scholarly journals Whole Genome Analysis of 132 Clinical Saccharomyces cerevisiae Strains Reveals Extensive Ploidy Variation

2016 ◽  
Author(s):  
Yuan O Zhu ◽  
Gavin J Sherlock ◽  
Dmitri A Petrov
Keyword(s):  
Large Scale ◽  
Genomic Variation ◽  
Whole Genome Analysis ◽  
Yeast Strains ◽  
Copy Numbers ◽  
Adaptive Processes ◽  
Chromosomal Copy ◽  
Commercial Sources ◽  
Ploidy Changes ◽  
Copy Number Changes

Budding yeast has undergone several independent transitions from commercial to clinical lifestyles. The frequency of such transitions suggests that clinical yeast strains are derived from environmentally available yeast populations, including commercial sources. However, despite their important role in adaptive evolution, the prevalence of polyploidy and aneuploidy has not extensively analyzed in clinical strains. In this study, we have looked for patterns governing the transition to clinical invasion in the largest screen of clinical yeast isolates to date. In particular, we have focused on the hypothesis that ploidy changes have influenced adaptive processes. We sequenced 145 yeast strains, 132 of which are clinical isolates. We found pervasive large-scale genomic variation in both overall ploidy (34% of strains identified as 3n/4n) and individual chromosomal copy numbers (36% of strains identified as aneuploid). We also found evidence for the highly dynamic nature of yeasts genomes, with 35 strains showing partial chromosomal copy number changes and 8 strains showing multiple independent chromosomal events. Intriguingly, a lineage identified to be baker/commercial derived with a unique damaging mutation in NDC80 was particularly prone to polyploidy, with 83% of its members being triploid or tetraploid. Polyploidy was in turn associated with a >2x increase in aneuploidy rates as compared to other lineages. This dataset provides a rich source of information of the genomics of clinical yeast strains and highlights the potential importance of large-scale genomic copy variation in yeast adaptation.

scholarly journals High-throughput multiplexed tandem repeat genotyping using targeted long-read sequencing

2019 ◽  
Author(s):  
Devika Ganesamoorthy ◽  
Mengjia Yan ◽  
Valentine Murigneux ◽  
Chenxi Zhou ◽  
Minh Duc Cao ◽  
...  
Keyword(s):  
Large Scale ◽  
Tandem Repeats ◽  
Gc Content ◽  
Genomic Variation ◽  
Population Variation ◽  
Small Subset ◽  
Sequence Coverage ◽  
Copy Numbers ◽  
Long Read ◽  
Highly Correlated

ABSTRACTTandem repeats (TRs) are highly prone to variation in copy numbers due to their repetitive and unstable nature, which makes them a major source of genomic variation between individuals. However, population variation of TRs have not been widely explored due to the limitations of existing tools, which are either low-throughput or restricted to a small subset of TRs. Here, we used SureSelect targeted sequencing approach combined with Nanopore sequencing to overcome these limitations. We achieved an average of 3062-fold target enrichment on a panel of 142 TR loci, generating an average of 97X sequence coverage on 7 samples utilizing 2 MinION flow-cells with 200ng of input DNA per sample. We identified a subset of 110 TR loci with length less than 2kb, and GC content greater than 25% for which we achieved an average genotyping rate of 75% and increasing to 91% for the highest-coverage sample. Alleles estimated from targeted long-read sequencing were concordant with gold standard PCR sizing analysis and moreover highly correlated with alleles estimated from whole genome long-read sequencing. We demonstrate a targeted long-read sequencing approach that enables simultaneous analysis of hundreds of TRs and accuracy is comparable to PCR sizing analysis. Our approach is feasible to scale for more targets and more samples facilitating large-scale analysis of TRs.

scholarly journals Genomic Comparison of Campylobacter spp. and Their Potential for Zoonotic Transmission between Birds, Primates, and Livestock

2016 ◽  
Vol 82 (24) ◽  
pp. 7165-7175 ◽  
Author(s):  
Allison M. Weis ◽  
Dylan B. Storey ◽  
Conor C. Taff ◽  
Andrea K. Townsend ◽  
Bihua C. Huang ◽  
...  
Keyword(s):  
Host Species ◽  
Large Scale ◽  
Genomic Variation ◽  
Zoonotic Transmission ◽  
Fluoroquinolone Resistance ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Pathogenic Potential ◽  
Content Type ◽  
New Genes

