Articles

Pooled extracellular receptor-ligand interaction screening using CRISPR activation

Extracellular interactions between cell surface receptors are necessary for signaling and adhesion but identifying them remains technically challenging. We describe a cell-based genome-wide approach employing ...

Authors: Zheng-Shan Chong, Shuhei Ohnishi, Kosuke Yusa and Gavin J. Wright

CODEX2: full-spectrum copy number variation detection by high-throughput DNA sequencing

High-throughput DNA sequencing enables detection of copy number variations (CNVs) on the genome-wide scale with finer resolution compared to array-based methods but suffers from biases and artifacts that lead ...

Authors: Yuchao Jiang, Rujin Wang, Eugene Urrutia, Ioannis N. Anastopoulos, Katherine L. Nathanson and Nancy R. Zhang

The bird’s-eye view on chromosome evolution

The study of the evolution of chromosomal number and structure has long been of interest to evolutionary biologists. However, this research has been hindered by the lack of chromosome-level genome assemblies f...

Authors: Guojie Zhang

N⁶-methyldeoxyadenosine directs nucleosome positioning in Tetrahymena DNA

N⁶-methyldeoxyadenosine (6mA or m⁶dA) was shown more than 40 years ago in simple eukaryotes. Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional char...

Authors: Guan-Zheng Luo, Ziyang Hao, Liangzhi Luo, Mingren Shen, Daniela Sparvoli, Yuqing Zheng, Zijie Zhang, Xiaocheng Weng, Kai Chen, Qiang Cui, Aaron P. Turkewitz and Chuan He

Ten things you should know about transposable elements

Transposable elements (TEs) are major components of eukaryotic genomes. However, the extent of their impact on genome evolution, function, and disease remain a matter of intense interrogation. The rise of geno...

Authors: Guillaume Bourque, Kathleen H. Burns, Mary Gehring, Vera Gorbunova, Andrei Seluanov, Molly Hammell, Michaël Imbeault, Zsuzsanna Izsvák, Henry L. Levin, Todd S. Macfarlan, Dixie L. Mager and Cédric Feschotte

KrakenUniq: confident and fast metagenomics classification using unique k-mer counts

False-positive identifications are a significant problem in metagenomics classification. We present KrakenUniq, a novel metagenomics classifier that combines the fast k-mer-based classification of Kraken with an ...

Authors: F. P. Breitwieser, D. N. Baker and S. L. Salzberg

Conferring DNA virus resistance with high specificity in plants using virus-inducible genome-editing system

The CRISPR/Cas9 system has recently been engineered to confer resistance to geminiviruses in plants. However, we show here that the usefulness of this antiviral strategy is undermined by off-target effects ide...

Authors: Xiang Ji, Xiaomin Si, Yi Zhang, Huawei Zhang, Feng Zhang and Caixia Gao

Genomes reveal marked differences in the adaptive evolution between orangutan species

Integrating demography and adaptive evolution is pivotal to understanding the evolutionary history and conservation of great apes. However, little is known about the adaptive evolution of our closest relatives...

Authors: Maja P. Mattle-Greminger, Tugce Bilgin Sonay, Alexander Nater, Marc Pybus, Tariq Desai, Guillem de Valles, Ferran Casals, Aylwyn Scally, Jaume Bertranpetit, Tomas Marques-Bonet, Carel P. van Schaik, Maria Anisimova and Michael Krützen

Genetic disease risks can be misestimated across global populations

Accurate assessment of health disparities requires unbiased knowledge of genetic risks in different populations. Unfortunately, most genome-wide association studies use genotyping arrays and European samples. ...

Authors: Michelle S. Kim, Kane P. Patel, Andrew K. Teng, Ali J. Berens and Joseph Lachance

VIPER: variability-preserving imputation for accurate gene expression recovery in single-cell RNA sequencing studies

We develop a method, VIPER, to impute the zero values in single-cell RNA sequencing studies to facilitate accurate transcriptome quantification at the single-cell level. VIPER is based on nonnegative sparse re...

Authors: Mengjie Chen and Xiang Zhou

LncRNAs in polyploid cotton interspecific hybrids are derived from transposon neofunctionalization

Interspecific hybridization and whole genome duplication are driving forces of genomic and organism diversification. But the effect of interspecific hybridization and whole genome duplication on the non-coding...

