Publications by authors named "Chew Yee Ngan"

61 Publications

Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription.

Cancer Cell 2021 Mar 30. Epub 2021 Mar 30.

The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA. Electronic address:

Extrachromosomal, circular DNA (ecDNA) is emerging as a prevalent yet less characterized oncogenic alteration in cancer genomes. We leverage ChIA-PET and ChIA-Drop chromatin interaction assays to characterize genome-wide ecDNA-mediated chromatin contacts that impact transcriptional programs in cancers. ecDNAs in glioblastoma patient-derived neurosphere and prostate cancer cell cultures are marked by widespread intra-ecDNA and genome-wide chromosomal interactions. ecDNA-chromatin contact foci are characterized by broad and high-level H3K27ac signals converging predominantly on chromosomal genes of increased expression levels. Prostate cancer cells harboring synthetic ecDNA circles composed of characterized enhancers result in the genome-wide activation of chromosomal gene transcription. Deciphering the chromosomal targets of ecDNAs at single-molecule resolution reveals an association with actively expressed oncogenes spatially clustered within ecDNA-directed interaction networks. Our results suggest that ecDNA can function as mobile transcriptional enhancers to promote tumor progression and manifest a potential synthetic aneuploidy mechanism of transcription control in cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ccell.2021.03.006DOI Listing
March 2021

Succession of physiological stages hallmarks the transcriptomic response of the fungus to lignocellulose.

Biotechnol Biofuels 2020 13;13:69. Epub 2020 Apr 13.

1School of Life Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD UK.

Background: Understanding how fungi degrade lignocellulose is a cornerstone of improving renewables-based biotechnology, in particular for the production of hydrolytic enzymes. Considerable progress has been made in investigating fungal degradation during time-points where CAZyme expression peaks. However, a robust understanding of the fungal survival strategies over its life time on lignocellulose is thereby missed. Here we aimed to uncover the physiological responses of the biotechnological workhorse and enzyme producer over its life time to six substrates important for biofuel production.

Results: We analysed the response of to the feedstock and compared it with our previous study on wheat straw, alone or in combination with hydrothermal or ionic liquid feedstock pretreatments. Conserved (substrate-independent) metabolic responses as well as those affected by pretreatment and feedstock were identified via multivariate analysis of genome-wide transcriptomics combined with targeted transcript and protein analyses and mapping to a metabolic model. Initial exposure to all substrates increased fatty acid beta-oxidation and lipid metabolism transcripts. In a strain carrying a deletion of the ortholog of the fatty acid beta-oxidation transcriptional regulator there was a reduction in expression of selected lignocellulose degradative CAZyme-encoding genes suggesting that beta-oxidation contributes to adaptation to lignocellulose. Mannan degradation expression was wheat straw feedstock-dependent and pectin degradation was higher on the untreated substrates. In the later life stages, known and novel secondary metabolite gene clusters were activated, which are of high interest due to their potential to synthesize bioactive compounds.

Conclusion: In this study, which includes the first transcriptional response of Aspergilli to , we highlighted that life time as well as substrate composition and structure (via variations in pretreatment and feedstock) influence the fungal responses to lignocellulose. We also demonstrated that the fungal response contains physiological stages that are conserved across substrates and are typically found outside of the conditions with high CAZyme expression, as exemplified by the stages that are dominated by lipid and secondary metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13068-020-01702-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155255PMC
April 2020

Chromatin interaction analyses elucidate the roles of PRC2-bound silencers in mouse development.

Nat Genet 2020 03 24;52(3):264-272. Epub 2020 Feb 24.

The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.

Lineage-specific gene expression is modulated by a balance between transcriptional activation and repression during animal development. Knowledge about enhancer-centered transcriptional activation has advanced considerably, but silencers and their roles in normal development remain poorly understood. Here, we performed chromatin interaction analyses of Polycomb repressive complex 2 (PRC2), a key inducer of transcriptional gene silencing, to uncover silencers, their molecular identity and associated chromatin connectivity. Systematic analysis of cis-regulatory silencer elements reveals their chromatin features and gene-targeting specificity. Deletion of certain PRC2-bound silencers in mice results in transcriptional derepression of their interacting genes and pleiotropic developmental phenotypes, including embryonic lethality. While some PRC2-bound elements function as silencers in pluripotent cells, they can transition into active tissue-specific enhancers during development, highlighting their regulatory versatility. Our study characterizes the molecular profile of silencers and their associated chromatin architectures, and suggests the possibility of targeted reactivation of epigenetically silenced genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-020-0581-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869692PMC
March 2020

Comparative Molecular Life History of Spontaneous Canine and Human Gliomas.

