Articles

Gene editing of the multi-copy H2A.B gene and its importance for fertility

Altering the biochemical makeup of chromatin by the incorporation of histone variants during development represents a key mechanism in regulating gene expression. The histone variant H2A.B, H2A.B.3 in mice, ap...

Authors: Nur Diana Anuar, Sebastian Kurscheid, Matt Field, Lei Zhang, Edward Rebar, Philip Gregory, Thierry Buchou, Josephine Bowles, Peter Koopman, David J. Tremethick and Tatiana A. Soboleva

Genomic introgression through interspecific hybridization counteracts genetic bottleneck during soybean domestication

Evidence of introgression, the transfer of genetic material, between crops and their wild relatives through spontaneous hybridization and subsequent backcrossing has been documented; however, the evolutionary ...

Authors: Xutong Wang, Liyang Chen and Jianxin Ma

Multiple-gene targeting and mismatch tolerance can confound analysis of genome-wide pooled CRISPR screens

Genome-wide loss-of-function screens using the CRISPR/Cas9 system allow the efficient discovery of cancer cell vulnerabilities. While several studies have focused on correcting for DNA cleavage toxicity biases...

Authors: Jean-Philippe Fortin, Jenille Tan, Karen E. Gascoigne, Peter M. Haverty, William F. Forrest, Michael R. Costa and Scott E. Martin

Guide RNAs with embedded barcodes boost CRISPR-pooled screens

We report a new method using re-designed guide RNAs with internal barcodes (iBARs) embedded in their loop regions. Our iBAR approach outperforms the conventional method by producing screening results with much...

Authors: Shiyou Zhu, Zhongzheng Cao, Zhiheng Liu, Yuan He, Yinan Wang, Pengfei Yuan, Wei Li, Feng Tian, Ying Bao and Wensheng Wei

Degradation of endogenous proteins and generation of a null-like phenotype in zebrafish using Trim-Away technology

Trim-Away is a recent technique to rapidly deplete a protein from any cell type. Guided by antibodies, TRIM21 selects proteins for destruction. However, the applicability of this method in model organisms has ...

Authors: Xiao Chen, Mi Liu, Hongyan Lou, Yiyi Lu, Meng-Tao Zhou, Rongying Ou, Yunsheng Xu and Kai-Fu Tang

Prediction of functional microRNA targets by integrative modeling of microRNA binding and target expression data

We perform a large-scale RNA sequencing study to experimentally identify genes that are downregulated by 25 miRNAs. This RNA-seq dataset is combined with public miRNA target binding data to systematically iden...

Authors: Weijun Liu and Xiaowei Wang

Where is genomics going next?

We polled the Editorial Board of Genome Biology to ask where they see genomics going in the next few years. Here are some of their responses.

Authors: Barbara Cheifet

Population structure of human gut bacteria in a diverse cohort from rural Tanzania and Botswana

Gut microbiota from individuals in rural, non-industrialized societies differ from those in individuals from industrialized societies. Here, we use 16S rRNA sequencing to survey the gut bacteria of seven non-i...

Authors: Matthew E. B. Hansen, Meagan A. Rubel, Aubrey G. Bailey, Alessia Ranciaro, Simon R. Thompson, Michael C. Campbell, William Beggs, Jaanki R. Dave, Gaonyadiwe G. Mokone, Sununguko Wata Mpoloka, Thomas Nyambo, Christian Abnet, Stephen J. Chanock, Frederic D. Bushman and Sarah A. Tishkoff

iGUIDE: an improved pipeline for analyzing CRISPR cleavage specificity

Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites and associated deletions remain nascent. Here, we ...

Authors: Christopher L. Nobles, Shantan Reddy, January Salas-McKee, Xiaojun Liu, Carl H. June, J. Joseph Melenhorst, Megan M. Davis, Yangbing Zhao and Frederic D. Bushman

Correction to: Applications and potential of genome editing in crop improvement

Following publication of the original article [1], the authors reported the following two errors.

Authors: Yi Zhang, Karen Massel, Ian D. Godwin and Caixia Gao

Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5

Cisplatin resistance is a major challenge for advanced head and neck cancer (HNC). Understanding the underlying mechanisms and developing effective strategies against cisplatin resistance are highly desired in...

Authors: Xing Qin, Haiyan Guo, Xiaoning Wang, Xueqin Zhu, Ming Yan, Xu Wang, Qin Xu, Jianbo Shi, Eryi Lu, Wantao Chen and Jianjun Zhang

Correction to: RNA G-quadruplexes at upstream open reading frames cause DHX36- and DHX9-dependent translation of human mRNAs

Following publication of the original article [1], the authors reported the following error in the name of the fourth author.

