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  • SNP-based quantitative deconvolution of biological mixtures: application to the detection of cows with subclinical mastitis by whole genome sequencing of tank milk
    Genome Res. (IF 11.093) Pub Date : 2020-06-26
    Wouter Coppieters; Latifa Karim; Michel Georges

    Biological products of importance in food (f.i. milk) and medical (f.i. donor blood derived products) sciences often correspond to mixtures of samples contributed by multiple individuals. Identifying which individuals contributed to the mixture and in what proportions may be of interest in several circumstances. We herein present a method that allows to do this by shallow whole genome sequencing of

    更新日期:2020-06-27
  • Dynamic transcriptional and chromatin accessibility landscape of medaka embryogenesis
    Genome Res. (IF 11.093) Pub Date : 
    Yingshu Li; Yongjie Liu; Hang Yang; Ting Zhang; Kiyoshi Naruse; Qiang Tu

    Medaka (Oryzias latipes) has become an important vertebrate model widely used in genetics, developmental biology, environmental sciences, and many other fields. A high-quality genome sequence and a variety of genetic tools are available for this model organism. However, existing genome annotation is still rudimentary, as it was mainly based on computational prediction and short-read RNA-seq data. Here

    更新日期:2020-06-26
  • Untangling the effects of cellular composition on coexpression analysis
    Genome Res. (IF 11.093) Pub Date : 2020-06-24
    Marjan Farahbod; Paul Pavlidis

    Coexpression analysis is widely used for inferring regulatory networks, predicting gene function, and interpretation of transcriptome profiling studies, based on methods such as clustering. The majority of such studies use data collected from bulk tissue, where the effects of cellular composition present a potential confound. However, the impact of composition on coexpression analysis have not been

    更新日期:2020-06-25
  • Quantitative analysis of Y-Chromosome gene expression across 36 human tissues.
    Genome Res. (IF 11.093) Pub Date : 2020-05-27
    Alexander K Godfrey,Sahin Naqvi,Lukáš Chmátal,Joel M Chick,Richard N Mitchell,Steven P Gygi,Helen Skaletsky,David C Page

    Little is known about how human Y-Chromosome gene expression directly contributes to differences between XX (female) and XY (male) individuals in nonreproductive tissues. Here, we analyzed quantitative profiles of Y-Chromosome gene expression across 36 human tissues from hundreds of individuals. Although it is often said that Y-Chromosome genes are lowly expressed outside the testis, we report many

    更新日期:2020-06-19
  • Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability.
    Genome Res. (IF 11.093) Pub Date : 2020-05-27
    Richard J Wang,Gregg W C Thomas,Muthuswamy Raveendran,R Alan Harris,Harshavardhan Doddapaneni,Donna M Muzny,John P Capitanio,Predrag Radivojac,Jeffrey Rogers,Matthew W Hahn

    Mutation is the ultimate source of all genetic novelty and the cause of heritable genetic disorders. Mutational burden has been linked to complex disease, including neurodevelopmental disorders such as schizophrenia and autism. The rate of mutation is a fundamental genomic parameter and direct estimates of this parameter have been enabled by accurate comparisons of whole-genome sequences between parents

    更新日期:2020-06-19
  • System-wide analyses of the fission yeast poly(A)+ RNA interactome reveal insights into organization and function of RNA-protein complexes.
    Genome Res. (IF 11.093) Pub Date : 2020-06-18
    Cornelia Kilchert,Tea Kecman,Emily Priest,Svenja Hester,Ebru Aydin,Krzysztof Kus,Oliver Rossbach,Alfredo Castello,Shabaz Mohammed,Lidia Vasiljeva

    Large RNA-binding complexes play a central role in gene expression and orchestrate production, function, and turnover of mRNAs. The accuracy and dynamics of RNA–protein interactions within these molecular machines are essential for their function and are mediated by RNA-binding proteins (RBPs). Here, we show that fission yeast whole-cell poly(A)+ RNA–protein crosslinking data provide information on

    更新日期:2020-06-19
  • The evolution of sex-biased gene expression in the Drosophila brain.
    Genome Res. (IF 11.093) Pub Date : 2020-06-18
    Samuel Khodursky,Nicolas Svetec,Sylvia M Durkin,Li Zhao

    Genes with sex-biased expression in Drosophila are thought to underlie sexually dimorphic phenotypes and have been shown to possess unique evolutionary properties. However, the forces and constraints governing the evolution of sex-biased genes in the somatic tissues of Drosophila are largely unknown. Using population-scale RNA sequencing data we show that sex-biased genes in the Drosophila brain are

    更新日期:2020-06-19
  • Coexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders.
    Genome Res. (IF 11.093) Pub Date : 2020-06-18
    Kaifang Pang,Li Wang,Wei Wang,Jian Zhou,Chao Cheng,Kihoon Han,Huda Y Zoghbi,Zhandong Liu