ABSTRACTCampylobacteris the leading cause of human gastroenteritis worldwide. Wild birds, including American crows, are abundant in urban, suburban, and agricultural settings and are likely zoonotic vectors ofCampylobacter. Their proximity to humans and livestock increases the potential spreading ofCampylobactervia crows between the environment, livestock, and humans. However, no studies have definitively demonstrated that crows are a vector for pathogenicCampylobacter. We used genomics to evaluate the zoonotic and pathogenic potential ofCampylobacterfrom crows to other animals with 184 isolates obtained from crows, chickens, cows, sheep, goats, humans, and nonhuman primates. Whole-genome analysis uncovered two distinct clades ofCampylobacter jejunigenotypes; the first contained genotypes found only in crows, while a second genotype contained “generalist” genomes that were isolated from multiple host species, including isolates implicated in human disease, primate gastroenteritis, and livestock abortion. Two major β-lactamase genes were observed frequently in these genomes (oxa-184, 55%, andoxa-61, 29%), whereoxa-184was associated only with crows andoxa-61was associated with generalists. Mutations ingyrA, indicative of fluoroquinolone resistance, were observed in 14% of the isolates. Tetracycline resistance (tetO) was present in 22% of the isolates, yet it occurred in 91% of the abortion isolates. Virulence genes were distributed throughout the genomes; however,cdtCalleles recapitulated the crow-only and generalist clades. A specificcdtCallele was associated with abortion in livestock and was concomitant withtetO. These findings indicate that crows harboring a generalistC. jejunigenotype may act as a vector for the zoonotic transmission ofCampylobacter.IMPORTANCEThis study examined the link between public health and the genomic variation ofCampylobacterin relation to disease in humans, primates, and livestock. Use of large-scale whole-genome sequencing enabled population-level assessment to find new genes that are linked to livestock disease. With 184Campylobactergenomes, we assessed virulence traits, antibiotic resistance susceptibility, and the potential for zoonotic transfer to observe that there is a “generalist” genotype that may move between host species.

scholarly journals tHapMix: simulating tumour samples through haplotype mixtures

2016 ◽  
Author(s):  
Sergii Ivakhno ◽  
Camilla Colombo ◽  
Stephen Tanner ◽  
Philip Tedder ◽  
Stefano Berri ◽  
...  
Keyword(s):  
Copy Number ◽  
Large Scale ◽  
Variant Calling ◽  
Copy Number Variant ◽  
Supplementary Information ◽  
Genome Diversity ◽  
Simulation Framework ◽  
Somatic Genome ◽  
Copy Number Changes ◽  
Sequencing Platforms

AbstractMotivationLarge-scale rearrangements and copy number changes combined with different modes of cloevolution create extensive somatic genome diversity, making it difficult to develop versatile and scalable oriant calling tools and create well-calibrated benchmarks.ResultsWe developed a new simulation framework tHapMix that enables the creation of tumour samples with different ploidy, purity and polyclonality features. It easily scales to simulation of hundreds of somatic genomes, while re-use of real read data preserves noise and biases present in sequencing platforms. We further demonstrate tHapMix utility by creating a simulated set of 140 somatic genomes and showing how it can be used in training and testing of somatic copy number variant calling tools.Availability and implementationtHapMix is distributed under an open source license and can be downloaded from https://github.com/Illumina/[email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals Distribution and ecological segregation on regional and microgeographic scales of the diploidCentaurea asperaL., the tetraploidC. seridisL., and their triploid hybrids (Compositae)

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5209 ◽  
Author(s):  
Alfonso Garmendia ◽  
Hugo Merle ◽  
Pablo Ruiz ◽  
Maria Ferriol
Keyword(s):  
Anthropogenic Disturbance ◽  
Large Scale ◽  
Latitudinal Gradient ◽  
Soil Parameters ◽  
Fine Scale ◽  
Contact Zones ◽  
Ecological Requirements ◽  
Adaptive Processes ◽  
Sympatric Cytotypes

