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  • Chromatin regulates expression of small RNAs to help maintain transposon methylome homeostasis in Arabidopsis
    Genome Biol. (IF 10.806) Pub Date : 2020-09-17
    Ranjith K. Papareddy; Katalin Páldi; Subramanian Paulraj; Ping Kao; Stefan Lutzmayer; Michael D. Nodine

    Eukaryotic genomes are partitioned into euchromatic and heterochromatic domains to regulate gene expression and other fundamental cellular processes. However, chromatin is dynamic during growth and development and must be properly re-established after its decondensation. Small interfering RNAs (siRNAs) promote heterochromatin formation, but little is known about how chromatin regulates siRNA expression

    更新日期:2020-09-18
  • Removing reference bias and improving indel calling in ancient DNA data analysis by mapping to a sequence variation graph
    Genome Biol. (IF 10.806) Pub Date : 2020-09-17
    Rui Martiniano; Erik Garrison; Eppie R. Jones; Andrea Manica; Richard Durbin

    During the last decade, the analysis of ancient DNA (aDNA) sequence has become a powerful tool for the study of past human populations. However, the degraded nature of aDNA means that aDNA molecules are short and frequently mutated by post-mortem chemical modifications. These features decrease read mapping accuracy and increase reference bias, in which reads containing non-reference alleles are less

    更新日期:2020-09-18
  • Bifrost: highly parallel construction and indexing of colored and compacted de Bruijn graphs
    Genome Biol. (IF 10.806) Pub Date : 2020-09-17
    Guillaume Holley; Páll Melsted

    Memory consumption of de Bruijn graphs is often prohibitive. Most de Bruijn graph-based assemblers reduce the complexity by compacting paths into single vertices, but this is challenging as it requires the uncompacted de Bruijn graph to be available in memory. We present a parallel and memory-efficient algorithm enabling the direct construction of the compacted de Bruijn graph without producing the

    更新日期:2020-09-18
  • Ultrasensitive deletion detection links mitochondrial DNA replication, disease, and aging
    Genome Biol. (IF 10.806) Pub Date : 2020-09-17
    Scott A. Lujan; Matthew J. Longley; Margaret H. Humble; Christopher A. Lavender; Adam Burkholder; Emma L. Blakely; Charlotte L. Alston; Grainne S. Gorman; Doug M. Turnbull; Robert McFarland; Robert W. Taylor; Thomas A. Kunkel; William C. Copeland

    Acquired human mitochondrial genome (mtDNA) deletions are symptoms and drivers of focal mitochondrial respiratory deficiency, a pathological hallmark of aging and late-onset mitochondrial disease. To decipher connections between these processes, we create LostArc, an ultrasensitive method for quantifying deletions in circular mtDNA molecules. LostArc reveals 35 million deletions (~ 470,000 unique spans)

    更新日期:2020-09-18
  • Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation
    Genome Biol. (IF 10.806) Pub Date : 2020-09-15
    Celestia Fang; Zhenjia Wang; Cuijuan Han; Stephanie L. Safgren; Kathryn A. Helmin; Emmalee R. Adelman; Valentina Serafin; Giuseppe Basso; Kyle P. Eagen; Alexandre Gaspar-Maia; Maria E. Figueroa; Benjamin D. Singer; Aakrosh Ratan; Panagiotis Ntziachristos; Chongzhi Zang

    The three-dimensional genome organization is critical for gene regulation and can malfunction in diseases like cancer. As a key regulator of genome organization, CCCTC-binding factor (CTCF) has been characterized as a DNA-binding protein with important functions in maintaining the topological structure of chromatin and inducing DNA looping. Among the prolific binding sites in the genome, several events

    更新日期:2020-09-15
  • AuthentiCT: a model of ancient DNA damage to estimate the proportion of present-day DNA contamination
    Genome Biol. (IF 10.806) Pub Date : 2020-09-15
    Stéphane Peyrégne; Benjamin M. Peter

    Contamination from present-day DNA is a fundamental issue when studying ancient DNA from historical or archaeological material, and quantifying the amount of contamination is essential for downstream analyses. We present AuthentiCT, a command-line tool to estimate the proportion of present-day DNA contamination in ancient DNA datasets generated from single-stranded DNA libraries. The prediction is

    更新日期:2020-09-15
  • Merqury: reference-free quality, completeness, and phasing assessment for genome assemblies
    Genome Biol. (IF 10.806) Pub Date : 2020-09-14
    Arang Rhie; Brian P. Walenz; Sergey Koren; Adam M. Phillippy

    Recent long-read assemblies often exceed the quality and completeness of available reference genomes, making validation challenging. Here we present Merqury, a novel tool for reference-free assembly evaluation based on efficient k-mer set operations. By comparing k-mers in a de novo assembly to those found in unassembled high-accuracy reads, Merqury estimates base-level accuracy and completeness. For

    更新日期:2020-09-14
  • Primo: integration of multiple GWAS and omics QTL summary statistics for elucidation of molecular mechanisms of trait-associated SNPs and detection of pleiotropy in complex traits
    Genome Biol. (IF 10.806) Pub Date : 2020-09-11
    Kevin J. Gleason; Fan Yang; Brandon L. Pierce; Xin He; Lin S. Chen