Cancer Cell 2020 02;37(2):243-257.e7

The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA. Electronic address:

Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome, and methylation sequencing of 83 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robust aneuploidy, mutational rates, relative timing of mutations, and DNA-methylation patterns. Our cross-species comparative genomic analysis provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ccell.2020.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132629PMC
February 2020

Longitudinal molecular trajectories of diffuse glioma in adults.

Nature 2019 12 20;576(7785):112-120. Epub 2019 Nov 20.

The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-019-1775-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897368PMC
December 2019

Ultra-long Read Sequencing for Whole Genomic DNA Analysis.

J Vis Exp 2019 03 15(145). Epub 2019 Mar 15.

Genome Technologies, Jackson Laboratory for Genomic Medicine;

Third generation single-molecule DNA sequencing technologies offer significantly longer read length that can facilitate the assembly of complex genomes and analysis of complex structural variants. Nanopore platforms perform single-molecule sequencing by directly measuring the current changes mediated by DNA passage through the pores and can generate hundreds of kilobase (kb) reads with minimal capital cost. This platform has been adopted by many researchers for a variety of applications. Achieving longer sequencing read lengths is the most critical factor to leverage the value of nanopore sequencing platforms. To generate ultra-long reads, special consideration is required to avoid DNA breakages and gain efficiency to generate productive sequencing templates. Here, we provide the detailed protocol of ultra-long DNA sequencing including high molecular weight (HMW) DNA extraction from fresh or frozen cells, library construction by mechanical shearing or transposase fragmentation, and sequencing on a nanopore device. From 20-25 µg of HMW DNA, the method can achieve N50 read length of 50-70 kb with mechanical shearing and N50 of 90-100 kb read length with transposase mediated fragmentation. The protocol can be applied to DNA extracted from mammalian cells to perform whole genome sequencing for the detection of structural variants and genome assembly. Additional improvements on the DNA extraction and enzymatic reactions will further increase the read length and expand its utility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3791/58954DOI Listing
March 2019

Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance.

Cell Stem Cell 2019 03;24(3):462-476.e6

The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. Electronic address:

The SOX2 transcription factor is critical for neural stem cell (NSC) maintenance and brain development. Through chromatin immunoprecipitation (ChIP) and chromatin interaction analysis (ChIA-PET), we determined genome-wide SOX2-bound regions and Pol II-mediated long-range chromatin interactions in brain-derived NSCs. SOX2-bound DNA was highly enriched in distal chromatin regions interacting with promoters and carrying epigenetic enhancer marks. Sox2 deletion caused widespread reduction of Pol II-mediated long-range interactions and decreased gene expression. Genes showing reduced expression in Sox2-deleted cells were significantly enriched in interactions between promoters and SOX2-bound distal enhancers. Expression of one such gene, Suppressor of Cytokine Signaling 3 (Socs3), rescued the self-renewal defect of Sox2-ablated NSCs. Our work identifies SOX2 as a major regulator of gene expression through connections to the enhancer network in NSCs. Through the definition of such a connectivity network, our study shows the way to the identification of genes and enhancers involved in NSC maintenance and neurodevelopmental disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.stem.2019.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506828PMC
March 2019

Multiplex chromatin interactions with single-molecule precision.

Nature 2019 02 18;566(7745):558-562. Epub 2019 Feb 18.

The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.

The genomes of multicellular organisms are extensively folded into 3D chromosome territories within the nucleus. Advanced 3D genome-mapping methods that combine proximity ligation and high-throughput sequencing (such as chromosome conformation capture, Hi-C), and chromatin immunoprecipitation techniques (such as chromatin interaction analysis by paired-end tag sequencing, ChIA-PET), have revealed topologically associating domains with frequent chromatin contacts, and have identified chromatin loops mediated by specific protein factors for insulation and regulation of transcription. However, these methods rely on pairwise proximity ligation and reflect population-level views, and thus cannot reveal the detailed nature of chromatin interactions. Although single-cell Hi-C potentially overcomes this issue, this method may be limited by the sparsity of data that is inherent to current single-cell assays. Recent advances in microfluidics have opened opportunities for droplet-based genomic analysis but this approach has not yet been adapted for chromatin interaction analysis. Here we describe a strategy for multiplex chromatin-interaction analysis via droplet-based and barcode-linked sequencing, which we name ChIA-Drop. We demonstrate the robustness of ChIA-Drop in capturing complex chromatin interactions with single-molecule precision, which has not been possible using methods based on population-level pairwise contacts. By applying ChIA-Drop to Drosophila cells, we show that chromatin topological structures predominantly consist of multiplex chromatin interactions with high heterogeneity; ChIA-Drop also reveals promoter-centred multivalent interactions, which provide topological insights into transcription.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-019-0949-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001875PMC
February 2019

