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  • TADsplimer reveals splits and mergers of topologically associating domains for epigenetic regulation of transcription
    Genome Biol. (IF 14.028) Pub Date : 2020-04-02
    Guangyu Wang; Qingshu Meng; Bo Xia; Shuo Zhang; Jie Lv; Dongyu Zhao; Yanqiang Li; Xin Wang; Lili Zhang; John P. Cooke; Qi Cao; Kaifu Chen

    We present TADsplimer, the first computational tool to systematically detect topologically associating domain (TAD) splits and mergers across the genome between Hi-C samples. TADsplimer recaptures splits and mergers of TADs with high accuracy in simulation analyses and defines hundreds of TAD splits and mergers between pairs of different cell types, such as endothelial cells and fibroblasts. Our work

    更新日期:2020-04-03
  • Lamina-associated domains: peripheral matters and internal affairs
    Genome Biol. (IF 14.028) Pub Date : 2020-04-02
    Nolwenn Briand; Philippe Collas

    At the nuclear periphery, associations of chromatin with the nuclear lamina through lamina-associated domains (LADs) aid functional organization of the genome. We review the organization of LADs and provide evidence of LAD heterogeneity from cell ensemble and single-cell data. LADs are typically repressive environments in the genome; nonetheless, we discuss findings of lamin interactions with regulatory

    更新日期:2020-04-03
  • Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome
    Genome Biol. (IF 14.028) Pub Date : 2020-04-01
    Takuro Horii; Sumiyo Morita; Shinjiro Hino; Mika Kimura; Yuko Hino; Hiroshi Kogo; Mitsuyoshi Nakao; Izuho Hatada

    Epigenetic modifications, including DNA methylation, play an important role in gene silencing and genome stability. Consequently, epigenetic dysregulation can cause several diseases, such as cancer, obesity, diabetes, autism, and imprinting disorders. We validate three methods for the generation of epigenome-edited mice using the dCas9-SunTag and single-chain variable fragment-TET1 catalytic domain

    更新日期:2020-04-01
  • CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma
    Genome Biol. (IF 14.028) Pub Date : 2020-03-31
    S. John Liu; Martina Malatesta; Brian V. Lien; Parna Saha; Shivani S. Thombare; Sung Jun Hong; Leslie Pedraza; Mark Koontz; Kyounghee Seo; Max A. Horlbeck; Daniel He; Harjus S. Birk; Miten Jain; Hugh E. Olsen; Mark Akeson; Jonathan S. Weissman; Michelle Monje; Nalin Gupta; David R. Raleigh; Erik M. Ullian; Daniel A. Lim

    Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current

    更新日期:2020-03-31
  • Avocado: a multi-scale deep tensor factorization method learns a latent representation of the human epigenome
    Genome Biol. (IF 14.028) Pub Date : 2020-03-30
    Jacob Schreiber; Timothy Durham; Jeffrey Bilmes; William Stafford Noble

    The human epigenome has been experimentally characterized by thousands of measurements for every basepair in the human genome. We propose a deep neural network tensor factorization method, Avocado, that compresses this epigenomic data into a dense, information-rich representation. We use this learned representation to impute epigenomic data more accurately than previous methods, and we show that machine

    更新日期:2020-03-31
  • Completing the ENCODE3 compendium yields accurate imputations across a variety of assays and human biosamples
    Genome Biol. (IF 14.028) Pub Date : 2020-03-30
    Jacob Schreiber; Jeffrey Bilmes; William Stafford Noble

    Recent efforts to describe the human epigenome have yielded thousands of epigenomic and transcriptomic datasets. However, due primarily to cost, the total number of such assays that can be performed is limited. Accordingly, we applied an imputation approach, Avocado, to a dataset of 3814 tracks of data derived from the ENCODE compendium, including measurements of chromatin accessibility, histone modification

    更新日期:2020-03-31
  • DeepMILO: a deep learning approach to predict the impact of non-coding sequence variants on 3D chromatin structure
    Genome Biol. (IF 14.028) Pub Date : 2020-03-26
    Tuan Trieu; Alexander Martinez-Fundichely; Ekta Khurana

    Non-coding variants have been shown to be related to disease by alteration of 3D genome structures. We propose a deep learning method, DeepMILO, to predict the effects of variants on CTCF/cohesin-mediated insulator loops. Application of DeepMILO on variants from whole-genome sequences of 1834 patients of twelve cancer types revealed 672 insulator loops disrupted in at least 10% of patients. Our results

    更新日期:2020-03-27
  • Characterisation of genetic regulatory effects for osteoporosis risk variants in human osteoclasts
    Genome Biol. (IF 14.028) Pub Date : 2020-03-26
    Benjamin H. Mullin; Jennifer Tickner; Kun Zhu; Jacob Kenny; Shelby Mullin; Suzanne J. Brown; Frank Dudbridge; Nathan J. Pavlos; Edward S. Mocarski; John P. Walsh; Jiake Xu; Scott G. Wilson