    To provide a comprehensive mechanistic interpretation of how known trait-associated SNPs affect complex traits, we propose a method, Primo, for integrative analysis of GWAS summary statistics with multiple sets of omics QTL summary statistics from different cellular conditions or studies. Primo examines association patterns of SNPs to complex and omics traits. In gene regions harboring known susceptibility

    更新日期:2020-09-11
  • sn-spMF: matrix factorization informs tissue-specific genetic regulation of gene expression
    Genome Biol. (IF 10.806) Pub Date : 2020-09-11
    Yuan He; Surya B. Chhetri; Marios Arvanitis; Kaushik Srinivasan; François Aguet; Kristin G. Ardlie; Alvaro N. Barbeira; Rodrigo Bonazzola; Hae Kyung Im; Christopher D. Brown; Alexis Battle

    Genetic regulation of gene expression, revealed by expression quantitative trait loci (eQTLs), exhibits complex patterns of tissue-specific effects. Characterization of these patterns may allow us to better understand mechanisms of gene regulation and disease etiology. We develop a constrained matrix factorization model, sn-spMF, to learn patterns of tissue-sharing and apply it to 49 human tissues

    更新日期:2020-09-11
  • A vast resource of allelic expression data spanning human tissues
    Genome Biol. (IF 10.806) Pub Date : 2020-09-11
    Stephane E. Castel; François Aguet; Pejman Mohammadi; Kristin G. Ardlie; Tuuli Lappalainen

    Allele expression (AE) analysis robustly measures cis-regulatory effects. Here, we present and demonstrate the utility of a vast AE resource generated from the GTEx v8 release, containing 15,253 samples spanning 54 human tissues for a total of 431 million measurements of AE at the SNP level and 153 million measurements at the haplotype level. In addition, we develop an extension of our tool phASER

    更新日期:2020-09-11
  • Impact of admixture and ancestry on eQTL analysis and GWAS colocalization in GTEx
    Genome Biol. (IF 10.806) Pub Date : 2020-09-11
    Nicole R. Gay; Michael Gloudemans; Margaret L. Antonio; Nathan S. Abell; Brunilda Balliu; YoSon Park; Alicia R. Martin; Shaila Musharoff; Abhiram S. Rao; François Aguet; Alvaro N. Barbeira; Rodrigo Bonazzola; Farhad Hormozdiari; Kristin G. Ardlie; Christopher D. Brown; Hae Kyung Im; Tuuli Lappalainen; Xiaoquan Wen; Stephen B. Montgomery

    Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings. The Genotype-Tissue Expression (GTEx) project largely contains individuals of European ancestry, but the v8 release also includes up to 15% of individuals of non-European ancestry. Assessing ancestry-based adjustments in GTEx improves portability of this research

    更新日期:2020-09-11
  • PTWAS: investigating tissue-relevant causal molecular mechanisms of complex traits using probabilistic TWAS analysis
    Genome Biol. (IF 10.806) Pub Date : 2020-09-11
    Yuhua Zhang; Corbin Quick; Ketian Yu; Alvaro Barbeira; Francesca Luca; Roger Pique-Regi; Hae Kyung Im; Xiaoquan Wen

    We propose a new computational framework, probabilistic transcriptome-wide association study (PTWAS), to investigate causal relationships between gene expressions and complex traits. PTWAS applies the established principles from instrumental variables analysis and takes advantage of probabilistic eQTL annotations to delineate and tackle the unique challenges arising in TWAS. PTWAS not only confers

    更新日期:2020-09-11
  • Estimating the quality of eukaryotic genomes recovered from metagenomic analysis with EukCC
    Genome Biol. (IF 10.806) Pub Date : 2020-09-10
    Paul Saary; Alex L. Mitchell; Robert D. Finn

    Microbial eukaryotes constitute a significant fraction of biodiversity and have recently gained more attention, but the recovery of high-quality metagenomic assembled eukaryotic genomes is limited by the current availability of tools. To help address this, we have developed EukCC, a tool for estimating the quality of eukaryotic genomes based on the automated dynamic selection of single copy marker

    更新日期:2020-09-10
  • STARR-seq identifies active, chromatin-masked, and dormant enhancers in pluripotent mouse embryonic stem cells
    Genome Biol. (IF 10.806) Pub Date : 2020-09-10
    Tianran Peng; Yanan Zhai; Yaser Atlasi; Menno ter Huurne; Hendrik Marks; Hendrik G. Stunnenberg; Wout Megchelenbrink

    Enhancers are distal regulators of gene expression that shape cell identity and control cell fate transitions. In mouse embryonic stem cells (mESCs), the pluripotency network is maintained by the function of a complex network of enhancers, that are drastically altered upon differentiation. Genome-wide chromatin accessibility and histone modification assays are commonly used as a proxy for identifying

    更新日期:2020-09-10
  • Metalign: efficient alignment-based metagenomic profiling via containment min hash
    Genome Biol. (IF 10.806) Pub Date : 2020-09-10
    Nathan LaPierre; Mohammed Alser; Eleazar Eskin; David Koslicki; Serghei Mangul

