4,603 results match your criteria Genome Research [Journal]


Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid.

Genome Res 2019 Apr 16. Epub 2019 Apr 16.

Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.

Metagenomic next-generation sequencing (mNGS) for pan-pathogen detection has been successfully tested in proof-of-concept case studies in patients with acute illness of unknown etiology but to date has been largely confined to research settings. Here, we developed and validated a clinical mNGS assay for diagnosis of infectious causes of meningitis and encephalitis from cerebrospinal fluid (CSF) in a licensed microbiology laboratory. A customized bioinformatics pipeline, SURPI+, was developed to rapidly analyze mNGS data, generate an automated summary of detected pathogens, and provide a graphical user interface for evaluating and interpreting results. Read More

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http://dx.doi.org/10.1101/gr.238170.118DOI Listing

Structural variants in 3000 rice genomes.

Genome Res 2019 Apr 16. Epub 2019 Apr 16.

International Rice Research Institute, Laguna 4031, Philippines.

Investigation of large structural variants (SVs) is a challenging yet important task in understanding trait differences in highly repetitive genomes. Combining different bioinformatic approaches for SV detection, we analyzed whole-genome sequencing data from 3000 rice genomes and identified 63 million individual SV calls that grouped into 1.5 million allelic variants. Read More

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http://dx.doi.org/10.1101/gr.241240.118DOI Listing

ATAC-seq reveals regional differences in enhancer accessibility during the establishment of spatial coordinates in the blastoderm.

Genome Res 2019 Apr 8. Epub 2019 Apr 8.

Ludwig-Maximilians Universität München, Fakultät für Biologie, Biozentrum, 82152 Planegg-Martinsried, Germany.

Establishment of spatial coordinates during embryogenesis relies on differential regulatory activity of axis patterning enhancers. Concentration gradients of activator and repressor transcription factors (TFs) provide positional information to each enhancer, which in turn promotes transcription of a target gene in a specific spatial pattern. However, the interplay between an enhancer regulatory activity and its accessibility as determined by local chromatin organization is not well understood. Read More

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http://dx.doi.org/10.1101/gr.242362.118DOI Listing

Identification of a primitive intestinal transcription factor network shared between esophageal adenocarcinoma and its precancerous precursor state.

Genome Res 2019 Apr 8. Epub 2019 Apr 8.

School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.

Esophageal adenocarcinoma (EAC) is one of the most frequent causes of cancer death, and yet compared to other common cancers, we know relatively little about the molecular composition of this tumor type. To further our understanding of this cancer, we have used open chromatin profiling to decipher the transcriptional regulatory networks that are operational in EAC. We have uncovered a transcription factor network that is usually found in primitive intestinal cells during embryonic development, centered on HNF4A and GATA6. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.243345.118
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http://dx.doi.org/10.1101/gr.243345.118DOI Listing
April 2019
3 Reads

Interplay between coding and exonic splicing regulatory sequences.

Genome Res 2019 Apr 8. Epub 2019 Apr 8.

Université Lyon, ENS de Lyon, Université Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, F-69007, Lyon, France.

The inclusion of exons during the splicing process depends on the binding of splicing factors to short low-complexity regulatory sequences. The relationship between exonic splicing regulatory sequences and coding sequences is still poorly understood. We demonstrate that exons that are coregulated by any given splicing factor share a similar nucleotide composition bias and preferentially code for amino acids with similar physicochemical properties because of the nonrandomness of the genetic code. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.241315.118
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http://dx.doi.org/10.1101/gr.241315.118DOI Listing
April 2019
2 Reads
14.630 Impact Factor

DNA (de)methylation in embryonic stem cells controls CTCF-dependent chromatin boundaries.

Genome Res 2019 Apr 4. Epub 2019 Apr 4.

School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, United Kingdom.