Authors: Ting Zhao, Xiaoyuan Tao, Shouli Feng, Luyao Wang, Hui Hong, Wei Ma, Guandong Shang, Shisong Guo, Yuxin He, Baoliang Zhou and Xueying Guan

Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders

Genetic influences on gene expression in the human fetal brain plausibly impact upon a variety of postnatal brain-related traits, including susceptibility to neuropsychiatric disorders. However, to date, there...

Authors: Heath E. O’Brien, Eilis Hannon, Matthew J. Hill, Carolina C. Toste, Matthew J. Robertson, Joanne E. Morgan, Gemma McLaughlin, Cathryn M. Lewis, Leonard C. Schalkwyk, Lynsey S. Hall, Antonio F. Pardiñas, Michael J. Owen, Michael C. O’Donovan, Jonathan Mill and Nicholas J. Bray

Live imaging and tracking of genome regions in CRISPR/dCas9 knock-in mice

CRISPR/dCas9 is a versatile tool that can be used to recruit various effectors and fluorescent molecules to defined genome regions where it can modulate genetic and epigenetic markers, or track the chromatin d...

Authors: Jinzhi Duan, Guangqing Lu, Yu Hong, Qingtao Hu, Xueying Mai, Jing Guo, Xiaofang Si, Fengchao Wang and Yu Zhang

Simulation-based benchmarking of isoform quantification in single-cell RNA-seq

Single-cell RNA-seq has the potential to facilitate isoform quantification as the confounding factor of a mixed population of cells is eliminated. However, best practice for using existing quantification metho...

Authors: Jennifer Westoby, Marcela Sjöberg Herrera, Anne C. Ferguson-Smith and Martin Hemberg

Recurrent mutations at estrogen receptor binding sites alter chromatin topology and distal gene expression in breast cancer

The mutational processes underlying non-coding cancer mutations and their biological significance in tumor evolution are poorly understood. To get better insights into the biological mechanisms of mutational p...

Authors: Jiekun Yang, Xiaolong Wei, Turan Tufan, Cem Kuscu, Hayrunnisa Unlu, Saadia Farooq, Elif Demirtas, Bryce M. Paschal and Mazhar Adli

LaminA/C regulates epigenetic and chromatin architecture changes upon aging of hematopoietic stem cells

The decline of hematopoietic stem cell (HSC) function upon aging contributes to aging-associated immune remodeling and leukemia pathogenesis. Aged HSCs show changes to their epigenome, such as alterations in D...

Authors: Ani Grigoryan, Novella Guidi, Katharina Senger, Thomas Liehr, Karin Soller, Gina Marka, Angelika Vollmer, Yolanda Markaki, Heinrich Leonhardt, Christian Buske, Daniel B. Lipka, Christoph Plass, Yi Zheng, Medhanie A. Mulaw, Hartmut Geiger and Maria Carolina Florian

Combining accurate tumor genome simulation with crowdsourcing to benchmark somatic structural variant detection

The phenotypes of cancer cells are driven in part by somatic structural variants. Structural variants can initiate tumors, enhance their aggressiveness, and provide unique therapeutic opportunities. Whole-geno...

Authors: Anna Y. Lee, Adam D. Ewing, Kyle Ellrott, Yin Hu, Kathleen E. Houlahan, J. Christopher Bare, Shadrielle Melijah G. Espiritu, Vincent Huang, Kristen Dang, Zechen Chong, Cristian Caloian, Takafumi N. Yamaguchi, Michael R. Kellen, Ken Chen, Thea C. Norman, Stephen H. Friend…

DNA methylation and de-methylation using hybrid site-targeting proteins

DNA methylation plays important roles in determining cellular identity, disease, and environmental responses, but little is known about the mechanisms that drive methylation changes during cellular differentia...

Authors: Yong Lei, Yung-Hsin Huang and Margaret A. Goodell

Genome editing: from tools to biological insights

Authors: Yixin Yao

CRISPR/Cas9 offers a new tool for studying the role of chromatin architecture in disease pathogenesis

A recent study used CRISPR/Cas9 to reveal long-range looping between disease-related genes and their regulatory elements that is mediated by the CCCTC-binding factor (CTCF) in prostate cancer.