    Metagenomic profiling, predicting the presence and relative abundances of microbes in a sample, is a critical first step in microbiome analysis. Alignment-based approaches are often considered accurate yet computationally infeasible. Here, we present a novel method, Metalign, that performs efficient and accurate alignment-based metagenomic profiling. We use a novel containment min hash approach to

    更新日期:2020-09-10
  • GetOrganelle: a fast and versatile toolkit for accurate de novo assembly of organelle genomes
    Genome Biol. (IF 10.806) Pub Date : 2020-09-10
    Jian-Jun Jin; Wen-Bin Yu; Jun-Bo Yang; Yu Song; Claude W. dePamphilis; Ting-Shuang Yi; De-Zhu Li

    GetOrganelle is a state-of-the-art toolkit to accurately assemble organelle genomes from whole genome sequencing data. It recruits organelle-associated reads using a modified “baiting and iterative mapping” approach, conducts de novo assembly, filters and disentangles the assembly graph, and produces all possible configurations of circular organelle genomes. For 50 published plant datasets, we are

    更新日期:2020-09-10
  • Natural display of nuclear-encoded RNA on the cell surface and its impact on cell interaction
    Genome Biol. (IF 10.806) Pub Date : 2020-09-10
    Norman Huang; Xiaochen Fan; Kathia Zaleta-Rivera; Tri C. Nguyen; Jiarong Zhou; Yingjun Luo; Jie Gao; Ronnie H. Fang; Zhangming Yan; Zhen Bouman Chen; Liangfang Zhang; Sheng Zhong

    Compared to proteins, glycans, and lipids, much less is known about RNAs on the cell surface. We develop a series of technologies to test for any nuclear-encoded RNAs that are stably attached to the cell surface and exposed to the extracellular space, hereafter called membrane-associated extracellular RNAs (maxRNAs). We develop a technique called Surface-seq to selectively sequence maxRNAs and validate

    更新日期:2020-09-10
  • COCOA: coordinate covariation analysis of epigenetic heterogeneity
    Genome Biol. (IF 10.806) Pub Date : 2020-09-07
    John T. Lawson; Jason P. Smith; Stefan Bekiranov; Francine E. Garrett-Bakelman; Nathan C. Sheffield

    A key challenge in epigenetics is to determine the biological significance of epigenetic variation among individuals. We present Coordinate Covariation Analysis (COCOA), a computational framework that uses covariation of epigenetic signals across individuals and a database of region sets to annotate epigenetic heterogeneity. COCOA is the first such tool for DNA methylation data and can also analyze

    更新日期:2020-09-08
  • Alignment and mapping methodology influence transcript abundance estimation
    Genome Biol. (IF 10.806) Pub Date : 2020-09-07
    Avi Srivastava; Laraib Malik; Hirak Sarkar; Mohsen Zakeri; Fatemeh Almodaresi; Charlotte Soneson; Michael I. Love; Carl Kingsford; Rob Patro

    The accuracy of transcript quantification using RNA-seq data depends on many factors, such as the choice of alignment or mapping method and the quantification model being adopted. While the choice of quantification model has been shown to be important, considerably less attention has been given to comparing the effect of various read alignment approaches on quantification accuracy. We investigate the

    更新日期:2020-09-08
  • Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease
    Genome Biol. (IF 10.806) Pub Date : 2020-09-07
    Xiaofeng Dong; Jordana Munoz-Basagoiti; Natasha Y. Rickett; Georgios Pollakis; William A. Paxton; Stephan Günther; Romy Kerber; Lisa F. P. Ng; Michael J. Elmore; N’faly Magassouba; Miles W. Carroll; David A. Matthews; Julian A. Hiscox

    Viral load is a major contributor to outcome in patients with Ebola virus disease (EVD), with high values leading to a fatal outcome. Evidence from the 2013–2016 Ebola virus (EBOV) outbreak indicated that different genotypes of the virus can have different phenotypes in patients. Additionally, due to the error-prone nature of viral RNA synthesis in an individual patient, the EBOV genome exists around

    更新日期:2020-09-08
  • The Tug1 lncRNA locus is essential for male fertility
    Genome Biol. (IF 10.806) Pub Date : 2020-09-07
    Jordan P. Lewandowski; Gabrijela Dumbović; Audrey R. Watson; Taeyoung Hwang; Emily Jacobs-Palmer; Nydia Chang; Christian Much; Kyle M. Turner; Christopher Kirby; Nimrod D. Rubinstein; Abigail F. Groff; Steve C. Liapis; Chiara Gerhardinger; Assaf Bester; Pier Paolo Pandolfi; John G. Clohessy; Hopi E. Hoekstra; Martin Sauvageau; John L. Rinn

    Several long noncoding RNAs (lncRNAs) have been shown to function as components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has greatly expanded, studying lncRNA function has been a challenge due to their diverse biological roles and because lncRNA loci can contain multiple molecular modes that may exert function. We previously