    A large number of genes have been implicated in neurodevelopmental disorders (NDDs), but their contributions to NDD pathology are difficult to decipher without understanding their diverse roles in different brain cell types. Here, we integrated NDD genetics with single-cell RNA sequencing data to assess coexpression enrichment patterns of various NDD gene sets. We identified mid-fetal cortical neural

    更新日期:2020-06-19
  • Ultra-low input single tube linked-read library method enables short-read second-generation sequencing systems to generate highly accurate and economical long-range sequencing information routinely.
    Genome Res. (IF 11.093) Pub Date : 2020-06-15
    Zhoutao Chen,Long Pham,Tsai-Chin Wu,Guoya Mo,Yu Xia,Peter L Chang,Devin Porter,Tan Phan,Huu Che,Hao Tran,Vikas Bansal,Justin Shaffer,Pedro Belda-Ferre,Gregory Humphrey,Rob Knight,Pavel Pevzner,Son Pham,Yong Wang,Ming Lei

    Long-range sequencing information is required for haplotype phasing, de novo assembly and structural variation detection. Current long-read sequencing technologies can provide valuable long-range information but at a high cost with low accuracy and high DNA input requirement. We have developed a single-tube Transposase Enzyme Linked Long-read Sequencing (TELL-seqTM) technology, which enables a low-cost

    更新日期:2020-06-15
  • Exploring dimension-reduced embeddings with Sleepwalk.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Svetlana Ovchinnikova,Simon Anders

    Dimension-reduction methods, such as t-SNE or UMAP, are widely used when exploring high-dimensional data describing many entities, for example, RNA-seq data for many single cells. However, dimension reduction is commonly prone to introducing artifacts, and we hence need means to see where a dimension-reduced embedding is a faithful representation of the local neighborhood and where it is not. We present

    更新日期:2020-05-01
  • MEDEA: analysis of transcription factor binding motifs in accessible chromatin.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Luca Mariani,Kathryn Weinand,Stephen S Gisselbrecht,Martha L Bulyk

    Deciphering the interplay between chromatin accessibility and transcription factor (TF) binding is fundamental to understanding transcriptional regulation, control of cellular states, and the establishment of new phenotypes. Recent genome-wide chromatin accessibility profiling studies have provided catalogs of putative open regions, where TFs can recognize their motifs and regulate gene expression

    更新日期:2020-05-01
  • Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Lingzhao Fang,Wentao Cai,Shuli Liu,Oriol Canela-Xandri,Yahui Gao,Jicai Jiang,Konrad Rawlik,Bingjie Li,Steven G Schroeder,Benjamin D Rosen,Cong-Jun Li,Tad S Sonstegard,Leeson J Alexander,Curtis P Van Tassell,Paul M VanRaden,John B Cole,Ying Yu,Shengli Zhang,Albert Tenesa,Li Ma,George E Liu

    By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest)

    更新日期:2020-05-01
  • Sense-antisense miRNA pairs constitute an elaborate reciprocal regulatory circuit.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Yulong Song,Lishi Li,Wenbing Yang,Qiang Fu,Wanying Chen,Zeng Fang,Wen Li,Nannan Gu,Rui Zhang

    Antisense transcription of protein-coding genes has been increasingly recognized as an important regulatory mechanism of gene expression. However, less is known about the extent and importance of antisense transcription of noncoding genes. Here, we investigate the breadth and dynamics of antisense transcription of miRNAs, a class of important noncoding RNAs. Because the antisense transcript of a miRNA

    更新日期:2020-05-01
  • Determining the impact of uncharacterized inversions in the human genome by droplet digital PCR.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Marta Puig,Jon Lerga-Jaso,Carla Giner-Delgado,Sarai Pacheco,David Izquierdo,Alejandra Delprat,Magdalena Gayà-Vidal,Jack F Regan,George Karlin-Neumann,Mario Cáceres

    Despite the interest in characterizing genomic variation, the presence of large repeats at the breakpoints hinders the analysis of many structural variants. This is especially problematic for inversions, since there is typically no gain or loss of DNA. Here, we tested novel linkage-based droplet digital PCR (ddPCR) assays to study 20 inversions ranging from 3.1 to 742 kb flanked by inverted repeats

    更新日期:2020-05-01
  • Global fitness landscapes of the Shine-Dalgarno sequence.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Syue-Ting Kuo,Ruey-Lin Jahn,Yuan-Ju Cheng,Yi-Lan Chen,Yun-Ju Lee,Florian Hollfelder,Jin-Der Wen,Hsin-Hung David Chou

