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Articles de revues sur le sujet « Haplotype assembly »

Auteur : Grafiati
Publié le 9 mars 2023
Mis à jour le 10 mars 2023

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1

Xu, Mengyang, Lidong Guo, Xiao Du, Lei Li, Brock A. Peters, Li Deng, Ou Wang et al. « Accurate haplotype-resolved assembly reveals the origin of structural variants for human trios ». Bioinformatics 37, no 15 (4 février 2021) : 2095–102. http://dx.doi.org/10.1093/bioinformatics/btab068.

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Abstract Motivation Achieving a near complete understanding of how the genome of an individual affects the phenotypes of that individual requires deciphering the order of variations along homologous chromosomes in species with diploid genomes. However, true diploid assembly of long-range haplotypes remains challenging. Results To address this, we have developed Haplotype-resolved Assembly for Synthetic long reads using a Trio-binning strategy, or HAST, which uses parental information to classify reads into maternal or paternal. Once sorted, these reads are used to independently de novo assemble the parent-specific haplotypes. We applied HAST to cobarcoded second-generation sequencing data from an Asian individual, resulting in a haplotype assembly covering 94.7% of the reference genome with a scaffold N50 longer than 11 Mb. The high haplotyping precision (∼99.7%) and recall (∼95.9%) represents a substantial improvement over the commonly used tool for assembling cobarcoded reads (Supernova), and is comparable to a trio-binning-based third generation long-read-based assembly method (TrioCanu) but with a significantly higher single-base accuracy [up to 99.99997% (Q65)]. This makes HAST a superior tool for accurate haplotyping and future haplotype-based studies. Availability and implementation The code of the analysis is available at https://github.com/BGI-Qingdao/HAST Supplementary information Supplementary data are available at Bioinformatics online.
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Siragusa, Enrico, Niina Haiminen, Richard Finkers, Richard Visser et Laxmi Parida. « Haplotype assembly of autotetraploid potato using integer linear programing ». Bioinformatics 35, no 18 (25 janvier 2019) : 3279–86. http://dx.doi.org/10.1093/bioinformatics/btz060.

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Abstract Summary Haplotype assembly of polyploids is an open issue in plant genomics. Recent experimental studies on highly heterozygous autotetraploid potato have shown that available methods do not deliver satisfying results in practice. We propose an optimal method to assemble haplotypes of highly heterozygous polyploids from Illumina short-sequencing reads. Our method is based on a generalization of the existing minimum fragment removal model to the polyploid case and on new integer linear programs to reconstruct optimal haplotypes. We validate our methods experimentally by means of a combined evaluation on simulated and experimental data based on 83 previously sequenced autotetraploid potato cultivars. Results on simulated data show that our methods produce highly accurate haplotype assemblies, while results on experimental data confirm a sensible improvement over the state of the art. Availability and implementation Executables for Linux at http://github.com/Computational Genomics/HaplotypeAssembler. Supplementary information Supplementary data are available at Bioinformatics online.
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Bahcall, Orli. « Single-haplotype genome assembly ». Nature Genetics 46, no 12 (24 novembre 2014) : 1257. http://dx.doi.org/10.1038/ng.3157.

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Rodriguez, Oscar L., Anna Ritz, Andrew J. Sharp et Ali Bashir. « MsPAC : a tool for haplotype-phased structural variant detection ». Bioinformatics 36, no 3 (9 août 2019) : 922–24. http://dx.doi.org/10.1093/bioinformatics/btz618.

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Abstract Summary While next-generation sequencing (NGS) has dramatically increased the availability of genomic data, phased genome assembly and structural variant (SV) analyses are limited by NGS read lengths. Long-read sequencing from Pacific Biosciences and NGS barcoding from 10x Genomics hold the potential for far more comprehensive views of individual genomes. Here, we present MsPAC, a tool that combines both technologies to partition reads, assemble haplotypes (via existing software) and convert assemblies into high-quality, phased SV predictions. MsPAC represents a framework for haplotype-resolved SV calls that moves one step closer to fully resolved, diploid genomes. Availability and implementation https://github.com/oscarlr/MsPAC. Supplementary information Supplementary data are available at Bioinformatics online.
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Sun, Hequan, Wen-Biao Jiao, Kristin Krause, José A. Campoy, Manish Goel, Kat Folz-Donahue, Christian Kukat, Bruno Huettel et Korbinian Schneeberger. « Chromosome-scale and haplotype-resolved genome assembly of a tetraploid potato cultivar ». Nature Genetics 54, no 3 (mars 2022) : 342–48. http://dx.doi.org/10.1038/s41588-022-01015-0.

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AbstractPotato is the most widely produced tuber crop worldwide. However, reconstructing the four haplotypes of its autotetraploid genome remained an unsolved challenge. Here, we report the 3.1 Gb haplotype-resolved (at 99.6% precision), chromosome-scale assembly of the potato cultivar ‘Otava’ based on high-quality long reads, single-cell sequencing of 717 pollen genomes and Hi-C data. Unexpectedly, ~50% of the genome was identical-by-descent due to recent inbreeding, which was contrasted by highly abundant structural rearrangements involving ~20% of the genome. Among 38,214 genes, only 54% were present in all four haplotypes with an average of 3.2 copies per gene. Taking the leaf transcriptome as an example, 11% of the genes were differently expressed in at least one haplotype, where 25% of them were likely regulated through allele-specific DNA methylation. Our work sheds light on the recent breeding history of potato, the functional organization of its tetraploid genome and has the potential to strengthen the future of genomics-assisted breeding.
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Si, Hongbo, Haris Vikalo et Sriram Vishwanath. « Information-Theoretic Analysis of Haplotype Assembly ». IEEE Transactions on Information Theory 63, no 6 (juin 2017) : 3468–79. http://dx.doi.org/10.1109/tit.2017.2686884.

