ORCID Profile
0000-0002-3741-7577
Current Organisations
Hiroshima University
,
Keio University
,
Karolinska Institutet
,
RIKEN
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Publisher: Wiley
Date: 11-05-2012
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.VIRUSRES.2010.08.014
Abstract: Since its first discovery two decades ago, porcine reproductive and respiratory syndrome virus (PRRSV) has been the subject of intensive research due to its huge impact on the worldwide swine industry. Thanks to the phylogenetic analyses, much has been learned concerning the genetic ersity and evolution history of the virus. In this review, we focused on the evolutionary and epidemiological aspects of PRRSV from a phylogenetic perspective. We first described the ersity and transmission dynamics of Type 1 and 2 PRRSV, respectively. Then, we focused on the more ancient evolutionary history of PRRSV: the time of onset of all existing PRRSV and an origin hypothesis were discussed. Finally, we summarized the results from previous recombination studies to assess the potential impact of recombination on the virus epidemiology.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.MEEGID.2013.03.015
Abstract: Recombination plays an important role in shaping the genetic ersity of a number of DNA and RNA viruses. Although some recent studies have reported bioinformatic evidence of mosaic sequences in a variety of influenza A viruses, it remains controversial as to whether these represent bona fide natural recombination events or laboratory artifacts. Importantly, mosaic genome structures can create significant topological incongruence during phylogenetic analyses, which can mislead additional phylogeny-based molecular evolutionary analyses such as molecular clock dating, the detection of selection pressures and phylogeographic inference. As a result, there is a strong need for systematic screenings for mosaic structures within the influenza virus genome database. We used a combination of sequence-based and phylogeny-based methods to identify 388 mosaic influenza genomic segments, of which 332 are previously unreported and are significantly supported by phylogenetic methods. It is impossible, however, to ascertain whether these represent natural recombinants. To facilitate the future identification of recombinants, reference sets of non-recombinant sequences were selected for use in an automatic screening protocol for detecting mosaic sequences. Tests using real and simulated mosaic sequences indicate that our screening protocol is both sensitive (average >90%) and accurate (average >77%) enough to identify a range of different mosaic patterns. The relatively high prevalence of mosaic influenza virus sequences implies that efficient systematic screens, such as that proposed here, should be performed routinely to detect natural recombinant strains, potential laboratory artifacts, and sequencing contaminants either prior to sequences being deposited in GenBank or before they are used for phylogenetic analyses.
Publisher: Springer Science and Business Media LLC
Date: 29-06-2014
DOI: 10.1038/NATURE13468
Abstract: Antigenic variation of the Plasmodium falciparum multicopy var gene family enables parasite evasion of immune destruction by host antibodies. Expression of a particular var subgroup, termed upsA, is linked to the obstruction of blood vessels in the brain and to the pathogenesis of human cerebral malaria. The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin-associated exoribonuclease, termed PfRNase II, that controls the silencing of upsA var genes by marking their transcription start site and intron-promoter regions leading to short-lived cryptic RNA. Parasites carrying a deficient PfRNase II gene produce full-length upsA var transcripts and intron-derived antisense long non-coding RNA. The presence of stable upsA var transcripts overcomes monoallelic expression, resulting in the simultaneous expression of both upsA and upsC type PfEMP1 proteins on the surface of in idual infected red blood cells. In addition, we observe an inverse relationship between transcript levels of PfRNase II and upsA-type var genes in parasites from severe malaria patients, implying a crucial role of PfRNase II in severe malaria. Our results uncover a previously unknown type of post-transcriptional gene silencing mechanism in malaria parasites with repercussions for other organisms. Additionally, the identification of RNase II as a parasite protein controlling the expression of virulence genes involved in pathogenesis in patients with severe malaria may provide new strategies for reducing malaria mortality.