Authors: Pierre Murat, Giovanni Marsico, Barbara Herdy, Avazeh T. Ghanbarian, Guillem Portella and Shankar Balasubramanian

Evolutionary genomics: the fruits of genomic approaches applied to evolutionary biology

Authors: Timothy R. Sands

Accurate prediction of cell type-specific transcription factor binding

Prediction of cell type-specific, in vivo transcription factor binding sites is one of the central challenges in regulatory genomics. Here, we present our approach that earned a shared first rank in the “ENCOD...

Authors: Jens Keilwagen, Stefan Posch and Jan Grau

An amplicon-based sequencing framework for accurately measuring intrahost virus diversity using PrimalSeq and iVar

How viruses evolve within hosts can dictate infection outcomes; however, reconstructing this process is challenging. We evaluate our multiplexed amplicon approach, PrimalSeq, to demonstrate how virus concentra...

Authors: Nathan D. Grubaugh, Karthik Gangavarapu, Joshua Quick, Nathaniel L. Matteson, Jaqueline Goes De Jesus, Bradley J. Main, Amanda L. Tan, Lauren M. Paul, Doug E. Brackney, Saran Grewal, Nikos Gurfield, Koen K. A. Van Rompay, Sharon Isern, Scott F. Michael, Lark L. Coffey, Nicholas J. Loman…

Systematic evaluation of C. elegans lincRNAs with CRISPR knockout mutants

Long intergenic RNAs (lincRNAs) play critical roles in eukaryotic cells, but systematic analyses of the lincRNAs of an animal for phenotypes are lacking. We generate CRISPR knockout strains for Caenorhabditis ele...

Authors: Shuai Wei, He Chen, Emmanuel Enoch Dzakah, Bin Yu, Xiaolin Wang, Tao Fu, Jingxin Li, Lei Liu, Shucheng Fang, Weihong Liu and Ge Shan

Keen on the tenure track job, are you? Know these things, you should

Success along the tenure track requires more than hard work and long hours. Here, the experiences of a recently tenured professor are distilled into a collection of tips to assist others along the path.

Authors: Benjamin F. Voight

GC-biased gene conversion conceals the prediction of the nearly neutral theory in avian genomes

The nearly neutral theory of molecular evolution predicts that the efficacy of natural selection increases with the effective population size. This prediction has been verified by independent observations in d...

Authors: Paulina Bolívar, Laurent Guéguen, Laurent Duret, Hans Ellegren and Carina F. Mugal

plyranges: a grammar of genomic data transformation

Bioconductor is a widely used R-based platform for genomics, but its host of complex genomic data structures places a cognitive burden on the user. For most tasks, the GRanges object would suffice, but there a...

Authors: Stuart Lee, Dianne Cook and Michael Lawrence

Recombination of ecologically and evolutionarily significant loci maintains genetic cohesion in the Pseudomonas syringae species complex

Pseudomonas syringae is a highly diverse bacterial species complex capable of causing a wide range of serious diseases on numerous agronomically important crops. We examine the evolutionary relationships of 391 a...

Authors: Marcus M. Dillon, Shalabh Thakur, Renan N. D. Almeida, Pauline W. Wang, Bevan S. Weir and David S. Guttman

Circadian oscillations of cytosine modification in humans contribute to epigenetic variability, aging, and complex disease

Maintenance of physiological circadian rhythm plays a crucial role in human health. Numerous studies have shown that disruption of circadian rhythm may increase risk for malignant, psychiatric, metabolic, and ...

Authors: Gabriel Oh, Karolis Koncevičius, Sasha Ebrahimi, Matthew Carlucci, Daniel Erik Groot, Akhil Nair, Aiping Zhang, Algimantas Kriščiūnas, Edward S. Oh, Viviane Labrie, Albert H. C. Wong, Juozas Gordevičius, Peixin Jia, Miki Susic and Art Petronis

The Network of Cancer Genes (NCG): a comprehensive catalogue of known and candidate cancer genes from cancer sequencing screens

The Network of Cancer Genes (NCG) is a manually curated repository of 2372 genes whose somatic modifications have known or predicted cancer driver roles. These genes were collected from 275 publications, inclu...

Authors: Dimitra Repana, Joel Nulsen, Lisa Dressler, Michele Bortolomeazzi, Santhilata Kuppili Venkata, Aikaterini Tourna, Anna Yakovleva, Tommaso Palmieri and Francesca D. Ciccarelli

RNA G-quadruplexes at upstream open reading frames cause DHX36- and DHX9-dependent translation of human mRNAs

RNA secondary structures in the 5′-untranslated regions (5′-UTR) of mRNAs are key to the post-transcriptional regulation of gene expression. While it is evident that non-canonical Hoogsteen-paired G-quadruplex...

Authors: Pierre Murat, Giovanni Marsico, Barbara Herdy, Avazeh Ghanbarian, Guillem Portella and Shankar Balasubramanian

Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses

Cells adapt to stress by altering gene expression at multiple levels. Here, we propose a new mechanism regulating stress-dependent gene expression at the level of translation, with coordinated interplay betwee...

