Abstract:
:Oncoviral infection is responsible for 12%-15% of cancer in humans. Convergent evidence from epidemiology, pathology, and oncology suggests that new viral etiologies for cancers remain to be discovered. Oncoviral profiles can be obtained from cancer genome sequencing data; however, widespread viral sequence contamination and noncausal viruses complicate the process of identifying genuine oncoviruses. Here, we propose a novel strategy to address these challenges by performing virome-wide screening of early-stage clonal viral integrations. To implement this strategy, we developed VIcaller, a novel platform for identifying viral integrations that are derived from any characterized viruses and shared by a large proportion of tumor cells using whole-genome sequencing (WGS) data. The sensitivity and precision were confirmed with simulated and benchmark cancer data sets. By applying this platform to cancer WGS data sets with proven or speculated viral etiology, we newly identified or confirmed clonal integrations of hepatitis B virus (HBV), human papillomavirus (HPV), Epstein-Barr virus (EBV), and BK Virus (BKV), suggesting the involvement of these viruses in early stages of tumorigenesis in affected tumors, such as HBV in TERT and KMT2B (also known as MLL4) gene loci in liver cancer, HPV and BKV in bladder cancer, and EBV in non-Hodgkin's lymphoma. We also showed the capacity of VIcaller to identify integrations from some uncharacterized viruses. This is the first study to systematically investigate the strategy and method of virome-wide screening of clonal integrations to identify oncoviruses. Searching clonal viral integrations with our platform has the capacity to identify virus-caused cancers and discover cancer viral etiologies.
journal_name
Genome Resjournal_title
Genome researchauthors
Chen X,Kost J,Sulovari A,Wong N,Liang WS,Cao J,Li Ddoi
10.1101/gr.242529.118subject
Has Abstractpub_date
2019-05-01 00:00:00pages
819-830issue
5eissn
1088-9051issn
1549-5469pii
gr.242529.118journal_volume
29pub_type
杂志文章相关文献
GENOME RESEARCH文献大全abstract::Large terminal fragments of human chromosomes 2p, 6p, 8q, 12q, and 18q were cloned using yeast artificial chromosomes (YACs). RecA-assisted restriction endonuclease (RARE) cleavage analysis of genomic DNA samples from II unrelated individuals using YAC-derived probes confirmed the telomeric localizations of the half-Y...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5.3.225
更新日期:1995-10-01 00:00:00
abstract::Although mRNA decay rates are a key determinant of the steady-state concentration for any given mRNA species, relatively little is known, on a population level, about what factors influence turnover rates and how these rates are integrated into cellular decisions. We decided to measure mRNA decay rates in two human ce...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.1272403
更新日期:2003-08-01 00:00:00
abstract::Translocations are known to affect the expression of genes at the breakpoints and, in the case of unbalanced translocations, alter the gene copy number. However, a comprehensive understanding of the functional impact of this class of variation is lacking. Here, we have studied the effect of balanced chromosomal rearra...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.103622.109
更新日期:2010-05-01 00:00:00
abstract::Gene expression can be regulated at multiple levels, but it is not known if and how there is broad coordination between regulation at the transcriptional and post-transcriptional levels. Transcription factors and chromatin regulate gene expression transcriptionally, whereas microRNAs (miRNAs) are small regulatory RNAs...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.238311.118
更新日期:2019-02-01 00:00:00
abstract::Although more than thirty mammalian genomes have been sequenced to draft quality, very few of these include the Y chromosome. This has limited our understanding of the evolutionary dynamics of gene persistence and loss, our ability to identify conserved regulatory elements, as well our knowledge of the extent to which...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.154286.112
更新日期:2013-09-01 00:00:00
abstract::We report the construction of a dense linkage map of the rat genome integrating 767 simple sequence length polymorphism markers, combined over three crosses with high rates of polymorphism. F2 populations from WKY x S (n = 159), BN x S (n = 91), and BN x GK (n = 139) were selected and genotyped for combinations of mic...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.7.5.434
更新日期:1997-05-01 00:00:00
abstract::CBX5, CBX1, and CBX3 (HP1α, β, and γ, respectively) play an evolutionarily conserved role in the formation and maintenance of heterochromatin. In addition, CBX5, CBX1, and CBX3 may also participate in transcriptional regulation of genes. Recently, CBX3 binding to the bodies of a subset of genes has been observed in hu...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.124818.111
更新日期:2012-08-01 00:00:00
abstract::The Polycomb group (PcG) and Trithorax group (TrxG) of proteins are required for stable and heritable maintenance of repressed and active gene expression states. Their antagonistic function on gene control, repression for PcG and activity for TrxG, is mediated by binding to chromatin and subsequent epigenetic modifica...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.114348.110
更新日期:2011-02-01 00:00:00
abstract::CRISPR/Cas9-mediated targeted mutagenesis allows efficient generation of loss-of-function alleles in zebrafish. To date, this technology has been primarily used to generate genetic knockout animals. Nevertheless, the study of the function of certain loci might require tight spatiotemporal control of gene inactivation....