    Osteoporosis is a complex disease with a strong genetic contribution. A recently published genome-wide association study (GWAS) for estimated bone mineral density (eBMD) identified 1103 independent genome-wide significant association signals. Most of these variants are non-coding, suggesting that regulatory effects may drive many of the associations. To identify genes with a role in osteoporosis, we

    更新日期:2020-03-27
  • A Cas12a ortholog with stringent PAM recognition followed by low off-target editing rates for genome editing
    Genome Biol. (IF 14.028) Pub Date : 2020-03-25
    Peng Chen; Jin Zhou; Yibin Wan; Huan Liu; Yongzheng Li; Zhaoxin Liu; Hongjian Wang; Jun Lei; Kai Zhao; Yiliang Zhang; Yan Wang; Xinghua Zhang; Lei Yin

    AsCas12a and LbCas12a nucleases are reported to be promising tools for genome engineering with protospacer adjacent motif (PAM) TTTV as the optimal. However, the C-containing PAM (CTTV, TCTV, TTCV, etc.) recognition by Cas12a might induce extra off-target edits at these non-canonical PAM sites. Here, we identify a novel Cas12a nuclease CeCas12a from Coprococcus eutactus, which is a programmable nuclease

    更新日期:2020-03-26
  • Diverse genetic mechanisms underlie worldwide convergent rice feralization
    Genome Biol. (IF 14.028) Pub Date : 2020-03-26
    Jie Qiu; Lei Jia; Dongya Wu; Xifang Weng; Lijuan Chen; Jian Sun; Meihong Chen; Lingfeng Mao; Bowen Jiang; Chuyu Ye; Guilherme Menegol Turra; Longbiao Guo; Guoyou Ye; Qian-Hao Zhu; Toshiyuki Imaizumi; Beng-Kah Song; Laura Scarabel; Aldo Merotto; Kenneth M. Olsen; Longjiang Fan

    Worldwide feralization of crop species into agricultural weeds threatens global food security. Weedy rice is a feral form of rice that infests paddies worldwide and aggressively outcompetes cultivated varieties. Despite increasing attention in recent years, a comprehensive understanding of the origins of weedy crop relatives and how a universal feralization process acts at the genomic and molecular

    更新日期:2020-03-26
  • Decode-seq: a practical approach to improve differential gene expression analysis
    Genome Biol. (IF 14.028) Pub Date : 2020-03-23
    Yingshu Li; Hang Yang; Hujun Zhang; Yongjie Liu; Hanqiao Shang; Herong Zhao; Ting Zhang; Qiang Tu

    Many differential gene expression analyses are conducted with an inadequate number of biological replicates. We describe an easy and effective RNA-seq approach using molecular barcoding to enable profiling of a large number of replicates simultaneously. This approach significantly improves the performance of differential gene expression analysis. Using this approach in medaka (Oryzias latipes), we

    更新日期:2020-03-24
  • HiNT: a computational method for detecting copy number variations and translocations from Hi-C data
    Genome Biol. (IF 14.028) Pub Date : 2020-03-23
    Su Wang; Soohyun Lee; Chong Chu; Dhawal Jain; Peter Kerpedjiev; Geoffrey M. Nelson; Jennifer M. Walsh; Burak H. Alver; Peter J. Park

    The three-dimensional conformation of a genome can be profiled using Hi-C, a technique that combines chromatin conformation capture with high-throughput sequencing. However, structural variations often yield features that can be mistaken for chromosomal interactions. Here, we describe a computational method HiNT (Hi-C for copy Number variation and Translocation detection), which detects copy number

    更新日期:2020-03-24
  • Obstacles to detecting isoforms using full-length scRNA-seq data
    Genome Biol. (IF 14.028) Pub Date : 2020-03-23
    Jennifer Westoby; Pavel Artemov; Martin Hemberg; Anne Ferguson-Smith

    Early single-cell RNA-seq (scRNA-seq) studies suggested that it was unusual to see more than one isoform being produced from a gene in a single cell, even when multiple isoforms were detected in matched bulk RNA-seq samples. However, these studies generally did not consider the impact of dropouts or isoform quantification errors, potentially confounding the results of these analyses. In this study

    更新日期:2020-03-24
  • Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection
    Genome Biol. (IF 14.028) Pub Date : 2020-03-23
    Zhilian Jia; Jingwei Li; Xiao Ge; Yonghu Wu; Ya Guo; Qiang Wu

    CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem. Using CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin (Pcdh) and β-globin clusters, function as an enhancer-blocking insulator by forming distinct

    更新日期:2020-03-24
  • High-resolution Repli-Seq defines the temporal choreography of initiation, elongation and termination of replication in mammalian cells
    Genome Biol. (IF 14.028) Pub Date : 2020-03-24
    Peiyao A. Zhao; Takayo Sasaki; David M. Gilbert

    DNA replication in mammalian cells occurs in a defined temporal order during S phase, known as the replication timing (RT) programme. Replication timing is developmentally regulated and correlated with chromatin conformation and local transcriptional potential. Here, we present RT profiles of unprecedented temporal resolution in two human embryonic stem cell lines, human colon carcinoma line HCT116