Linked-read Sequencing Analysis Reveals Tumor-specific Genome Variation Landscapes in Neurofibromatosis Type 2 (NF2) Patients.

Otol Neurotol 2019 02;40(2):e150-e159

The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.

Hypothesis: We hypothesize that genomic variants including deletions, insertions, inversions, and tandem duplications beyond the changes in tumor suppressor NF2 gene affect gene expression of tumor-specific pathways in vestibular schwannomas (VS) patients with Neurofibromatosis type 2 (NF2), thus contributing to their clinical behavior.

Background: Genomic variation could reconfigure transcription in NF2 transformation process. Therefore, genome-wide high-resolution characterization of structural variants (SV) landscapes in NF2 tumors can expand our understanding of the genes regulating the clinical phenotypes in NF2-associated VS.

Methods: We performed whole-genome haplotype-specific structural variation analysis using synthetic linked reads generated through microfluidics-based barcoding of high molecular weight DNA followed by high-coverage Illumina paired-end whole-genome sequencing from 10 patients' tumors of different growth rates and their matching blood samples.

Results: NF2 tumor-specific deletions and large SVs were detected and can be classified based on their association with tumor growth rates. Through detailed annotation of these mutations, we uncover common alleles affected by these deletions and large SVs that can be associated with signaling pathways implicated in cell proliferation and tumorigenesis.

Conclusion: The genomic variation landscape of NF2-related VS was investigated through whole-genome linked-read sequencing. Large SVs, in addition to deletions, were identified and may serve as modulators of clinical behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAO.0000000000002096DOI Listing
February 2019

Sox2 conditional mutation in mouse causes ataxic symptoms, cerebellar vermis hypoplasia, and postnatal defects of Bergmann glia.

Glia 2018 09 6;66(9):1929-1946. Epub 2018 May 6.

Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, Milano, 20126, Italy.

Sox2 is a transcription factor active in the nervous system, within different cell types, ranging from radial glia neural stem cells to a few specific types of differentiated glia and neurons. Mutations in the human SOX2 transcription factor gene cause various central nervous system (CNS) abnormalities, involving hippocampus and eye defects, as well as ataxia. Conditional Sox2 mutation in mouse, with different Cre transgenes, previously recapitulated different essential features of the disease, such as hippocampus and eye defects. In the cerebellum, Sox2 is active from early embryogenesis in the neural progenitors of the cerebellar primordium; Sox2 expression is maintained, postnatally, within Bergmann glia (BG), a differentiated cell type essential for Purkinje neurons functionality and correct motor control. By performing Sox2 Cre-mediated ablation in the developing and postnatal mouse cerebellum, we reproduced ataxia features. Embryonic Sox2 deletion (with Wnt1Cre) leads to reduction of the cerebellar vermis, known to be commonly related to ataxia, preceded by deregulation of Otx2 and Gbx2, critical regulators of vermis development. Postnatally, BG is progressively disorganized, mislocalized, and reduced in mutants. Sox2 postnatal deletion, specifically induced in glia (with GLAST-CreERT2), reproduces the BG defect, and causes (milder) ataxic features. Our results define a role for Sox2 in cerebellar function and development, and identify a functional requirement for Sox2 within postnatal BG, of potential relevance for ataxia in mouse mutants, and in human patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/glia.23448DOI Listing
September 2018

Picky comprehensively detects high-resolution structural variants in nanopore long reads.

Nat Methods 2018 06 30;15(6):455-460. Epub 2018 Apr 30.

The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.