    Shine-Dalgarno sequences (SD) in prokaryotic mRNA facilitate protein translation by pairing with rRNA in ribosomes. Although conventionally defined as AG-rich motifs, recent genomic surveys reveal great sequence diversity, questioning how SD functions. Here, we determined the molecular fitness (i.e., translation efficiency) of 49 synthetic 9-nt SD genotypes in three distinct mRNA contexts in Escherichia

    更新日期:2020-05-01
  • Polymorphic centromere locations in the pathogenic yeast Candida parapsilosis.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Mihaela Ola,Caoimhe E O'Brien,Aisling Y Coughlan,Qinxi Ma,Paul D Donovan,Kenneth H Wolfe,Geraldine Butler

    Centromeres pose an evolutionary paradox: strongly conserved in function but rapidly changing in sequence and structure. However, in the absence of damage, centromere locations are usually conserved within a species. We report here that isolates of the pathogenic yeast species Candida parapsilosis show within-species polymorphism for the location of centromeres on two of its eight chromosomes. Its

    更新日期:2020-05-01
  • Genome-wide CRISPR screening reveals genes essential for cell viability and resistance to abiotic and biotic stresses in Bombyx mori.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Jiasong Chang,Ruolin Wang,Kai Yu,Tong Zhang,Xiaoxu Chen,Yue Liu,Run Shi,Xiaogang Wang,Qingyou Xia,Sanyuan Ma

    High-throughput genetic screens are powerful methods to interrogate gene function on a genome-wide scale and identify genes responsible to certain stresses. Here, we developed a piggyBac strategy to deliver pooled sgRNA libraries stably into cell lines. We used this strategy to conduct a screen based on genome-wide clustered regularly interspaced short palindromic repeat technology (CRISPR)-Cas9 in

    更新日期:2020-05-01
  • Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Ekaterina Khrameeva,Ilia Kurochkin,Dingding Han,Patricia Guijarro,Sabina Kanton,Malgorzata Santel,Zhengzong Qian,Shen Rong,Pavel Mazin,Marat Sabirov,Matvei Bulat,Olga Efimova,Anna Tkachev,Song Guo,Chet C Sherwood,J Gray Camp,Svante Pääbo,Barbara Treutlein,Philipp Khaitovich

    Identification of gene expression traits unique to the human brain sheds light on the molecular mechanisms underlying human evolution. Here, we searched for uniquely human gene expression traits by analyzing 422 brain samples from humans, chimpanzees, bonobos, and macaques representing 33 anatomical regions, as well as 88,047 cell nuclei composing three of these regions. Among 33 regions, cerebral

    更新日期:2020-05-01
  • CRISPR-Cas9-mediated pinpoint microbial genome editing aided by target-mismatched sgRNAs.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Ho Joung Lee,Hyun Ju Kim,Sang Jun Lee

    Genome editing has been revolutionized by the CRISPR-Cas9 system. CRISPR-Cas9 is composed of single-molecular guide RNA (sgRNA) and a proteinaceous Cas9 nuclease, which recognizes a specific target sequence and a protospacer adjacent motif (PAM) sequence and, subsequently, cleaves the targeted DNA sequence. This CRISPR-Cas9 system has been used as an efficient negative-selection tool to cleave unedited

    更新日期:2020-05-01
  • Dynamic effects of interacting genes underlying rice flowering-time phenotypic plasticity and global adaptation.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Tingting Guo,Qi Mu,Jinyu Wang,Adam E Vanous,Akio Onogi,Hiroyoshi Iwata,Xianran Li,Jianming Yu

    The phenotypic variation of living organisms is shaped by genetics, environment, and their interaction. Understanding phenotypic plasticity under natural conditions is hindered by the apparently complex environment and the interacting genes and pathways. Herein, we report findings from the dissection of rice flowering-time plasticity in a genetic mapping population grown in natural long-day field environments

    更新日期:2020-05-01
  • Intragenic repeat expansion in the cell wall protein gene HPF1 controls yeast chronological aging.
    Genome Res. (IF 11.093) Pub Date : 2020-05-01
    Benjamin P Barré,Johan Hallin,Jia-Xing Yue,Karl Persson,Ekaterina Mikhalev,Agurtzane Irizar,Sylvester Holt,Dawn Thompson,Mikael Molin,Jonas Warringer,Gianni Liti

    Aging varies among individuals due to both genetics and environment, but the underlying molecular mechanisms remain largely unknown. Using a highly recombined Saccharomyces cerevisiae population, we found 30 distinct quantitative trait loci (QTLs) that control chronological life span (CLS) in calorie-rich and calorie-restricted environments and under rapamycin exposure. Calorie restriction and rapamycin