    更新日期:2020-03-24
  • VALOR2: characterization of large-scale structural variants using linked-reads
    Genome Biol. (IF 14.028) Pub Date : 2020-03-19
    Fatih Karaoğlanoğlu; Camir Ricketts; Ezgi Ebren; Marzieh Eslami Rasekh; Iman Hajirasouliha; Can Alkan

    Most existing methods for structural variant detection focus on discovery and genotyping of deletions, insertions, and mobile elements. Detection of balanced structural variants with no gain or loss of genomic segments, for example, inversions and translocations, is a particularly challenging task. Furthermore, there are very few algorithms to predict the insertion locus of large interspersed segmental

    更新日期:2020-03-20
  • Benchmarking of computational error-correction methods for next-generation sequencing data
    Genome Biol. (IF 14.028) Pub Date : 2020-03-17
    Keith Mitchell; Jaqueline J. Brito; Igor Mandric; Qiaozhen Wu; Sergey Knyazev; Sei Chang; Lana S. Martin; Aaron Karlsberg; Ekaterina Gerasimov; Russell Littman; Brian L. Hill; Nicholas C. Wu; Harry Taegyun Yang; Kevin Hsieh; Linus Chen; Eli Littman; Taylor Shabani; German Enik; Douglas Yao; Ren Sun; Jan Schroeder; Eleazar Eskin; Alex Zelikovsky; Pavel Skums; Mihai Pop; Serghei Mangul

    Recent advancements in next-generation sequencing have rapidly improved our ability to study genomic material at an unprecedented scale. Despite substantial improvements in sequencing technologies, errors present in the data still risk confounding downstream analysis and limiting the applicability of sequencing technologies in clinical tools. Computational error correction promises to eliminate sequencing

    更新日期:2020-03-19
  • BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty
    Genome Biol. (IF 14.028) Pub Date : 2020-03-16
    Simone Tiberi; Mark D. Robinson

    Alternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we present BANDITS, a R/Bioconductor package to perform differential splicing, at both gene and transcript level, based on RNA-seq data. BANDITS uses a Bayesian hierarchical structure to explicitly

    更新日期:2020-03-16
  • Renaissance minds in 21st century science
    Genome Biol. (IF 14.028) Pub Date : 2020-03-13
    Itai Yanai; Martin Lercher

    The hypothesis-testing mode of science, which François Jacob called “day science,” operates within the confines of a particular scientific field. As highly specialized experts, we confidently and safely follow the protocols of our paradigms and research programs [1, 2]. But there is another side of science, which Jacob called “night science”: the much less structured process by which new ideas arise

    更新日期:2020-03-16
  • Ultraplexing: increasing the efficiency of long-read sequencing for hybrid assembly with k-mer-based multiplexing
    Genome Biol. (IF 14.028) Pub Date : 2020-03-14
    Alexander T. Dilthey; Sebastian A. Meyer; Achim J. Kaasch

    Hybrid genome assembly has emerged as an important technique in bacterial genomics, but cost and labor requirements limit large-scale application. We present Ultraplexing, a method to improve per-sample sequencing cost and hands-on time of Nanopore sequencing for hybrid assembly by at least 50% compared to molecular barcoding while maintaining high assembly quality. Ultraplexing requires the availability

    更新日期:2020-03-16
  • Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium
    Genome Biol. (IF 14.028) Pub Date : 2020-03-11
    Juri Kazakevych; Jérémy Denizot; Anke Liebert; Mariana Portovedo; Mia Mosavie; Payal Jain; Claudia Stellato; Claire Fraser; Renan Oliveira Corrêa; Marina Célestine; Raphaël Mattiuz; Hanneke Okkenhaug; J. Ross Miller; Marco Aurélio Ramirez Vinolo; Marc Veldhoen; Patrick Varga-Weisz

    How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we explore its role in this tissue. Specific deletion of Smarcad1

    更新日期:2020-03-12
  • CHOP: haplotype-aware path indexing in population graphs
    Genome Biol. (IF 14.028) Pub Date : 2020-03-11
    Tom Mokveld; Jasper Linthorst; Zaid Al-Ars; Henne Holstege; Marcel Reinders

    The practical use of graph-based reference genomes depends on the ability to align reads to them. Performing substring queries to paths through these graphs lies at the core of this task. The combination of increasing pattern length and encoded variations inevitably leads to a combinatorial explosion of the search space. Instead of heuristic filtering or pruning steps to reduce the complexity, we propose

    更新日期:2020-03-12
  • Hemispheric asymmetry in the human brain and in Parkinson’s disease is linked to divergent epigenetic patterns in neurons
    Genome Biol. (IF 14.028) Pub Date : 2020-03-09
    Peipei Li; Elizabeth Ensink; Sean Lang; Lee Marshall; Meghan Schilthuis; Jared Lamp; Irving Vega; Viviane Labrie

    Hemispheric asymmetry in neuronal processes is a fundamental feature of the human brain and drives symptom lateralization in Parkinson’s disease (PD), but its molecular determinants are unknown. Here, we identify divergent epigenetic patterns involved in hemispheric asymmetry by profiling DNA methylation in isolated prefrontal cortex neurons from control and PD brain hemispheres. DNA methylation is

