4,535 results match your criteria Genome Research [Journal]


A quantitative framework for characterizing the evolutionary history of mammalian gene expression.

Genome Res 2018 Dec 14. Epub 2018 Dec 14.

Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 752 36 Uppsala, Sweden.

The evolutionary history of a gene helps predict its function and relationship to phenotypic traits. Although sequence conservation is commonly used to decipher gene function and assess medical relevance, methods for functional inference from comparative expression data are lacking. Here, we use RNA-seq across seven tissues from 17 mammalian species to show that expression evolution across mammals is accurately modeled by the Ornstein-Uhlenbeck process, a commonly proposed model of continuous trait evolution. Read More

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http://dx.doi.org/10.1101/gr.237636.118DOI Listing
December 2018

Nucleosome remodeling at origins of global genome-nucleotide excision repair occurs at the boundaries of higher-order chromatin structure.

Genome Res 2018 Dec 14. Epub 2018 Dec 14.

Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Repair of UV-induced DNA damage requires chromatin remodeling. How repair is initiated in chromatin remains largely unknown. We recently demonstrated that global genome-nucleotide excision repair (GG-NER) in chromatin is organized into domains in relation to open reading frames. Read More

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http://dx.doi.org/10.1101/gr.237198.118DOI Listing
December 2018

Hormone-control regions mediate steroid receptor-dependent genome organization.

Genome Res 2018 Dec 14. Epub 2018 Dec 14.

Gene Regulation, Stem Cells and Cancer Program, Center for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona 08003, Spain.

In breast cancer cells, some topologically associating domains (TADs) behave as hormonal gene regulation units, within which gene transcription is coordinately regulated in response to steroid hormones. Here we further describe that responsive TADs contain 20- to 100-kb-long clusters of intermingled estrogen receptor (ESR1) and progesterone receptor (PGR) binding sites, hereafter called hormone-control regions (HCRs). In T47D cells, we identified more than 200 HCRs, which are frequently bound by unliganded ESR1 and PGR. Read More

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http://dx.doi.org/10.1101/gr.243824.118DOI Listing
December 2018

Transposable element insertions in fission yeast drive adaptation to environmental stress.

Genome Res 2018 Dec 12. Epub 2018 Dec 12.

Section on Eukaryotic Transposable Elements, Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

Cells are regularly exposed to a range of naturally occurring stress that can restrict growth or cause lethality. In response, cells activate expression networks with hundreds of genes that together increase resistance to common environmental insults. However, stress response networks can be insufficient to ensure survival, which raises the question of whether cells possess genetic programs that can promote adaptation to novel forms of stress. Read More

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http://dx.doi.org/10.1101/gr.239699.118DOI Listing
December 2018

Rapid reversible changes in compartments and local chromatin organization revealed by hyperosmotic shock.

Genome Res 2018 Dec 6. Epub 2018 Dec 6.

Cell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, E-08003 Barcelona, Spain.

Nuclear architecture is decisive for the assembly of transcriptional responses. However, how chromosome organization is dynamically modulated to permit rapid and transient transcriptional changes in response to environmental challenges remains unclear. Here we show that hyperosmotic stress disrupts different levels of chromosome organization, ranging from A/B compartment changes to reduction in the number and insulation of topologically associating domains (TADs). Read More

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http://dx.doi.org/10.1101/gr.238527.118DOI Listing
December 2018

Minerva: an alignment- and reference-free approach to deconvolve Linked-Reads for metagenomics.

Genome Res 2018 Dec 6. Epub 2018 Dec 6.

Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine of Cornell University, New York, New York 10065, USA.

Emerging Linked-Read technologies (aka read cloud or barcoded short-reads) have revived interest in short-read technology as a viable approach to understand large-scale structures in genomes and metagenomes. Linked-Read technologies, such as the 10x Chromium system, use a microfluidic system and a specialized set of 3' barcodes (aka UIDs) to tag short DNA reads sourced from the same long fragment of DNA; subsequently, the tagged reads are sequenced on standard short-read platforms. This approach results in interesting compromises. Read More

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http://dx.doi.org/10.1101/gr.235499.118DOI Listing
December 2018

Epigenetic mapping of the metabolome reveals mediators of the epigenotype-phenotype map.

Genome Res 2018 Nov 30. Epub 2018 Nov 30.

Laboratory of Genetics, Wageningen University and Research, 6708 PB Wageningen, The Netherlands.