Coordinated changes of DNA (de)methylation, nucleosome positioning, and chromatin binding of the architectural protein CTCF play an important role for establishing cell-type-specific chromatin states during differentiation. To elucidate molecular mechanisms that link these processes, we studied the perturbed DNA modification landscape in mouse embryonic stem cells (ESCs) carrying a double knockout (DKO) of the and dioxygenases. These enzymes are responsible for the conversion of 5-methylcytosine (5mC) into its hydroxymethylated (5hmC), formylated (5fC), or carboxylated (5caC) forms. Read More

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http://dx.doi.org/10.1101/gr.239707.118DOI Listing

Efficient and unique co-barcoding of second-generation sequencing reads from long DNA molecules enabling cost effective and accurate sequencing, haplotyping, and de novo assembly.

Genome Res 2019 Apr 2. Epub 2019 Apr 2.

Complete Genomics

Here we describe single tube long fragment read (stLFR), a technology that enables sequence data from long DNA molecules using economical second-generation sequencing technology. It is based on adding the same barcode sequence to sub-fragments of the original long DNA molecule (DNA co-barcoding). To achieve this efficiently, stLFR uses the surface of microbeads to create millions of miniaturized barcoding reactions in a single tube. Read More

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http://dx.doi.org/10.1101/gr.245126.118DOI Listing
April 2019
2 Reads

A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS.

Genome Res 2019 Apr 2. Epub 2019 Apr 2.

Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, New York, 10032, USA.

Large-scale sequencing efforts in amyotrophic lateral sclerosis (ALS) have implicated novel genes using gene-based collapsing methods. However, pathogenic mutations may be concentrated in specific genic regions. To address this, we developed two collapsing strategies: One focuses rare variation collapsing on homology-based protein domains as the unit for collapsing, and the other is a gene-level approach that, unlike standard methods, leverages existing evidence of purifying selection against missense variation on said domains. Read More

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http://dx.doi.org/10.1101/gr.243592.118DOI Listing
April 2019
1 Read
14.630 Impact Factor

The accessible chromatin landscape of the murine hippocampus at single-cell resolution.

Genome Res 2019 Apr 1. Epub 2019 Apr 1.

Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97239, USA.

Here we present a comprehensive map of the accessible chromatin landscape of the mouse hippocampus at single-cell resolution. Substantial advances of this work include the optimization of a single-cell combinatorial indexing assay for transposase accessible chromatin (sci-ATAC-seq); a software suite, , for the rapid processing and visualization of single-cell combinatorial indexing data sets; and a valuable resource of hippocampal regulatory networks at single-cell resolution. We used sci-ATAC-seq to produce 2346 high-quality single-cell chromatin accessibility maps with a mean unique read count per cell of 29,201 from both fresh and frozen hippocampi, observing little difference in accessibility patterns between the preparations. Read More

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http://dx.doi.org/10.1101/gr.243725.118DOI Listing
April 2019
1 Read

Analysis of 100 high-coverage genomes from a pedigreed captive baboon colony.

Genome Res 2019 Mar 29. Epub 2019 Mar 29.

Institute for Human Genetics, University of California, San Francisco, California 94143, USA.

Baboons (genus ) are broadly studied in the wild and in captivity. They are widely used as a nonhuman primate model for biomedical studies, and the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute has maintained a large captive baboon colony for more than 50 yr. Unlike other model organisms, however, the genomic resources for baboons are severely lacking. Read More

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http://dx.doi.org/10.1101/gr.247122.118DOI Listing
March 2019
14.630 Impact Factor

Brown rat demography reveals pre-commensal structure in eastern Asia before expansion into Southeast Asia.

Genome Res 2019 Mar 25. Epub 2019 Mar 25.

Louis Calder Center, Fordham University, Armonk, New York 10504, USA.

Fossil evidence indicates that the globally distributed brown rat () originated in northern China and Mongolia. Historical records report the human-mediated invasion of rats into Europe in the 1500s, followed by global spread because of European imperialist activity during the 1600s-1800s. We analyzed 14 genomes representing seven previously identified evolutionary clusters, and tested alternative demographic models to infer patterns of range expansion, divergence times, and changes in effective population () size for this globally important pest species. Read More

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http://dx.doi.org/10.1101/gr.235754.118DOI Listing

Detection of vancomycin-resistant hospital-adapted lineages in municipal wastewater treatment plants indicates widespread distribution and release into the environment.