Authors: Xiang Guo and Ann Dean

Understanding and repurposing CRISPR-mediated alternative splicing

Two new studies refine our understanding of CRISPR-associated exon skipping and redefine its utility in engineering alternative splicing.

Authors: Jordan L. Smith, Haiwei Mou and Wen Xue

Comparative genomics reveals the distinct evolutionary trajectories of the robust and complex coral lineages

Despite the biological and economic significance of scleractinian reef-building corals, the lack of large molecular datasets for a representative range of species limits understanding of many aspects of their ...

Authors: Hua Ying, Ira Cooke, Susanne Sprungala, Weiwen Wang, David C. Hayward, Yurong Tang, Gavin Huttley, Eldon E. Ball, Sylvain Forêt and David J. Miller

omniCLIP: probabilistic identification of protein-RNA interactions from CLIP-seq data

CLIP-seq methods allow the generation of genome-wide maps of RNA binding protein – RNA interaction sites. However, due to differences between different CLIP-seq assays, existing computational approaches to ana...

Authors: Philipp Drewe-Boss, Hans-Hermann Wessels and Uwe Ohler

Visualizing the dynamics of histone variants in the S-phase nucleus

Histone variants constitute a fundamental feature of the epigenome. However, their dynamics during normal and challenged DNA replication and their distribution in the three-dimensional space of the nucleus rem...

Authors: Stella Maxouri, Stavros Taraviras and Zoi Lygerou

Phytophthora methylomes are modulated by 6mA methyltransferases and associated with adaptive genome regions

Filamentous plant pathogen genomes often display a bipartite architecture with gene-sparse, repeat-rich compartments serving as a cradle for adaptive evolution. The extent to which this two-speed genome archit...

Authors: Han Chen, Haidong Shu, Liyuan Wang, Fan Zhang, Xi Li, Sylvans Ochieng Ochola, Fei Mao, Hongyu Ma, Wenwu Ye, Tingting Gu, Lubin Jiang, Yufeng Wu, Yuanchao Wang, Sophien Kamoun and Suomeng Dong

RefSeq database growth influences the accuracy of k-mer-based lowest common ancestor species identification

In order to determine the role of the database in taxonomic sequence classification, we examine the influence of the database over time on k-mer-based lowest common ancestor taxonomic classification. We present t...

Authors: Daniel J. Nasko, Sergey Koren, Adam M. Phillippy and Todd J. Treangen

Parents in science

As part of our Q&A series, Genome Biology spoke to four scientists about their personal experiences as parents in their careers to highlight the challenges of researchers having children and the support they need...

Authors: Emily Perry, Kristin Tessmar-Raible and Florian Raible

Bottlenecks for genome-edited crops on the road from lab to farm

Gene discovery and government regulation are bottlenecks for the widespread adoption of genome-edited crops. We propose a culture of sharing and integrating crop data to accelerate the discovery and prioritiza...

Authors: Armin Scheben and David Edwards

CRISPR-Cas9 off-targeting assessment with nucleic acid duplex energy parameters

Recent experimental efforts of CRISPR-Cas9 systems have shown that off-target binding and cleavage are a concern for the system and that this is highly dependent on the selected guide RNA (gRNA) design. Comput...

Authors: Ferhat Alkan, Anne Wenzel, Christian Anthon, Jakob Hull Havgaard and Jan Gorodkin

Alternative polyadenylation factors link cell cycle to migration

In response to a wound, fibroblasts are activated to migrate toward the wound, to proliferate and to contribute to the wound healing process. We hypothesize that changes in pre-mRNA processing occurring as fib...

Authors: Mithun Mitra, Elizabeth L Johnson, Vinay S Swamy, Lois E Nersesian, David C Corney, David G Robinson, Daniel G Taylor, Aaron M Ambrus, David Jelinek, Wei Wang, Sandra L Batista and Hilary A Coller

Canonical and single-cell Hi-C reveal distinct chromatin interaction sub-networks of mammalian transcription factors

Transcription factor (TF) binding to regulatory DNA sites is a key determinant of cell identity within multi-cellular organisms and has been studied extensively in relation to site affinity and chromatin modif...

