A draft human pangenome reference

Nature, Journal Year: 2023, Volume and Issue: 617(7960), P. 312 - 324

Published: May 10, 2023

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 sequences 1,115 gene duplications relative to existing reference GRCh38. Roughly 90 additional derived variation. Using our analyse short-read data reduced small variant discovery errors by 34% increased number detected per haplotype 104% compared with GRCh38-based workflows, which enabled typing vast majority sample.

Language: Английский

---

Semi-automated assembly of high-quality diploid human reference genomes

Nature, Journal Year: 2022, Volume and Issue: 611(7936), P. 519 - 531

Published: Oct. 19, 2022

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 Reference Consortium formed goal creating high-quality, cost-effective, diploid assemblies for pangenome that genetic diversity 6 Here, in our first scientific report, we determined combination sequencing assembly approaches yield most complete accurate minimal manual curation. Approaches used highly long reads parent–child data graph-based haplotype phasing during outperformed those did not. Developing top-performing methods, containing only approximately four per chromosome on average, chromosomes within ±1% length CHM13. Nearly 48% protein-coding genes have non-synonymous amino acid changes between haplotypes, centromeric regions showed highest diversity. Our findings serve foundation assembling near-complete genomes at scale capture global variation single nucleotides structural rearrangements.

Language: Английский

---

Features and applications of haplotypes in crop breeding

Communications Biology, Journal Year: 2021, Volume and Issue: 4(1)

Published: Nov. 4, 2021

Abstract Climate change with altered pest-disease dynamics and rising abiotic stresses threatens resource-constrained agricultural production systems worldwide. Genomics-assisted breeding (GAB) approaches have greatly contributed to enhancing crop efficiency delivering better varieties. Fast-growing capacity affordability of DNA sequencing has motivated large-scale germplasm projects, thus opening exciting avenues for mining haplotypes applications. This review article highlights ways mine apply them complex trait dissection in GAB including haplotype-GWAS, haplotype-based breeding, haplotype-assisted genomic selection. Improvement strategies that efficiently deploy superior hasten progress will be key safeguarding global food security.

Language: Английский

---

A Draft Human Pangenome Reference

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 9, 2022

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 duplications relative to existing reference, GRCh38. Roughly 90 additional derive variation. Using our analyze short-read data reduces errors when discovering small by 34% boosts detected per haplotype 104% compared GRCh38-based workflows, using previous diversity sets genome assemblies.

Language: Английский

---

LongPhase: an ultra-fast chromosome-scale phasing algorithm for small and large variants

Bioinformatics, Journal Year: 2022, Volume and Issue: 38(7), P. 1816 - 1822

Published: Jan. 26, 2022

Abstract Motivation Long-read phasing has been used for reconstructing diploid genomes, improving variant calling and resolving microbial strains in metagenomics. However, the blocks of existing methods are broken by large Structural Variations (SVs), efficiency is unsatisfactory population-scale phasing. Results This article presents a novel algorithm, LongPhase, which can simultaneously phase single nucleotide polymorphisms (SNPs) SVs human genome 10–20 min, 10× faster than state-of-the-art WhatsHap, HapCUT2 Margin. In particular, co-phasing SNPs produces much larger haplotype (N50 = 25 Mbp) those 10–15 Mbp). We show that LongPhase combined with Nanopore ultra-long reads cost-effective highly contiguous solution, produce between one 26 per chromosome arm without need additional trios, chromosome-conformation strand-seq data. Availabilityand implementation freely available at https://github.com/twolinin/LongPhase/. Supplementary information data Bioinformatics online.

Language: Английский

---

Analysis of metagenomic data

Nature Reviews Methods Primers, Journal Year: 2025, Volume and Issue: 5(1)

Published: Jan. 23, 2025

Language: Английский

---

Development and validation of a minimal SNP genotyping panel for the differentiation of Cannabis sativa cultivars

BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 28, 2025

Due to its previously illicit nature, Cannabis sativa had not fully reaped the benefits of recent innovations in genomics and plant sciences. However, Canada's legalization C. products derived from flower 2018 triggered significant new demand for robust genotyping tools assist breeders meeting consumer demands. Early molecular marker-based research on focused screening sex chemotype, more has sought use markers target traits agronomic interest, study populations differentiate between cultivars. In this study, we have conducted whole genome sequencing 32 cultivars, mined data SNPs, developed a reduced SNP panel discriminate sequenced then validated 20-SNP using DNA cultivars tested assays commercially available dried flower. The assay conversion rate was higher extracted fresh material than samples. called genotypes were internally consistent, highlighting discrepancies detected observed assays. primary contributions work are clearly document process used develop minimal panels, feasibility such panels outline improvements goals future iterations PCR-based, enable efficient development identify screen Our key recommendations increase sampling density account intra-cultivar variability; leverage read length paired-end short-read technology; conduct in-depth pre- post-processing reads, mapping, variant calling data; integrate trait-associated loci multi-purpose panels; iterative approaches vitro validation ensure that only most discriminant performant SNPs retained.

Language: Английский

---

Single-cell genome-wide concurrent haplotyping and copy-number profiling through genotyping-by-sequencing

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 50(11), P. e63 - e63

Published: Feb. 11, 2022

Abstract Single-cell whole-genome haplotyping allows simultaneous detection of haplotypes associated with monogenic diseases, chromosome copy-numbering and subsequently, has revealed mosaicism in embryos embryonic stem cells. Methods, such as karyomapping haplarithmisis, were deployed a generic genome-wide approach for preimplantation genetic testing (PGT) are replacing traditional PGT methods. While current methods primarily rely on single-nucleotide polymorphism (SNP) array, we envision sequencing-based to become more accessible cost-efficient. Here, developed novel methodology haplotype copy-number profile single Following DNA amplification, genomic size complexity is reduced through restriction enzyme digestion genotyped sequencing. This single-cell genotyping-by-sequencing (scGBS) the input an algorithm previously SNP array-based haplotyping. We established technical parameters analysis pipeline enabling accurate concurrent profiling demonstrate its value human blastomere trophectoderm samples application disorders. Furthermore, method work other species analyzing blastomeres bovine embryos. Our scGBS opens up path any diploid genomes could make way into clinic application.

Language: Английский

---

Towards routine chromosome-scale haplotype-resolved reconstruction in cancer genomics

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 13, 2023

Abstract Cancer genomes are highly complex and heterogeneous. The standard short-read sequencing analytical methods unable to provide the complete precise base-level structural variant landscape of cancer genomes. In this work, we apply high-resolution long accurate HiFi long-range Hi-C melanoma COLO829 line. Also, develop an efficient graph-based approach that processes these data types for chromosome-scale haplotype-resolved reconstruction characterise landscape. Our method produces high-quality phased scaffolds on chromosome level three healthy samples line in less than half a day even absence trio information, outperforming existing state-of-the-art methods. cell line, here show our identifies characterises somatic calls important repeat elements were missed short-read-based call sets. also finds chromosome-level (germline somatic) with 19,956 insertions, 14,846 deletions, 421 duplications, 52 inversions 498 translocations at base resolution. simple pstools should facilitate better personalised diagnosis disease management, including predicting therapeutic responses.

Language: Английский

---

Hapsolutely: a user-friendly tool integrating haplotype phasing, network construction and haploweb calculation

Bioinformatics Advances, Journal Year: 2024, Volume and Issue: 4(1)

Published: Jan. 1, 2024

Abstract Motivation Haplotype networks are a routine approach to visualize relationships among alleles. Such visual analysis of single-locus data is still importance, especially in species diagnosis and delimitation, where limited amount sequence usually available sufficient, along with other datasets the framework integrative taxonomy. In diploid organisms, this often requires separating (phasing) sequences heterozygotic positions, typically separate programs required for phasing, reformatting input files, haplotype network construction. We therefore developed Hapsolutely, user-friendly program an ergonomic graphical user interface that integrates phasing from five approaches network/genealogy reconstruction. Results Among novel options implemented, Hapsolutely reconstruction steps networks, supports partition common SPART SPART-XML formats, calculates visualizes haplowebs fields recombination, thus allowing comparison allele distribution sharing subsets purpose delimitation. The new tool has been specifically focus on workflow alpha-taxonomy, exploring recombination across alternative partitions may help Availability implementation written Python, code Phase, SeqPHASE, PopART C++ Haxe. Compiled stand-alone executables MS Windows Mac OS detailed manual can be downloaded https://www.itaxotools.org; source openly GitHub (https://github.com/iTaxoTools/Hapsolutely).

Language: Английский

---