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Mousavi, Sayyed R. « Improved haplotype assembly using Xor genotypes ». Journal of Theoretical Biology 298 (avril 2012) : 122–30. http://dx.doi.org/10.1016/j.jtbi.2012.01.003.

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Chu, Wai Keung, Peter Edge, Ho Suk Lee, Vikas Bansal, Vineet Bafna, Xiaohua Huang et Kun Zhang. « Ultraaccurate genome sequencing and haplotyping of single human cells ». Proceedings of the National Academy of Sciences 114, no 47 (24 octobre 2017) : 12512–17. http://dx.doi.org/10.1073/pnas.1707609114.

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Accurate detection of variants and long-range haplotypes in genomes of single human cells remains very challenging. Common approaches require extensive in vitro amplification of genomes of individual cells using DNA polymerases and high-throughput short-read DNA sequencing. These approaches have two notable drawbacks. First, polymerase replication errors could generate tens of thousands of false-positive calls per genome. Second, relatively short sequence reads contain little to no haplotype information. Here we report a method, which is dubbed SISSOR (single-stranded sequencing using microfluidic reactors), for accurate single-cell genome sequencing and haplotyping. A microfluidic processor is used to separate the Watson and Crick strands of the double-stranded chromosomal DNA in a single cell and to randomly partition megabase-size DNA strands into multiple nanoliter compartments for amplification and construction of barcoded libraries for sequencing. The separation and partitioning of large single-stranded DNA fragments of the homologous chromosome pairs allows for the independent sequencing of each of the complementary and homologous strands. This enables the assembly of long haplotypes and reduction of sequence errors by using the redundant sequence information and haplotype-based error removal. We demonstrated the ability to sequence single-cell genomes with error rates as low as 10−8 and average 500-kb-long DNA fragments that can be assembled into haplotype contigs with N50 greater than 7 Mb. The performance could be further improved with more uniform amplification and more accurate sequence alignment. The ability to obtain accurate genome sequences and haplotype information from single cells will enable applications of genome sequencing for diverse clinical needs.
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Newman, Chris, Ming-shan Tsai, Christina D. Buesching, Peter W. H. Holland et David W. Macdonald. « The genome sequence of the European badger, Meles meles (Linnaeus, 1758) ». Wellcome Open Research 7 (23 septembre 2022) : 239. http://dx.doi.org/10.12688/wellcomeopenres.18230.1.

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We present a haplotype resolved, diploid genome assembly from a male Meles meles (European badger; Chordata; Mammalia; Carnivora; Mustelidae) using the trio binning approach. The genome sequence is 2,739 megabases in span. The majority of the assembly (95.16%) is scaffolded into 23 chromosomal pseudomolecules with the X and Y sex chromosomes assembled. The complete mitochondrial genome was also assembled and is 16.4 kilobases in length.
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Mohades, M. M., M. H. Kahaei et H. Mohades. « Haplotype assembly using Riemannian trust-region method ». Digital Signal Processing 112 (mai 2021) : 102999. http://dx.doi.org/10.1016/j.dsp.2021.102999.

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Chen, Zhi-Zhong, Fei Deng, Chao Shen, Yiji Wang et Lusheng Wang. « Better ILP-Based Approaches to Haplotype Assembly ». Journal of Computational Biology 23, no 7 (juillet 2016) : 537–52. http://dx.doi.org/10.1089/cmb.2015.0035.

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Puljiz, Zrinka, et Haris Vikalo. « Decoding Genetic Variations : Communications-Inspired Haplotype Assembly ». IEEE/ACM Transactions on Computational Biology and Bioinformatics 13, no 3 (1 mai 2016) : 518–30. http://dx.doi.org/10.1109/tcbb.2015.2462367.

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Zhao, Yu-Ying, Ling-Yun Wu, Ji-Hong Zhang, Rui-Sheng Wang et Xiang-Sun Zhang. « Haplotype assembly from aligned weighted SNP fragments ». Computational Biology and Chemistry 29, no 4 (août 2005) : 281–87. http://dx.doi.org/10.1016/j.compbiolchem.2005.05.001.

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Majidian, Sina, et Mohammad Hossein Kahaei. « NGS based haplotype assembly using matrix completion ». PLOS ONE 14, no 3 (26 mars 2019) : e0214455. http://dx.doi.org/10.1371/journal.pone.0214455.

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Mousavi, Sayyed R., Maryam Mirabolghasemi, Nadia Bargesteh et Majid Talebi. « Effective haplotype assembly via maximum Boolean satisfiability ». Biochemical and Biophysical Research Communications 404, no 2 (janvier 2011) : 593–98. http://dx.doi.org/10.1016/j.bbrc.2010.12.001.

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Yang, Chentao, Yang Zhou, Stephanie Marcus, Giulio Formenti, Lucie A. Bergeron, Zhenzhen Song, Xupeng Bi et al. « Evolutionary and biomedical insights from a marmoset diploid genome assembly ». Nature 594, no 7862 (28 avril 2021) : 227–33. http://dx.doi.org/10.1038/s41586-021-03535-x.

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AbstractThe accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes and diseases1. Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an primate model system that is widely used in biomedical research2,3. The full spectrum of heterozygosity between the two haplotypes involves 1.36% of the genome—much higher than the 0.13% indicated by the standard estimation based on single-nucleotide heterozygosity alone. The de novo mutation rate is 0.43 × 10−8 per site per generation, and the paternal inherited genome acquired twice as many mutations as the maternal. Our diploid assembly enabled us to discover a recent expansion of the sex-differentiation region and unique evolutionary changes in the marmoset Y chromosome. In addition, we identified many genes with signatures of positive selection that might have contributed to the evolution of Callithrix biological features. Brain-related genes were highly conserved between marmosets and humans, although several genes experienced lineage-specific copy number variations or diversifying selection, with implications for the use of marmosets as a model system.
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Cheng, Haoyu, Gregory T. Concepcion, Xiaowen Feng, Haowen Zhang et Heng Li. « Haplotype-resolved de novo assembly using phased assembly graphs with hifiasm ». Nature Methods 18, no 2 (février 2021) : 170–75. http://dx.doi.org/10.1038/s41592-020-01056-5.