    更新日期:2020-05-01
  • Suppressor mutations in Mecp2-null mice implicate the DNA damage response in Rett syndrome pathology.
    Genome Res. (IF 11.093) Pub Date : 2020-04-21
    Adebola Enikanolaiye,Julie Ruston,Rong Zeng,Christine Taylor,Marijke Schrock,Christie M Buchovecky,Jay Shendure,Elif Acar,Monica J Justice

    Mutations in X-linked methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT). To identify functional pathways that could inform therapeutic entry points, we carried out a genetic screen for secondary mutations that improved phenotypes in Mecp2/Y mice after mutagenesis with N-ethyl-N-nitrosourea (ENU). Here, we report the isolation of 106 founder animals that show suppression of Mecp2-null traits

    更新日期:2020-04-01
  • Complete characterization of the human immune cell transcriptome using accurate full-length cDNA sequencing.
    Genome Res. (IF 11.093) Pub Date : 2020-04-20
    Charles Cole,Ashley Byrne,Matthew Adams,Roger Volden,Christopher Vollmers

    The human immune system relies on highly complex and diverse transcripts and the proteins they encode. These include transcripts encoding human leukocyte antigen (HLA) receptors as well as B cell and T cell receptors (BCR and TCR). Determining which alleles an individual possesses for each HLA gene (high-resolution HLA typing) is essential to establish donor-recipient compatibility in organ and bone

    更新日期:2020-04-01
  • Characterizing and inferring quantitative cell cycle phase in single-cell RNA-seq data analysis.
    Genome Res. (IF 11.093) Pub Date : 2020-04-20
    Chiaowen Joyce Hsiao,PoYuan Tung,John D Blischak,Jonathan E Burnett,Kenneth A Barr,Kushal K Dey,Matthew Stephens,Yoav Gilad

    Cellular heterogeneity in gene expression is driven by cellular processes, such as cell cycle and cell-type identity, and cellular environment such as spatial location. The cell cycle, in particular, is thought to be a key driver of cell-to-cell heterogeneity in gene expression, even in otherwise homogeneous cell populations. Recent advances in single-cell RNA-sequencing (scRNA-seq) facilitate detailed

    更新日期:2020-04-01
  • Leveraging mouse chromatin data for heritability enrichment informs common disease architecture and reveals cortical layer contributions to schizophrenia.
    Genome Res. (IF 11.093) Pub Date : 2020-04-17
    Paul W Hook,Andrew S McCallion

    Genome-wide association studies have implicated thousands of noncoding variants across common human phenotypes. However, they cannot directly inform the cellular context in which disease-associated variants act. Here, we use open chromatin profiles from discrete mouse cell populations to address this challenge. We applied stratified linkage disequilibrium score regression and evaluated heritability

    更新日期:2020-04-01
  • Arabidopsis retrotransposon virus-like particles and their regulation by epigenetically activated small RNA.
    Genome Res. (IF 11.093) Pub Date : 2020-04-17
    Seung Cho Lee,Evan Ernst,Benjamin Berube,Filipe Borges,Jean-Sebastien Parent,Paul Ledon,Andrea Schorn,Robert A Martienssen

    In Arabidopsis, LTR retrotransposons are activated by mutations in the chromatin gene DECREASE in DNA METHYLATION 1 (DDM1), giving rise to 21- to 22-nt epigenetically activated siRNA (easiRNA) that depend on RNA DEPENDENT RNA POLYMERASE 6 (RDR6). We purified virus-like particles (VLPs) from ddm1 and ddm1rdr6 mutants in which genomic RNA is reverse transcribed into complementary DNA. High-throughput

    更新日期:2020-04-01
  • Noncoding regions underpin avian bill shape diversification at macroevolutionary scales.
    Genome Res. (IF 11.093) Pub Date : 2020-04-08
    Leeban Yusuf,Matthew C Heatley,Joseph P G Palmer,Henry J Barton,Christopher R Cooney,Toni I Gossmann

    Recent progress has been made in identifying genomic regions implicated in trait evolution on a microevolutionary scale in many species, but whether these are relevant over macroevolutionary time remains unclear. Here, we directly address this fundamental question using bird beak shape, a key evolutionary innovation linked to patterns of resource use, divergence, and speciation, as a model trait. We

    更新日期:2020-04-01
  • Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcriptional control.
    Genome Res. (IF 11.093) Pub Date : 2020-04-06
    Valentina Casa,Macarena Moronta Gines,Eduardo Gade Gusmao,Johan A Slotman,Anne Zirkel,Natasa Josipovic,Edwin Oole,Wilfred F J van IJcken,Adriaan B Houtsmuller,Argyris Papantonis,Kerstin S Wendt

    Cohesin is a ring-shaped multiprotein complex that is crucial for 3D genome organization and transcriptional regulation during differentiation and development. It also confers sister chromatid cohesion and facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A, and RAD21, cohesin in somatic cells contains one of two orthologous STAG subunits, STAG1 or STAG2. How these variable subunits