Acquired genomic structural variants (SVs) are major hallmarks of cancer genomes, but they are challenging to reconstruct from short-read sequencing data. Here we exploited the long reads of the nanopore platform using our customized pipeline, Picky ( https://github.com/TheJacksonLaboratory/Picky ), to reveal SVs of diverse architecture in a breast cancer model. We identified the full spectrum of SVs with superior specificity and sensitivity relative to short-read analyses, and uncovered repetitive DNA as the major source of variation. Examination of genome-wide breakpoints at nucleotide resolution uncovered micro-insertions as the common structural features associated with SVs. Breakpoint density across the genome is associated with the propensity for interchromosomal connectivity and was found to be enriched in promoters and transcribed regions of the genome. Furthermore, we observed an over-representation of reciprocal translocations from chromosomal double-crossovers through phased SVs. We demonstrate that Picky analysis is an effective tool for comprehensive detection of SVs in cancer genomes from long-read data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41592-018-0002-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990454PMC
June 2018

Linking secondary metabolites to gene clusters through genome sequencing of six diverse species.

Proc Natl Acad Sci U S A 2018 01 9;115(4):E753-E761. Epub 2018 Jan 9.

Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800 Lyngby, Denmark;

The fungal genus of is highly interesting, containing everything from industrial cell factories, model organisms, and human pathogens. In particular, this group has a prolific production of bioactive secondary metabolites (SMs). In this work, four diverse species (, , , and ) have been whole-genome PacBio sequenced to provide genetic references in three sections. and also were sequenced for SM elucidation. Thirteen genomes were analyzed with comparative genomics to determine phylogeny and genetic diversity, showing that each presented genome contains 15-27% genes not found in other sequenced Aspergilli. In particular, was compared with the pathogenic species This suggests that can produce most of the same allergens, virulence, and pathogenicity factors as , suggesting that could be as pathogenic as Furthermore, SMs were linked to gene clusters based on biological and chemical knowledge and analysis, genome sequences, and predictive algorithms. We thus identify putative SM clusters for aflatoxin, chlorflavonin, and ochrindol in , , and , respectively, and novofumigatonin, -cycloechinulin, and -aszonalenins in Our study delivers six fungal genomes, showing the large diversity found in the genus; highlights the potential for discovery of beneficial or harmful SMs; and supports reports of pathogenicity. It also shows how biological, biochemical, and genomic information can be combined to identify genes involved in the biosynthesis of specific SMs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1715954115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789934PMC
January 2018

Genome Sequence of sp. Strain MCTG156(2b) Isolated from a Phytoplankton Net Trawl on the Scottish West Coast.

Genome Announc 2017 Aug 31;5(35). Epub 2017 Aug 31.

DOE Joint Genome Institute, Walnut Creek, California, USA.

sp. strain MCTG156(2b) was isolated from a phytoplankton net sample collected on the west coast of Scotland and was selected based on its ability to degrade polycyclic aromatic hydrocarbons. Here, we present the genome sequence of this strain, which is 5,113,782 bp, with 5,142 genes and an average G+C content of 60.7%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/genomeA.00837-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578838PMC
August 2017

Genome Sequence of sp. Strain MCTG156(1a), Isolated from a Scottish Coastal Phytoplankton Net Sample.

Genome Announc 2017 Aug 10;5(32). Epub 2017 Aug 10.

DOE Joint Genome Institute, Walnut Creek, California, USA.

sp. strain MCTG156(1a) was isolated from a phytoplankton net sample collected on the west coast of Scotland and selected based on its ability to degrade polycyclic aromatic hydrocarbons. Here, we present the genome sequence of this strain, which comprises 3,881,122 bp with 3,949 genes and an average G+C content of 62.7%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/genomeA.00796-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552998PMC
August 2017

Absence of genome reduction in diverse, facultative endohyphal bacteria.

Microb Genom 2017 02 28;3(2):e000101. Epub 2017 Feb 28.

1​School of Plant Sciences, University of Arizona, Tucson, AZ 85721, USA.