    更新日期:2020-09-08
  • The wild grape genome sequence provides insights into the transition from dioecy to hermaphroditism during grape domestication.
    Genome Biol. (IF 10.806) Pub Date : 2020-09-07
    Hélène Badouin,Amandine Velt,François Gindraud,Timothée Flutre,Vincent Dumas,Sonia Vautrin,William Marande,Jonathan Corbi,Erika Sallet,Jérémy Ganofsky,Sylvain Santoni,Dominique Guyot,Eugenia Ricciardelli,Kristen Jepsen,Jos Käfer,Hélène Berges,Eric Duchêne,Franck Picard,Philippe Hugueney,Raquel Tavares,Roberto Bacilieri,Camille Rustenholz,Gabriel A B Marais

    A key step in domestication of the grapevine was the transition from separate sexes (dioecy) in wild Vitis vinifera ssp. sylvestris (V. sylvestris) to hermaphroditism in cultivated Vitis vinifera ssp. sativa (V. vinifera). It is known that V. sylvestris has an XY system and V. vinifera a modified Y haplotype (Yh) and that the sex locus is small, but it has not previously been precisely characterized

    更新日期:2020-09-07
  • EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data.
    Genome Biol. (IF 10.806) Pub Date : 2020-09-04
    Andrew E Teschendorff,Tianyu Zhu,Charles E Breeze,Stephan Beck

    Cell type heterogeneity presents a challenge to the interpretation of epigenome data, compounded by the difficulty in generating reliable single-cell DNA methylomes for large numbers of cells and samples. We present EPISCORE, a computational algorithm that performs virtual microdissection of bulk tissue DNA methylation data at single cell-type resolution for any solid tissue. EPISCORE applies a probabilistic

    更新日期:2020-09-05
  • A hypothesis is a liability.
    Genome Biol. (IF 10.806) Pub Date : 2020-09-03
    Itai Yanai,Martin Lercher

    “ ‘When someone seeks,’ said Siddhartha, ‘then it easily happens that his eyes see only the thing that he seeks, and he is able to find nothing, to take in nothing. [...] Seeking means: having a goal. But finding means: being free, being open, having no goal.’ ” Hermann Hesse There is a hidden cost to having a hypothesis. It arises from the relationship between night science and day science, the two

    更新日期:2020-09-03
  • Fine-tuning sugar content in strawberry
    Genome Biol. (IF 10.806) Pub Date : 2020-09-03
    Sinian Xing; Kunling Chen; Haocheng Zhu; Rui Zhang; Huawei Zhang; Bingbing Li; Caixia Gao

    Fine-tuning quantitative traits for continuous subtle phenotypes is highly advantageous. We engineer the highly conserved upstream open reading frame (uORF) of FvebZIPs1.1 in strawberry (Fragaria vesca), using base editor A3A-PBE. Seven novel alleles are generated. Sugar content of the homozygous T1 mutant lines is 33.9–83.6% higher than that of the wild-type. We also recover a series of transgene-free

    更新日期:2020-09-03
  • 1200 high-quality metagenome-assembled genomes from the rumen of African cattle and their relevance in the context of sub-optimal feeding.
    Genome Biol. (IF 10.806) Pub Date : 2020-09-03
    Toby Wilkinson,Daniel Korir,Moses Ogugo,Robert D Stewart,Mick Watson,Edith Paxton,John Goopy,Christelle Robert

    The Boran (Bos indicus), indigenous Zebu cattle breed from sub-Saharan Africa, is remarkably well adapted to harsh tropical environments. Due to financial constraints and low-quality forage, African livestock are rarely fed at 100% maintenance energy requirements (MER) and the effect of sub-optimal restricted feeding on the rumen microbiome of African Zebu cattle remains largely unexplored. We collected

    更新日期:2020-09-03
  • A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation.
    Genome Biol. (IF 10.806) Pub Date : 2020-09-01
    Baokun Sui,Dong Chen,Wei Liu,Qiong Wu,Bin Tian,Yingying Li,Jing Hou,Shiyong Liu,Juan Xie,Hao Jiang,Zhaochen Luo,Lei Lv,Fei Huang,Ruiming Li,Chengguang Zhang,Yuling Tian,Min Cui,Ming Zhou,Huanchun Chen,Zhen F Fu,Yi Zhang,Ling Zhao

    The central nervous system (CNS) is vulnerable to viral infection, yet few host factors in the CNS are known to defend against invasion by neurotropic viruses. Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in a wide variety of biological processes and are highly abundant in the mammalian brain, but their roles in defending against invasion of pathogens into the CNS remain

    更新日期:2020-09-01
  • pipeComp, a general framework for the evaluation of computational pipelines, reveals performant single cell RNA-seq preprocessing tools.
    Genome Biol. (IF 10.806) Pub Date : 2020-09-01
    Pierre-Luc Germain,Anthony Sonrel,Mark D Robinson

    We present pipeComp ( https://github.com/plger/pipeComp ), a flexible R framework for pipeline comparison handling interactions between analysis steps and relying on multi-level evaluation metrics. We apply it to the benchmark of single-cell RNA-sequencing analysis pipelines using simulated and real datasets with known cell identities, covering common methods of filtering, doublet detection, normalization