    更新日期:2020-04-01
  • Rapid evolution of piRNA-mediated silencing of an invading transposable element was driven by abundant de novo mutations.
    Genome Res. (IF 11.093) Pub Date : 2020-04-01
    Shuo Zhang,Beverly Pointer,Erin S Kelleher

    The regulation of transposable element (TE) activity by small RNAs is a ubiquitous feature of germlines. However, despite the obvious benefits to the host in terms of ensuring the production of viable gametes and maintaining the integrity of the genomes they carry, it remains controversial whether TE regulation evolves adaptively. We examined the emergence and evolutionary dynamics of repressor alleles

    更新日期:2020-04-01
  • Transcriptome reconstruction and functional analysis of eukaryotic marine plankton communities via high-throughput metagenomics and metatranscriptomics.
    Genome Res. (IF 11.093) Pub Date : 2020-03-23
    Alexey Vorobev,Marion Dupouy,Quentin Carradec,Tom O Delmont,Anita Annamalé,Patrick Wincker,Eric Pelletier

    Large-scale metagenomic and metatranscriptomic data analyses are often restricted by their gene-centric approach, limiting the ability to understand organismal and community biology. De novo assembly of large and mosaic eukaryotic genomes from complex meta-omics data remains a challenging task, especially in comparison with more straightforward bacterial and archaeal systems. Here, we use a transcriptome

    更新日期:2020-04-01
  • Time course regulatory analysis based on paired expression and chromatin accessibility data.
    Genome Res. (IF 11.093) Pub Date : 2020-03-18
    Zhana Duren,Xi Chen,Jingxue Xin,Yong Wang,Wing Hung Wong

    A time course experiment is a widely used design in the study of cellular processes such as differentiation or response to stimuli. In this paper, we propose time course regulatory analysis (TimeReg) as a method for the analysis of gene regulatory networks based on paired gene expression and chromatin accessibility data from a time course. TimeReg can be used to prioritize regulatory elements, to extract

    更新日期:2020-04-01
  • Inhibition of transcription leads to rewiring of locus-specific chromatin proteomes.
    Genome Res. (IF 11.093) Pub Date : 2020-03-18
    Deepani W Poramba-Liyanage,Tessy Korthout,Christine E Cucinotta,Ila van Kruijsbergen,Tibor van Welsem,Dris El Atmioui,Huib Ovaa,Toshio Tsukiyama,Fred van Leeuwen

    Transcription of a chromatin template involves the concerted interaction of many different proteins and protein complexes. Analyses of specific factors showed that these interactions change during stress and upon developmental switches. However, how the binding of multiple factors at any given locus is coordinated has been technically challenging to investigate. Here we used Epi-Decoder in yeast to

    更新日期:2020-04-01
  • RETrace: simultaneous retrospective lineage tracing and methylation profiling of single cells.
    Genome Res. (IF 11.093) Pub Date : 2020-03-03
    Christopher Jen-Yue Wei,Kun Zhang

    Retrospective lineage tracing harnesses naturally occurring mutations in cells to elucidate single cell development. Common single-cell phylogenetic fate mapping methods have utilized highly mutable microsatellite loci found within the human genome. Such methods were limited by the introduction of in vitro noise through polymerase slippage inherent in DNA amplification, which we characterized to be

    更新日期:2020-04-01
  • T-Cell Immunity against the Hepatitis C Virus: A Persistent Research Priority in an Era of Highly Effective Therapy.
    Genome Res. (IF 11.093) Pub Date : 2020-03-23
    Stephanie Smith,Jonathan R Honegger,Christopher Walker

    Approximately 70% of acute hepatitis C virus (HCV) infections become chronic, indicating that the virus is exceptionally well adapted to persist in humans with otherwise normal immune function. Robust, lifelong replication of this small RNA virus does not require a generalized failure of immunity. HCV effectively subverts innate and adaptive host defenses while leaving immunity against other viruses

    更新日期:2020-03-26
  • Neural Substrates and Circuits of Drug Addiction.
    Genome Res. (IF 11.093) Pub Date : 2020-03-23
    Matthew W Feltenstein,Ronald E See,Rita A Fuchs

    Drug addiction is a chronic relapsing disorder, and a significant amount of research has been devoted to understand the factors that contribute to the development, loss of control, and persistence of compulsive addictive behaviors. In this review, we provide an overview of various theories of addiction to drugs of abuse and the neurobiology involved in elements of the addiction cycle. Specific focus

    更新日期:2020-03-26
  • H7N9 Influenza Virus in China.
    Genome Res. (IF 11.093) Pub Date : 2020-03-23
    Chengjun Li,Hualan Chen

