Articles

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

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

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

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…

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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…

Genome editing: from tools to biological insights

Authors: Yixin Yao

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

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

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

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

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

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

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

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

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

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

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

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