    更新日期:2020-03-09
  • A benchmark of algorithms for the analysis of pooled CRISPR screens
    Genome Biol. (IF 14.028) Pub Date : 2020-03-09
    Sunil Bodapati; Timothy P. Daley; Xueqiu Lin; James Zou; Lei S. Qi

    Genome-wide pooled CRISPR-Cas-mediated knockout, activation, and repression screens are powerful tools for functional genomic investigations. Despite their increasing importance, there is currently little guidance on how to design and analyze CRISPR-pooled screens. Here, we provide a review of the commonly used algorithms in the computational analysis of pooled CRISPR screens. We develop a comprehensive

    更新日期:2020-03-09
  • High-resolution modeling of the selection on local mRNA folding strength in coding sequences across the tree of life
    Genome Biol. (IF 14.028) Pub Date : 2020-03-09
    Michael Peeri; Tamir Tuller

    mRNA can form local secondary structure within the protein-coding sequence, and the strength of this structure is thought to influence gene expression regulation. Previous studies suggest that secondary structure strength may be maintained under selection, but the details of this phenomenon are not well understood. We perform a comprehensive study of the selection on local mRNA folding strengths considering

    更新日期:2020-03-09
  • Decontamination of ambient RNA in single-cell RNA-seq with DecontX
    Genome Biol. (IF 14.028) Pub Date : 2020-03-05
    Shiyi Yang; Sean E. Corbett; Yusuke Koga; Zhe Wang; W Evan Johnson; Masanao Yajima; Joshua D. Campbell

    Droplet-based microfluidic devices have become widely used to perform single-cell RNA sequencing (scRNA-seq). However, ambient RNA present in the cell suspension can be aberrantly counted along with a cell’s native mRNA and result in cross-contamination of transcripts between different cell populations. DecontX is a novel Bayesian method to estimate and remove contamination in individual cells. DecontX

    更新日期:2020-03-06
  • WhatsGNU: a tool for identifying proteomic novelty
    Genome Biol. (IF 14.028) Pub Date : 2020-03-05
    Ahmed M. Moustafa; Paul J. Planet

    To understand diversity in enormous collections of genome sequences, we need computationally scalable tools that can quickly contextualize individual genomes based on their similarities and identify features of each genome that make them unique. We present WhatsGNU, a tool based on exact match proteomic compression that, in seconds, classifies any new genome and provides a detailed report of protein

    更新日期:2020-03-06
  • Multiplexed capture of spatial configuration and temporal dynamics of locus-specific 3D chromatin by biotinylated dCas9
    Genome Biol. (IF 14.028) Pub Date : 2020-03-05
    Xin Liu; Yong Chen; Yuannyu Zhang; Yuxuan Liu; Nan Liu; Giovanni A. Botten; Hui Cao; Stuart H. Orkin; Michael Q. Zhang; Jian Xu

    The spatiotemporal control of 3D genome is fundamental for gene regulation, yet it remains challenging to profile high-resolution chromatin structure at cis-regulatory elements (CREs). Using C-terminally biotinylated dCas9, endogenous biotin ligases, and pooled sgRNAs, we describe the dCas9-based CAPTURE method for multiplexed analysis of locus-specific chromatin interactions. The redesigned system

    更新日期:2020-03-06
  • The genome evolution and domestication of tropical fruit mango.
    Genome Biol. (IF 14.028) Pub Date : 2020-03-06
    Peng Wang,Yingfeng Luo,Jianfeng Huang,Shenghan Gao,Guopeng Zhu,Zhiguo Dang,Jiangtao Gai,Meng Yang,Min Zhu,Huangkai Zhang,Xiuxu Ye,Aiping Gao,Xinyu Tan,Sen Wang,Shuangyang Wu,Edgar B Cahoon,Beibei Bai,Zhichang Zhao,Qian Li,Junya Wei,Huarui Chen,Ruixiong Luo,Deyong Gong,Kexuan Tang,Bing Zhang,Zhangguang Ni,Guodi Huang,Songnian Hu,Yeyuan Chen

    BACKGROUND Mango is one of the world's most important tropical fruits. It belongs to the family Anacardiaceae, which includes several other economically important species, notably cashew, sumac and pistachio from other genera. Many species in this family produce family-specific urushiols and related phenols, which can induce contact dermatitis. RESULTS We generate a chromosome-scale genome assembly

    更新日期:2020-03-06
  • Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS.
    Genome Biol. (IF 14.028) Pub Date : 2020-03-03
    Yibin Liu,Jingfei Cheng,Paulina Siejka-Zielińska,Carika Weldon,Hannah Roberts,Maria Lopopolo,Andrea Magri,Valentina D'Arienzo,James M Harris,Jane A McKeating,Chun-Xiao Song