Authors: Cheryl Chan, Phuong Pham, Peter C. Dedon and Thomas J. Begley

SCOPE-Seq: a scalable technology for linking live cell imaging and single-cell RNA sequencing

Optically decodable beads link the identity of a sample to a measurement through an optical barcode, enabling libraries of biomolecules to be captured on beads in solution and decoded by fluorescence. This app...

Authors: Jinzhou Yuan, Jenny Sheng and Peter A. Sims

Illuminating the genome-wide activity of genome editors for safe and effective therapeutics

Genome editing holds remarkable promise to transform human medicine as new therapies that can directly address the genetic causes of disease. However, concerns remain about possible undesired biological conseq...

Authors: Yong Cheng and Shengdar Q. Tsai

Making supplemental information more accessible

Supplemental information is difficult to organize, review, and understand. Genome Biology has listed some new recommendations for the organization of supplemental data.

Authors: Barbara Cheifet

Predicting age from the transcriptome of human dermal fibroblasts

Biomarkers of aging can be used to assess the health of individuals and to study aging and age-related diseases. We generate a large dataset of genome-wide RNA-seq profiles of human dermal fibroblasts from 133...

Authors: Jason G. Fleischer, Roberta Schulte, Hsiao H. Tsai, Swati Tyagi, Arkaitz Ibarra, Maxim N. Shokhirev, Ling Huang, Martin W. Hetzer and Saket Navlakha

Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics

Despite rapid developments in single cell sequencing, sample-specific batch effects, detection of cell multiplets, and experimental costs remain outstanding challenges. Here, we introduce Cell Hashing, where o...

Authors: Marlon Stoeckius, Shiwei Zheng, Brian Houck-Loomis, Stephanie Hao, Bertrand Z. Yeung, William M. Mauck III, Peter Smibert and Rahul Satija

We simply cannot go on being so vague about ‘function’

Function is an onerous concept, as the recent study by Steven Salzberg and colleagues demonstrates. We should be careful and always specific in using the ‘F-word’.

Authors: W. Ford Doolittle

Exploring the genetic basis of human population differences in DNA methylation and their causal impact on immune gene regulation

DNA methylation is influenced by both environmental and genetic factors and is increasingly thought to affect variation in complex traits and diseases. Yet, the extent of ancestry-related differences in DNA me...

Authors: Lucas T. Husquin, Maxime Rotival, Maud Fagny, Hélène Quach, Nora Zidane, Lisa M. McEwen, Julia L. MacIsaac, Michael S. Kobor, Hugues Aschard, Etienne Patin and Lluis Quintana-Murci

FORGe: prioritizing variants for graph genomes

There is growing interest in using genetic variants to augment the reference genome into a graph genome, with alternative sequences, to improve read alignment accuracy and reduce allelic bias. While adding a v...

Authors: Jacob Pritt, Nae-Chyun Chen and Ben Langmead

Analysis of 3D genomic interactions identifies candidate host genes that transposable elements potentially regulate

The organization of chromatin in the nucleus plays an essential role in gene regulation. About half of the mammalian genome comprises transposable elements. Given their repetitive nature, reads associated with...

Authors: Ramya Raviram, Pedro P. Rocha, Vincent M. Luo, Emily Swanzey, Emily R. Miraldi, Edward B. Chuong, Cédric Feschotte, Richard Bonneau and Jane A. Skok

Enhancers in the Peril lincRNA locus regulate distant but not local genes

Recently, it has become clear that some promoters function as long-range regulators of gene expression. However, direct and quantitative assessment of enhancer activity at long intergenic noncoding RNA (lincRN...

Authors: Abigail F. Groff, A. Rasim Barutcu, Jordan P. Lewandowski and John L. Rinn

A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1

Friend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. However, little is kn...

Authors: Naifei Chen, Gang Zhao, Xu Yan, Zheng Lv, Hongmei Yin, Shilin Zhang, Wei Song, Xueli Li, Lingyu Li, Zhonghua Du, Lin Jia, Lei Zhou, Wei Li, Andrew R. Hoffman, Ji-Fan Hu and Jiuwei Cui

Comparison of computational methods for the identification of topologically associating domains

Chromatin folding gives rise to structural elements among which are clusters of densely interacting DNA regions termed topologically associating domains (TADs). TADs have been characterized across multiple spe...

Authors: Marie Zufferey, Daniele Tavernari, Elisa Oricchio and Giovanni Ciriello

Genomic landscape of oxidative DNA damage and repair reveals regioselective protection from mutagenesis

DNA is subject to constant chemical modification and damage, which eventually results in variable mutation rates throughout the genome. Although detailed molecular mechanisms of DNA damage and repair are well ...