Genome Res 2019 04 21;29(4):626-634. Epub 2019 Mar 21.

Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom.

Vancomycin-resistant (VREfm) is a leading cause of healthcare-associated infection. Reservoirs of VREfm are largely assumed to be nosocomial although there is a paucity of data on alternative sources. Here, we describe an integrated epidemiological and genomic analysis of associated with bloodstream infection and isolated from wastewater. Read More

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http://dx.doi.org/10.1101/gr.232629.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442392PMC
April 2019
1 Read
14.630 Impact Factor

The origins and evolution of chromosomes, dosage compensation, and mechanisms underlying venom regulation in snakes.

Genome Res 2019 04 21;29(4):590-601. Epub 2019 Mar 21.

Department of Biology, University of Texas at Arlington, Arlington, Texas 76010, USA.

Here we use a chromosome-level genome assembly of a prairie rattlesnake (), together with Hi-C, RNA-seq, and whole-genome resequencing data, to study key features of genome biology and evolution in reptiles. We identify the rattlesnake Z Chromosome, including the recombining pseudoautosomal region, and find evidence for partial dosage compensation driven by an evolutionary accumulation of a female-biased up-regulation mechanism. Comparative analyses with other amniotes provide new insight into the origins, structure, and function of reptile microchromosomes, which we demonstrate have markedly different structure and function compared to macrochromosomes. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.240952.118
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http://dx.doi.org/10.1101/gr.240952.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442385PMC
April 2019
7 Reads
14.630 Impact Factor

Identification of human silencers by correlating cross-tissue epigenetic profiles and gene expression.

Genome Res 2019 04 18;29(4):657-667. Epub 2019 Mar 18.

Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA.

Compared to enhancers, silencers are notably difficult to identify and validate experimentally. In search for human silencers, we utilized H3K27me3-DNase I hypersensitive site (DHS) peaks with tissue specificity negatively correlated with the expression of nearby genes across 25 diverse cell lines. These regions are predicted to be silencers since they are physically linked, using Hi-C loops, or associated, using expression quantitative trait loci (eQTL) results, with a decrease in gene expression much more frequently than general H3K27me3-DHSs. Read More

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http://dx.doi.org/10.1101/gr.247007.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442386PMC

Chromothripsis during telomere crisis is independent of NHEJ, and consistent with a replicative origin.

Genome Res 2019 Mar 14. Epub 2019 Mar 14.

Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom.

Telomere erosion, dysfunction, and fusion can lead to a state of cellular crisis characterized by large-scale genome instability. We investigated the impact of a telomere-driven crisis on the structural integrity of the genome by undertaking whole-genome sequence analyses of clonal populations of cells that had escaped crisis. Quantification of large-scale structural variants revealed patterns of rearrangement consistent with chromothripsis but formed in the absence of functional nonhomologous end-joining pathways. Read More

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http://dx.doi.org/10.1101/gr.240705.118DOI Listing
March 2019
3 Reads

A virome-wide clonal integration analysis platform for discovering cancer viral etiology.

Genome Res 2019 Mar 14. Epub 2019 Mar 14.

Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 05405, USA.

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. Read More

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http://dx.doi.org/10.1101/gr.242529.118DOI Listing
March 2019
1 Read
14.630 Impact Factor

GenTree, an integrated resource for analyzing the evolution and function of primate-specific coding genes.

Genome Res 2019 04 12;29(4):682-696. Epub 2019 Mar 12.

Key Laboratory of Zoological Systematics and Evolution and State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

The origination of new genes contributes to phenotypic evolution in humans. Two major challenges in the study of new genes are the inference of gene ages and annotation of their protein-coding potential. To tackle these challenges, we created GenTree, an integrated online database that compiles age inferences from three major methods together with functional genomic data for new genes. Read More

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http://dx.doi.org/10.1101/gr.238733.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442393PMC
April 2019
1 Read

Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses.

Genome Res 2019 04 11;29(4):697-709. Epub 2019 Mar 11.

Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.

Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here, we generated chromatin maps and transcriptomes from four tissues and one cell type from young, middle-aged, and old mice-yielding 143 high-quality data sets. Read More

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http://dx.doi.org/10.1101/gr.240093.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442391PMC
April 2019
2 Reads

Coexpression patterns define epigenetic regulators associated with neurological dysfunction.

Genome Res 2019 04 11;29(4):532-542. Epub 2019 Mar 11.

McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Coding variants in epigenetic regulators are emerging as causes of neurological dysfunction and cancer. However, a comprehensive effort to identify disease candidates within the human epigenetic machinery (EM) has not been performed; it is unclear whether features exist that distinguish between variation-intolerant and variation-tolerant EM genes, and between EM genes associated with neurological dysfunction versus cancer. Here, we rigorously define 295 genes with a direct role in epigenetic regulation (writers, erasers, remodelers, readers). Read More

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http://dx.doi.org/10.1101/gr.239442.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442390PMC

Accurate analysis of genuine CRISPR editing events with ampliCan.

Genome Res 2019 Mar 8. Epub 2019 Mar 8.

Department of Informatics/Computational Biology Unit, University of Bergen, Bergen 5008, Norway.

We present ampliCan, an analysis tool for genome editing that unites highly precise quantification and visualization of genuine genome editing events. ampliCan features nuclease-optimized alignments, filtering of experimental artifacts, event-specific normalization, and off-target read detection and quantifies insertions, deletions, HDR repair, as well as targeted base editing. It is scalable to thousands of amplicon sequencing-based experiments from any genome editing experiment, including CRISPR. Read More

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http://dx.doi.org/10.1101/gr.244293.118DOI Listing
March 2019
5 Reads

Experimental and pan-cancer genome analyses reveal widespread contribution of acrylamide exposure to carcinogenesis in humans.

Genome Res 2019 04 7;29(4):521-531. Epub 2019 Mar 7.

Molecular Mechanisms and Biomarkers Group, International Agency for Research on Cancer, Lyon 69008, France.

Humans are frequently exposed to acrylamide, a probable human carcinogen found in commonplace sources such as most heated starchy foods or tobacco smoke. Prior evidence has shown that acrylamide causes cancer in rodents, yet epidemiological studies conducted to date are limited and, thus far, have yielded inconclusive data on association of human cancers with acrylamide exposure. In this study, we experimentally identify a novel and unique mutational signature imprinted by acrylamide through the effects of its reactive metabolite glycidamide. Read More

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http://dx.doi.org/10.1101/gr.242453.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442384PMC
April 2019
2 Reads

Differences in firing efficiency, chromatin, and transcription underlie the developmental plasticity of the DNA replication origins.

Genome Res 2019 Mar 7. Epub 2019 Mar 7.

Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, Nicolas Cabrera 1, Cantoblanco, 28049 Madrid, Spain.

Eukaryotic genome replication depends on thousands of DNA replication origins (ORIs). A major challenge is to learn ORI biology in multicellular organisms in the context of growing organs to understand their developmental plasticity. We have identified a set of ORIs of and their chromatin landscape at two stages of post-embryonic development. Read More

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http://dx.doi.org/10.1101/gr.240986.118DOI Listing

Long-read single-molecule maps of the functional methylome.

Genome Res 2019 04 7;29(4):646-656. Epub 2019 Mar 7.

School of Chemistry, Center for Nanoscience and Nanotechnology, Center for Light-Matter Interaction, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv 6997801, Israel.

We report on the development of a methylation analysis workflow for optical detection of fluorescent methylation profiles along chromosomal DNA molecules. In combination with Bionano Genomics genome mapping technology, these profiles provide a hybrid genetic/epigenetic genome-wide map composed of DNA molecules spanning hundreds of kilobase pairs. The method provides kilobase pair-scale genomic methylation patterns comparable to whole-genome bisulfite sequencing (WGBS) along genes and regulatory elements. Read More

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http://dx.doi.org/10.1101/gr.240739.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442387PMC
April 2019
14.630 Impact Factor

Orientation-aware plasma cell-free DNA fragmentation analysis in open chromatin regions informs tissue of origin.