Fungi interact closely with bacteria, both on the surfaces of the hyphae and within their living tissues (i.e. endohyphal bacteria, EHB). These EHB can be obligate or facultative symbionts and can mediate diverse phenotypic traits in their hosts. Although EHB have been observed in many lineages of fungi, it remains unclear how widespread and general these associations are, and whether there are unifying ecological and genomic features can be found across EHB strains as a whole. We cultured 11 bacterial strains after they emerged from the hyphae of diverse Ascomycota that were isolated as foliar endophytes of cupressaceous trees, and generated nearly complete genome sequences for all. Unlike the genomes of largely obligate EHB, the genomes of these facultative EHB resembled those of closely related strains isolated from environmental sources. Although all analysed genomes encoded structures that could be used to interact with eukaryotic hosts, pathways previously implicated in maintenance and establishment of EHB symbiosis were not universally present across all strains. Independent isolation of two nearly identical pairs of strains from different classes of fungi, coupled with recent experimental evidence, suggests horizontal transfer of EHB across endophytic hosts. Given the potential for EHB to influence fungal phenotypes, these genomes could shed light on the mechanisms of plant growth promotion or stress mitigation by fungal endophytes during the symbiotic phase, as well as degradation of plant material during the saprotrophic phase. As such, these findings contribute to the illumination of a new dimension of functional biodiversity in fungi.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1099/mgen.0.000101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361626PMC
February 2017

Complete Genome Sequence of ATCC 49181, a Phylogenetically Distinct Ammonia-Oxidizing Bacterium Isolated from Arctic Waters.

Genome Announc 2017 Mar 16;5(11). Epub 2017 Mar 16.

DOE Joint Genome Institute, Walnut Creek, California, USA.

ATCC 49181 is a cold-tolerant marine ammonia-oxidizing bacterium isolated from seawater collected in the Gulf of Alaska. The high-quality complete genome contains a 2.87-Mbp chromosome and a 56.6-kbp plasmid. Chemolithoautotrophic modules encoding ammonia oxidation and CO fixation were identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/genomeA.00011-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356046PMC
March 2017

Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus.

Authors:
Ronald P de Vries Robert Riley Ad Wiebenga Guillermo Aguilar-Osorio Sotiris Amillis Cristiane Akemi Uchima Gregor Anderluh Mojtaba Asadollahi Marion Askin Kerrie Barry Evy Battaglia Özgür Bayram Tiziano Benocci Susanna A Braus-Stromeyer Camila Caldana David Cánovas Gustavo C Cerqueira Fusheng Chen Wanping Chen Cindy Choi Alicia Clum Renato Augusto Corrêa Dos Santos André Ricardo de Lima Damásio George Diallinas Tamás Emri Erzsébet Fekete Michel Flipphi Susanne Freyberg Antonia Gallo Christos Gournas Rob Habgood Matthieu Hainaut María Laura Harispe Bernard Henrissat Kristiina S Hildén Ryan Hope Abeer Hossain Eugenia Karabika Levente Karaffa Zsolt Karányi Nada Kraševec Alan Kuo Harald Kusch Kurt LaButti Ellen L Lagendijk Alla Lapidus Anthony Levasseur Erika Lindquist Anna Lipzen Antonio F Logrieco Andrew MacCabe Miia R Mäkelä Iran Malavazi Petter Melin Vera Meyer Natalia Mielnichuk Márton Miskei Ákos P Molnár Giuseppina Mulé Chew Yee Ngan Margarita Orejas Erzsébet Orosz Jean Paul Ouedraogo Karin M Overkamp Hee-Soo Park Giancarlo Perrone Francois Piumi Peter J Punt Arthur F J Ram Ana Ramón Stefan Rauscher Eric Record Diego Mauricio Riaño-Pachón Vincent Robert Julian Röhrig Roberto Ruller Asaf Salamov Nadhira S Salih Rob A Samson Erzsébet Sándor Manuel Sanguinetti Tabea Schütze Kristina Sepčić Ekaterina Shelest Gavin Sherlock Vicky Sophianopoulou Fabio M Squina Hui Sun Antonia Susca Richard B Todd Adrian Tsang Shiela E Unkles Nathalie van de Wiele Diana van Rossen-Uffink Juliana Velasco de Castro Oliveira Tammi C Vesth Jaap Visser Jae-Hyuk Yu Miaomiao Zhou Mikael R Andersen David B Archer Scott E Baker Isabelle Benoit Axel A Brakhage Gerhard H Braus Reinhard Fischer Jens C Frisvad Gustavo H Goldman Jos Houbraken Berl Oakley István Pócsi Claudio Scazzocchio Bernhard Seiboth Patricia A vanKuyk Jennifer Wortman Paul S Dyer Igor V Grigoriev

Genome Biol 2017 02 14;18(1):28. Epub 2017 Feb 14.

US Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, 94598, USA.

Background: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus.

Results: We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli.

Conclusions: Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-017-1151-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307856PMC
February 2017

DNA methylation and gene expression regulation associated with vascularization in Sorghum bicolor.

New Phytol 2017 May 10;214(3):1213-1229. Epub 2017 Feb 10.

Department of Plant Biology and Genome Center, UC Davis, Davis, CA, 95616, USA.

Plant secondary cell walls constitute the majority of plant biomass. They are predominantly found in xylem cells, which are derived from vascular initials during vascularization. Little is known about these processes in grass species despite their emerging importance as biomass feedstocks. The targeted biofuel crop Sorghum bicolor has a sequenced and well-annotated genome, making it an ideal monocot model for addressing vascularization and biomass deposition. Here we generated tissue-specific transcriptome and DNA methylome data from sorghum shoots, roots and developing root vascular and nonvascular tissues. Many genes associated with vascular development in other species show enriched expression in developing vasculature. However, several transcription factor families varied in vascular expression in sorghum compared with Arabidopsis and maize. Furthermore, differential expression of genes associated with DNA methylation were identified between vascular and nonvascular tissues, implying that changes in DNA methylation are a feature of sorghum root vascularization, which we confirmed using tissue-specific DNA methylome data. Roots treated with a DNA methylation inhibitor also showed a significant decrease in root length. Tissues and organs can be discriminated based on their genomic methylation patterns and methylation context. Consequently, tissue-specific changes in DNA methylation are part of the normal developmental process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nph.14448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655736PMC
May 2017

Expression of CAZymes is determined by compositional changes in wheat straw generated by hydrothermal or ionic liquid pretreatments.

Biotechnol Biofuels 2017 7;10:35. Epub 2017 Feb 7.

School of Life Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD UK.

Background: The capacity of fungi, such as to degrade lignocellulose is harnessed in biotechnology to generate biofuels and high-value compounds from renewable feedstocks. Most feedstocks are currently pretreated to increase enzymatic digestibility: improving our understanding of the transcriptomic responses of fungi to pretreated lignocellulosic substrates could help to improve the mix of activities and reduce the production costs of commercial lignocellulose saccharifying cocktails.

Results: We investigated the responses of to untreated, ionic liquid and hydrothermally pretreated wheat straw over a 5-day time course using RNA-seq and targeted proteomics. The ionic liquid pretreatment altered the cellulose crystallinity while retaining more of the hemicellulosic sugars than the hydrothermal pretreatment. Ionic liquid pretreatment of straw led to a dynamic induction and repression of genes, which was correlated with the higher levels of pentose sugars saccharified from the ionic liquid-pretreated straw. Hydrothermal pretreatment of straw led to reduced levels of transcripts of genes encoding carbohydrate-active enzymes as well as the derived proteins and enzyme activities. Both pretreatments abolished the expression of a large set of genes encoding pectinolytic enzymes. These reduced levels could be explained by the removal of parts of the lignocellulose by the hydrothermal pretreatment. The time course also facilitated identification of temporally limited gene induction patterns.

Conclusions: The presented transcriptomic and biochemical datasets demonstrate that pretreatments caused modifications of the lignocellulose, to both specific structural features as well as the organisation of the overall lignocellulosic structure, that determined transcript levels. The experimental setup allowed reliable detection of substrate-specific gene expression patterns as well as hitherto non-expressed genes. Our data suggest beneficial effects of using untreated and IL-pretreated straw, but not HT-pretreated straw, as feedstock for CAZyme production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13068-017-0700-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294722PMC
February 2017

Near-Complete Genome Sequence of Thalassospira sp. Strain KO164 Isolated from a Lignin-Enriched Marine Sediment Microcosm.

Genome Announc 2016 Nov 23;4(6). Epub 2016 Nov 23.

Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, Tennessee, USA

Thalassospira sp. strain KO164 was isolated from eastern Mediterranean seawater and sediment laboratory microcosms enriched on insoluble organosolv lignin under oxic conditions. The near-complete genome sequence presented here will facilitate analyses into this deep-ocean bacterium's ability to degrade recalcitrant organics such as lignin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/genomeA.01297-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122680PMC
November 2016

High-Quality Draft Genome Sequence of Thermocrinis jamiesonii GBS1T Isolated from Great Boiling Spring, Nevada.

