elements).
Abstract The major DNA sequencing technologies in use today produce either highly-accurate short reads or noisy long reads. We developed a protocol based on single-molecule, circular consensus (CCS) to generate (99.8%) averaging 13.5 kb and applied it sequence the well-characterized human HG002/NA24385. optimized existing tools comprehensively detect variants, achieving precision recall above 99.91% for SNVs, 95.98% indels, 95.99% structural variants. estimate that 2,434 discordances are...
The mutational landscape of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common pediatric cancer, is not fully described partially because commonly applied short-read next generation sequencing has a limited ability to identify structural variations. By combining comprehensive analysis variants (SVs), single-nucleotide (SNVs), and small insertions-deletions, new subtype-defining therapeutic targets may be detected. We analyzed somatic alterations in 60 patients diagnosed...
Advances in long-read sequencing (LRS) technologies continue to make whole-genome more complete, affordable, and accurate. LRS provides significant advantages over short-read approaches, including phased de novo genome assembly, access previously excluded genomic regions, discovery of complex structural variants (SVs) associated with disease. Limitations remain respect cost, scalability, platform-dependent read accuracy the tradeoffs between sequence coverage sensitivity variant are...
The linear human reference genome that we use today does not represent the haplotypic diversity of global population. This raises bias in genomic read alignment and limits our ability to call large structural variations (SV), especially at highly polymorphic loci. Thus, many SV alleles remain unresolved. Recent efforts transition a graph-based resulted generation first draft pangenome reference, but tools SVs relative are presently lacking. In this study, present SVarp algorithm, aiming...
A bstract Typical analysis workflows map reads to a reference genome in order detect genetic variants. Generating such alignments introduces references biases, particular against insertion alleles absent the and comes with substantial computational burden. In contrast, recent k-mer-based genotyping methods are fast, but struggle repetitive or duplicated regions of genome. We propose novel algorithm, called PanGenie, that leverages pangenome built from haplotype-resolved assemblies...
Advances in long-read sequencing (LRS) technology continue to make whole-genome more complete, affordable, and accurate. LRS provides significant advantages over short-read approaches, including phased