    In early 2013, human infections caused by a novel H7N9 avian influenza virus (AIV) were first reported in China; these infections caused severe disease and death. The virus was initially low pathogenic to poultry, enabling it to spread widely in different provinces, especially in live poultry markets. Importantly, the H7N9 low pathogenic AIVs (LPAIVs) evolved into highly pathogenic AIVs (HPAIVs) in

    更新日期:2020-03-26
  • Genetic Vulnerability to Opioid Addiction.
    Genome Res. (IF 11.093) Pub Date : 2020-03-23
    Brian Reed,Mary Jeanne Kreek

    Opioid addiction, also referred to as opioid use disorder, continues to be a devastating problem throughout the world. Familial relation and twin studies have revealed opioid addiction, like other addictive diseases, to be profoundly influenced by genetics. Genetics studies of opioid addiction have affirmed the importance of genetics contributors in susceptibility to develop opioid addiction, and also

    更新日期:2020-03-26
  • Equine Influenza
    Genome Res. (IF 11.093) Pub Date : 2020-03-09
    Thomas M. Chambers

    Horses are the third major mammalian species, along with humans and swine, long known to be subject to acute upper respiratory disease from influenza A virus infection. The viruses responsible are subtype H7N7, which is believed extinct, and H3N8, which circulates worldwide. The equine influenza lineages are clearly divergent from avian influenza lineages of the same subtypes. Their genetic evolution

    更新日期:2020-03-26
  • Antivirals Targeting the Neuraminidase
    Genome Res. (IF 11.093) Pub Date : 2020-03-09
    Larisa Gubareva; Teena Mohan

    The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and

    更新日期:2020-03-26
  • Systems Biological Analysis of Immune Response to Influenza Vaccination.
    Genome Res. (IF 11.093) Pub Date : 2020-03-09
    Mario Cortese,Amy C Sherman,Nadine G Rouphael,Bali Pulendran

    The last decade has witnessed tremendous progress in immunology and vaccinology, owing to several scientific and technological breakthroughs. Systems vaccinology is a field that has emerged at the forefront of vaccine research and development and provides a unique way to probe immune responses to vaccination in humans. The goals of systems vaccinology are to use systems-based approaches to define signatures

    更新日期:2020-03-26
  • Non-Hodgkin Lymphomas: Malignancies Arising from Mature B Cells
    Genome Res. (IF 11.093) Pub Date : 2020-03-09
    Jennifer Shingleton; Jie Wang; Carolyn Baloh; Tushar Dave; Nicholas Davis; Lanie Happ; Othmane Jadi; Rachel Kositsky; Xiang Li; Cassandra Love; Razvan Panea; Qiu Qin; Anupama Reddy; Naina Singhi; Eileen Smith; Devang Thakkar; Sandeep S. Dave

    Non-Hodgkin lymphomas (NHLs) are a diverse group of entities, both clinically and molecularly. Here, we review the evolution of classification schemes in B-cell lymphoma, noting the now standard WHO classification system that is based on immune cell-of-origin and molecular phenotypes. We review how lymphomas arise throughout the B-cell development process as well as the molecular and clinical features

    更新日期:2020-03-26
  • Family-Based Designs that Disentangle Inherited Factors from Pre- and Postnatal Environmental Exposures: In Vitro Fertilization, Discordant Sibling Pairs, Maternal versus Paternal Comparisons, and Adoption Designs
    Genome Res. (IF 11.093) Pub Date : 2020-03-09
    Anita Thapar; Frances Rice

    Identifying environmental risk and protective exposures that have causal effects on health is an important scientific goal. Many environmental exposures are nonrandomly allocated and influenced by dispositional factors including inherited ones. We review family-based designs that can separate the influence of environmental exposures from inherited influences shared between parent and offspring. We

    更新日期:2020-03-26
  • HCV Assembly and Egress via Modifications in Host Lipid Metabolic Systems
    Genome Res. (IF 11.093) Pub Date : 2020-03-02
    Kunitada Shimotohno

    Hepatitis C virus (HCV) proliferates by hijacking the host lipid machinery. In vitro replication systems revealed many aspects of the virus life cycle; in particular, viral utilization of host lipid metabolism during HCV proliferation. HCV interacts with lipid droplets (LDs) before starting the process of virus capsid formation at the lipid-rich endoplasmic reticulum (ER) membrane compartment. HCV

    更新日期:2020-03-26
  • Integrating Family-Based and Mendelian Randomization Designs
    Genome Res. (IF 11.093) Pub Date : 2020-03-02
    Liang-Dar Hwang; Neil M. Davies; Nicole M. Warrington; David M. Evans

    Most Mendelian randomization (MR) studies published in the literature to date have involved analyses of unrelated, putatively independent sets of individuals. However, estimates obtained from these sorts of studies are subject to a range of biases including dynastic effects, assortative mating, residual population stratification, and horizontal pleiotropy. The inclusion of related individuals in MR