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Abdullah, Abu-Bakar Muhammad, Md Monowar Hossain et Pintu Chandra Shill. « HapPart : partitioning algorithm for multiple haplotyping from haplotype conflict graph ». International Journal of Electrical and Computer Engineering (IJECE) 12, no 3 (1 juin 2022) : 2856. http://dx.doi.org/10.11591/ijece.v12i3.pp2856-2866.

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<span>Each chromosome in the human genome has two copies. The haplotype assembly challenge entails reconstructing two haplotypes (chromosomes) using aligned fragments genomic sequence. Plants viz. wheat, paddy and banana have more than two chromosomes. Multiple haplotype reconstruction has been a major research topic. For reconstructing multiple haplotypes for a polyploid organism, several approaches have been designed. The researchers are still fascinated to the computational challenge. This article introduces a partitioning algorithm, HapPart for dividing the fragments into </span><em><span>k</span></em><span>-groups focusing on reducing the computational time. HapPart uses minimum error correction curve to determine the value of </span><em><span>k</span></em><span> at which the growth of gain measures for two consecutive values of </span><em><span>k</span></em><span>-multiplied by its diversity is maximum. Haplotype conflict graph is used for constructing all possible number of groups. The dissimilarity between two haplotypes represents the distance between two nodes in graph. For merging two nodes with the minimum distance between them this algorithm ensures minimum error among fragments in same group. Experimental results on real and simulated data show that HapPart can partition fragments efficiently and with less computational time.</span>
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Cai, Changxiao, Sujay Sanghavi et Haris Vikalo. « Structured Low-Rank Matrix Factorization for Haplotype Assembly ». IEEE Journal of Selected Topics in Signal Processing 10, no 4 (juin 2016) : 647–57. http://dx.doi.org/10.1109/jstsp.2016.2547860.

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Schwartz, Russell. « Theory and Algorithms for the Haplotype Assembly Problem ». Communications in Information and Systems 10, no 1 (2010) : 23–38. http://dx.doi.org/10.4310/cis.2010.v10.n1.a2.

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Wong, Thomas K. F., Teng Li, Louis Ranjard, Steven H. Wu, Jeet Sukumaran et Allen G. Rodrigo. « An assembly-free method of phylogeny reconstruction using short-read sequences from pooled samples without barcodes ». PLOS Computational Biology 17, no 9 (13 septembre 2021) : e1008949. http://dx.doi.org/10.1371/journal.pcbi.1008949.

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A current strategy for obtaining haplotype information from several individuals involves short-read sequencing of pooled amplicons, where fragments from each individual is identified by a unique DNA barcode. In this paper, we report a new method to recover the phylogeny of haplotypes from short-read sequences obtained using pooled amplicons from a mixture of individuals, without barcoding. The method, AFPhyloMix, accepts an alignment of the mixture of reads against a reference sequence, obtains the single-nucleotide-polymorphisms (SNP) patterns along the alignment, and constructs the phylogenetic tree according to the SNP patterns. AFPhyloMix adopts a Bayesian inference model to estimate the phylogeny of the haplotypes and their relative abundances, given that the number of haplotypes is known. In our simulations, AFPhyloMix achieved at least 80% accuracy at recovering the phylogenies and relative abundances of the constituent haplotypes, for mixtures with up to 15 haplotypes. AFPhyloMix also worked well on a real data set of kangaroo mitochondrial DNA sequences.
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Malar C, Mathu, Jennifer D. Yuzon, Subhadeep Das, Abhishek Das, Arijit Panda, Samrat Ghosh, Brett M. Tyler, Takao Kasuga et Sucheta Tripathy. « Haplotype-Phased Genome Assembly of Virulent Phytophthora ramorum Isolate ND886 Facilitated by Long-Read Sequencing Reveals Effector Polymorphisms and Copy Number Variation ». Molecular Plant-Microbe Interactions® 32, no 8 (août 2019) : 1047–60. http://dx.doi.org/10.1094/mpmi-08-18-0222-r.

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Phytophthora ramorum is a destructive pathogen that causes sudden oak death disease. The genome sequence of P. ramorum isolate Pr102 was previously produced, using Sanger reads, and contained 12 Mb of gaps. However, isolate Pr102 had shown reduced aggressiveness and genome abnormalities. In order to produce an improved genome assembly for P. ramorum, we performed long-read sequencing of highly aggressive P. ramorum isolate CDFA1418886 (abbreviated as ND886). We generated a 60.5-Mb assembly of the ND886 genome using the Pacific Biosciences (PacBio) sequencing platform. The assembly includes 302 primary contigs (60.2 Mb) and nine unplaced contigs (265 kb). Additionally, we found a ‘highly repetitive’ component from the PacBio unassembled unmapped reads containing tandem repeats that are not part of the 60.5-Mb genome. The overall repeat content in the primary assembly was much higher than the Pr102 Sanger version (48 versus 29%), indicating that the long reads have captured repetitive regions effectively. The 302 primary contigs were phased into 345 haplotype blocks and 222,892 phased variants, of which the longest phased block was 1,513,201 bp with 7,265 phased variants. The improved phased assembly facilitated identification of 21 and 25 Crinkler effectors and 393 and 394 RXLR effector genes from two haplotypes. Of these, 24 and 25 RXLR effectors were newly predicted from haplotypes A and B, respectively. In addition, seven new paralogs of effector Avh207 were found in contig 54, not reported earlier. Comparison of the ND886 assembly with Pr102 V1 assembly suggests that several repeat-rich smaller scaffolds within the Pr102 V1 assembly were possibly misassembled; these regions are fully encompassed now in ND886 contigs. Our analysis further reveals that Pr102 is a heterokaryon with multiple nuclear types in the sequences corresponding to contig 10 of ND886 assembly.
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Zhou, Qian, Dié Tang, Wu Huang, Zhongmin Yang, Yu Zhang, John P. Hamilton, Richard G. F. Visser et al. « Haplotype-resolved genome analyses of a heterozygous diploid potato ». Nature Genetics 52, no 10 (28 septembre 2020) : 1018–23. http://dx.doi.org/10.1038/s41588-020-0699-x.