Genome Res 2019 03;29(3):418-427

Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China.

Cell-free DNA (cfDNA) in human plasma is a class of biomarkers with many current and potential future diagnostic applications. Recent studies have shown that cfDNA molecules are not randomly fragmented and possess information related to their tissues of origin. Pathologies causing death of cells from particular tissues result in perturbations in the relative distribution of DNA from the affected tissues. Read More

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http://dx.doi.org/10.1101/gr.242719.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396422PMC
March 2019
1 Read

Cohesin occupancy and composition at enhancers and promoters are linked to DNA replication origin proximity in .

Genome Res 2019 04 22;29(4):602-612. Epub 2019 Feb 22.

Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri 63104, USA.

Cohesin consists of the SMC1-SMC3-Rad21 tripartite ring and the SA protein that interacts with Rad21. The Nipped-B protein loads cohesin topologically around chromosomes to mediate sister chromatid cohesion and facilitate long-range control of gene transcription. It is largely unknown how Nipped-B and cohesin associate specifically with gene promoters and transcriptional enhancers, or how sister chromatid cohesion is established. Read More

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http://dx.doi.org/10.1101/gr.243832.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442380PMC

TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells.

Genome Res 2019 04 22;29(4):564-575. Epub 2019 Feb 22.

Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.

The epigenetic regulator is frequently mutated in hematological diseases. Mutations have been shown to arise in hematopoietic stem cells early in disease development and lead to altered DNA methylation landscapes and an increased risk of hematopoietic malignancy. Here, we show by genome-wide mapping of TET2 binding sites in different cell types that TET2 localizes to regions of open chromatin and cell-type-specific enhancers. Read More

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http://dx.doi.org/10.1101/gr.239277.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442383PMC
April 2019
1 Read

Bayesian-based noninvasive prenatal diagnosis of single-gene disorders.

Genome Res 2019 03 20;29(3):428-438. Epub 2019 Feb 20.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel.

In the last decade, noninvasive prenatal diagnosis (NIPD) has emerged as an effective procedure for early detection of inherited diseases during pregnancy. This technique is based on using cell-free DNA (cfDNA) and fetal cfDNA (cffDNA) in maternal blood, and hence, has minimal risk for the mother and fetus compared with invasive techniques. NIPD is currently used for identifying chromosomal abnormalities (in some instances) and for single-gene disorders (SGDs) of paternal origin. Read More

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http://dx.doi.org/10.1101/gr.235796.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396420PMC
March 2019
2 Reads

New guidelines for DNA methylome studies regarding 5-hydroxymethylcytosine for understanding transcriptional regulation.

Genome Res 2019 04 19;29(4):543-553. Epub 2019 Feb 19.

Department of Computer Science and Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

Many DNA methylome profiling methods cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Because 5mC typically acts as a repressive mark whereas 5hmC is an intermediate form during active demethylation, the inability to separate their signals could lead to incorrect interpretation of the data. Is the extra information contained in 5hmC signals worth the additional experimental and computational costs? Here we combine whole-genome bisulfite sequencing (WGBS) and oxidative WGBS (oxWGBS) data in various human tissues to investigate the quantitative relationships between gene expression and the two forms of DNA methylation at promoters, transcript bodies, and immediate downstream regions. Read More

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http://dx.doi.org/10.1101/gr.240036.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442395PMC
April 2019
3 Reads
14.630 Impact Factor

Improved discovery of genetic interactions using CRISPRiSeq across multiple environments.

Genome Res 2019 04 19;29(4):668-681. Epub 2019 Feb 19.

Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.

Large-scale genetic interaction (GI) screens in yeast have been invaluable for our understanding of molecular systems biology and for characterizing novel gene function. Owing in part to the high costs and long experiment times required, a preponderance of GI data has been generated in a single environmental condition. However, an unknown fraction of GIs may be specific to other conditions. Read More

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http://dx.doi.org/10.1101/gr.246603.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442382PMC
April 2019
1 Read

Ribosomal DNA harbors an evolutionarily conserved clock of biological aging.

Genome Res 2019 03 14;29(3):325-333. Epub 2019 Feb 14.