    更新日期:2020-09-01
  • RNA G-quadruplex structures exist and function in vivo in plants.
    Genome Biol. (IF 10.806) Pub Date : 2020-09-01
    Xiaofei Yang,Jitender Cheema,Yueying Zhang,Hongjing Deng,Susan Duncan,Mubarak Ishaq Umar,Jieyu Zhao,Qi Liu,Xiaofeng Cao,Chun Kit Kwok,Yiliang Ding

    Guanine-rich sequences are able to form complex RNA structures termed RNA G-quadruplexes in vitro. Because of their high stability, RNA G-quadruplexes are proposed to exist in vivo and are suggested to be associated with important biological relevance. However, there is a lack of direct evidence for RNA G-quadruplex formation in living eukaryotic cells. Therefore, it is unclear whether any purported

    更新日期:2020-09-01
  • CSS: cluster similarity spectrum integration of single-cell genomics data.
    Genome Biol. (IF 10.806) Pub Date : 2020-09-01
    Zhisong He,Agnieska Brazovskaja,Sebastian Ebert,J Gray Camp,Barbara Treutlein

    It is a major challenge to integrate single-cell sequencing data across experiments, conditions, batches, time points, and other technical considerations. New computational methods are required that can integrate samples while simultaneously preserving biological information. Here, we propose an unsupervised reference-free data representation, cluster similarity spectrum (CSS), where each cell is represented

    更新日期:2020-09-01
  • sgBE: a structure-guided design of sgRNA architecture specifies base editing window and enables simultaneous conversion of cytosine and adenosine.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-28
    Yanhong Wang,Lifang Zhou,Rui Tao,Nan Liu,Jie Long,Fengming Qin,Wenling Tang,Yang Yang,Qiang Chen,Shaohua Yao

    We present a base editing system, in which base editors are attached to different sites of sgRNA scaffold (sgBE). Each independent sgBE has its own specific editing pattern for a given target site. Among tested sgBEs, sgBE-SL4, in which deaminase is attached to the last stem-loop of sgRNA, yields the highest editing efficiency in the window several nucleotides next to the one edited by BE3. sgBE enables

    更新日期:2020-08-28
  • Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-28
    Paul J Hop,René Luijk,Lucia Daxinger,Maarten van Iterson,Koen F Dekkers,Rick Jansen,,Joyce B J van Meurs,Peter A C 't Hoen,M Arfan Ikram,Marleen M J van Greevenbroek,Dorret I Boomsma,P Eline Slagboom,Jan H Veldink,Erik W van Zwet,Bastiaan T Heijmans

    DNA methylation is a key epigenetic modification in human development and disease, yet there is limited understanding of its highly coordinated regulation. Here, we identify 818 genes that affect DNA methylation patterns in blood using large-scale population genomics data. By employing genetic instruments as causal anchors, we establish directed associations between gene expression and distant DNA

    更新日期:2020-08-28
  • 3DeFDR: statistical methods for identifying cell type-specific looping interactions in 5C and Hi-C data.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-28
    Lindsey R Fernandez,Thomas G Gilgenast,Jennifer E Phillips-Cremins

    An important unanswered question in chromatin biology is the extent to which long-range looping interactions change across developmental models, genetic perturbations, drug treatments, and disease states. Computational tools for rigorous assessment of cell type-specific loops across multiple biological conditions are needed. We present 3DeFDR, a simple and effective statistical tool for classifying

    更新日期:2020-08-28
  • A systematic evaluation of single-cell RNA-sequencing imputation methods.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-27
    Wenpin Hou,Zhicheng Ji,Hongkai Ji,Stephanie C Hicks

    The rapid development of single-cell RNA-sequencing (scRNA-seq) technologies has led to the emergence of many methods for removing systematic technical noises, including imputation methods, which aim to address the increased sparsity observed in single-cell data. Although many imputation methods have been developed, there is no consensus on how methods compare to each other. Here, we perform a systematic

    更新日期:2020-08-27
  • PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-26
    Zheng-Zheng Tang,Gregory R Sliwoski,Guanhua Chen,Bowen Jin,William S Bush,Bingshan Li,John A Capra

    Germline disease-causing variants are generally more spatially clustered in protein 3-dimensional structures than benign variants. Motivated by this tendency, we develop a fast and powerful protein-structure-based scan (PSCAN) approach for evaluating gene-level associations with complex disease and detecting signal variants. We validate PSCAN’s performance on synthetic data and two real data sets for

    更新日期:2020-08-26
  • Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-26
    Jason K Sa,Nakho Chang,Hye Won Lee,Hee Jin Cho,Michele Ceccarelli,Luigi Cerulo,Jinlong Yin,Sung Soo Kim,Francesca P Caruso,Mijeong Lee,Donggeon Kim,Young Taek Oh,Yeri Lee,Nam-Gu Her,Byeongkwi Min,Hye-Jin Kim,Da Eun Jeong,Hye-Mi Kim,Hyunho Kim,Seok Chung,Hyun Goo Woo,Jeongwu Lee,Doo-Sik Kong,Ho Jun Seol,Jung-Il Lee,Jinho Kim,Woong-Yang Park,Qianghu Wang,Erik P Sulman,Amy B Heimberger,Michael Lim,Jong

    Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages. We explore the transcriptional regulatory networks

    更新日期:2020-08-26
  • Improved reference genome of the arboviral vector Aedes albopictus.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-26
    Umberto Palatini,Reem A Masri,Luciano V Cosme,Sergey Koren,Françoise Thibaud-Nissen,James K Biedler,Flavia Krsticevic,J Spencer Johnston,Rebecca Halbach,Jacob E Crawford,Igor Antoshechkin,Anna-Bella Failloux,Elisa Pischedda,Michele Marconcini,Jay Ghurye,Arang Rhie,Atashi Sharma,Dmitry A Karagodin,Jeremy Jenrette,Stephanie Gamez,Pascal Miesen,Patrick Masterson,Adalgisa Caccone,Maria V Sharakhova,Zhijian

    The Asian tiger mosquito Aedes albopictus is globally expanding and has become the main vector for human arboviruses in Europe. With limited antiviral drugs and vaccines available, vector control is the primary approach to prevent mosquito-borne diseases. A reliable and accurate DNA sequence of the Ae. albopictus genome is essential to develop new approaches that involve genetic manipulation of mosquitoes

    更新日期:2020-08-26
  • Author Correction: SMURF-seq: efficient copy number profiling on long-read sequencers.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-25
    Rishvanth K Prabakar,Liya Xu,James Hicks,Andrew D Smith

    An amendment to this paper has been published and can be accessed via the original article.

    更新日期:2020-08-25
  • Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-24
    Chongwei Bi,Lin Wang,Baolei Yuan,Xuan Zhou,Yu Li,Sheng Wang,Yuhong Pang,Xin Gao,Yanyi Huang,Mo Li

    Quantifying the genetic heterogeneity of a cell population is essential to understanding of biological systems. We develop a universal method to label individual DNA molecules for single-base-resolution haplotype-resolved quantitative characterization of diverse types of rare variants, with frequency as low as 4 × 10−5, using both short- or long-read sequencing platforms. It provides the first quantitative

    更新日期:2020-08-24
  • Tuning parameters of dimensionality reduction methods for single-cell RNA-seq analysis.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-24
    Felix Raimundo,Celine Vallot,Jean-Philippe Vert

    Many computational methods have been developed recently to analyze single-cell RNA-seq (scRNA-seq) data. Several benchmark studies have compared these methods on their ability for dimensionality reduction, clustering, or differential analysis, often relying on default parameters. Yet, given the biological diversity of scRNA-seq datasets, parameter tuning might be essential for the optimal usage of

    更新日期:2020-08-24
  • GBAT: a gene-based association test for robust detection of trans-gene regulation.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-24
    Xuanyao Liu,Joel A Mefford,Andrew Dahl,Yuan He,Meena Subramaniam,Alexis Battle,Alkes L Price,Noah Zaitlen

    The observation that disease-associated genetic variants typically reside outside of exons has inspired widespread investigation into the genetic basis of transcriptional regulation. While associations between the mRNA abundance of a gene and its proximal SNPs (cis-eQTLs) are now readily identified, identification of high-quality distal associations (trans-eQTLs) has been limited by a heavy multiple

    更新日期:2020-08-24
  • DNA polymerase stalling at structured DNA constrains the expansion of short tandem repeats.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-21
    Pierre Murat,Guillaume Guilbaud,Julian E Sale

    Short tandem repeats (STRs) contribute significantly to de novo mutagenesis, driving phenotypic diversity and genetic disease. Although highly diverse, their repetitive sequences induce DNA polymerase slippage and stalling, leading to length and sequence variation. However, current studies of DNA synthesis through STRs are restricted to a handful of selected sequences, limiting our broader understanding

    更新日期:2020-08-21
  • Cis and trans effects differentially contribute to the evolution of promoters and enhancers.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-20
    Kaia Mattioli,Winona Oliveros,Chiara Gerhardinger,Daniel Andergassen,Philipp G Maass,John L Rinn,Marta Melé

    Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects are caused by genetic variants located on the same DNA molecule as the target gene, trans effects are due to genetic variants that affect diffusible elements. Previous studies have mostly assessed the impact of cis and trans effects at the gene level. However, how cis and trans effects differentially

    更新日期:2020-08-20
  • CRISPR and transposon in vivo screens for cancer drivers and therapeutic targets.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-19
    Imran Noorani,Allan Bradley,Jorge de la Rosa

    Human cancers harbor substantial genetic, epigenetic, and transcriptional changes, only some of which drive oncogenesis at certain times during cancer evolution. Identifying the cancer-driver alterations amongst the vast swathes of “passenger” changes still remains a major challenge. Transposon and CRISPR screens in vivo provide complementary methods for achieving this, and each platform has its own

    更新日期:2020-08-19
  • Methods for copy number aberration detection from single-cell DNA-sequencing data.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-17
    Xian F Mallory,Mohammadamin Edrisi,Nicholas Navin,Luay Nakhleh

    Copy number aberrations (CNAs), which are pathogenic copy number variations (CNVs), play an important role in the initiation and progression of cancer. Single-cell DNA-sequencing (scDNAseq) technologies produce data that is ideal for inferring CNAs. In this review, we review eight methods that have been developed for detecting CNAs in scDNAseq data, and categorize them according to the steps of a seven-step

