Multiscale Analysis of Pangenome Enables Improved Representation of Genomic Diversity For Repetitive And Clinically Relevant Genes

Chin, Chen-Shan; Behera, Sairam; Khalak, Asif; Sedlazeck, Fritz J.; Wagner, Justin; Zook, Justin M.

doi:10.1101/2022.08.05.502980

Cited by 10 publications

(8 citation statements)

References 74 publications

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“…c . Structural differences revealed using PRG-TK 97 against GRCh38-Y and GRCh37-Y in the euchromatic region of the Y chromosome.…”

Section: Extended Data Figuresmentioning

confidence: 99%

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The complete sequence of a human Y chromosome

Rhie

Nurk

Čechová

et al. 2022

Preprint

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The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure including long palindromes, tandem repeats, and segmental duplications. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029 base pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, revealing the complete ampliconic structures of TSPY, DAZ, and RBMY; 42 additional protein-coding genes, mostly from the TSPY gene family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a prior assembly of the CHM13 genome and mapped available population variation, clinical variants, and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.

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“…c . Structural differences revealed using PRG-TK 97 against GRCh38-Y and GRCh37-Y in the euchromatic region of the Y chromosome.…”

Section: Extended Data Figuresmentioning

confidence: 99%

“…Identity was computed from matches and mismatches over positions with alignments, excluding gaps. c. Structural differences revealed using PRG-TK97 against GRCh38-Y and GRCh37-Y in the euchromatic region of the Y chromosome.Extended Data Fig. 4 | Repeat discovery and annotation of T2T-Y.…”

mentioning

confidence: 99%

The complete sequence of a human Y chromosome

Rhie

Nurk

Čechová

et al. 2022

Preprint

Self Cite

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“…The HLA class II region is highly structured (Klitz et al 2003; Norman et al 2017; Chin et al 2023), which is commonly characterized by DR haplotype. Following earlier work (Houwaart et al 2023), HLA DR haplotype is defined by the combination of HLA-DRB1 allele groups and the presence or absence of DRB3/4/5 genes.…”

Section: Resultsmentioning

confidence: 99%

Full resolution HLA and KIR genes annotation for human genome assemblies

Zhou,

Song,

2024

Preprint

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The HLA (Human Leukocyte Antigen) genes and the KIR (Killer cell Immunoglobulin-like Receptor) genes are critical to immune responses and are associated with many immune-related diseases. Located in highly polymorphic regions, they are hard to be studied with traditional short-read alignment-based methods. Although modern long-read assemblers can often assemble these genes, using existing tools to annotate HLA and KIR genes in these assemblies remains a non-trivial task. Here, we describe Immuannot, a new computation tool to annotate the gene structures of HLA and KIR genes and to type the allele of each gene. Applying Immuannot to 56 regional and 212 whole-genome assemblies from previous studies, we annotated 9,931 HLA and KIR genes and found that almost half of these genes, 4,068, had novel sequences compared to the current Immuno Polymorphism Database (IPD). These novel gene sequences were represented by 2,664 distinct alleles, some of which contained non-synonymous variations resulting in 92 novel protein sequences. We demonstrated the complex haplotype structures at the two loci and reported the linkage between HLA/KIR haplotypes and gene alleles. We anticipate that Immuannot will speed up the discovery of new HLA/KIR alleles and enable the association of HLA/KIR haplotype structures with clinical outcomes in the future.

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“…Competing pipelines don’t use any workflow management system to connect their processes (Chin et al ., 2023), or their workflow language of choice is e.g. Toil (Vivian et al ., 2017; Hickey et al ., 2023) which makes them less user-friendly, less cluster efficient, and less portable (Wratten et al ., 2021).…”

Section: Discussionmentioning

confidence: 99%

Cluster efficient pangenome graph construction with nf-core/pangenome

Heumos,

Heuer,

Hanssen

et al. 2024

Preprint

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Motivation: Pangenome 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. Results: To overcome these limitations, we present nf-core/pangenome, a reference-unbiased approach implemented in Nextflow following nf-core's 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. Availability: nf-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. Contact: simon.heumos@qbic.uni-tuebingen.de, sven.nahnsen@qbic.uni-tuebingen.de

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Multiscale Analysis of Pangenome Enables Improved Representation of Genomic Diversity For Repetitive And Clinically Relevant Genes

Cited by 10 publications

References 74 publications

The complete sequence of a human Y chromosome

The complete sequence of a human Y chromosome

Full resolution HLA and KIR genes annotation for human genome assemblies

Cluster efficient pangenome graph construction with nf-core/pangenome

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