Ashley D. Sanders
A5044232354- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Gene expression and cancer classification
- Lymphoma Diagnosis and Treatment
- Genetic Mapping and Diversity in Plants and Animals
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- Origins and Evolution of Life
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Inflammatory Bowel Disease
- Plant Disease Resistance and Genetics
- Advanced MRI Techniques and Applications
- Enzyme Catalysis and Immobilization
- Molecular Biology Techniques and Applications
- Evolution and Genetic Dynamics
- Cancer Immunotherapy and Biomarkers
Max Delbrück Center
2021-2024
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2021-2024
Charité - Universitätsmedizin Berlin
2021-2024
University of British Columbia
2011-2024
Washington University in St. Louis
2023
Orthopädische Universitätsklinik
2022-2023
Helmholtz Association of German Research Centres
2023
European Molecular Biology Laboratory
2017-2022
Humboldt-Universität zu Berlin
2022
Freie Universität Berlin
2022
The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies human genetic diversity and disease association. Here, we apply a suite long-read, short-read, strand-specific technologies, optical mapping, variant discovery algorithms to comprehensively analyze three trios define the full spectrum variation in haplotype-resolved manner. We identify 818,054 indel (<50 bp) 27,622 SVs (≥50 per genome. also discover 156 inversions genome 58 intersect...
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...
A high-quality rhesus macaque genome Genome technology has improved substantially since the first full organismal genomes were generated. Applying new technology, Warren et al. refined of macaque, a model nonhuman primate. Long-read and other recent advances in sequencing applied to generate with far fewer gaps helped refine locations numbers repetitive elements. Furthermore, authors performed resequencing among populations identify genetic variability macaque. Thus, previously incomplete...
Abstract The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society 1,2 . However, it still many gaps and errors, does not represent biological genome as is blend multiple individuals 3,4 Recently, telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but derived from hydatidiform mole cell line nearly homozygous 5 To address these limitations, Human Pangenome...
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...
Dysregulation at the intestinal epithelial barrier is a driver of inflammatory bowel disease (IBD). However, molecular mechanisms failure are not well understood. Here, we demonstrate dysregulated mitochondrial fusion in cells (IECs) patients with IBD and show that impaired sufficient to drive chronic inflammation. We found reduced expression fusion–related genes, such as dynamin-related guanosine triphosphatase (GTPase) optic atrophy 1 ( OPA1 ), fragmented networks crypt IECs IBD. Mice Opa1...
Abstract The sequence and assembly of human genomes using long‐read sequencing technologies has revolutionized our understanding structural variation genome organization. We compared the accuracy, continuity, gene annotation assemblies generated from either high‐fidelity (HiFi) or continuous (CLR) datasets same complete hydatidiform mole genome. find that HiFi data assemble an additional 10% duplicated regions more accurately represent structure tandem repeats, as validated with orthogonal...
We aimed to assess the prognostic significance of follicular lymphoma-associated macrophages in era rituximab treatment and maintenance.We applied immunohistochemistry for CD68 CD163 two large tissue microarrays (TMA). The first TMA included samples from 186 patients BC Cancer Agency (BCCA) who had been treated with first-line systemic including rituximab, cyclophosphamide, vincristine, prednisone. second contained 395 PRIMA trial doxorubicin, prednisone, randomized maintenance or...
Short tandem repeats (STRs) and variable number (VNTRs) are important sources of natural disease-causing variation, yet they have been problematic to resolve in reference genomes genotype with short-read technology. We created a framework model the evolution instability STRs VNTRs apes. phased assembled 3 ape (chimpanzee, gorilla, orangutan) using long-read 10x Genomics linked-read sequence data for 21,442 human discovered 6 haplotype-resolved assemblies Yoruban, Chinese, Puerto Rican...
Abstract The diploid nature of the human genome is neglected in many analyses done today, where a perceived as set unphased variants with respect to reference genome. This lack haplotype-level can be explained by methods that produce dense and accurate chromosome-length haplotypes at reasonable costs. Here we introduce an integrative phasing strategy combines global, but sparse obtained from strand-specific single-cell sequencing (Strand-seq) dense, yet local, haplotype information available...
There has been tremendous progress in phased genome assembly production by combining long-read data with parental information or linked-read data. Nevertheless, a typical generated trio-hifiasm still generates more than 140 gaps. We perform detailed analysis of gaps, breaks, and misorientations from 182 haploid assemblies obtained diversity panel 77 unique human samples. Although trio-based approaches using HiFi are the current gold standard, chromosome-wide phasing accuracy is comparable...
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...
Identifying genomic features that differ between individuals and cells can help uncover the functional variants drive phenotypes disease susceptibilities. For this, single-cell studies are paramount, as it becomes increasingly clear contribution of rare but cellular subpopulations is important for prognosis, management, progression. Until now, studying these associations has been challenged by our inability to map structural rearrangements accurately comprehensively. To overcome we coupled...
Abstract Many disciplines, from human genetics and oncology to plant breeding, microbiology virology, commonly face the challenge of analyzing rapidly increasing numbers genomes. In case Homo sapiens , number sequenced genomes will approach hundreds thousands in next few years. Simply scaling up established bioinformatics pipelines not be sufficient for leveraging full potential such rich genomic datasets. Instead, novel, qualitatively different computational methods paradigms are needed. We...
Haplotypes are fundamental to fully characterize the diploid genome of an individual, yet methods directly chart unique genetic makeup each parental chromosome lacking. Here we introduce single-cell DNA template strand sequencing (Strand-seq) as a novel approach phasing genomes along entire length all chromosomes. We demonstrate this by building complete haplotype for HapMap individual (NA12878) at high accuracy (concordance 99.3%), without using generational information or statistical...