Identifying the sources of natural variation underlying metabolic differences between plants will enable a better understanding of plant metabolism and provide insights into the regulatory networks that govern plant growth and morphology. So far, however, the contribution of epigenetic variation to metabolic diversity has been largely ignored. In the present study, we utilized a panel of epigenetic recombinant inbred lines (epiRILs) to assess the impact of epigenetic variation on the metabolic composition. Read More

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http://dx.doi.org/10.1101/gr.232371.117DOI Listing
November 2018

Comparison and assessment of family- and population-based genotype imputation methods in large pedigrees.

Genome Res 2018 Dec 4. Epub 2018 Dec 4.

Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha, Qatar.

Genotype imputation is widely used in genome-wide association studies to boost variant density, allowing increased power in association testing. Many studies currently include pedigree data due to increasing interest in rare variants coupled with the availability of appropriate analysis tools. The performance of population-based (subjects are unrelated) imputation methods is well established. Read More

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http://dx.doi.org/10.1101/gr.236315.118DOI Listing
December 2018
1 Read

Accelerated rates of large-scale mutations in the presence of copper and nickel.

Genome Res 2018 Nov 28. Epub 2018 Nov 28.

Department of Biology, McGill University, Montréal, Québec H3A 1B1, Canada.

Mutation rate variation has been under intense investigation for decades. Despite these efforts, little is known about the extent to which environmental stressors accelerate mutation rates and influence the genetic load of populations. Moreover, most studies on stressors have focused on unicellular organisms and point mutations rather than large-scale deletions and duplications (copy number variations [CNVs]). Read More

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http://dx.doi.org/10.1101/gr.234724.118DOI Listing
November 2018

Damage-responsive elements in regeneration.

Genome Res 2018 12 20;28(12):1852-1866. Epub 2018 Nov 20.

Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona 08028, Catalonia, Spain.

One of the most important questions in regenerative biology is to unveil how and when genes change expression and trigger regeneration programs. The resetting of gene expression patterns during response to injury is governed by coordinated actions of genomic regions that control the activity of multiple sequence-specific DNA binding proteins. Using genome-wide approaches to interrogate chromatin function, we here identify the elements that regulate tissue recovery in imaginal discs, which show a high regenerative capacity after genetically induced cell death. Read More

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http://dx.doi.org/10.1101/gr.233098.117DOI Listing
December 2018
5 Reads

Quantification of somatic mutation flow across individual cell division events by lineage sequencing.

Genome Res 2018 12 20;28(12):1901-1918. Epub 2018 Nov 20.

Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.

Mutation data reveal the dynamic equilibrium between DNA damage and repair processes in cells and are indispensable to the understanding of age-related diseases, tumor evolution, and the acquisition of drug resistance. However, available genome-wide methods have a limited ability to resolve rare somatic variants and the relationships between these variants. Here, we present lineage sequencing, a new genome sequencing approach that enables somatic event reconstruction by providing quality somatic mutation call sets with resolution as high as the single-cell level in subject lineages. Read More

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http://dx.doi.org/10.1101/gr.238543.118DOI Listing
December 2018
4 Reads

Widespread roles of enhancer-like transposable elements in cell identity and long-range genomic interactions.

Genome Res 2018 Nov 19. Epub 2018 Nov 19.

CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

A few families of transposable elements (TEs) have been shown to evolve into -regulatory elements (CREs). Here, to extend these studies to all classes of TEs in the human genome, we identified widespread enhancer-like repeats (ELRs) and find that ELRs reliably mark cell identities, are enriched for lineage-specific master transcription factor binding sites, and are mostly primate-specific. In particular, elements of MIR and L2 TE families whose abundance co-evolved across chordate genomes, are found as ELRs in most human cell types examined. Read More

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http://dx.doi.org/10.1101/gr.235747.118DOI Listing
November 2018

Genetic analysis of isoform usage in the human anti-viral response reveals influenza-specific regulation of transcripts under balancing selection.

Genome Res 2018 12 16;28(12):1812-1825. Epub 2018 Nov 16.

Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.