Publisher: Microbiology Society
Date: 12-2008
DOI: 10.1099/VIR.0.2008/004101-0
Abstract: Birnaviruses are bi-segmented double-stranded RNA (dsRNA) viruses infecting insects, avian species and a wide range of aquatic species. Although homologous recombination is a common phenomenon in positive-sense RNA viruses, recombination in dsRNA viruses is rarely reported. Here we performed a comprehensive survey on homologous recombination in all available sequences ( ) of the family Birnaviridae based on phylogenetic incongruence. Although inter-species recombination was not evident, potential intra-species recombination events were detected in aquabirnaviruses and infectious bursal disease virus (IBDV). Eight potential recombination events were identified and the possibility that these events were non-naturally occurring was assessed case by case. Five of the eight events were identified in IBDVs and all of these five events involved live attenuated vaccine strains. This finding suggests that homologous recombination between vaccine and wild-type IBDV strains may have occurred the potential risk of mass vaccination using live vaccines is discussed. This is the first report of evidence for homologous recombination within the family Birnaviridae .
Publisher: Public Library of Science (PLoS)
Date: 22-08-2023
Publisher: Cold Spring Harbor Laboratory
Date: 12-08-2022
Abstract: In eukaryotes, capped RNAs include long transcripts such as messenger RNAs and long noncoding RNAs, as well as shorter transcripts such as spliceosomal RNAs, small nucleolar RNAs, and enhancer RNAs. Long capped transcripts can be profiled using cap analysis gene expression (CAGE) sequencing and other methods. Here, we describe a sequencing library preparation protocol for short capped RNAs, apply it to a differentiation time course of the human cell line THP-1, and systematically compare the landscape of short capped RNAs to that of long capped RNAs. Transcription initiation peaks associated with genes in the sense direction have a strong preference to produce either long or short capped RNAs, with one out of six peaks detected in the short capped RNA libraries only. Gene-associated short capped RNAs have highly specific 3′ ends, typically overlapping splice sites. Enhancers also preferentially generate either short or long capped RNAs, with 10% of enhancers observed in the short capped RNA libraries only. Enhancers producing either short or long capped RNAs show enrichment for GWAS-associated disease SNPs. We conclude that deep sequencing of short capped RNAs reveals new families of noncoding RNAs and elucidates the ersity of transcripts generated at known and novel promoters and enhancers.
Publisher: Springer Science and Business Media LLC
Date: 03-2017
DOI: 10.1038/NATURE21374
Publisher: Springer Science and Business Media LLC
Date: 21-01-2019
DOI: 10.1038/S41467-018-08126-5
Abstract: Single-cell transcriptomic profiling is a powerful tool to explore cellular heterogeneity. However, most of these methods focus on the 3′-end of polyadenylated transcripts and provide only a partial view of the transcriptome. We introduce C1 CAGE, a method for the detection of transcript 5′-ends with an original s le multiplexing strategy in the C1 TM microfluidic system. We first quantifiy the performance of C1 CAGE and find it as accurate and sensitive as other methods in the C1 system. We then use it to profile promoter and enhancer activities in the cellular response to TGF-β of lung cancer cells and discover subpopulations of cells differing in their response. We also describe enhancer RNA dynamics revealing transcriptional bursts in subsets of cells with transcripts arising from either strand in a mutually exclusive manner, validated using single molecule fluorescence in situ hybridization.