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Abstract Potato (Solanum tuberosum L.) is the most important tuber crop worldwide. Efforts are underway to transform the crop from a clonally propagated tetraploid into a seed-propagated, inbred-line-based hybrid, but this process requires a better understanding of potato genome. Here, we report the 1.67-Gb haplotype-resolved assembly of a diploid potato, RH89-039-16, using a combination of multiple sequencing strategies, including circular consensus sequencing. Comparison of the two haplotypes revealed ~2.1% intragenomic diversity, including 22,134 predicted deleterious mutations in 10,642 annotated genes. In 20,583 pairs of allelic genes, 16.6% and 30.8% exhibited differential expression and methylation between alleles, respectively. Deleterious mutations and differentially expressed alleles were dispersed throughout both haplotypes, complicating strategies to eradicate deleterious alleles or stack beneficial alleles via meiotic recombination. This study offers a holistic view of the genome organization of a clonally propagated diploid species and provides insights into technological evolution in resolving complex genomes.
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Giguere, Daniel J., Alexander T. Bahcheli, Samuel S. Slattery, Rushali R. Patel, Tyler S. Browne, Martin Flatley, Bogumil J. Karas, David R. Edgell et Gregory B. Gloor. « Telomere-to-telomere genome assembly of Phaeodactylum tricornutum ». PeerJ 10 (5 juillet 2022) : e13607. http://dx.doi.org/10.7717/peerj.13607.

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Phaeodactylum tricornutum is a marine diatom with a growing genetic toolbox available and is being used in many synthetic biology applications. While most of the genome has been assembled, the currently available genome assembly is not a completed telomere-to-telomere assembly. Here, we used Oxford Nanopore long reads to build a telomere-to-telomere genome for Phaeodactylum tricornutum. We developed a graph-based approach to extract all unique telomeres, and used this information to manually correct assembly errors. In total, we found 25 nuclear chromosomes that comprise all previously assembled fragments, in addition to the chloroplast and mitochondrial genomes. We found that chromosome 19 has filtered long-read coverage and a quality estimate that suggests significantly less haplotype sequence variation than the other chromosomes. This work improves upon the previous genome assembly and provides new opportunities for genetic engineering of this species, including creating designer synthetic chromosomes.
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Patterson, Murray, Tobias Marschall, Nadia Pisanti, Leo van Iersel, Leen Stougie, Gunnar W. Klau et Alexander Schönhuth. « WhatsHap : Weighted Haplotype Assembly for Future-Generation Sequencing Reads ». Journal of Computational Biology 22, no 6 (juin 2015) : 498–509. http://dx.doi.org/10.1089/cmb.2014.0157.

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Cao, Hongzhi, Honglong Wu, Ruibang Luo, Shujia Huang, Yuhui Sun, Xin Tong, Yinlong Xie et al. « De novo assembly of a haplotype-resolved human genome ». Nature Biotechnology 33, no 6 (25 mai 2015) : 617–22. http://dx.doi.org/10.1038/nbt.3200.

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Wu, Ling-Yun, Zhenping Li, Rui-Sheng Wang, Xiang-Sun Zhang et Luonan Chen. « Self-organizing map approaches for the haplotype assembly problem ». Mathematics and Computers in Simulation 79, no 10 (juin 2009) : 3026–37. http://dx.doi.org/10.1016/j.matcom.2009.01.021.

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Siragusa, Enrico, Niina Haiminen, Richard Finkers, Richard Visser et Laxmi Parida. « Haplotype assembly of autotetraploid potato using integer linear programing ». Bioinformatics 35, no 21 (6 juillet 2019) : 4534. http://dx.doi.org/10.1093/bioinformatics/btz511.

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Chen, Xiao, Qinke Peng, Libin Han, Tao Zhong et Tao Xu. « An effective haplotype assembly algorithm based on hypergraph partitioning ». Journal of Theoretical Biology 358 (octobre 2014) : 85–92. http://dx.doi.org/10.1016/j.jtbi.2014.05.034.

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Das, Shreepriya, et Haris Vikalo. « Optimal Haplotype Assembly via a Branch-and-Bound Algorithm ». IEEE Transactions on Molecular, Biological and Multi-Scale Communications 3, no 1 (mars 2017) : 1–12. http://dx.doi.org/10.1109/tmbmc.2016.2640306.

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Mohades, Mohamad Mahdi, Sina Majidian et Mohammad Hossein Kahaei. « Haplotype Assembly Using Manifold Optimization and Error Correction Mechanism ». IEEE Signal Processing Letters 26, no 6 (juin 2019) : 868–72. http://dx.doi.org/10.1109/lsp.2019.2910383.

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Krieger, Elizabeth, Urmila Sivagnanaling, Katherine Webb, Rehan Qayyum et Amir Ahmed Toor. « Variability in Killler Immunglobulin like Receptor Gene Expression As a Periodic Function of Gene Position on Chromosome 19 ». Blood 134, Supplement_1 (13 novembre 2019) : 3608. http://dx.doi.org/10.1182/blood-2019-132270.