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.196170.115
更新日期:2016-05-01 00:00:00
abstract::DNA transposons, or class 2 transposable elements, have successfully propagated in a wide variety of genomes. However, it is widely believed that DNA transposon activity has ceased in mammalian genomes for at least the last 40 million years. We recently reported evidence for the relatively recent activity of hAT and H...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.071886.107
更新日期:2008-05-01 00:00:00
abstract::Previously, we have described novel families of genes, warthog (wrt) and groundhog (grd), in Caenorhabditis elegans. They are related to Hedgehog (Hh) through the carboxy-terminal autoprocessing domain (called Hog or Hint). A comprehensive survey revealed 10 genes with Hog/Hint modules in C. elegans. Five of these are...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.9.10.909
更新日期:1999-10-01 00:00:00
abstract::Chromosomal aberrations have been thought to be random events. However, recent findings introduce a new paradigm in which certain DNA segments have the potential to adopt unusual conformations that lead to genomic instability and nonrandom chromosomal rearrangement. One of the best-studied examples is the palindromic ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.079244.108
更新日期:2009-02-01 00:00:00
abstract::Double anal fin (Da) is a medaka with an autosomal semidominant mutation that causes mirror image duplication of the ventral region concentrating on the caudal region. The chromosomal location of the Da gene and its sequence have remained unknown. We constructed a medaka linkage map as a first step to approach positio...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.9.12.1277
更新日期:1999-12-01 00:00:00
abstract::Development of composite inflorescences in the plant family Asteraceae has features that cannot be studied in the traditional model plants for flower development. In Gerbera hybrida, inflorescences are composed of morphologically different types of flowers tightly packed into a flower head (capitulum). Individual flor...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.3043705
更新日期:2005-04-01 00:00:00
abstract::Drosophila melanogaster plays an important role in molecular, genetic, and genomic studies of heredity, development, metabolism, behavior, and human disease. The initial reference genome sequence reported more than a decade ago had a profound impact on progress in Drosophila research, and improving the accuracy and co...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.185579.114
更新日期:2015-03-01 00:00:00
abstract::In this communication, we describe the use of specialized transposons (Tn5 derivatives) to create deletions in the Escherichia coli K-12 chromosome. These transposons are essentially rearranged composite transposons that have been assembled to promote the use of the internal transposon ends, resulting in intramolecula...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.611403
更新日期:2003-04-01 00:00:00
abstract::Chronic bacterial infections of the lung are the leading cause of morbidity and mortality in cystic fibrosis patients. Tracking bacterial evolution during chronic infections can provide insights into how host selection pressures-including immune responses and therapeutic interventions-shape bacterial genomes. We carri...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.213363.116
更新日期:2017-04-01 00:00:00
abstract::Human genomic data of many types are readily available, but the complexity and scale of human molecular biology make it difficult to integrate this body of data, understand it from a systems level, and apply it to the study of specific pathways or genetic disorders. An investigator could best explore a particular prot...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.082214.108
更新日期:2009-06-01 00:00:00
abstract::The regulation of gene expression is mediated at the transcriptional level by enhancer regions that are bound by sequence-specific transcription factors (TFs). Recent studies have shown that the in vivo binding sites of single TFs differ between developmental or cellular contexts. How this context-specific binding is ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.132811.111
更新日期:2012-10-01 00:00:00