Authors: Xiaoyan Ma, Daphne Ezer, Boris Adryan and Tim J. Stevens

PINES: phenotype-informed tissue weighting improves prediction of pathogenic noncoding variants

Functional characterization of the noncoding genome is essential for biological understanding of gene regulation and disease. Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding ...

Authors: Corneliu A. Bodea, Adele A. Mitchell, Alex Bloemendal, Aaron G. Day-Williams, Heiko Runz and Shamil R. Sunyaev

Clust: automatic extraction of optimal co-expressed gene clusters from gene expression data

Identifying co-expressed gene clusters can provide evidence for genetic or physical interactions. Thus, co-expression clustering is a routine step in large-scale analyses of gene expression data. We show that ...

Authors: Basel Abu-Jamous and Steven Kelly

Chromosome-level assembly reveals extensive rearrangement in saker falcon and budgerigar, but not ostrich, genomes

The number of de novo genome sequence assemblies is increasing exponentially; however, relatively few contain one scaffold/contig per chromosome. Such assemblies are essential for studies of genotype-to-phenot...

Authors: Rebecca E O’Connor, Marta Farré, Sunitha Joseph, Joana Damas, Lucas Kiazim, Rebecca Jennings, Sophie Bennett, Eden A Slack, Emily Allanson, Denis M Larkin and Darren K Griffin

SCoPE-MS: mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation

Some exciting biological questions require quantifying thousands of proteins in single cells. To achieve this goal, we develop Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS) and validate its ability to...

Authors: Bogdan Budnik, Ezra Levy, Guillaume Harmange and Nikolai Slavov

Harnessing accurate non-homologous end joining for efficient precise deletion in CRISPR/Cas9-mediated genome editing

Many applications of CRISPR/Cas9-mediated genome editing require Cas9-induced non-homologous end joining (NHEJ), which was thought to be error prone. However, with directly ligatable ends, Cas9-induced DNA dou...

Authors: Tao Guo, Yi-Li Feng, Jing-Jing Xiao, Qian Liu, Xiu-Na Sun, Ji-Feng Xiang, Na Kong, Si-Cheng Liu, Guo-Qiao Chen, Yue Wang, Meng-Meng Dong, Zhen Cai, Hui Lin, Xiu-Jun Cai and An-Yong Xie

CRISPRO: identification of functional protein coding sequences based on genome editing dense mutagenesis

CRISPR/Cas9 pooled screening permits parallel evaluation of comprehensive guide RNA libraries to systematically perturb protein coding sequences in situ and correlate with functional readouts. For the analysis...

Authors: Vivien A. C. Schoonenberg, Mitchel A. Cole, Qiuming Yao, Claudio Macias-Treviño, Falak Sher, Patrick G. Schupp, Matthew C. Canver, Takahiro Maeda, Luca Pinello and Daniel E. Bauer

Discovering in vivo cytokine-eQTL interactions from a lupus clinical trial

Cytokines are critical to human disease and are attractive therapeutic targets given their widespread influence on gene regulation and transcription. Defining the downstream regulatory mechanisms influenced by...

Authors: Emma E. Davenport, Tiffany Amariuta, Maria Gutierrez-Arcelus, Kamil Slowikowski, Harm-Jan Westra, Yang Luo, Ciyue Shen, Deepak A. Rao, Ying Zhang, Stephen Pearson, David von Schack, Jean S. Beebe, Nan Bing, Sally John, Michael S. Vincent, Baohong Zhang…

SeqOthello: querying RNA-seq experiments at scale

We present SeqOthello, an ultra-fast and memory-efficient indexing structure to support arbitrary sequence query against large collections of RNA-seq experiments. It takes SeqOthello only 5 min and 19.1 GB mem...

Authors: Ye Yu, Jinpeng Liu, Xinan Liu, Yi Zhang, Eamonn Magner, Erik Lehnert, Chen Qian and Jinze Liu

Chromosome evolution at the origin of the ancestral vertebrate genome

It has been proposed that more than 450 million years ago, two successive whole genome duplications took place in a marine chordate lineage before leading to the common ancestor of vertebrates. A precise recon...