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Killer Immunoglobulin Like Receptors (KIR) are expressed on natural killer (NK) and T cell surface. KIR interactions with KIR-ligands have been implicated in outcomes of hematopoietic stem cell transplantation, placental implantation, autoimmune disease and viral infections. While these KIR interactions are clearly important our understanding of what governs their expression is lacking. The KIR Locus is made up of a highly polymorphic and homologous set of genes located on Chromosome 19q13.4 within the leukocyte receptor complex. Unique to the KIR Gene Cluster, KIR haplotypes not only vary allelically, but they also differ in the number of KIR genes present in different individuals, ranging from 7 to 12 genes. KIR haplotypes have been divided into 2 broad groups; Haplotypes A & B, based on the number of activating and inhibitory KIR genes they possess; where haplotype A contains only one activating allele KIR2DS4 and haplotype B contains various combinations of activating alleles. Expression of KIR on the NK cell surface stochastic, with some KIR found more commonly then others. In this abstract we aim to explore the relationship of KIR gene expression and the organization of the KIR gene locus using available genomic and tissue expression data. KIR gene coordinates on chromosome 19 were collected using the UCSC Genome Browser GRCh38/hg38 gene assembly and the NCBI gene website gene assembly NC_000019.10. Initial KIR gene nucleotide position along chromosome 19 were obtained and converted to angular distance (A.D. in radians) from reference. This was done to account for the double helical nature of DNA molecules, using the following equation A.D. = 2px/10.4; where x is the initial KIR gene nucleotide coordinate. Haplotype A was utilized as an initial test case as gene expression data are available for the genes in this haplotype. GTEX Portal was used to collect mRNA expression for each of the haplotype A genes, KIR-2DL1, -2DL3, -2DL4, -2DP1, -2DS4, -3DL1, -3DL2, -3DL3 & -3DP1, including total (median), splenic and whole blood expression in Reads/Kilobase of transcript/million mapped reads (RPKM). Gene expression was determined via RNA-seq of 53 tissues from 570 donors. KIR haplotype A is located along chromosome 19 between nucleotide position 55,236,713 and 55,370,584 which corresponded with an A.D. of 33,354,476 to 33,435,314 radians. When the KIR gene expression was aligned with the coordinates of the corresponding gene on the KIR locus a distinct periodic pattern of variation in expression levels was observed across the KIR genes comprising Haplotype A (Figure 1). This was true for total KIR expression from across various organs, as well as in blood and splenic tissue. This is borne out by expression data on several Haplotype A KIR genes reported in the literature (Figure 1, yellow curve). These observations suggesting that KIR gene expression may be a periodic function of the gene coordinates on the chromosome are analogous to the periodicity observed in T cell receptor VDJ recombination (Meier et al, BBMT 2019 25(5);868). This observation supports the idea that the spiral structure of the helical DNA molecules coiled around the histone molecules and their arrangement on chromosomes may have a fundamental influence on the expression of different genes, perhaps in conjunction with known epigenetic influence of DNA methylation and histone acetylation. This may also point to a role for the non-coding DNA in regulation of gene expression. We posit that the helical DNA chromosome structure may have a fundamental role in determining gene expression, as exemplified by the KIR and T cell receptor gene loci. This knowledge may allow an improved understanding of variability in global gene expression. Disclosures No relevant conflicts of interest to declare.
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Baaijens, Jasmijn A., Bastiaan Van der Roest, Johannes Köster, Leen Stougie et Alexander Schönhuth. « Full-length de novo viral quasispecies assembly through variation graph construction ». Bioinformatics 35, no 24 (30 mai 2019) : 5086–94. http://dx.doi.org/10.1093/bioinformatics/btz443.

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Abstract Motivation Viruses populate their hosts as a viral quasispecies: a collection of genetically related mutant strains. Viral quasispecies assembly is the reconstruction of strain-specific haplotypes from read data, and predicting their relative abundances within the mix of strains is an important step for various treatment-related reasons. Reference genome independent (‘de novo’) approaches have yielded benefits over reference-guided approaches, because reference-induced biases can become overwhelming when dealing with divergent strains. While being very accurate, extant de novo methods only yield rather short contigs. The remaining challenge is to reconstruct full-length haplotypes together with their abundances from such contigs. Results We present Virus-VG as a de novo approach to viral haplotype reconstruction from preassembled contigs. Our method constructs a variation graph from the short input contigs without making use of a reference genome. Then, to obtain paths through the variation graph that reflect the original haplotypes, we solve a minimization problem that yields a selection of maximal-length paths that is, optimal in terms of being compatible with the read coverages computed for the nodes of the variation graph. We output the resulting selection of maximal length paths as the haplotypes, together with their abundances. Benchmarking experiments on challenging simulated and real datasets show significant improvements in assembly contiguity compared to the input contigs, while preserving low error rates compared to the state-of-the-art viral quasispecies assemblers. Availability and implementation Virus-VG is freely available at https://bitbucket.org/jbaaijens/virus-vg. Supplementary information Supplementary data are available at Bioinformatics online.
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34

Le Meur, M., C. Waltzinger, P. Gerlinger, C. Benoist et D. Mathis. « Restricted assembly of MHC class II molecules in transgenic mice. » Journal of Immunology 142, no 1 (1 janvier 1989) : 323–27. http://dx.doi.org/10.4049/jimmunol.142.1.323.