    更新日期:2020-08-17
  • DiMSum: an error model and pipeline for analyzing deep mutational scanning data and diagnosing common experimental pathologies.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-17
    Andre J Faure,Jörn M Schmiedel,Pablo Baeza-Centurion,Ben Lehner

    Deep mutational scanning (DMS) enables multiplexed measurement of the effects of thousands of variants of proteins, RNAs, and regulatory elements. Here, we present a customizable pipeline, DiMSum, that represents an end-to-end solution for obtaining variant fitness and error estimates from raw sequencing data. A key innovation of DiMSum is the use of an interpretable error model that captures the main

    更新日期:2020-08-17
  • Correction to: PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-17
    Imran Noorani,Jorge de la Rosa,Yoon Ha Choi,Alexander Strong,Hannes Ponstingl,M S Vijayabaskar,Jusung Lee,Eunmin Lee,Angela Richard-Londt,Mathias Friedrich,Federica Furlanetto,Rocio Fuente,Ruby Banerjee,Fengtang Yang,Frances Law,Colin Watts,Roland Rad,George Vassiliou,Jong Kyoung Kim,Thomas Santarius,Sebastian Brandner,Allan Bradley

    An amendment to this paper has been published and can be accessed via the original article.

    更新日期:2020-08-17
  • Sc3.0: revamping and minimizing the yeast genome.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-13
    Junbiao Dai,Jef D Boeke,Zhouqing Luo,Shuangying Jiang,Yizhi Cai

    Recent improvements in DNA synthesis and editing techniques enable engineering the entire genome of an organism, offering new tools to directly probe relationships between genotype and phenotype. Genome synthesis potentially allows the researchers to gain a much greater degree of control of an organism, and it also leads to a completely new way to understand the biology of genomes. In 2008, the first

    更新日期:2020-08-14
  • Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-12
    Luca Nanni,Stefano Ceri,Colin Logie

    Topologically associating domains (TADs) are genomic regions of self-interaction. Additionally, it is known that TAD boundaries are enriched in CTCF binding sites. In turn, CTCF sites are known to be asymmetric, whereby the convergent configuration of a pair of CTCF sites leads to the formation of a chromatin loop in vivo. However, to date, it has been unclear how to reconcile TAD structure with CTCF-based

    更新日期:2020-08-12
  • The asynchronous establishment of chromatin 3D architecture between in vitro fertilized and uniparental preimplantation pig embryos.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-10
    Feifei Li,Danyang Wang,Ruigao Song,Chunwei Cao,Zhihua Zhang,Yu Wang,Xiaoli Li,Jiaojiao Huang,Qiang Liu,Naipeng Hou,Bingxiang Xu,Xiao Li,Xiaomeng Gao,Yan Jia,Jianguo Zhao,Yanfang Wang

    Pigs are important animals for agricultural and biomedical research, and improvement is needed for use of the assisted reproductive technologies. Determining underlying mechanisms of epigenetic reprogramming in the early stage of preimplantation embryos derived from in vitro fertilization (IVF), parthenogenesis, and androgenesis will not only contribute to assisted reproductive technologies of pigs

    更新日期:2020-08-11
  • An evolutionary driver of interspersed segmental duplications in primates.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-10
    Stuart Cantsilieris,Susan M Sunkin,Matthew E Johnson,Fabio Anaclerio,John Huddleston,Carl Baker,Max L Dougherty,Jason G Underwood,Arvis Sulovari,PingHsun Hsieh,Yafei Mao,Claudia Rita Catacchio,Maika Malig,AnneMarie E Welch,Melanie Sorensen,Katherine M Munson,Weihong Jiang,Santhosh Girirajan,Mario Ventura,Bruce T Lamb,Ronald A Conlon,Evan E Eichler

    The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the evolution of LCR16a, a putative driver of this phenomenon that encodes one of the most rapidly evolving human–ape gene families, nuclear pore interacting protein

    更新日期:2020-08-11
  • A seventeenth-century Mycobacterium tuberculosis genome supports a Neolithic emergence of the Mycobacterium tuberculosis complex.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-10
    Susanna Sabin,Alexander Herbig,Åshild J Vågene,Torbjörn Ahlström,Gracijela Bozovic,Caroline Arcini,Denise Kühnert,Kirsten I Bos

    Although tuberculosis accounts for the highest mortality from a bacterial infection on a global scale, questions persist regarding its origin. One hypothesis based on modern Mycobacterium tuberculosis complex (MTBC) genomes suggests their most recent common ancestor followed human migrations out of Africa approximately 70,000 years before present. However, studies using ancient genomes as calibration

    更新日期:2020-08-11
  • The chromosome-level wintersweet (Chimonanthus praecox) genome provides insights into floral scent biosynthesis and flowering in winter.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-10
    Junzhong Shang,Jingpu Tian,Huihui Cheng,Qiaomu Yan,Lai Li,Abbas Jamal,Zhongping Xu,Lin Xiang,Christopher A Saski,Shuangxia Jin,Kaige Zhao,Xiuqun Liu,Longqing Chen