    更新日期:2020-03-26
  • Influenza Polymerase Inhibitors: Mechanisms of Action and Resistance
    Genome Res. (IF 11.093) Pub Date : 2020-03-02
    Emi Takashita

    The influenza virus RNA-dependent RNA polymerase is highly conserved among influenza A, B, C, and D viruses. It comprises three subunits: polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and polymerase acidic protein (PA) in influenza A and B viruses or polymerase 3 protein (P3) in influenza C and D viruses. Because this polymerase is essential for influenza virus replication, it

    更新日期:2020-03-26
  • H5 Influenza Viruses in Egypt
    Genome Res. (IF 11.093) Pub Date : 2020-03-02
    Rabeh El-Shesheny; Ahmed Kandeil; Ahmed Mostafa; Mohamed A. Ali; Richard J. Webby

    For almost a decade, Egypt has been endemic for highly pathogenic avian influenza (HPAI) A(H5N1) viruses. In addition to being catastrophic for poultry production, A(H5N1) has also caused 359 human infections in the country (∼40% of global cases), with 120 being fatal. From 2017, A(H5N1) viruses have been gradually replaced by HPAI A(H5N8) viruses seeded from Southeast Asia through Europe; no human

    更新日期:2020-03-26
  • Mouse Models of Myeloid Malignancies
    Genome Res. (IF 11.093) Pub Date : 2020-02-18
    Faisal Basheer; George Vassiliou

    Mouse models of human myeloid malignancies support the detailed and focused investigation of selected driver mutations and represent powerful tools in the study of these diseases. Carefully developed murine models can closely recapitulate human myeloid malignancies in vivo, enabling the interrogation of a number of aspects of these diseases including their preclinical course, interactions with the

    更新日期:2020-03-26
  • Influenza Therapeutics in Clinical Practice—Challenges and Recent Advances
    Genome Res. (IF 11.093) Pub Date : 2020-02-10
    John H. Beigel; Frederick G. Hayden

    In the last few years, several new direct-acting influenza antivirals have been licensed, and others have advanced in clinical development. The increasing diversity of antiviral classes should allow an adequate public health response should a resistant virus to one agent or class widely circulate. One new antiviral, baloxavir marboxil, has been approved in the United States for treatment of influenza

    更新日期:2020-03-26
  • Epigenetic Mechanisms in Leukemias and Lymphomas
    Genome Res. (IF 11.093) Pub Date : 2020-02-03
    Cihangir Duy; Wendy Béguelin; Ari Melnick

    Although we are just beginning to understand the mechanisms that regulate the epigenome, aberrant epigenetic programming has already emerged as a hallmark of hematologic malignancies including acute myeloid leukemia (AML) and B-cell lymphomas. Although these diseases arise from the hematopoietic system, the epigenetic mechanisms that drive these malignancies are quite different. Yet, in all of these

    更新日期:2020-03-26
  • The Role of the Central Amygdala in Alcohol Dependence
    Genome Res. (IF 11.093) Pub Date : 2020-01-27
    Marisa Roberto; Dean Kirson; Sophia Khom

    Alcohol dependence is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking, loss of control in limiting intake, and the emergence of a withdrawal syndrome in the absence of the drug. Accumulating evidence suggests an important role for synaptic transmission in the central nucleus of the amygdala (CeA) in mediating alcohol-related behaviors and neuroadaptive mechanisms

    更新日期:2020-03-26
  • Influenza Vaccine Effectiveness: New Insights and Challenges
    Genome Res. (IF 11.093) Pub Date : 2020-01-27
    Huong Q. McLean; Edward A. Belongia

    Methods for assessing influenza vaccine efficacy and effectiveness have evolved over six decades. Randomized trials remain the gold standard for licensure, but observational studies are needed for annual assessment of vaccine effectiveness (VE). The test-negative design (TND) has become the de facto standard for these field studies. Patients who seek medical care with acute respiratory illness are

    更新日期:2020-03-26
  • Swine Influenza A Viruses and the Tangled Relationship with Humans
    Genome Res. (IF 11.093) Pub Date : 2020-01-27
    Tavis K. Anderson; Jennifer Chang; Zebulun W. Arendsee; Divya Venkatesh; Carine K. Souza; J. Brian Kimble; Nicola S. Lewis; C. Todd Davis; Amy L. Vincent

    Influenza A viruses (IAVs) are the causative agents of one of the most important viral respiratory diseases in pigs and humans. Human and swine IAV are prone to interspecies transmission, leading to regular incursions from human to pig and vice versa. This bidirectional transmission of IAV has heavily influenced the evolutionary history of IAV in both species. Transmission of distinct human seasonal