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Abstract Studies on cell lines transfected with MHC class II genes have revealed important limitations on the assembly of haplotype-mismatched A alpha:A beta complexes. These findings led to the speculation that pairing restrictions, if applied in a cell type-specific fashion, might be involved in various autoimmune phenomena. We have investigated pairing restrictions in vivo by analyzing transgenic mice that carry an Ak alpha chain, an Ak beta chain, or the Ak alpha:Ak beta complex on an H-2b or H-2s background. Our conclusion is that the assembly of haplotype-mismatched A alpha:A beta complexes is limited in vivo, and that this is equally true for all cell types examined, regardless of their role in the immune response.
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Ke, Ziqi, et Haris Vikalo. « A Graph Auto-Encoder for Haplotype Assembly and Viral Quasispecies Reconstruction ». Proceedings of the AAAI Conference on Artificial Intelligence 34, no 01 (3 avril 2020) : 719–26. http://dx.doi.org/10.1609/aaai.v34i01.5414.

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Reconstructing components of a genomic mixture from data obtained by means of DNA sequencing is a challenging problem encountered in a variety of applications including single individual haplotyping and studies of viral communities. High-throughput DNA sequencing platforms oversample mixture components to provide massive amounts of reads whose relative positions can be determined by mapping the reads to a known reference genome; assembly of the components, however, requires discovery of the reads' origin – an NP-hard problem that the existing methods struggle to solve with the required level of accuracy. In this paper, we present a learning framework based on a graph auto-encoder designed to exploit structural properties of sequencing data. The algorithm is a neural network which essentially trains to ignore sequencing errors and infers the posterior probabilities of the origin of sequencing reads. Mixture components are then reconstructed by finding consensus of the reads determined to originate from the same genomic component. Results on realistic synthetic as well as experimental data demonstrate that the proposed framework reliably assembles haplotypes and reconstructs viral communities, often significantly outperforming state-of-the-art techniques. Source codes, datasets and supplementary document are available at https://github.com/WuLoli/GAEseq.
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Tregaskes, Clive A., Michael Harrison, Anna K. Sowa, Andy van Hateren, Lawrence G. Hunt, Olli Vainio et Jim Kaufman. « Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity ». Proceedings of the National Academy of Sciences 113, no 3 (22 décembre 2015) : 692–97. http://dx.doi.org/10.1073/pnas.1511859113.

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The chicken major histocompatibility complex (MHC) has strong genetic associations with resistance and susceptibility to certain infectious pathogens. The cell surface expression level of MHC class I molecules varies as much as 10-fold between chicken haplotypes and is inversely correlated with diversity of peptide repertoire and with resistance to Marek’s disease caused by an oncogenic herpesvirus. Here we show that the average thermostability of class I molecules isolated from cells also varies, being higher for high-expressing MHC haplotypes. However, we find roughly the same amount of class I protein synthesized by high- and low-expressing MHC haplotypes, with movement to the cell surface responsible for the difference in expression. Previous data show that chicken TAP genes have high allelic polymorphism, with peptide translocation specific for each MHC haplotype. Here we use assembly assays with peptide libraries to show that high-expressing B15 class I molecules can bind a much wider variety of peptides than are found on the cell surface, with the B15 TAPs restricting the peptides available. In contrast, the translocation specificity of TAPs from the low-expressing B21 haplotype is even more permissive than the promiscuous binding shown by the dominantly expressed class I molecule. B15/B21 heterozygote cells show much greater expression of B15 class I molecules than B15/B15 homozygote cells, presumably as a result of receiving additional peptides from the B21 TAPs. Thus, chicken MHC haplotypes vary in several correlated attributes, with the most obvious candidate linking all these properties being molecular interactions within the peptide-loading complex (PLC).
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Koren, Sergey, Arang Rhie, Brian P. Walenz, Alexander T. Dilthey, Derek M. Bickhart, Sarah B. Kingan, Stefan Hiendleder, John L. Williams, Timothy P. L. Smith et Adam M. Phillippy. « De novo assembly of haplotype-resolved genomes with trio binning ». Nature Biotechnology 36, no 12 (22 octobre 2018) : 1174–82. http://dx.doi.org/10.1038/nbt.4277.

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38

Edge, Peter, Vineet Bafna et Vikas Bansal. « HapCUT2 : robust and accurate haplotype assembly for diverse sequencing technologies ». Genome Research 27, no 5 (9 décembre 2016) : 801–12. http://dx.doi.org/10.1101/gr.213462.116.

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39

Lippert, R. « Algorithmic strategies for the single nucleotide polymorphism haplotype assembly problem ». Briefings in Bioinformatics 3, no 1 (1 janvier 2002) : 23–31. http://dx.doi.org/10.1093/bib/3.1.23.

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40

Pirola, Yuri, Simone Zaccaria, Riccardo Dondi, Gunnar W. Klau, Nadia Pisanti et Paola Bonizzoni. « HapCol : accurate and memory-efficient haplotype assembly from long reads ». Bioinformatics 32, no 11 (26 août 2015) : 1610–17. http://dx.doi.org/10.1093/bioinformatics/btv495.

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41

He, D., A. Choi, K. Pipatsrisawat, A. Darwiche et E. Eskin. « Optimal algorithms for haplotype assembly from whole-genome sequence data ». Bioinformatics 26, no 12 (6 juin 2010) : i183—i190. http://dx.doi.org/10.1093/bioinformatics/btq215.

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Chen, Zhi-Zhong, Fei Deng et Lusheng Wang. « Exact algorithms for haplotype assembly from whole-genome sequence data ». Bioinformatics 29, no 16 (18 juin 2013) : 1938–45. http://dx.doi.org/10.1093/bioinformatics/btt349.

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43

Giordani, T., G. Usai, M. Castellacci, A. Vangelisti, F. Mascagni, M. Ventimiglia, S. Simoni, L. Natali et A. Cavallini. « Haplotype-phased genome assembly for Ficus carica breeding ». Acta Horticulturae, no 1349 (octobre 2022) : 13–18. http://dx.doi.org/10.17660/actahortic.2022.1349.3.