    We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range

    更新日期:2020-03-03
  • Longitudinal survey of microbiome associated with particulate matter in a megacity.
    Genome Biol. (IF 14.028) Pub Date : 2020-03-03
    Nan Qin,Peng Liang,Chunyan Wu,Guanqun Wang,Qian Xu,Xiao Xiong,Tingting Wang,Moreno Zolfo,Nicola Segata,Huanlong Qin,Rob Knight,Jack A Gilbert,Ting F Zhu

    BACKGROUND While the physical and chemical properties of airborne particulate matter (PM) have been extensively studied, their associated microbiome remains largely unexplored. Here, we performed a longitudinal metagenomic survey of 106 samples of airborne PM2.5 and PM10 in Beijing over a period of 6 months in 2012 and 2013, including those from several historically severe smog events. RESULTS We observed

    更新日期:2020-03-03
  • NanoVar: accurate characterization of patients' genomic structural variants using low-depth nanopore sequencing.
    Genome Biol. (IF 14.028) Pub Date : 2020-03-03
    Cheng Yong Tham,Roberto Tirado-Magallanes,Yufen Goh,Melissa J Fullwood,Bryan T H Koh,Wilson Wang,Chin Hin Ng,Wee Joo Chng,Alexandre Thiery,Daniel G Tenen,Touati Benoukraf

    The recent advent of third-generation sequencing technologies brings promise for better characterization of genomic structural variants by virtue of having longer reads. However, long-read applications are still constrained by their high sequencing error rates and low sequencing throughput. Here, we present NanoVar, an optimized structural variant caller utilizing low-depth (8X) whole-genome sequencing

    更新日期:2020-03-03
  • gscreend: modelling asymmetric count ratios in CRISPR screens to decrease experiment size and improve phenotype detection.
    Genome Biol. (IF 14.028) Pub Date : 2020-03-02
    Katharina Imkeller,Giulia Ambrosi,Michael Boutros,Wolfgang Huber

    Pooled CRISPR screens are a powerful tool to probe genotype-phenotype relationships at genome-wide scale. However, criteria for optimal design are missing, and it remains unclear how experimental parameters affect results. Here, we report that random decreases in gRNA abundance are more likely than increases due to bottle-neck effects during the cell proliferation phase. Failure to consider this asymmetry

    更新日期:2020-03-02
  • Regenerating zebrafish fin epigenome is characterized by stable lineage-specific DNA methylation and dynamic chromatin accessibility.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-27
    Hyung Joo Lee,Yiran Hou,Yujie Chen,Zea Z Dailey,Aiyana Riddihough,Hyo Sik Jang,Ting Wang,Stephen L Johnson

    BACKGROUND Zebrafish can faithfully regenerate injured fins through the formation of a blastema, a mass of proliferative cells that can grow and develop into the lost body part. After amputation, various cell types contribute to blastema formation, where each cell type retains fate restriction and exclusively contributes to regeneration of its own lineage. Epigenetic changes that are associated with

    更新日期:2020-02-28
  • A rare codon-based translational program of cell proliferation.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-27
    Joao C Guimaraes,Nitish Mittal,Alexandra Gnann,Dominik Jedlinski,Andrea Riba,Katarzyna Buczak,Alexander Schmidt,Mihaela Zavolan

    BACKGROUND The speed of translation elongation is primarily determined by the abundance of tRNAs. Thus, the codon usage influences the rate with which individual mRNAs are translated. As the nature of tRNA pools and modifications can vary across biological conditions, codon elongation rates may also vary, leading to fluctuations in the protein production from individual mRNAs. Although it has been

    更新日期:2020-02-27
  • Allosteric inhibition of CRISPR-Cas9 by bacteriophage-derived peptides.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-26
    Yan-Ru Cui,Shao-Jie Wang,Jun Chen,Jie Li,Wenzhang Chen,Shuyue Wang,Bing Meng,Wei Zhu,Zhuhong Zhang,Bei Yang,Biao Jiang,Guang Yang,Peixiang Ma,Jia Liu

    BACKGROUND CRISPR-Cas9 has been developed as a therapeutic agent for various infectious and genetic diseases. In many clinically relevant applications, constitutively active CRISPR-Cas9 is delivered into human cells without a temporal control system. Excessive and prolonged expression of CRISPR-Cas9 can lead to elevated off-target cleavage. The need for modulating CRISPR-Cas9 activity over time and

    更新日期:2020-02-27
  • Author Correction: Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-25
    Robert C Kaplan,Zheng Wang,Mykhaylo Usyk,Daniela Sotres-Alvarez,Martha L Daviglus,Neil Schneiderman,Gregory A Talavera,Marc D Gellman,Bharat Thyagarajan,Jee-Young Moon,Yoshiki Vázquez-Baeza,Daniel McDonald,Jessica S Williams-Nguyen,Michael C Wu,Kari E North,Justin Shaffer,Christopher C Sollecito,Qibin Qi,Carmen R Isasi,Tao Wang,Rob Knight,Robert D Burk

    Following publication of the original paper [1], an error was reported in the third paragraph in the section "Analysis of GMB composition and its correlates" (page 3 of the PDF). The first sentence of the text should refer to Table 2, but mistakenly refers to Table 1.