Department of Environmental Health, Program in Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.

The ribosomal DNA (rDNA) is the most evolutionarily conserved segment of the genome and gives origin to the nucleolus, an energy intensive nuclear organelle and major hub influencing myriad molecular processes from cellular metabolism to epigenetic states of the genome. The rDNA/nucleolus has been directly and mechanistically implicated in aging and longevity in organisms as diverse as yeasts, , and humans. The rDNA is also a significant target of DNA methylation that silences supernumerary rDNA units and regulates nucleolar activity. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.241745.118
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http://dx.doi.org/10.1101/gr.241745.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396418PMC
March 2019
26 Reads

Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development.

Genome Res 2019 03 13;29(3):506-519. Epub 2019 Feb 13.

International Institute of Molecular and Cell Biology in Warsaw, Laboratory of Zebrafish Developmental Genomics, 02-109 Warsaw, Poland.

Organogenesis involves dynamic regulation of gene transcription and complex multipathway interactions. Despite our knowledge of key factors regulating various steps of heart morphogenesis, considerable challenges in understanding its mechanism still exist because little is known about their downstream targets and interactive regulatory network. To better understand transcriptional regulatory mechanism driving heart development and the consequences of its disruption in vivo, we performed time-series analyses of the transcriptome and genome-wide chromatin accessibility in isolated cardiomyocytes (CMs) from wild-type zebrafish embryos at developmental stages corresponding to heart tube morphogenesis, looping, and maturation. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.244491.118
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http://dx.doi.org/10.1101/gr.244491.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396412PMC
March 2019
6 Reads

Evolution of gene regulation in ruminants differs between evolutionary breakpoint regions and homologous synteny blocks.

Genome Res 2019 04 13;29(4):576-589. Epub 2019 Feb 13.

Royal Veterinary College, University of London, London NW1 0TU, United Kingdom.

The role of chromosome rearrangements in driving evolution has been a long-standing question of evolutionary biology. Here we focused on ruminants as a model to assess how rearrangements may have contributed to the evolution of gene regulation. Using reconstructed ancestral karyotypes of Cetartiodactyls, Ruminants, Pecorans, and Bovids, we traced patterns of gross chromosome changes. Read More

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http://dx.doi.org/10.1101/gr.239863.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442394PMC
April 2019
4 Reads

Comprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562.

Genome Res 2019 03 8;29(3):472-484. Epub 2019 Feb 8.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.

K562 is widely used in biomedical research. It is one of three tier-one cell lines of ENCODE and also most commonly used for large-scale CRISPR/Cas9 screens. Although its functional genomic and epigenomic characteristics have been extensively studied, its genome sequence and genomic structural features have never been comprehensively analyzed. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.234948.118
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http://dx.doi.org/10.1101/gr.234948.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396411PMC
March 2019
6 Reads

Mapping global and local coevolution across 600 species to identify novel homologous recombination repair genes.

Genome Res 2019 03 4;29(3):439-448. Epub 2019 Feb 4.

Department of Developmental Biology and Cancer Research, Institute for Medical Research-Israel-Canada, Hebrew University of Jerusalem, Jerusalem 91120, Israel.

The homologous recombination repair (HRR) pathway repairs DNA double-strand breaks in an error-free manner. Mutations in HRR genes can result in increased mutation rate and genomic rearrangements, and are associated with numerous genetic disorders and cancer. Despite intensive research, the HRR pathway is not yet fully mapped. Read More

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http://dx.doi.org/10.1101/gr.241414.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396423PMC
March 2019
3 Reads

CG dinucleotides enhance promoter activity independent of DNA methylation.

Genome Res 2019 04 1;29(4):554-563. Epub 2019 Feb 1.

Friedrich Miescher Institute for Biomedical Research, CH 4058 Basel, Switzerland.

Most mammalian RNA polymerase II initiation events occur at CpG islands, which are rich in CpGs and devoid of DNA methylation. Despite their relevance for gene regulation, it is unknown to what extent the CpG dinucleotide itself actually contributes to promoter activity. To address this question, we determined the transcriptional activity of a large number of chromosomally integrated promoter constructs and monitored binding of transcription factors assumed to play a role in CpG island activity. Read More

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http://dx.doi.org/10.1101/gr.241653.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442381PMC
April 2019
1 Read

Chromatin architecture reorganization during neuronal cell differentiation in genome.