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44

Garg, Shilpa, John Aach, Heng Li, Isaac Sebenius, Richard Durbin et George Church. « A haplotype-aware de novo assembly of related individuals using pedigree sequence graph ». Bioinformatics 36, no 8 (20 décembre 2019) : 2385–92. http://dx.doi.org/10.1093/bioinformatics/btz942.

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Abstract Motivation Reconstructing high-quality haplotype-resolved assemblies for related individuals has important applications in Mendelian diseases and population genomics. Through major genomics sequencing efforts such as the Personal Genome Project, the Vertebrate Genome Project (VGP) and the Genome in a Bottle project (GIAB), a variety of sequencing datasets from trios of diploid genomes are becoming available. Current trio assembly approaches are not designed to incorporate long- and short-read data from mother–father–child trios, and therefore require relatively high coverages of costly long-read data to produce high-quality assemblies. Thus, building a trio-aware assembler capable of producing accurate and chromosomal-scale diploid genomes of all individuals in a pedigree, while being cost-effective in terms of sequencing costs, is a pressing need of the genomics community. Results We present a novel pedigree sequence graph based approach to diploid assembly using accurate Illumina data and long-read Pacific Biosciences (PacBio) data from all related individuals, thereby generalizing our previous work on single individuals. We demonstrate the effectiveness of our pedigree approach on a simulated trio of pseudo-diploid yeast genomes with different heterozygosity rates, and real data from human chromosome. We show that we require as little as 30× coverage Illumina data and 15× PacBio data from each individual in a trio to generate chromosomal-scale phased assemblies. Additionally, we show that we can detect and phase variants from generated phased assemblies. Availability and implementation https://github.com/shilpagarg/WHdenovo.
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Sato, S., C. Ohnishi, Y. Uemoto et E. Kobayashi. « Haplotype analysis within quantitative trait locus affecting intramuscular fat content on porcine chromosome ». Czech Journal of Animal Science 56, No. 12 (22 décembre 2011) : 521–28. http://dx.doi.org/10.17221/4414-cjas.

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Previous results of fine mapping for quantitative trait loci affecting intramuscular fat content identified a 3.0-Mb chromosome interval on porcine chromosome 7, which contains at least 9 genes, based on the pig genome assembly. Therefore, we proposed these nine genes (LOC100154481, LOC100155711, LOC100155276, SPATA7, PTPN21, ZCH14, EML5, TTC8, and FOXN3) as positional candidate genes. The coding exons of the nine genes were characterized, and 45 polymorphisms were detected in F<sub>2</sub> Duroc &times; Meishan population. Within the nine genes, 10 non-synonymous substitutions and 1 insertion were genotyped among three European breeds (Landrace, Large White, and Duroc) and 1 Chinese breed (Meishan). Genotyping data was used to perform the haplotype analysis. Polymorphisms were found in all the studied genes, except ZCH14. We surveyed the frequency of 33 haplotypes that formed non-synonymous substitutions in four breeds. One of them was distributed widely in the Landrace, Large White, and Meishan breeds, but not in Duroc. Each breed had different major haplotypes. &nbsp;
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Shirasawa, Kenta, Tomoya Esumi, Hideki Hirakawa, Hideyuki Tanaka, Akihiro Itai, Andrea Ghelfi, Hideki Nagasaki et Sachiko Isobe. « Phased genome sequence of an interspecific hybrid flowering cherry, ‘Somei-Yoshino’ (Cerasus × yedoensis) ». DNA Research 26, no 5 (23 juillet 2019) : 379–89. http://dx.doi.org/10.1093/dnares/dsz016.

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Abstract We report the phased genome sequence of an interspecific hybrid, the flowering cherry ‘Somei-Yoshino’ (Cerasus × yedoensis). The sequence data were obtained by single-molecule real-time sequencing technology, split into two subsets based on genome information of the two probable ancestors, and assembled to obtain two haplotype phased genome sequences of the interspecific hybrid. The resultant genome assembly consisting of the two haplotype sequences spanned 690.1 Mb with 4,552 contigs and an N50 length of 1.0 Mb. We predicted 95,076 high-confidence genes, including 94.9% of the core eukaryotic genes. Based on a high-density genetic map, we established a pair of eight pseudomolecule sequences, with highly conserved structures between the two haplotype sequences with 2.4 million sequence variants. A whole genome resequencing analysis of flowering cherries suggested that ‘Somei-Yoshino’ might be derived from a cross between C. spachiana and either C. speciosa or its relatives. A time-course transcriptome analysis of floral buds and flowers suggested comprehensive changes in gene expression in floral bud development towards flowering. These genome and transcriptome data are expected to provide insights into the evolution and cultivation of flowering cherry and the molecular mechanism underlying flowering.
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47

Li, Taotao, Duo Du, Dandan Zhang, Yicheng Lin, Jiakang Ma, Mengyu Zhou, Weida Meng et al. « CRISPR-based targeted haplotype-resolved assembly of a megabase region ». Nature Communications 14, no 1 (3 janvier 2023). http://dx.doi.org/10.1038/s41467-022-35389-w.

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AbstractConstructing high-quality haplotype-resolved genome assemblies has substantially improved the ability to detect and characterize genetic variants. A targeted approach providing readily access to the rich information from haplotype-resolved genome assemblies will be appealing to groups of basic researchers and medical scientists focused on specific genomic regions. Here, using the 4.5 megabase, notoriously difficult-to-assemble major histocompatibility complex (MHC) region as an example, we demonstrated an approach to construct haplotype-resolved assembly of the targeted genomic region with the CRISPR-based enrichment. Compared to the results from haplotype-resolved genome assembly, our targeted approach achieved comparable completeness and accuracy with reduced computing complexity, sequencing cost, as well as the amount of starting materials. Moreover, using the targeted assembled personal MHC haplotypes as the reference both improves the quantification accuracy for sequencing data and enables allele-specific functional genomics analyses of the MHC region. Given its highly efficient use of resources, our approach can greatly facilitate population genetic studies of targeted regions, and may pave a new way to elucidate the molecular mechanisms in disease etiology.
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48

Sankararaman, Abishek, Haris Vikalo et François Baccelli. « ComHapDet : a spatial community detection algorithm for haplotype assembly ». BMC Genomics 21, S9 (septembre 2020). http://dx.doi.org/10.1186/s12864-020-06935-x.