Genome Announc 2016 Oct 20;4(5). Epub 2016 Oct 20.

School of Life Sciences, University of Nevada, Las Vegas, Las Vegas, Nevada, USA

The draft genome of Thermocrinis jamiesonii GBS1 is 1,315,625 bp in 10 contigs and encodes 1,463 predicted genes. The presence of sox genes and various glycoside hydrolases and the absence of uptake NiFe hydrogenases (hyaB) are consistent with a requirement for thiosulfate and suggest the ability to use carbohydrate polymers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/genomeA.01112-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073254PMC
October 2016

Permanent draft genome of DSM 3134, a moderately thermophilic, obligately chemolithoautotrophic member of the .

Stand Genomic Sci 2016 26;11:74. Epub 2016 Sep 26.

DOE Joint Genome Institute, Walnut Creek, CA 94598 USA.

DSM 3134 was originally isolated (1983) from the waters of a sulfidic spring entering the Roman Baths (Temple of Sulis-Minerva) at Bath, United Kingdom and is an obligate chemolithoautotroph growing at the expense of reduced sulfur species. This strain has a genome size of 2,958,498 bp. Here we report the genome sequence, annotation and characteristics. The genome comprises 2,902 protein coding and 66 RNA coding genes. Genes responsible for the transaldolase variant of the Calvin-Benson-Bassham cycle were identified along with a biosynthetic horseshoe of Krebs' cycle . Terminal oxidases were identified, cytochrome oxidase (, EC 1.9.3.1) and ubiquinol oxidase (, EC 1.10.3.10). Metalloresistance genes involved in pathways of arsenic and cadmium resistance were found. Evidence of horizontal gene transfer accounting for 5.9 % of the protein-coding genes was found, including transfer from spp. and Bath, isolated from the same spring. A gene cluster was found, similar in structure to those from other - by comparison with and , an additional gene between and was found, annotated as a DUF302-family protein of unknown function. As the Kelly-Friedrich pathway of thiosulfate oxidation (encoded by ) is not used in spp., the role of the operon (if any) in this species remains unknown. We speculate that DUF302 and genes may have a role in periplasmic trithionate oxidation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40793-016-0188-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037610PMC
September 2016

Application of Long Sequence Reads To Improve Genomes for Clostridium thermocellum AD2, Clostridium thermocellum LQRI, and Pelosinus fermentans R7.

Genome Announc 2016 Sep 29;4(5). Epub 2016 Sep 29.

Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, Tennessee, USA Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA BioEnergy Science Center, Oak Ridge, Tennessee, USA

We and others have shown the utility of long sequence reads to improve genome assembly quality. In this study, we generated PacBio DNA sequence data to improve the assemblies of draft genomes for Clostridium thermocellum AD2, Clostridium thermocellum LQRI, and Pelosinus fermentans R7.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043559PMC
http://dx.doi.org/10.1128/genomeA.01043-16DOI Listing
September 2016

Genome Sequence of Marinobacter sp. Strain MCTG268 Isolated from the Cosmopolitan Marine Diatom Skeletonema costatum.

Genome Announc 2016 Sep 8;4(5). Epub 2016 Sep 8.

DOE Joint Genome Institute, Walnut Creek, California, USA.

Marinobacter sp. strain MCTG268 was isolated from the cosmopolitan marine diatom Skeletonema costatum and can degrade oil hydrocarbons as sole sources of carbon and energy. Here, we present the genome sequence of this strain, which is 4,449,396 bp with 4,157 genes and an average G+C content of 57.0%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/genomeA.00937-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017223PMC
September 2016

Genome Sequence of Arenibacter algicola Strain TG409, a Hydrocarbon-Degrading Bacterium Associated with Marine Eukaryotic Phytoplankton.

Genome Announc 2016 Aug 4;4(4). Epub 2016 Aug 4.

DOE Joint Genome Institute, Walnut Creek, California, USA.

Arenibacter algicola strain TG409 was isolated from Skeletonema costatum and exhibits the ability to utilize polycyclic aromatic hydrocarbons as sole sources of carbon and energy. Here, we present the genome sequence of this strain, which is 5,550,230 bp with 4,722 genes and an average G+C content of 39.7%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/genomeA.00765-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974315PMC
August 2016

Complete genome of Nitrosospira briensis C-128, an ammonia-oxidizing bacterium from agricultural soil.