While genetic variants are known to be associated with overall gene abundance in stimulated immune cells, less is known about their effects on alternative isoform usage. By analyzing RNA-seq profiles of monocyte-derived dendritic cells from 243 individuals, we uncovered thousands of unannotated isoforms synthesized in response to influenza infection and type 1 interferon stimulation. We identified more than a thousand quantitative trait loci (QTLs) associated with alternate isoform usage (isoQTLs), many of which are independent of expression QTLs (eQTLs) for the same gene. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.240390.118
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http://dx.doi.org/10.1101/gr.240390.118DOI Listing
December 2018
7 Reads

DIG-seq: a genome-wide CRISPR off-target profiling method using chromatin DNA.

Genome Res 2018 12 9;28(12):1894-1900. Epub 2018 Nov 9.

Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.

To investigate whether and how CRISPR-Cas9 on-target and off-target activities are affected by chromatin in eukaryotic cells, we first identified a series of identical endogenous DNA sequences present in both open and closed chromatin regions and then measured mutation frequencies at these sites in human cells using Cas9 complexed with matched or mismatched sgRNAs. Unlike matched sgRNAs, mismatched sgRNAs were highly sensitive to chromatin states, suggesting that off-target but not on-target DNA cleavage is hindered by chromatin. We next performed Digenome-seq using cell-free chromatin DNA (now termed DIG-seq) and histone-free genomic DNA in parallel and found that only a subset of sites, cleaved in histone-free DNA, were cut in chromatin DNA, suggesting that chromatin can inhibit Cas9 off-target effects in favor of its genome-wide specificity in cells. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.236620.118
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http://dx.doi.org/10.1101/gr.236620.118DOI Listing
December 2018
7 Reads

Defining TP53 pioneering capabilities with competitive nucleosome binding assays.

Genome Res 2018 Nov 8. Epub 2018 Nov 8.

New York State Center of Excellence in Bioinformatics and Life Sciences and Department of Biochemistry, State University of New York at Buffalo, Buffalo, New York 14203, USA.

Accurate gene expression requires the targeting of transcription factors (TFs) to regulatory sequences often occluded within nucleosomes. The ability to target a TF binding site (TFBS) within a nucleosome has been the defining characteristic for a special class of TFs known as pioneer factors. Recent studies suggest TP53 functions as a pioneer factor that can target its TFBS within nucleosomes, but it remains unclear how TP53 binds to nucleosomal DNA. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.234104.117
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http://dx.doi.org/10.1101/gr.234104.117DOI Listing
November 2018
3 Reads

A physical and genetic map of identifies extensive rearrangements at the loci.

Genome Res 2018 Nov 8. Epub 2018 Nov 8.

Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

is widely cultivated for medicinal, food, industrial, and recreational use, but much remains unknown regarding its genetics, including the molecular determinants of cannabinoid content. Here, we describe a combined physical and genetic map derived from a cross between the drug-type strain Purple Kush and the hemp variety "Finola." The map reveals that cannabinoid biosynthesis genes are generally unlinked but that aromatic prenyltransferase (), which produces the substrate for THCA and CBDA synthases (THCAS and CBDAS), is tightly linked to a known marker for total cannabinoid content. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.242594.118
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http://dx.doi.org/10.1101/gr.242594.118DOI Listing
November 2018
10 Reads

HD-Marker: a highly multiplexed and flexible approach for targeted genotyping of more than 10,000 genes in a single-tube assay.

Genome Res 2018 12 8;28(12):1919-1930. Epub 2018 Nov 8.

MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.

Targeted genotyping of transcriptome-scale genetic markers is highly attractive for genetic, ecological, and evolutionary studies, but achieving this goal in a cost-effective manner remains a major challenge, especially for laboratories working on nonmodel organisms. Here, we develop a high-throughput, sequencing-based GoldenGate approach (called HD-Marker), which addresses the array-related issues of original GoldenGate methodology and allows for highly multiplexed and flexible targeted genotyping of more than 12,000 loci in a single-tube assay (in contrast to fewer than 3100 in the original GoldenGate assay). We perform extensive analyses to demonstrate the power and performance of HD-Marker on various multiplex levels (296, 795, 1293, and 12,472 genic SNPs) across two sequencing platforms in two nonmodel species (the scallops and ), with extremely high capture rate (98%-99%) and genotyping accuracy (97%-99%). Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.235820.118
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http://dx.doi.org/10.1101/gr.235820.118DOI Listing
December 2018
23 Reads

SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA.

Genome Res 2018 12 7;28(12):1943-1956. Epub 2018 Nov 7.

Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.