abstract::The recently identified mouse obese (ob) gene apparently encodes a secreted protein that may function in the signaling pathway of adipose tissue. Mutations in the mouse ob gene are associated with the early development of gross obesity. A detailed knowledge concerning the RNA expression pattern and precise genomic loc...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5.1.5
更新日期:1995-08-01 00:00:00
abstract::Retrotransposons commonly encode a reverse transcriptase (RT), but other functional domains are variable. The acquisition of new domains is the dominant evolutionary force that brings structural variety to retrotransposons. Non-long-terminal-repeat (non-LTR) retrotransposons are classified into two groups by their str...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.3271405
更新日期:2005-08-01 00:00:00
abstract::Analyzing vertebrate genomes requires rapid mRNA/DNA and cross-species protein alignments. A new tool, BLAT, is more accurate and 500 times faster than popular existing tools for mRNA/DNA alignments and 50 times faster for protein alignments at sensitivity settings typically used when comparing vertebrate sequences. B...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.229202
更新日期:2002-04-01 00:00:00
abstract::Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.099622.109
更新日期:2010-01-01 00:00:00
abstract::The very small fraction of putative binding sites (BSs) that are occupied by transcription factors (TFs) in vivo can be highly variable across different cell types. This observation has been partly attributed to changes in chromatin accessibility and histone modification (HM) patterns surrounding BSs. Previous studies...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.220079.116
更新日期:2018-01-11 00:00:00
abstract::Dictyostelium discoideum (DD), an extensively studied model organism for cell and developmental biology, belongs to the most derived group 4 of social amoebas, a clade of altruistic multicellular organisms. To understand genome evolution over long time periods and the genetic basis of social evolution, we sequenced th...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.121137.111
更新日期:2011-11-01 00:00:00
abstract::We have developed a simplified method for multiplex PCR based on the use of chimeric primers. Each primer contains a 3' region complementary to sequence-specific recognition sites and a 5' region made up of an unrelated 20-nucleotide sequence. Identical reaction conditions, cycling times, and annealing temperatures ha...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5.5.488
更新日期:1995-12-01 00:00:00
abstract::Single-cell sequencing (SCS) is a powerful new tool for investigating evolution and diversity in cancer and understanding the role of rare cells in tumor progression. These methods have begun to unravel key questions in cancer biology that have been difficult to address with bulk tumor measurements. Over the past five...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.191098.115
更新日期:2015-10-01 00:00:00
abstract::We present a powerful application of ultra high-throughput sequencing, SAGE-Seq, for the accurate quantification of normal and neoplastic mammary epithelial cell transcriptomes. We develop data analysis pipelines that allow the mapping of sense and antisense strands of mitochondrial and RefSeq genes, the normalization...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.108217.110
更新日期:2010-12-01 00:00:00
abstract::GeneID is a program to predict genes in anonymous genomic sequences designed with a hierarchical structure. In the first step, splice sites, and start and stop codons are predicted and scored along the sequence using position weight matrices (PWMs). In the second step, exons are built from the sites. Exons are scored ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.10.4.511
更新日期:2000-04-01 00:00:00
abstract::We present a database of copy number variations (CNVs) detected in 2026 disease-free individuals, using high-density, SNP-based oligonucleotide microarrays. This large cohort, comprised mainly of Caucasians (65.2%) and African-Americans (34.2%), was analyzed for CNVs in a single study using a uniform array platform an...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.083501.108
更新日期:2009-09-01 00:00:00