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Abstract Background Haplotypes, the ordered lists of single nucleotide variations that distinguish chromosomal sequences from their homologous pairs, may reveal an individual’s susceptibility to hereditary and complex diseases and affect how our bodies respond to therapeutic drugs. Reconstructing haplotypes of an individual from short sequencing reads is an NP-hard problem that becomes even more challenging in the case of polyploids. While increasing lengths of sequencing reads and insert sizes helps improve accuracy of reconstruction, it also exacerbates computational complexity of the haplotype assembly task. This has motivated the pursuit of algorithmic frameworks capable of accurate yet efficient assembly of haplotypes from high-throughput sequencing data. Results We propose a novel graphical representation of sequencing reads and pose the haplotype assembly problem as an instance of community detection on a spatial random graph. To this end, we construct a graph where each read is a node with an unknown community label associating the read with the haplotype it samples. Haplotype reconstruction can then be thought of as a two-step procedure: first, one recovers the community labels on the nodes (i.e., the reads), and then uses the estimated labels to assemble the haplotypes. Based on this observation, we propose – a novel assembly algorithm for diploid and ployploid haplotypes which allows both bialleleic and multi-allelic variants. Conclusions Performance of the proposed algorithm is benchmarked on simulated as well as experimental data obtained by sequencing Chromosome 5 of tetraploid biallelic Solanum-Tuberosum (Potato). The results demonstrate the efficacy of the proposed method and that it compares favorably with the existing techniques.
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Fruzangohar, Mario, William A. Timmins, Olena Kravchuk et Julian Taylor. « HaploMaker : An improved algorithm for rapid haplotype assembly of genomic sequences ». GigaScience 11 (2022). http://dx.doi.org/10.1093/gigascience/giac038.

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Abstract Background In diploid organisms, whole-genome haplotype assembly relies on the accurate identification and assignment of heterozygous single-nucleotide polymorphism alleles to the correct homologous chromosomes. This appropriate phasing of these alleles ensures that combinations of single-nucleotide polymorphisms on any chromosome, called haplotypes, can then be used in downstream genetic analysis approaches including determining their potential association with important phenotypic traits. A number of statistical algorithms and complementary computational software tools have been developed for whole-genome haplotype construction from genomic sequence data. However, many algorithms lack the ability to phase long haplotype blocks and simultaneously achieve a competitive accuracy. Results In this research we present HaploMaker, a novel reference-based haplotype assembly algorithm capable of accurately and efficiently phasing long haplotypes using paired-end short reads and longer Pacific Biosciences reads from diploid genomic sequences. To achieve this we frame the problem as a directed acyclic graph with edges weighted on read evidence and use efficient path traversal and minimization techniques to optimally phase haplotypes. We compared the HaploMaker algorithm with 3 other common reference-based haplotype assembly tools using public haplotype data of human individuals from the Platinum Genome project. With short-read sequences, the HaploMaker algorithm maintained a competitively low switch error rate across all haplotype lengths and was superior in phasing longer genomic regions. For longer Pacific Biosciences reads, the phasing accuracy of HaploMaker remained competitive for all block lengths and generated substantially longer block lengths than the competing algorithms. Conclusions HaploMaker provides an improved haplotype assembly algorithm for diploid genomic sequences by accurately phasing longer haplotypes. The computationally efficient and portable nature of the Java implementation of the algorithm will ensure that it has maximal impact in reference-sequence–based haplotype assembly applications.
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Karl, Julie A., Trent M. Prall, Hailey E. Bussan, Joshua M. Varghese, Aparna Pal, Roger W. Wiseman et David H. O'Connor. « Complete sequencing of a cynomolgus macaque major histocompatibility complex haplotype ». Genome Research, 28 février 2023, gr.277429.122. http://dx.doi.org/10.1101/gr.277429.122.

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Macaques provide the most widely used nonhuman primate models for studying immunology and pathogenesis of human diseases. While the macaque major histocompatibility complex (MHC) region shares most features with the human leukocyte antigen (HLA) region, macaques have an expanded repertoire of MHC class I genes. Although a chimera of two rhesus macaque MHC haplotypes was first published in 2004, the structural diversity of MHC genomic organization in macaques remains poorly understood due to a lack of adequate genomic reference sequences. We used ultra-long Oxford Nanopore and high-accuracy PacBio HiFi sequences to fully assemble the ~5.2 Mb M3 haplotype of an MHC-homozygous, Mauritian-origin cynomolgus macaque (Macaca fascicularis). The MHC homozygosity allowed us to assemble a single MHC haplotype unambiguously and avoid chimeric assemblies that hampered previous efforts to characterize this exceptionally complex genomic region in macaques. The high quality of this new assembly is exemplified by the identification of an extended cluster of sixMafa-AGgenes that contains a recent duplication with a remarkably similar ~48.5 kb block of sequence. The MHC class II region of this M3 haplotype is similar to the previously sequenced rhesus macaque haplotype and HLA class II haplotypes. The MHC class I region, in contrast, contains 13MHC-Bgenes, fourMHC-Agenes, and threeMHC-Egenes (versus 19MHC-B, twoMHC-A, and oneMHC-Ein the previously sequenced haplotype). These results provide an unambiguously assembled single contiguous cynomolgus macaque MHC haplotype with fully curated gene annotations that will inform infectious disease and transplantation research.
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