Cap analysis of gene expression (CAGE) is a methodology for genome-wide quantitative mapping of mRNA 5' ends to precisely capture transcription start sites at a single nucleotide resolution. In combination with high-throughput sequencing, CAGE has revolutionized our understanding of the rules of transcription initiation, led to discovery of new core promoter sequence features, and discovered transcription initiation at enhancers genome-wide. The biggest limitation of CAGE is that even the most recently improved version (nAnT-iCAGE) still requires large amounts of total cellular RNA (5 µg), preventing its application to scarce biological samples such as those from early embryonic development or rare cell types. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.235937.118
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http://dx.doi.org/10.1101/gr.235937.118DOI Listing
December 2018
4 Reads

Noncoding transcription influences the replication initiation program through chromatin regulation.

Genome Res 2018 12 6;28(12):1882-1893. Epub 2018 Nov 6.

Department of Cell Biology, University of Geneva, 1211 Genève 4, Switzerland.

In eukaryotic organisms, replication initiation follows a temporal program. Among the parameters that regulate this program in , chromatin structure has been at the center of attention without considering the contribution of transcription. Here, we revisit the replication initiation program in the light of widespread genomic noncoding transcription. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.239582.118
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http://dx.doi.org/10.1101/gr.239582.118DOI Listing
December 2018
7 Reads

Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate.

Genome Res 2018 12 6;28(12):1767-1778. Epub 2018 Nov 6.

Department of Biology, Penn State University, University Park, Pennsylvania 16802, USA.

DNA conformation may deviate from the classical B-form in ∼13% of the human genome. Non-B DNA regulates many cellular processes; however, its effects on DNA polymerization speed and accuracy have not been investigated genome-wide. Such an inquiry is critical for understanding neurological diseases and cancer genome instability. Read More

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http://dx.doi.org/10.1101/gr.241257.118DOI Listing
December 2018
1 Read

LTRs activated by Epstein-Barr virus-induced transformation of B cells alter the transcriptome.

Genome Res 2018 12 31;28(12):1791-1798. Epub 2018 Oct 31.

Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, California 91010, USA.

Endogenous retroviruses (ERVs) are ancient viral elements that have accumulated in the genome through retrotransposition events. Although they have lost their ability to transpose, many of the long terminal repeats (LTRs) that originally flanked full-length ERVs maintain the ability to regulate transcription. While these elements are typically repressed in somatic cells, they can function as transcriptional enhancers and promoters when this repression is lost. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.233585.117
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http://dx.doi.org/10.1101/gr.233585.117DOI Listing
December 2018
1 Read

Evolutionary conservation of Y Chromosome ampliconic gene families despite extensive structural variation.

Genome Res 2018 12 31;28(12):1841-1851. Epub 2018 Oct 31.

Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas 77843, USA.

Despite claims that the mammalian Y Chromosome is on a path to extinction, comparative sequence analysis of primate Y Chromosomes has shown the decay of the ancestral single-copy genes has all but ceased in this eutherian lineage. The suite of single-copy Y-linked genes is highly conserved among the majority of eutherian Y Chromosomes due to strong purifying selection to retain dosage-sensitive genes. In contrast, the ampliconic regions of the Y Chromosome, which contain testis-specific genes that encode the majority of the transcripts on eutherian Y Chromosomes, are rapidly evolving and are thought to undergo species-specific turnover. Read More

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http://dx.doi.org/10.1101/gr.237586.118DOI Listing
December 2018
1 Read

NanoPARE: parallel analysis of RNA 5' ends from low-input RNA.

Genome Res 2018 12 24;28(12):1931-1942. Epub 2018 Oct 24.

Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna Biocenter (VBC), 1030 Vienna, Austria.

Diverse RNA 5' ends are generated through both transcriptional and post-transcriptional processes. These important modes of gene regulation often vary across cell types and can contribute to the diversification of transcriptomes and thus cellular differentiation. Therefore, the identification of primary and processed 5' ends of RNAs is important for their functional characterization. Read More

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http://dx.doi.org/10.1101/gr.239202.118DOI Listing
December 2018

Ranking noncanonical 5' splice site usage by genome-wide RNA-seq analysis and splicing reporter assays.

Genome Res 2018 12 24;28(12):1826-1840. Epub 2018 Oct 24.

Institute of Virology, Medical Faculty, Heinrich Heine University Düsseldorf, D-40225 Düsseldorf, Germany.