Genome Res 2019 04 1;29(4):613-625. Epub 2019 Feb 1.

School of Biological Sciences, University of Essex, Colchester, CO4 3SQ, United Kingdom.

The organization of the genome into topologically associating domains (TADs) was shown to have a regulatory role in development and cellular function, but the mechanism involved in TAD establishment is still unclear. Here, we present the first high-resolution contact map of neuronal cells (BG3) and identify different classes of TADs by comparing this to genome organization in embryonic cells (Kc167). We find that only some TADs are conserved in both cell lines, whereas the rest are cell-type-specific. Read More

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http://dx.doi.org/10.1101/gr.246710.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442379PMC
April 2019
2 Reads

Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells.

Genome Res 2019 03 29;29(3):449-463. Epub 2019 Jan 29.

Center for Computational Biology, Flatiron Institute, New York, New York 10010, USA.

Transcriptional regulatory networks (TRNs) provide insight into cellular behavior by describing interactions between transcription factors (TFs) and their gene targets. The assay for transposase-accessible chromatin (ATAC)-seq, coupled with TF motif analysis, provides indirect evidence of chromatin binding for hundreds of TFs genome-wide. Here, we propose methods for TRN inference in a mammalian setting, using ATAC-seq data to improve gene expression modeling. Read More

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http://dx.doi.org/10.1101/gr.238253.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396413PMC

The circular RNome of primary breast cancer.

Genome Res 2019 03 28;29(3):356-366. Epub 2019 Jan 28.

Erasmus MC Cancer Institute and Cancer Genomics Netherlands, University Medical Center Rotterdam, Department of Medical Oncology, 3015GD Rotterdam, the Netherlands.

Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.238121.118
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http://dx.doi.org/10.1101/gr.238121.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396421PMC
March 2019
23 Reads

Single-cell sequencing of primate preimplantation embryos reveals chromosome elimination via cellular fragmentation and blastomere exclusion.

Genome Res 2019 03 25;29(3):367-382. Epub 2019 Jan 25.

Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.

Aneuploidy that arises during meiosis and/or mitosis is a major contributor to early embryo loss. We previously showed that human preimplantation embryos encapsulate missegregated chromosomes into micronuclei while undergoing cellular fragmentation and that fragments can contain chromosomal material, but the source of this DNA was unknown. Here, we leveraged the use of a nonhuman primate model and single-cell DNA-sequencing (scDNA-seq) to examine the chromosomal content of 471 individual samples comprising 254 blastomeres, 42 polar bodies, and 175 cellular fragments from a large number ( = 50) of disassembled rhesus cleavage-stage embryos. Read More

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http://dx.doi.org/10.1101/gr.239830.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396419PMC
March 2019
2 Reads

High-throughput functional analysis of lncRNA core promoters elucidates rules governing tissue specificity.

Genome Res 2019 03 25;29(3):344-355. Epub 2019 Jan 25.

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

Transcription initiates at both coding and noncoding genomic elements, including mRNA and long noncoding RNA (lncRNA) core promoters and enhancer RNAs (eRNAs). However, each class has a different expression profile with lncRNAs and eRNAs being the most tissue specific. How these complex differences in expression profiles and tissue specificities are encoded in a single DNA sequence remains unresolved. Read More

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http://dx.doi.org/10.1101/gr.242222.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396428PMC
March 2019
2 Reads

Contrasting roles of the RSC and ISW1/CHD1 chromatin remodelers in RNA polymerase II elongation and termination.

Genome Res 2019 03 25;29(3):407-417. Epub 2019 Jan 25.

Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

Most yeast genes have a nucleosome-depleted region (NDR) at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. We have examined the interplay between RSC (a conserved essential SWI/SNF-type complex that determines NDR size) and the ISW1, CHD1, and ISW2 nucleosome spacing enzymes in chromatin organization and transcription, using isogenic strains lacking all combinations of these enzymes. The contributions of these remodelers to chromatin organization are largely combinatorial, distinct, and nonredundant, supporting a model in which the +1 nucleosome is positioned by RSC and then used as a reference nucleosome by the spacing enzymes. Read More

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http://dx.doi.org/10.1101/gr.242032.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396426PMC
March 2019
2 Reads

A chromosome-scale assembly of the axolotl genome.

Genome Res 2019 02 24;29(2):317-324. Epub 2019 Jan 24.

Department of Neuroscience, University of Kentucky, Lexington, Kentucky 40506, USA.

The axolotl () provides critical models for studying regeneration, evolution, and development. However, its large genome (∼32 Gb) presents a formidable barrier to genetic analyses. Recent efforts have yielded genome assemblies consisting of thousands of unordered scaffolds that resolve gene structures, but do not yet permit large-scale analyses of genome structure and function. Read More

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http://genome.cshlp.org/lookup/doi/10.1101/gr.241901.118
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http://dx.doi.org/10.1101/gr.241901.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360810PMC
February 2019
6 Reads

Fast and flexible bacterial genomic epidemiology with PopPUNK.

Genome Res 2019 02 24;29(2):304-316. Epub 2019 Jan 24.

MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London W2 1PG, United Kingdom.

The routine use of genomics for disease surveillance provides the opportunity for high-resolution bacterial epidemiology. Current whole-genome clustering and multilocus typing approaches do not fully exploit core and accessory genomic variation, and they cannot both automatically identify, and subsequently expand, clusters of significantly similar isolates in large data sets spanning entire species. Here, we describe PopPUNK (ulation artitioning sing ucleotide -mers), a software implementing scalable and expandable annotation- and alignment-free methods for population analysis and clustering. Read More

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http://dx.doi.org/10.1101/gr.241455.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360808PMC
February 2019
3 Reads

JACKS: joint analysis of CRISPR/Cas9 knockout screens.

Genome Res 2019 03 23;29(3):464-471. Epub 2019 Jan 23.

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom.

Genome-wide CRISPR/Cas9 knockout screens are revolutionizing mammalian functional genomics. However, their range of applications remains limited by signal variability from different guide RNAs that target the same gene, which confounds gene effect estimation and dictates large experiment sizes. To address this problem, we report JACKS, a Bayesian method that jointly analyzes screens performed with the same guide RNA library. Read More

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http://dx.doi.org/10.1101/gr.238923.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396427PMC
March 2019
6 Reads

Pou5f3, SoxB1, and Nanog remodel chromatin on high nucleosome affinity regions at zygotic genome activation.

Genome Res 2019 03 23;29(3):383-395. Epub 2019 Jan 23.

Department of Developmental Biology, Institute of Biology I, Faculty of Biology, Albert Ludwigs University of Freiburg, 79104, Freiburg, Germany.

The zebrafish embryo is transcriptionally mostly quiescent during the first 10 cell cycles, until the main wave of zygotic genome activation (ZGA) occurs, accompanied by fast chromatin remodeling. At ZGA, homologs of the mammalian stem cell transcription factors (TFs) Pou5f3, Nanog, and Sox19b bind to thousands of developmental enhancers to initiate transcription. So far, how these TFs influence chromatin dynamics at ZGA has remained unresolved. Read More

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http://dx.doi.org/10.1101/gr.240572.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396415PMC
March 2019
1 Read

A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA.

Genome Res 2019 02 22;29(2):193-207. Epub 2019 Jan 22.

Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Xin Hua Hospital, Shanghai Jiao Tong University, Shanghai 200240, China.

Cell behaviors are dictated by epigenetic and transcriptional programs. Little is known about how extracellular stimuli modulate these programs to reshape gene expression and control cell behavioral responses. Here, we interrogated the epigenetic and transcriptional response of endothelial cells to VEGFA treatment and found rapid chromatin changes that mediate broad transcriptomic alterations. Read More

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http://dx.doi.org/10.1101/gr.239053.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360815PMC
February 2019
4 Reads