Authors: Anna R. Poetsch, Simon J. Boulton and Nicholas M. Luscombe

NmeCas9 is an intrinsically high-fidelity genome-editing platform

The development of CRISPR genome editing has transformed biomedical research. Most applications reported thus far rely upon the Cas9 protein from Streptococcus pyogenes SF370 (SpyCas9). With many RNA guides, wild...

Authors: Nadia Amrani, Xin D. Gao, Pengpeng Liu, Alireza Edraki, Aamir Mir, Raed Ibraheim, Ankit Gupta, Kanae E. Sasaki, Tong Wu, Paul D. Donohoue, Alexander H. Settle, Alexandra M. Lied, Kyle McGovern, Chris K. Fuller, Peter Cameron, Thomas G. Fazzio…

miRTrace reveals the organismal origins of microRNA sequencing data

We present here miRTrace, the first algorithm to trace microRNA sequencing data back to their taxonomic origins. This is a challenge with profound implications for forensics, parasitology, food control, and re...

Authors: Wenjing Kang, Yrin Eldfjell, Bastian Fromm, Xavier Estivill, Inna Biryukova and Marc R. Friedländer

Downregulation of RdDM during strawberry fruit ripening

Recently, DNA methylation was proposed to regulate fleshy fruit ripening. Fleshy fruits can be distinguished by their ripening process as climacteric fruits, such as tomatoes, or non-climacteric fruits, such a...

Authors: Jingfei Cheng, Qingfeng Niu, Bo Zhang, Kunsong Chen, Ruihua Yang, Jian-Kang Zhu, Yijing Zhang and Zhaobo Lang

Understanding tumor ecosystems by single-cell sequencing: promises and limitations

Cellular heterogeneity within and across tumors has been a major obstacle in understanding and treating cancer, and the complex heterogeneity is masked if bulk tumor tissues are used for analysis. The advent o...

Authors: Xianwen Ren, Boxi Kang and Zemin Zhang

Applications and potential of genome editing in crop improvement

Genome-editing tools provide advanced biotechnological techniques that enable the precise and efficient targeted modification of an organism’s genome. Genome-editing systems have been utilized in a wide variet...

Authors: Yi Zhang, Karen Massel, Ian D. Godwin and Caixia Gao

A new look at an old question: when did the second whole genome duplication occur in vertebrate evolution?

A recent study used 61 extant animal genomes to reconstruct the chromosomes of the hypothetical amniote ancestor. Comparison of this karyotype to the 17 chordate linkage groups previously inferred in the ances...

Authors: Linda Z. Holland and Daniel Ocampo Daza

CHESS: a new human gene catalog curated from thousands of large-scale RNA sequencing experiments reveals extensive transcriptional noise

We assembled the sequences from deep RNA sequencing experiments by the Genotype-Tissue Expression (GTEx) project, to create a new catalog of human genes and transcripts, called CHESS. The new database contains...

Authors: Mihaela Pertea, Alaina Shumate, Geo Pertea, Ales Varabyou, Florian P. Breitwieser, Yu-Chi Chang, Anil K. Madugundu, Akhilesh Pandey and Steven L. Salzberg

Linking single-cell measurements of mass, growth rate, and gene expression

Mass and growth rate are highly integrative measures of cell physiology not discernable via genomic measurements. Here, we introduce a microfluidic platform enabling direct measurement of single-cell mass and ...

Authors: Robert J. Kimmerling, Sanjay M. Prakadan, Alejandro J. Gupta, Nicholas L. Calistri, Mark M. Stevens, Selim Olcum, Nathan Cermak, Riley S. Drake, Kristine Pelton, Frederik De Smet, Keith L. Ligon, Alex K. Shalek and Scott R. Manalis

Transparent peer review trial: the results

We describe the results of our year-long trial of transparent peer review and announce the adoption of transparent review as permanent policy.

Authors: Andrew Cosgrove and Barbara Cheifet

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

Livestock 2.0 – genome editing for fitter, healthier, and more productive farmed animals

The human population is growing, and as a result we need to produce more food whilst reducing the impact of farming on the environment. Selective breeding and genomic selection have had a transformational impa...

Authors: Christine Tait-Burkard, Andrea Doeschl-Wilson, Mike J. McGrew, Alan L. Archibald, Helen M. Sang, Ross D. Houston, C. Bruce Whitelaw and Mick Watson

GRIPT: a novel case-control analysis method for Mendelian disease gene discovery

Despite rapid progress of next-generation sequencing (NGS) technologies, the disease-causing genes underpinning about half of all Mendelian diseases remain elusive. One main challenge is the high genetic heter...

Authors: Jun Wang, Li Zhao, Xia Wang, Yong Chen, Mingchu Xu, Zachry T. Soens, Zhongqi Ge, Peter Ronghan Wang, Fei Wang and Rui Chen

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