Stand Genomic Sci 2016 28;11:46. Epub 2016 Jul 28.

DOE Joint Genome Institute, Walnut Creek, CA USA.

Nitrosospira briensis C-128 is an ammonia-oxidizing bacterium isolated from an acid agricultural soil. N. briensis C-128 was sequenced with PacBio RS technologies at the DOE-Joint Genome Institute through their Community Science Program (2010). The high-quality finished genome contains one chromosome of 3.21 Mb and no plasmids. We identified 3073 gene models, 3018 of which are protein coding. The two-way average nucleotide identity between the chromosomes of Nitrosospira multiformis ATCC 25196 and Nitrosospira briensis C-128 was found to be 77.2 %. Multiple copies of modules encoding chemolithotrophic metabolism were identified in their genomic context. The gene inventory supports chemolithotrophic metabolism with implications for function in soil environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40793-016-0168-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964001PMC
July 2016

Integrative epigenomic analysis reveals unique epigenetic signatures involved in unipotency of mouse female germline stem cells.

Genome Biol 2016 07 27;17(1):162. Epub 2016 Jul 27.

Shanghai Center for Systems Biomedicine, Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

Background: Germline stem cells play an essential role in establishing the fertility of an organism. Although extensively characterized, the regulatory mechanisms that govern the fundamental properties of mammalian female germline stem cells remain poorly understood.

Results: We generate genome-wide profiles of the histone modifications H3K4me1, H3K27ac, H3K4me3, and H3K27me3, DNA methylation, and RNA polymerase II occupancy and perform transcriptome analysis in mouse female germline stem cells. Comparison of enhancer regions between embryonic stem cells and female germline stem cells identifies the lineage-specific enhancers involved in germline stem cell features. Additionally, our results indicate that DNA methylation primarily contributes to female germline stem cell unipotency by suppressing the somatic program and is potentially involved in maintenance of sexual identity when compared with male germline stem cells. Moreover, we demonstrate down-regulation of Prmt5 triggers differentiation and thus uncover a role for Prmt5 in maintaining the undifferentiated status of female germline stem cells.

Conclusions: The genome-wide epigenetic signatures and the transcription regulators identified here provide an invaluable resource for understanding the fundamental features of mouse female germline stem cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-016-1023-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963954PMC
July 2016

High-Quality Draft Genomes from Thermus caliditerrae YIM 77777 and T. tengchongensis YIM 77401, Isolates from Tengchong, China.

Genome Announc 2016 Apr 28;4(2). Epub 2016 Apr 28.

School of Life Sciences, University of Nevada, Las Vegas, Las Vegas, Nevada, USA Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, Las Vegas, Nevada, USA

The draft genomes of Thermus  tengchongensis YIM 77401 and T. caliditerrae YIM 77777 are 2,562,314 and 2,218,114 bp and encode 2,726 and 2,305 predicted genes, respectively. Gene content and growth experiments demonstrate broad metabolic capacity, including starch hydrolysis, thiosulfate oxidation, arsenite oxidation, incomplete denitrification, and polysulfide reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/genomeA.00312-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850857PMC
April 2016

High-quality draft genome sequence of the Thermus amyloliquefaciens type strain YIM 77409(T) with an incomplete denitrification pathway.

Stand Genomic Sci 2016 27;11:20. Epub 2016 Feb 27.

School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV USA ; Nevada Institute of Personalized Medicine, University of Nevada Las Vegas, Las Vegas, NV USA.

Thermus amyloliquefaciens type strain YIM 77409(T) is a thermophilic, Gram-negative, non-motile and rod-shaped bacterium isolated from Niujie Hot Spring in Eryuan County, Yunnan Province, southwest China. In the present study we describe the features of strain YIM 77409(T) together with its genome sequence and annotation. The genome is 2,160,855 bp long and consists of 6 scaffolds with 67.4 % average GC content. A total of 2,313 genes were predicted, comprising 2,257 protein-coding and 56 RNA genes. The genome is predicted to encode a complete glycolysis, pentose phosphate pathway, and tricarboxylic acid cycle. Additionally, a large number of transporters and enzymes for heterotrophy highlight the broad heterotrophic lifestyle of this organism. A denitrification gene cluster included genes predicted to encode enzymes for the sequential reduction of nitrate to nitrous oxide, consistent with the incomplete denitrification phenotype of this strain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40793-016-0140-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769583PMC
February 2016