Although polyploidy is considered a ubiquitous process in plants, the establishment of new polyploid species may be hindered by ecological competition with parental diploid taxa. In such cases, the adaptive processes that result in the ecological divergence of diploids and polyploids can lead to their co-existence. In contrast, non-adaptive processes can lead to the co-existence of diploids and polyploids or to differentiated distributions, particularly when the minority cytotype disadvantage effect comes into play. Although large-scale studies of cytotype distributions have been widely conducted, the segregation of sympatric cytotypes on fine scales has been poorly studied. We analysed the spatial distribution and ecological requirements of the tetraploidCentaurea seridisand the diploidCentaurea asperain east Spain on a large scale, and also microspatially in contact zones where both species hybridise and give rise to sterile triploid hybrids. On the fine scale, the position of eachCentaureaindividual was recorded along with soil parameters, accompanying species cover and plant richness. On the east Spanish coast, a slight latitudinal gradient was found. TetraploidC. seridisindividuals were located northerly and diploidC. asperaindividuals southerly. Tetraploids were found only in the habitats with strong anthropogenic disturbance. In disturbed locations with well-developed semi-fixed or fixed dunes, diploids and tetraploids could co-exist and hybridise. However, on a fine scale, although taxa were spatially segregated in contact zones, they were not ecologically differentiated. This finding suggests the existence of non-adaptive processes that have led to their co-existence. Triploid hybrids were closer to diploid allogamous mothers (C. aspera) than to tetraploid autogamous fathers (C. seridis). This may result in a better ability to compete for space in the tetraploid minor cytotype, which might facilitate its long-term persistence.

scholarly journals ABySS 2.0: Resource-Efficient Assembly of Large Genomes using a Bloom Filter

2016 ◽  
Author(s):  
Shaun D Jackman ◽  
Benjamin P Vandervalk ◽  
Hamid Mohamadi ◽  
Justin Chu ◽  
Sarah Yeo ◽  
...  
Keyword(s):  
Human Genome ◽  
Dna Sequences ◽  
Message Passing ◽  
Large Scale ◽  
De Novo ◽  
Bloom Filter ◽  
Genomic Variation ◽  
De Bruijn Graph ◽  
Single Individual ◽  
Probabilistic Data Structure

AbstractThe assembly of DNA sequences de novo is fundamental to genomics research. It is the first of many steps towards elucidating and characterizing whole genomes. Downstream applications, including analysis of genomic variation between species, between or within individuals critically depends on robustly assembled sequences. In the span of a single decade, the sequence throughput of leading DNA sequencing instruments has increased drastically, and coupled with established and planned large-scale, personalized medicine initiatives to sequence genomes in the thousands and even millions, the development of efficient, scalable and accurate bioinformatics tools for producing high-quality reference draft genomes is timely.With ABySS 1.0, we originally showed that assembling the human genome using short 50 bp sequencing reads was possible by aggregating the half terabyte of compute memory needed over several computers using a standardized message-passing system (MPI). We present here its re-design, which departs from MPI and instead implements algorithms that employ a Bloom filter, a probabilistic data structure, to represent a de Bruijn graph and reduce memory requirements.We present assembly benchmarks of human Genome in a Bottle 250 bp Illumina paired-end and 6 kbp mate-pair libraries from a single individual, yielding a NG50 (NGA50) scaffold contiguity of 3.5 (3.0) Mbp using less than 35 GB of RAM, a modest memory requirement by today’s standard that is often available on a single computer. We also investigate the use of BioNano Genomics and 10x Genomics’ Chromium data to further improve the scaffold contiguity of this assembly to 42 (15) Mbp.

scholarly journals Frequent birth-and-death events throughout perforin-1 evolution

2020 ◽  
Author(s):  
Miguel Araujo-Voces ◽  
Victor Quesada
Keyword(s):  
Preliminary Analysis ◽  
Large Scale ◽  
Mammalian Species ◽  
Genomic Data ◽  
Start Codon ◽  
High Similarity ◽  
Gene Encoding ◽  
Coding Sequences ◽  
Copy Numbers ◽  
Multiple Species