    更新日期:2020-03-26
  • The Structure, Function, and Pathobiology of the Influenza A and B Virus Ion Channels
    Genome Res. (IF 11.093) Pub Date : 2020-01-27
    Robert A. Lamb

    Influenza A virus AM2 protein is an integral membrane protein that is an ion channel (also known as a viroporin). The channel has 24 extracellular residues, 19 residues that span the membrane once and acts as both the channel pore and also the membrane anchoring domain, and a 54-residue cytoplasmic tail. The M2 protein has four identical chains linked via two disulfide bonds that form a four-helix

    更新日期:2020-03-26
  • Normal Hematopoiesis Is a Balancing Act of Self-Renewal and Regeneration
    Genome Res. (IF 11.093) Pub Date : 2020-01-27
    Oakley C. Olson; Yoon-A Kang; Emmanuelle Passegué

    The hematopoietic system is highly organized to maintain its functional integrity and to meet lifelong organismal demands. Hematopoietic stem cells (HSCs) must balance self-renewal with differentiation and the regeneration of the blood system. It is a complex balancing act between these competing HSC functions. Although highly quiescent at steady state, HSCs become activated in response to inflammatory

    更新日期:2020-03-26
  • Influenza Reverse Genetics—Historical Perspective
    Genome Res. (IF 11.093) Pub Date : 2020-01-21
    Gabriele Neumann

    The generation of wild-type, mutant, and reassortant influenza viruses from viral cDNAs (reverse genetics) is now a basic molecular virology technique in many influenza virus laboratories. Here, I describe the original RNA polymerase I reverse genetics system and the modifications that have been developed in past years. Together, these technologies have made possible many advances in basic and applied

    更新日期:2020-03-26
  • Pathobiological Origins and Evolutionary History of Highly Pathogenic Avian Influenza Viruses
    Genome Res. (IF 11.093) Pub Date : 2020-01-21
    Dong-Hun Lee; Miria Ferreira Criado; David E. Swayne

    High-pathogenicity avian influenza (HPAI) viruses have arisen from low-pathogenicity avian influenza (LPAI) viruses via changes in the hemagglutinin proteolytic cleavage site, which include mutation of multiple nonbasic to basic amino acids, duplication of basic amino acids, or recombination with insertion of cellular or viral amino acids. Between 1959 and 2019, a total of 42 natural, independent H5

    更新日期:2020-03-26
  • The Epidemiology, Virology, and Pathogenicity of Human Infections with Avian Influenza Viruses
    Genome Res. (IF 11.093) Pub Date : 2020-01-21
    Dayan Wang; Wenfei Zhu; Lei Yang; Yuelong Shu

    Influenza is a global challenge, and future pandemics of influenza are inevitable. One of the lessons learned from past pandemics is that all pandemic influenza viruses characterized to date possess viral genes originating from avian influenza viruses (AIVs). During the past decades, a wide range of AIVs have overcome the species barrier and infected humans with different clinical manifestations ranging

    更新日期:2020-03-26
  • Opioid-Induced Molecular and Cellular Plasticity of Ventral Tegmental Area Dopamine Neurons
    Genome Res. (IF 11.093) Pub Date : 2020-01-21
    Marie A. Doyle; Michelle S. Mazei-Robison

    Opioid drugs are highly valued as potent analgesics; however, there are significant risks associated with long-term use because of their abuse liability. Opioids cause changes in ventral tegmental area (VTA) gene expression and cell activity that have been linked to addiction-related behaviors in rodent models. Here, we focus on VTA dopamine (DA) neurons and review the cellular, structural, and synaptic

    更新日期:2020-03-26
  • Interferon-Free Hepatitis C Virus Therapy
    Genome Res. (IF 11.093) Pub Date : 2020-01-21
    Jean-Michel Pawlotsky

    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with ∼71 million chronically infected individuals worldwide. Treatment of patients with HCV-related liver disease has advanced considerably thanks to the development of new direct-acting antiviral drugs that are now administered as highly potent, safe, and well-tolerated combinations with a high barrier to resistance. International

    更新日期:2020-03-26
  • Influenza Vaccines Delivered in Early Childhood Could Turn Antigenic Sin into Antigenic Blessings
    Genome Res. (IF 11.093) Pub Date : 2020-01-21
    Michael Worobey; Stanley Plotkin; Scott E. Hensley

    Substantial evidence has accumulated that “original antigenic sin” is a central factor shaping immune responses against influenza viruses. Here, we argue that this propensity of initial influenza virus exposure to establish a lifelong immunological imprint presents a remarkable opportunity: Immunization of infants prior to their initial, natural viral exposure could circumvent narrow immunological

    更新日期:2020-03-26
Contents have been reproduced by permission of the publishers.
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