    更新日期:2020-02-26
  • Linked optical and gene expression profiling of single cells at high-throughput.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-24
    Jesse Q Zhang,Christian A Siltanen,Leqian Liu,Kai-Chun Chang,Zev J Gartner,Adam R Abate

    Single-cell RNA sequencing has emerged as a powerful tool for characterizing cells, but not all phenotypes of interest can be observed through changes in gene expression. Linking sequencing with optical analysis has provided insight into the molecular basis of cellular function, but current approaches have limited throughput. Here, we present a high-throughput platform for linked optical and gene expression

    更新日期:2020-02-25
  • Author Correction: 547 transcriptomes from 44 brain areas reveal features of the aging brain in non-human primates.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-24
    Ming-Li Li,Shi-Hao Wu,Jin-Jin Zhang,Hang-Yu Tian,Yong Shao,Zheng-Bo Wang,David M Irwin,Jia-Li Li,Xin-Tian Hu,Dong-Dong Wu

    Following publication of the original paper [1], the authors reported an error in the affiliation of Xin-Tian Hu, who is also affiliated with "Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China".

    更新日期:2020-02-24
  • Carnelian uncovers hidden functional patterns across diverse study populations from whole metagenome sequencing reads.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-24
    Sumaiya Nazeen,Yun William Yu,Bonnie Berger

    Microbial populations exhibit functional changes in response to different ambient environments. Although whole metagenome sequencing promises enough raw data to study those changes, existing tools are limited in their ability to directly compare microbial metabolic function across samples and studies. We introduce Carnelian, an end-to-end pipeline for metabolic functional profiling uniquely suited

    更新日期:2020-02-24
  • ncHMR detector: a computational framework to systematically reveal non-classical functions of histone modification regulators.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-24
    Shengen Hu,Dawei Huo,Zhaowei Yu,Yujie Chen,Jing Liu,Lin Liu,Xudong Wu,Yong Zhang

    Recently, several non-classical functions of histone modification regulators (HMRs), independent of their known histone modification substrates and products, have been reported to be essential for specific cellular processes. However, there is no framework designed for identifying such functions systematically. Here, we develop ncHMR detector, the first computational framework to predict non-classical

    更新日期:2020-02-24
  • Histone H3K27 acetylation is dispensable for enhancer activity in mouse embryonic stem cells.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-21
    Tiantian Zhang,Zhuqiang Zhang,Qiang Dong,Jun Xiong,Bing Zhu

    H3K27ac is well recognized as a marker for active enhancers and a great indicator of enhancer activity. However, its functional impact on transcription has not been characterized. By substituting lysine 27 in histone variant H3.3 with arginine in mouse embryonic stem cells, we diminish the vast majority of H3K27ac at enhancers. However, the transcriptome is largely undisturbed in these mutant cells

    更新日期:2020-02-21
  • Publisher Correction: Host-associated microbiomes are predicted by immune system complexity and climate.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-20
    Douglas C Woodhams,Molly C Bletz,C Guilherme Becker,Hayden A Bender,Daniel Buitrago-Rosas,Hannah Diebboll,Roger Huynh,Patrick J Kearns,Jordan Kueneman,Emmi Kurosawa,Brandon C LaBumbard,Casandra Lyons,Kerry McNally,Klaus Schliep,Nachiket Shankar,Amanda G Tokash-Peters,Miguel Vences,Ross Whetstone

    Following publication of the original paper [1], it was reported that an error in the processing of Fig. 8 occurred. In the online HTML version of the article, Fig. 8 was presented as a duplication of Fig. 7. The original article [1] has been corrected.

    更新日期:2020-02-20
  • Author Correction: Interaction between the microbiome and TP53 in human lung cancer.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-20
    K Leigh Greathouse,James R White,Ashely J Vargas,Valery V Bliskovsky,Jessica A Beck,Natalia von Muhlinen,Eric C Polley,Elise D Bowman,Mohammed A Khan,Ana I Robles,Tomer Cooks,Bríd M Ryan,Noah Padgett,Amiran H Dzutsev,Giorgio Trinchieri,Marbin A Pineda,Sven Bilke,Paul S Meltzer,Alexis N Hokenstad,Tricia M Stickrod,Marina R Walther-Antonio,Joshua P Earl,Joshua C Mell,Jaroslaw E Krol,Sergey V Balashov

    Following publication of the original paper [1], the authors submitted a new Additional file 5 to replace the one containing formatting issues. The updated Additional file 5 is published in this correction.