Authors: Christine Sacerdot, Alexandra Louis, Céline Bon, Camille Berthelot and Hugues Roest Crollius

CRISPR-induced exon skipping is dependent on premature termination codon mutations

In previous studies, CRISPR/Cas9 was shown to induce unexpected exon skipping; however, the mechanism by which this phenomenon is triggered is controversial. By analyzing 22 gene-edited rabbit lines generated ...

Authors: Tingting Sui, Yuning Song, Zhiquan Liu, Mao Chen, Jichao Deng, Yuanyuan Xu, Liangxue Lai and Zhanjun Li

Holo-Seq: single-cell sequencing of holo-transcriptome

Current single-cell RNA-seq approaches are hindered by preamplification bias, loss of strand of origin information, and the inability to observe small-RNA and mRNA dual transcriptomes. Here, we introduce a sin...

Authors: Zhengyun Xiao, Guo Cheng, Yang Jiao, Chen Pan, Ran Li, Danmei Jia, Jing Zhu, Chao Wu, Min Zheng and Junling Jia

A comparative study of endoderm differentiation in humans and chimpanzees

There is substantial interest in the evolutionary forces that shaped the regulatory framework in early human development. Progress in this area has been slow because it is difficult to obtain relevant biologic...

Authors: Lauren E. Blake, Samantha M. Thomas, John D. Blischak, Chiaowen Joyce Hsiao, Claudia Chavarria, Marsha Myrthil, Yoav Gilad and Bryan J. Pavlovic

CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops

Recent genome-wide association studies (GWAS) have identified more than 100 loci associated with increased risk of prostate cancer, most of which are in non-coding regions of the genome. Understanding the func...

Authors: Yu Guo, Andrew A. Perez, Dennis J. Hazelett, Gerhard A. Coetzee, Suhn Kyong Rhie and Peggy J. Farnham

CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens

Pooled CRISPR screens allow researchers to interrogate genetic causes of complex phenotypes at the genome-wide scale and promise higher specificity and sensitivity compared to competing technologies. Unfortuna...

Authors: Timothy P. Daley, Zhixiang Lin, Xueqiu Lin, Yanxia Liu, Wing Hung Wong and Lei S. Qi

PHLI-seq: constructing and visualizing cancer genomic maps in 3D by phenotype-based high-throughput laser-aided isolation and sequencing

Spatial mapping of genomic data to tissue context in a high-throughput and high-resolution manner has been challenging due to technical limitations. Here, we describe PHLI-seq, a novel approach that enables hi...

Authors: Sungsik Kim, Amos Chungwon Lee, Han-Byoel Lee, Jinhyun Kim, Yushin Jung, Han Suk Ryu, Yongju Lee, Sangwook Bae, Minju Lee, Kyungmin Lee, Ryong Nam Kim, Woong-Yang Park, Wonshik Han and Sunghoon Kwon

Modularity of genes involved in local adaptation to climate despite physical linkage

Linkage among genes experiencing different selection pressures can make natural selection less efficient. Theory predicts that when local adaptation is driven by complex and non-covarying stresses, increased l...

Authors: Katie E Lotterhos, Sam Yeaman, Jon Degner, Sally Aitken and Kathryn A Hodgins

Evolutionary and developmental dynamics of sex-biased gene expression in common frogs with proto-Y chromosomes

The patterns of gene expression on highly differentiated sex chromosomes differ drastically from those on autosomes, due to sex-specific patterns of selection and inheritance. As a result, X chromosomes are of...

Authors: Wen-Juan Ma, Paris Veltsos, Roberto Sermier, Darren J Parker and Nicolas Perrin

Reconstruction of avian ancestral karyotypes reveals differences in the evolutionary history of macro- and microchromosomes

Reconstruction of ancestral karyotypes is critical for our understanding of genome evolution, allowing for the identification of the gross changes that shaped extant genomes. The identification of such changes...

Authors: Joana Damas, Jaebum Kim, Marta Farré, Darren K Griffin and Denis M Larkin

Predicting microRNA targeting efficacy in Drosophila

MicroRNAs (miRNAs) are short regulatory RNAs that derive from hairpin precursors. Important for understanding the functional roles of miRNAs is the ability to predict the messenger RNA (mRNA) targets most resp...

Authors: Vikram Agarwal, Alexander O. Subtelny, Prathapan Thiru, Igor Ulitsky and David P. Bartel