    Wintersweet (Chimonanthus praecox), an important ornamental plant, has evolved unique fragrant aroma and winter-flowering properties, which are critical for its successful sexual reproduction. However, the molecular mechanisms underlying these traits are largely unknown in this species. In addition, wintersweet is also a typical representative species of the magnoliids, where the phylogenetic position

    更新日期:2020-08-11
  • ContamLD: estimation of ancient nuclear DNA contamination using breakdown of linkage disequilibrium.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-10
    Nathan Nakatsuka,Éadaoin Harney,Swapan Mallick,Matthew Mah,Nick Patterson,David Reich

    We report a method called ContamLD for estimating autosomal ancient DNA (aDNA) contamination by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the introduction of contaminant DNA. ContamLD leverages the idea that contaminants should have haplotypes uncorrelated to those of the studied individual. Using simulated data, we confirm that ContamLD accurately infers contamination

    更新日期:2020-08-11
  • Integrative analyses of single-cell transcriptome and regulome using MAESTRO.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-07
    Chenfei Wang,Dongqing Sun,Xin Huang,Changxin Wan,Ziyi Li,Ya Han,Qian Qin,Jingyu Fan,Xintao Qiu,Yingtian Xie,Clifford A Meyer,Myles Brown,Ming Tang,Henry Long,Tao Liu,X Shirley Liu

    We present Model-based AnalysEs of Transcriptome and RegulOme (MAESTRO), a comprehensive open-source computational workflow ( http://github.com/liulab-dfci/MAESTRO ) for the integrative analyses of single-cell RNA-seq (scRNA-seq) and ATAC-seq (scATAC-seq) data from multiple platforms. MAESTRO provides functions for pre-processing, alignment, quality control, expression and chromatin accessibility quantification

    更新日期:2020-08-08
  • Demystifying "drop-outs" in single-cell UMI data.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-06
    Tae Hyun Kim,Xiang Zhou,Mengjie Chen

    Many existing pipelines for scRNA-seq data apply pre-processing steps such as normalization or imputation to account for excessive zeros or “drop-outs." Here, we extensively analyze diverse UMI data sets to show that clustering should be the foremost step of the workflow. We observe that most drop-outs disappear once cell-type heterogeneity is resolved, while imputing or normalizing heterogeneous data

    更新日期:2020-08-06
  • The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-06
    Adam Kosti,Patricia Rosa de Araujo,Wei-Qing Li,Gabriela D A Guardia,Jennifer Chiou,Caihong Yi,Debashish Ray,Fabiana Meliso,Yi-Ming Li,Talia Delambre,Mei Qiao,Suzanne S Burns,Franziska K Lorbeer,Fanny Georgi,Markus Flosbach,Sarah Klinnert,Anne Jenseit,Xiufen Lei,Carolina Romero Sandoval,Kevin Ha,Hong Zheng,Renu Pandey,Aleksandra Gruslova,Yogesh K Gupta,Andrew Brenner,Erzsebet Kokovay,Timothy R Hughes

    RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in RBP expression and function are often observed in cancer and influence critical pathways implicated in tumor initiation and growth. Identification and characterization of oncogenic RBPs and their regulatory networks provide new opportunities for targeted therapy. We identify the RNA-binding protein SERBP1 as

    更新日期:2020-08-06
  • Contiguous and stochastic CHH methylation patterns of plant DRM2 and CMT2 revealed by single-read methylome analysis.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-06
    Keith D Harris,Assaf Zemach

    Cytosine methylome data is commonly generated through next-generation sequencing, with analyses averaging methylation states of individual reads. We propose an alternative method of analysing single-read methylome data. Using this method, we identify patterns relating to the mechanism of two plant non-CG-methylating enzymes, CMT2 and DRM2. CMT2-methylated regions show higher stochasticity, while DRM2-methylated

    更新日期:2020-08-06
  • Insulator-based loops mediate the spreading of H3K27me3 over distant micro-domains repressing euchromatin genes.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-03
    Alexandre Heurteau,Charlène Perrois,David Depierre,Olivier Fosseprez,Jonathan Humbert,Stéphane Schaak,Olivier Cuvier

    Chromosomes are subdivided spatially to delimit long-range interactions into topologically associating domains (TADs). TADs are often flanked by chromatin insulators and transcription units that may participate in such demarcation. Remarkably, single-cell Drosophila TAD units correspond to dynamic heterochromatin nano-compartments that can self-assemble. The influence of insulators on such dynamic

    更新日期:2020-08-03
  • Elucidating the role of the gastrointestinal microbiota in racial and ethnic health disparities.
    Genome Biol. (IF 10.806) Pub Date : 2020-08-03
    Doratha A Byrd,Tiffany L Carson,Faustine Williams,Emily Vogtmann

    In the United States (US), racial and ethnic disparities in health outcomes persist despite advancement in biomedical technology, treatments, and public health interventions [1]. Historically, understanding the underlying causes of these disparities has been difficult. Racial and ethnic disparities are not attributable to a single factor, such as genetics, but to multi-factorial and complex factors

    更新日期:2020-08-03