Publisher: Elsevier BV
Date: 12-2009
Publisher: Cold Spring Harbor Laboratory
Date: 20-02-2020
Abstract: Long noncoding RNAs (lncRNAs) have emerged as key coordinators of biological and cellular processes. Characterizing lncRNA expression across cells and tissues is key to understanding their role in determining phenotypes, including human diseases. We present here FC-R2, a comprehensive expression atlas across a broadly defined human transcriptome, inclusive of over 109,000 coding and noncoding genes, as described in the FANTOM CAGE-Associated Transcriptome (FANTOM-CAT) study. This atlas greatly extends the gene annotation used in the original recount2 resource. We demonstrate the utility of the FC-R2 atlas by reproducing key findings from published large studies and by generating new results across normal and diseased human s les. In particular, we (a) identify tissue-specific transcription profiles for distinct classes of coding and noncoding genes, (b) perform differential expression analysis across thirteen cancer types, identifying novel noncoding genes potentially involved in tumor pathogenesis and progression, and (c) confirm the prognostic value for several enhancer lncRNAs expression in cancer. Our resource is instrumental for the systematic molecular characterization of lncRNA by the FANTOM6 Consortium. In conclusion, comprised of over 70,000 s les, the FC-R2 atlas will empower other researchers to investigate functions and biological roles of both known coding genes and novel lncRNAs.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2017
Abstract: The promoter landscape of several non-human model organisms is far from complete. As a part of FANTOM5 data collection, we generated 13 profiles of transcription initiation activities in dog and rat aortic smooth muscle cells, mesenchymal stem cells and hepatocytes by employing CAGE (Cap Analysis of Gene Expression) technology combined with single molecule sequencing. Our analyses show that the CAGE profiles recapitulate known transcription start sites (TSSs) consistently, in addition to uncover novel TSSs. Our dataset can be thus used with high confidence to support gene annotation in dog and rat species. We identified 28,497 and 23,147 CAGE peaks, or promoter regions, for rat and dog respectively, and associated them to known genes. This approach could be seen as a standard method for improvement of existing gene models, as well as discovery of novel genes. Given that the FANTOM5 data collection includes dog and rat matched cell types in human and mouse as well, this data would also be useful for cross-species studies.
Publisher: Springer Science and Business Media LLC
Date: 21-08-2017
DOI: 10.1038/NBT.3947
Publisher: eLife Sciences Publications, Ltd
Date: 09-03-2020
DOI: 10.7554/ELIFE.52155
Abstract: In recent years, functional genomics approaches combining genetic information with bulk RNA-sequencing data have identified the downstream expression effects of disease-associated genetic risk factors through so-called expression quantitative trait locus (eQTL) analysis. Single-cell RNA-sequencing creates enormous opportunities for mapping eQTLs across different cell types and in dynamic processes, many of which are obscured when using bulk methods. Rapid increase in throughput and reduction in cost per cell now allow this technology to be applied to large-scale population genetics studies. To fully leverage these emerging data resources, we have founded the single-cell eQTLGen consortium (sc-eQTLGen), aimed at pinpointing the cellular contexts in which disease-causing genetic variants affect gene expression. Here, we outline the goals, approach and potential utility of the sc-eQTLGen consortium. We also provide a set of study design considerations for future single-cell eQTL studies.
Publisher: Cold Spring Harbor Laboratory
Date: 07-2020
Abstract: Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2 .
Publisher: Public Library of Science (PLoS)
Date: 17-04-2014
Publisher: American Society for Microbiology
Date: 09-2010
DOI: 10.1128/JVI.02551-09
Abstract: Type 2 (or North American-like) porcine reproductive and respiratory syndrome virus (PRRSV) was first recorded in 1987 in the United States and now occurs in most commercial swine industries throughout the world. In this study, we investigated the epidemiological and evolutionary behaviors of type 2 PRRSV. Based on phylogenetic analyses of 8,624 ORF5 sequences, we described a comprehensive picture of the ersity of type 2 PRRSVs and systematically classified all available sequences into lineages and sublineages, including a number of previously undescribed lineages. With the rapid growth of sequence deposition into the databases, it would be technically difficult for veterinary researchers to genotype their sequences by reanalyzing all sequences in the databases. To this end, a set of reference sequences was established based on our classification system, which represents the principal ersity of all available sequences and can readily be used for further genotyping studies. In addition, we further investigated the demographic histories of these lineages and sublineages by using Bayesian coalescence analyses, providing evolutionary insights into several important epidemiological events of type 2 PRRSV. Moreover, by using a phylogeographic approach, we were able to estimate the transmission frequencies between the pig-producing states in the United States and identified several states as the major sources of viral spread, i.e., “transmission centers.” In summary, this study represents the most extensive phylogenetic analyses of type 2 PRRSV to date, providing a basis for future genotyping studies and dissecting the epidemiology of type 2 PRRSV from phylogenetic perspectives.
No related grants have been discovered for Chung-Chau Hon.