Most human pathogenic mutations in 5' splice sites affect the canonical GT in positions +1 and +2, leading to noncanonical dinucleotides. On the other hand, noncanonical dinucleotides are observed under physiological conditions in ∼1% of all human 5'ss. It is therefore a challenging task to understand the pathogenic mutation mechanisms underlying the conditions under which noncanonical 5'ss are used. Read More

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http://dx.doi.org/10.1101/gr.235861.118DOI Listing
December 2018
10 Reads

Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions.

Genome Res 2018 12 24;28(12):1867-1881. Epub 2018 Oct 24.

Institut Curie, PSL Research University, CNRS, UMR3664, F-75005 Paris, France.

The eukaryotic genome is divided into chromosomal domains of heterochromatin and euchromatin. Transcriptionally silent heterochromatin is found at subtelomeric regions, leading to the telomeric position effect (TPE) in yeast, fly, and human. Heterochromatin generally initiates and spreads from defined loci, and diverse mechanisms prevent the ectopic spread of heterochromatin into euchromatin. Read More

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http://dx.doi.org/10.1101/gr.236554.118DOI Listing
December 2018

Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes.

Genome Res 2018 12 24;28(12):1779-1790. Epub 2018 Oct 24.

Clinical Genetics Group, MRC-Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.

Mosaic mutations present in the germline have important implications for reproductive risk and disease transmission. We previously demonstrated a phenomenon occurring in the male germline, whereby specific mutations arising spontaneously in stem cells (spermatogonia) lead to clonal expansion, resulting in elevated mutation levels in sperm over time. This process, termed "selfish spermatogonial selection," explains the high spontaneous birth prevalence and strong paternal age-effect of disorders such as achondroplasia and Apert, Noonan and Costello syndromes, with direct experimental evidence currently available for specific positions of six genes (, , , , , and ). Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.239186.118
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http://dx.doi.org/10.1101/gr.239186.118DOI Listing
December 2018
3 Reads

Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.

Genome Res 2018 11 23;28(11):1601-1610. Epub 2018 Oct 23.

State Key Laboratory of Genetic Resources and Evolution/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.

Centenarians (CENs) are excellent subjects to study the mechanisms of human longevity and healthy aging. Here, we analyzed the transcriptomes of 76 centenarians, 54 centenarian-children, and 41 spouses of centenarian-children by RNA sequencing and found that, among the significantly differentially expressed genes (SDEGs) exhibited by CENs, the autophagy-lysosomal pathway is significantly up-regulated. Overexpression of several genes from this pathway, , , , and , could promote autophagy and delay senescence in cultured IMR-90 cells, while overexpression of the homolog of , , extended the life span in transgenic flies. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.220780.117
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http://dx.doi.org/10.1101/gr.220780.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211641PMC
November 2018
16 Reads
14.630 Impact Factor

Targeted genotyping of variable number tandem repeats with adVNTR.

Genome Res 2018 11 23;28(11):1709-1719. Epub 2018 Oct 23.

Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California 92093, USA.

Whole-genome sequencing is increasingly used to identify Mendelian variants in clinical pipelines. These pipelines focus on single-nucleotide variants (SNVs) and also structural variants, while ignoring more complex repeat sequence variants. Here, we consider the problem of genotyping (VNTRs), composed of inexact tandem duplications of short (6-100 bp) repeating units. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.235119.118
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http://dx.doi.org/10.1101/gr.235119.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211647PMC
November 2018
2 Reads

Global transcriptional activity dynamics reveal functional enhancer RNAs.

Genome Res 2018 12 23;28(12):1799-1811. Epub 2018 Oct 23.

Department of Biological Sciences and Center for Systems Biology, University of Texas at Dallas, Richardson, Texas 75080, USA.

Active enhancers of the human genome generate long noncoding transcripts known as enhancer RNAs (eRNAs). How dynamic transcriptional changes of eRNAs are physically and functionally linked with target gene transcription remains unclear. To investigate the dynamic functional relationships among eRNAs and target promoters, we obtained a dense time series of GRO-seq and ChIP-seq data to generate a time-resolved enhancer activity map of a cell undergoing an innate antiviral immune response. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.233486.117
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http://dx.doi.org/10.1101/gr.233486.117DOI Listing
December 2018
1 Read

Aberrant expression impacts the pan-cancer genomic landscape.

Genome Res 2018 11 19;28(11):1611-1620. Epub 2018 Oct 19.