Abstract Background Through its ability to open pores in cell membranes, perforin-1 plays a key role in the immune system. Consistent with this role, the gene encoding perforin shows hallmarks of complex evolutionary events, including amplification and pseudogenization, in multiple species. A large proportion of these events occurred in phyla for which scarce genomic data were available. However, recent large-scale genomics projects have added a wealth of information on those phyla. Using this input, we annotated perforin-1 homologs in more than eighty species including mammals, reptiles, birds, amphibians and fishes. Results We have annotated more than 400 perforin genes in all groups studied. Most mammalian species only have one perforin locus, which may contain a related pseudogene. However, we found four independent small expansions in unrelated members of this class. We could reconstruct the full-length coding sequences of only a few avian perforin genes, although we found incomplete and truncated forms of these gene in other birds. In the rest of reptilia, perforin-like genes can be found in at least three different loci containing up to twelve copies. Notably, mammals, non-avian reptiles, amphibians, and possibly teleosts share at least one perforin-1 locus as assessed by flanking genes. Finally, fish genomes contain multiple perforin loci with varying copy numbers and diverse exon/intron patterns. We have also found evidence for shorter genes with high similarity to the C2 domain of perforin in several teleosts. A preliminary analysis suggests that these genes arose at least twice during evolution from perforin-1 homologs. Conclusions The assisted annotation of new genomic assemblies shows complex patterns of birth-and-death events in the evolution of perforin. These events include duplication/pseudogenization in mammals, multiple amplifications and losses in reptiles and fishes and at least one case of partial duplication with a novel start codon in fishes.

scholarly journals Local Evolutionary Patterns of Human Respiratory Syncytial Virus Derived from Whole-Genome Sequencing

2015 ◽  
Vol 89 (7) ◽  
pp. 3444-3454 ◽  
Author(s):  
Charles N. Agoti ◽  
James R. Otieno ◽  
Patrick K. Munywoki ◽  
Alexander G. Mwihuri ◽  
Patricia A. Cane ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Large Scale ◽  
Vaccine Development ◽  
Human Respiratory Syncytial Virus ◽  
Genomic Variation ◽  
Genomic Sequences ◽  
The Novel ◽  
Sequencing Method ◽  
The World ◽  
Syncytial Virus

ABSTRACTHuman respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies.IMPORTANCEThe new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment.

scholarly journals DNA Amplifications and Aneuploidy, High Proliferative Activity and Impaired Cell Cycle Control Characterize Breast Carcinomas with Poor Prognosis

2003 ◽  
Vol 25 (3) ◽  
pp. 103-114 ◽  
Author(s):  
Harald Blegen ◽  
John S. Will ◽  
B. Michael Ghadimi ◽  
Hesed‐Padilla Nash ◽  
Anders Zetterberg ◽  
...  
Keyword(s):  
Copy Number ◽  
Proliferative Activity ◽  
Distant Metastases ◽  
Comparative Genomic ◽  
Short Term ◽  
Ki 67 ◽  
Chromosomal Copy ◽  
Copy Number Changes ◽  
Long Term Survivors

In order to explore whether specific cytogenetic abnormalities can be used to stratify tumors with a distinctly different clinical course, we performed comparative genomic hybridization (CGH) of tumors from patients who were diagnosed with metastatic disease after an interval of less than 2 years or who remained free from distant metastases for more than 10 years. All patients presented with distant metastases after mastectomy indicating that none of the patients in this study was cured and free of remaining tumor cells. Tumors in the group of short‐term survivors showed a higher average number of chromosomal copy alterations compared to the long‐term survivors. Of note, the number of sub‐chromosomal high‐level copy number increases (amplifications) was significantly increased in the group of short‐term survivors. In both short‐ and long‐term survivors recurrent chromosomal gains were mapped to chromosomes 1q, 4q, 8q, and 5p. Copy number changes that were more frequent in the group of short‐term survivors included gains of chromosome 3q, 9p, 11p and 11q and loss of 17p. Our results indicate that low‐ and high grade malignant breast adenocarcinomas are characterized by a specific pattern of chromosomal copy number changes. Furthermore, immunohistochemical evaluation of the expression levels of Ki‐67, p27KIP1, p21WAF1, p53, cyclin A and cyclin E revealed a correlation between increased proliferative activity and poor outcome.

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