    更新日期:2020-02-20
  • A framework for transcriptome-wide association studies in breast cancer in diverse study populations.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-20
    Arjun Bhattacharya,Montserrat García-Closas,Andrew F Olshan,Charles M Perou,Melissa A Troester,Michael I Love

    BACKGROUND The relationship between germline genetic variation and breast cancer survival is largely unknown, especially in understudied minority populations who often have poorer survival. Genome-wide association studies (GWAS) have interrogated breast cancer survival but often are underpowered due to subtype heterogeneity and clinical covariates and detect loci in non-coding regions that are difficult

    更新日期:2020-02-20
  • Comprehensive assessment of computational algorithms in predicting cancer driver mutations.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-20
    Hu Chen,Jun Li,Yumeng Wang,Patrick Kwok-Shing Ng,Yiu Huen Tsang,Kenna R Shaw,Gordon B Mills,Han Liang

    BACKGROUND The initiation and subsequent evolution of cancer are largely driven by a relatively small number of somatic mutations with critical functional impacts, so-called driver mutations. Identifying driver mutations in a patient's tumor cells is a central task in the era of precision cancer medicine. Over the decade, many computational algorithms have been developed to predict the effects of missense

    更新日期:2020-02-20
  • Protein velocity and acceleration from single-cell multiomics experiments.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-18
    Gennady Gorin,Valentine Svensson,Lior Pachter

    The simultaneous quantification of protein and RNA makes possible the inference of past, present, and future cell states from single experimental snapshots. To enable such temporal analysis from multimodal single-cell experiments, we introduce an extension of the RNA velocity method that leverages estimates of unprocessed transcript and protein abundances to extrapolate cell states. We apply the model

    更新日期:2020-02-19
  • Mutational signatures: experimental design and analytical framework.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-14
    Gene Koh,Xueqing Zou,Serena Nik-Zainal

    Mutational signatures provide a powerful alternative for understanding the pathophysiology of cancer. Currently, experimental efforts aimed at validating and understanding the etiologies of cancer-derived mutational signatures are underway. In this review, we highlight key aspects of mutational signature experimental design and describe the analytical framework. We suggest guidelines and quality control

    更新日期:2020-02-18
  • A willow sex chromosome reveals convergent evolution of complex palindromic repeats.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-14
    Ran Zhou,David Macaya-Sanz,Craig H Carlson,Jeremy Schmutz,Jerry W Jenkins,David Kudrna,Aditi Sharma,Laura Sandor,Shengqiang Shu,Kerrie Barry,Gerald A Tuskan,Tao Ma,Jianquan Liu,Matthew Olson,Lawrence B Smart,Stephen P DiFazio

    BACKGROUND Sex chromosomes have arisen independently in a wide variety of species, yet they share common characteristics, including the presence of suppressed recombination surrounding sex determination loci. Mammalian sex chromosomes contain multiple palindromic repeats across the non-recombining region that show sequence conservation through gene conversion and contain genes that are crucial for

    更新日期:2020-02-18
  • Assembly of hundreds of novel bacterial genomes from the chicken caecum.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-12
    Laura Glendinning,Robert D Stewart,Mark J Pallen,Kellie A Watson,Mick Watson

    BACKGROUND Chickens are a highly important source of protein for a large proportion of the human population. The caecal microbiota plays a crucial role in chicken nutrition through the production of short-chain fatty acids, nitrogen recycling, and amino acid production. In this study, we sequence DNA from caecal content samples taken from 24 chickens belonging to either a fast or a slower growing breed

    更新日期:2020-02-12
  • Genotyping structural variants in pangenome graphs using the vg toolkit.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-12
    Glenn Hickey,David Heller,Jean Monlong,Jonas A Sibbesen,Jouni Sirén,Jordan Eizenga,Eric T Dawson,Erik Garrison,Adam M Novak,Benedict Paten

    Structural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide an effective means for leveraging SV catalogs for short-read SV genotyping experiments. We benchmark vg against state-of-the-art SV genotypers using three sequence-resolved SV catalogs generated

    更新日期:2020-02-12
  • Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-12
    Christian H Holland,Jovan Tanevski,Javier Perales-Patón,Jan Gleixner,Manu P Kumar,Elisabetta Mereu,Brian A Joughin,Oliver Stegle,Douglas A Lauffenburger,Holger Heyn,Bence Szalai,Julio Saez-Rodriguez

    BACKGROUND Many functional analysis tools have been developed to extract functional and mechanistic insight from bulk transcriptome data. With the advent of single-cell RNA sequencing (scRNA-seq), it is in principle possible to do such an analysis for single cells. However, scRNA-seq data has characteristics such as drop-out events and low library sizes. It is thus not clear if functional TF and pathway

    更新日期:2020-02-12
  • A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-10
    Sooncheol Lee,Douglas Micalizzi,Samuel S Truesdell,Syed I A Bukhari,Myriam Boukhali,Jennifer Lombardi-Story,Yasutaka Kato,Min-Kyung Choo,Ipsita Dey-Guha,Fei Ji,Benjamin T Nicholson,David T Myers,Dongjun Lee,Maria A Mazzola,Radhika Raheja,Adam Langenbucher,Nicholas J Haradhvala,Michael S Lawrence,Roopali Gandhi,Christopher Tiedje,Manuel D Diaz-Muñoz,David A Sweetser,Ruslan Sadreyev,David Sykes,Wilhelm