Ontario Institute for Cancer Research, Department of Computational Biology, Toronto, Ontario M5G 0A3, Canada.

The binding of PRDM9 to chromatin is a key step in the induction of DNA double-strand breaks associated with meiotic recombination hotspots; it is normally expressed solely in germ cells. We interrogated 1879 cancer samples in 39 different cancer types and found that is unexpectedly expressed in 20% of these tumors even after stringent gene homology correction. The expression levels of in tumors are significantly higher than those found in healthy neighboring tissues and in healthy nongerm tissue databases. Read More

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http://dx.doi.org/10.1101/gr.231696.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211651PMC
November 2018

Maftools: efficient and comprehensive analysis of somatic variants in cancer.

Genome Res 2018 11 19;28(11):1747-1756. Epub 2018 Oct 19.

Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.

Numerous large-scale genomic studies of matched tumor-normal samples have established the somatic landscapes of most cancer types. However, the downstream analysis of data from somatic mutations entails a number of computational and statistical approaches, requiring usage of independent software and numerous tools. Here, we describe an R Bioconductor package, Maftools, which offers a multitude of analysis and visualization modules that are commonly used in cancer genomic studies, including driver gene identification, pathway, signature, enrichment, and association analyses. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.239244.118
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http://dx.doi.org/10.1101/gr.239244.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211645PMC
November 2018
5 Reads

Chromosome assembly of large and complex genomes using multiple references.

Genome Res 2018 11 19;28(11):1720-1732. Epub 2018 Oct 19.

BioTuring Incorporated, San Diego, California 92121, USA.

Despite the rapid development of sequencing technologies, the assembly of mammalian-scale genomes into complete chromosomes remains one of the most challenging problems in bioinformatics. To help address this difficulty, we developed Ragout 2, a reference-assisted assembly tool that works for large and complex genomes. By taking one or more target assemblies (generated from an NGS assembler) and one or multiple related reference genomes, Ragout 2 infers the evolutionary relationships between the genomes and builds the final assemblies using a genome rearrangement approach. Read More

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http://dx.doi.org/10.1101/gr.236273.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211643PMC
November 2018
1 Read

Cell-type-specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes.

Genome Res 2018 11 17;28(11):1621-1635. Epub 2018 Oct 17.

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Most expression quantitative trait locus (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type-specific regulatory landscape of human melanocytes, which give rise to melanoma but account for <5% of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We identified 597,335 -eQTL SNPs prior to linkage disequilibrium (LD) pruning and 4997 eGenes (FDR < 0. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.233304.117
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http://dx.doi.org/10.1101/gr.233304.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211648PMC
November 2018
5 Reads

High-salt-recovered sequences are associated with the active chromosomal compartment and with large ribonucleoprotein complexes including nuclear bodies.

Genome Res 2018 11 4;28(11):1733-1746. Epub 2018 Oct 4.

IGMM, Université de Montpellier, CNRS, F-34293, Montpellier, France.

The mammalian cell nucleus contains numerous discrete suborganelles named nuclear bodies. While recruitment of specific genomic regions into these large ribonucleoprotein (RNP) complexes critically contributes to higher-order functional chromatin organization, such regions remain ill-defined. We have developed the high-salt-recovered sequences-sequencing (HRS-seq) method, a straightforward genome-wide approach whereby we isolated and sequenced genomic regions associated with large high-salt insoluble RNP complexes. Read More

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http://dx.doi.org/10.1101/gr.237073.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211644PMC
November 2018
1 Read

Chromatin conformation and transcriptional activity are permissive regulators of DNA replication initiation in .

Genome Res 2018 11 2;28(11):1688-1700. Epub 2018 Oct 2.

Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

Chromatin structure has emerged as a key contributor to spatial and temporal control over the initiation of DNA replication. However, despite genome-wide correlations between early replication of gene-rich, accessible euchromatin and late replication of gene-poor, inaccessible heterochromatin, a causal relationship between chromatin structure and replication initiation remains elusive. Here, we combined histone gene engineering and whole-genome sequencing in to determine how perturbing chromatin structure affects replication initiation. Read More

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http://dx.doi.org/10.1101/gr.239913.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211642PMC
November 2018
14.630 Impact Factor

High-throughput characterization of genetic effects on DNA-protein binding and gene transcription.

Genome Res 2018 11 25;28(11):1701-1708. Epub 2018 Sep 25.

Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48202, USA.

Many variants associated with complex traits are in noncoding regions and contribute to phenotypes by disrupting regulatory sequences. To characterize these variants, we developed a streamlined protocol for a high-throughput reporter assay, Biallelic Targeted STARR-seq (BiT-STARR-seq), that identifies allele-specific expression (ASE) while accounting for PCR duplicates through unique molecular identifiers. We tested 75,501 oligos (43,500 SNPs) and identified 2720 SNPs with significant ASE (FDR < 10%). Read More

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http://dx.doi.org/10.1101/gr.237354.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211638PMC
November 2018
6 Reads

The gene repressor complex NuRD interacts with the histone variant H3.3 at promoters of active genes.

Genome Res 2018 11 25;28(11):1646-1655. Epub 2018 Sep 25.

Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

The histone variant H3.3 is deposited across active genes, regulatory regions, and telomeres. It remains unclear how H3. Read More

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http://dx.doi.org/10.1101/gr.236224.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211640PMC
November 2018

The genomic architecture and molecular evolution of ant odorant receptors.

Genome Res 2018 11 24;28(11):1757-1765. Epub 2018 Sep 24.

Laboratory of Social Evolution and Behavior, The Rockefeller University, New York, New York 10065, USA.

The massive expansions of odorant receptor (OR) genes in ant genomes are notable examples of rapid genome evolution and adaptive gene duplication. However, the molecular mechanisms leading to gene family expansion remain poorly understood, partly because available ant genomes are fragmentary. Here, we present a highly contiguous, chromosome-level assembly of the clonal raider ant genome, revealing the largest known OR repertoire in an insect. Read More

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http://dx.doi.org/10.1101/gr.237123.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211649PMC
November 2018

Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome.

Genome Res 2018 10 19;28(10):1467-1480. Epub 2018 Sep 19.

March of Dimes Prematurity Research Center at Stanford University, Stanford, California 94305, USA.

Recent studies suggest that the microbiome has an impact on gestational health and outcome. However, characterization of the pregnancy-associated microbiome has largely relied on 16S rRNA gene amplicon-based surveys. Here, we describe an assembly-driven, metagenomics-based, longitudinal study of the vaginal, gut, and oral microbiomes in 292 samples from 10 subjects sampled every three weeks throughout pregnancy. Read More

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http://dx.doi.org/10.1101/gr.236000.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169887PMC
October 2018
1 Read

Young genes have distinct gene structure, epigenetic profiles, and transcriptional regulation.

Genome Res 2018 11 19;28(11):1675-1687. Epub 2018 Sep 19.

Department of Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.

Species-specific, new, or "orphan" genes account for 10%-30% of eukaryotic genomes. Although initially considered to have limited function, an increasing number of orphan genes have been shown to provide important phenotypic innovation. How new genes acquire regulatory sequences for proper temporal and spatial expression is unknown. Read More

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http://dx.doi.org/10.1101/gr.234872.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211652PMC
November 2018
1 Read

Deep taxon sampling reveals the evolutionary dynamics of novel gene families in nematodes.

Genome Res 2018 11 19;28(11):1664-1674. Epub 2018 Sep 19.

Department of Integrative Evolutionary Biology, Max-Planck-Institute for Developmental Biology, Max-Planck-Ring 9, 72076 Tübingen, Germany.

The widespread identification of genes without detectable homology in related taxa is a hallmark of genome sequencing projects in animals, together with the abundance of gene duplications. Such genes have been called novel, young, taxon-restricted, or orphans, but little is known about the mechanisms accounting for their origin, age, and mode of evolution. Phylogenomic studies relying on deep and systematic taxon sampling and using the comparative method can provide insight into the evolutionary dynamics acting on novel genes. Read More

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http://dx.doi.org/10.1101/gr.234971.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211646PMC
November 2018

Targeted genome fragmentation with CRISPR/Cas9 enables fast and efficient enrichment of small genomic regions and ultra-accurate sequencing with low DNA input (CRISPR-DS).

Genome Res 2018 10 19;28(10):1589-1599. Epub 2018 Sep 19.

Department of Pathology, University of Washington, Seattle, Washington 98195, USA.