    BACKGROUND Quiescence (G0) is a transient, cell cycle-arrested state. By entering G0, cancer cells survive unfavorable conditions such as chemotherapy and cause relapse. While G0 cells have been studied at the transcriptome level, how post-transcriptional regulation contributes to their chemoresistance remains unknown. RESULTS We induce chemoresistant and G0 leukemic cells by serum starvation or chemotherapy

    更新日期:2020-02-10
  • Purifying selection of long dsRNA is the first line of defense against false activation of innate immunity.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-07
    Michal Barak,Hagit T Porath,Gilad Finkelstein,Binyamin A Knisbacher,Ilana Buchumenski,Shalom Hillel Roth,Erez Y Levanon,Eli Eisenberg

    BACKGROUND Mobile elements comprise a large fraction of metazoan genomes. Accumulation of mobile elements is bound to produce multiple putative double-stranded RNA (dsRNA) structures within the transcriptome. These endogenous dsRNA structures resemble viral RNA and may trigger false activation of the innate immune response, leading to severe damage to the host cell. Adenosine to inosine (A-to-I) RNA

    更新日期:2020-02-07
  • Systematic functional identification of cancer multi-drug resistance genes.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-07
    Man-Tat Lau,Shila Ghazanfar,Ashleigh Parkin,Angela Chou,Jourdin R Rouaen,Jamie B Littleboy,Danielle Nessem,Thang M Khuong,Damien Nevoltris,Peter Schofield,David Langley,Daniel Christ,Jean Yang,Marina Pajic,G Gregory Neely

    BACKGROUND Drug resistance is a major obstacle in cancer therapy. To elucidate the genetic factors that regulate sensitivity to anti-cancer drugs, we performed CRISPR-Cas9 knockout screens for resistance to a spectrum of drugs. RESULTS In addition to known drug targets and resistance mechanisms, this study revealed novel insights into drug mechanisms of action, including cellular transporters, drug

    更新日期:2020-02-07
  • Publisher Correction: Co-opted transposons help perpetuate conserved higher-order chromosomal structures.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-07
    Mayank N K Choudhary,Ryan Z Friedman,Julia T Wang,Hyo Sik Jang,Xiaoyu Zhuo,Ting Wang

    Following publication of the original paper [1], an error was reported in the processing of Fig. 2. The correct Fig. 2 is supplied below and the original article [1] has been corrected. The publishers apologize for the error.

    更新日期:2020-02-07
  • Admixture-enabled selection for rapid adaptive evolution in the Americas.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-07
    Emily T Norris,Lavanya Rishishwar,Aroon T Chande,Andrew B Conley,Kaixiong Ye,Augusto Valderrama-Aguirre,I King Jordan

    BACKGROUND Admixture occurs when previously isolated populations come together and exchange genetic material. We hypothesize that admixture can enable rapid adaptive evolution in human populations by introducing novel genetic variants (haplotypes) at intermediate frequencies, and we test this hypothesis through the analysis of whole genome sequences sampled from admixed Latin American populations in

    更新日期:2020-02-07
  • Opportunities and challenges in long-read sequencing data analysis.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-07
    Shanika L Amarasinghe,Shian Su,Xueyi Dong,Luke Zappia,Matthew E Ritchie,Quentin Gouil

    Long-read technologies are overcoming early limitations in accuracy and throughput, broadening their application domains in genomics. Dedicated analysis tools that take into account the characteristics of long-read data are thus required, but the fast pace of development of such tools can be overwhelming. To assist in the design and analysis of long-read sequencing projects, we review the current landscape

    更新日期:2020-02-07
  • Eleven grand challenges in single-cell data science.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-07
    David Lähnemann,Johannes Köster,Ewa Szczurek,Davis J McCarthy,Stephanie C Hicks,Mark D Robinson,Catalina A Vallejos,Kieran R Campbell,Niko Beerenwinkel,Ahmed Mahfouz,Luca Pinello,Pavel Skums,Alexandros Stamatakis,Camille Stephan-Otto Attolini,Samuel Aparicio,Jasmijn Baaijens,Marleen Balvert,Buys de Barbanson,Antonio Cappuccio,Giacomo Corleone,Bas E Dutilh,Maria Florescu,Victor Guryev,Rens Holmer,Katharina

    The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands-or even millions-of cells analyzed in a single experiment amount to a data revolution in single-cell biology and pose unique data science problems. Here, we outline eleven challenges that will be central to bringing this emerging field

    更新日期:2020-02-07
  • Lisa: inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data.
    Genome Biol. (IF 14.028) Pub Date : 2020-02-07
    Qian Qin,Jingyu Fan,Rongbin Zheng,Changxin Wan,Shenglin Mei,Qiu Wu,Hanfei Sun,Myles Brown,Jing Zhang,Clifford A Meyer,X Shirley Liu

    We developed Lisa (http://lisa.cistrome.org/) to predict the transcriptional regulators (TRs) of differentially expressed or co-expressed gene sets. Based on the input gene sets, Lisa first uses histone mark ChIP-seq and chromatin accessibility profiles to construct a chromatin model related to the regulation of these genes. Using TR ChIP-seq peaks or imputed TR binding sites, Lisa probes the chromatin

    更新日期:2020-02-07
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