Next-generation sequencing methods suffer from low recovery, uneven coverage, and false mutations. DNA fragmentation by sonication is a major contributor to these problems because it produces randomly sized fragments, PCR amplification bias, and end artifacts. In addition, oligonucleotide-based hybridization capture, a common target enrichment method, has limited efficiency for small genomic regions, contributing to low recovery. Read More

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http://dx.doi.org/10.1101/gr.235291.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169890PMC
October 2018
1 Read

Transcriptional fates of human-specific segmental duplications in brain.

Genome Res 2018 10 18;28(10):1566-1576. Epub 2018 Sep 18.

Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA.

Despite the importance of duplicate genes for evolutionary adaptation, accurate gene annotation is often incomplete, incorrect, or lacking in regions of segmental duplication. We developed an approach combining long-read sequencing and hybridization capture to yield full-length transcript information and confidently distinguish between nearly identical genes/paralogs. We used biotinylated probes to enrich for full-length cDNA from duplicated regions, which were then amplified, size-fractionated, and sequenced using single-molecule, long-read sequencing technology, permitting us to distinguish between highly identical genes by virtue of multiple paralogous sequence variants. Read More

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http://dx.doi.org/10.1101/gr.237610.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169893PMC
October 2018
1 Read

Crosstalk between alternative polyadenylation and miRNAs in the regulation of protein translational efficiency.

Genome Res 2018 11 18;28(11):1656-1663. Epub 2018 Sep 18.

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega Center, Guangzhou, 510006, China.

3' UTRs play important roles in the gene regulation network via their influence on mRNA stability, translational efficiency, and subcellular localization. For a given gene, 3' UTRs of different lengths generated by alternative polyadenylation (APA) may result in functional differences in regulation. The mechanistic details of how length changes of 3' UTRs alter gene function remain unclear. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.231506.117
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http://dx.doi.org/10.1101/gr.231506.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211650PMC
November 2018
2 Reads

Gene regulation underlies environmental adaptation in house mice.

Genome Res 2018 11 7;28(11):1636-1645. Epub 2018 Sep 7.

Department of Integrative Biology and Museum of Vertebrate Zoology, University of California, Berkeley, California 94720, USA.

Changes in -regulatory regions are thought to play a major role in the genetic basis of adaptation. However, few studies have linked -regulatory variation with adaptation in natural populations. Here, using a combination of exome and RNA-seq data, we performed expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses to study the genetic architecture of regulatory variation in wild house mice () using individuals from five populations collected along a latitudinal cline in eastern North America. Read More

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http://dx.doi.org/10.1101/gr.238998.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211637PMC
November 2018

Pioneering, chromatin remodeling, and epigenetic constraint in early T-cell gene regulation by SPI1 (PU.1).

Genome Res 2018 10 31;28(10):1508-1519. Epub 2018 Aug 31.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.

SPI1 (also known as PU.1) is a dominant but transient regulator in early T-cell precursors and a potent transcriptional controller of developmentally important pro-T-cell genes. Before T-lineage commitment, open chromatin is frequently occupied by PU. Read More

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http://dx.doi.org/10.1101/gr.231423.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169891PMC
October 2018

Coregulation of ribosomal RNA with hundreds of genes contributes to phenotypic variation.

Genome Res 2018 10 30;28(10):1555-1565. Epub 2018 Aug 30.

State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China 100101.

Ribosomal repeats occupy 5% of a plant genome, yet there has been little study of their diversity in the modern age of genomics. Ribosomal copy number and expression variation present an opportunity to tap a novel source of diversity. In the present study, we estimated the ribosomal DNA (rDNA) copy number and ribosomal RNA (rRNA) expression for a population of maize inbred lines and investigated the potential role of rDNA and rRNA dosage in regulating global gene expression. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.229716.117
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http://dx.doi.org/10.1101/gr.229716.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169892PMC
October 2018
4 Reads

Study of mitotic chromatin supports a model of bookmarking by histone modifications and reveals nucleosome deposition patterns.

Genome Res 2018 10 30;28(10):1455-1466. Epub 2018 Aug 30.

Department of Microbiology and Molecular Genetics, Institute of Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.

Mitosis encompasses key molecular changes including chromatin condensation, nuclear envelope breakdown, and reduced transcription levels. Immediately after mitosis, the interphase chromatin structure is reestablished and transcription resumes. The reestablishment of the interphase chromatin is probably achieved by "bookmarking," i. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.230300.117
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http://dx.doi.org/10.1101/gr.230300.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169886PMC
October 2018
1 Read