Articles

Comprehensive evaluation of structural variation detection algorithms for whole genome sequencing

Structural variations (SVs) or copy number variations (CNVs) greatly impact the functions of the genes encoded in the genome and are responsible for diverse human diseases. Although a number of existing SV det...

Authors: Shunichi Kosugi, Yukihide Momozawa, Xiaoxi Liu, Chikashi Terao, Michiaki Kubo and Yoichiro Kamatani

Chromatin accessibility plays a key role in selective targeting of Hox proteins

Hox transcription factors specify segmental diversity along the anterior-posterior body axis in metazoans. While the different Hox family members show clear functional specificity in vivo, they all show simila...

Authors: Damiano Porcelli, Bettina Fischer, Steven Russell and Robert White

Multiplexed promoterless gene expression with CRISPReader

Genes are comprised of DNA codes and contain promoters and other control elements for reading these codes. The rapid development of clustered regularly interspaced short palindromic repeats (CRISPR) technology...

Authors: Hengji Zhan, Qun Zhou, Qunjun Gao, Jianfa Li, Weiren Huang and Yuchen Liu

A genomic atlas of systemic interindividual epigenetic variation in humans

DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindiv...

Authors: Chathura J. Gunasekara, C. Anthony Scott, Eleonora Laritsky, Maria S. Baker, Harry MacKay, Jack D. Duryea, Noah J. Kessler, Garrett Hellenthal, Alexis C. Wood, Kelly R. Hodges, Manisha Gandhi, Amy B. Hair, Matt J. Silver, Sophie E. Moore, Andrew M. Prentice, Yumei Li…

Genome-wide analysis of DNA replication timing in single cells: Yes! We’re all individuals

Recent studies have accomplished the extraordinary feat of measuring the exact status of DNA replication in individual cells. We outline how these studies have revealed surprising uniformity in how cells repli...

Authors: Anne D. Donaldson and Conrad A. Nieduszynski

At the forefront of the sequencing revolution—notes from the RNGS19 conference

Herein we present a meeting report on the third edition of the ‘Revolutionizing Next-Generation Sequencing’ conference, organized by the Flemish life-science research institute VIB and held at Antwerp, Belgium...

Authors: Sander Wuyts and Nicola Segata

Genomics and data science: an application within an umbrella

Data science allows the extraction of practical insights from large-scale data. Here, we contextualize it as an umbrella term, encompassing several disparate subdomains. We focus on how genomics fits as a spec...

Authors: Fábio C. P. Navarro, Hussein Mohsen, Chengfei Yan, Shantao Li, Mengting Gu, William Meyerson and Mark Gerstein

Mouse microbiomes: overlooked culprits of experimental variability

Recent studies have found differences between almost genetically identical mice that were attributable to differences between their microbiomes. One example of mice from different vendors having different susc...

Authors: Maria-Luisa Alegre

OSCA: a tool for omic-data-based complex trait analysis

The rapid increase of omic data has greatly facilitated the investigation of associations between omic profiles such as DNA methylation (DNAm) and complex traits in large cohorts. Here, we propose a mixed-line...

Authors: Futao Zhang, Wenhan Chen, Zhihong Zhu, Qian Zhang, Marta F. Nabais, Ting Qi, Ian J. Deary, Naomi R. Wray, Peter M. Visscher, Allan F. McRae and Jian Yang

WhoGEM: an admixture-based prediction machine accurately predicts quantitative functional traits in plants

The explosive growth of genomic data provides an opportunity to make increased use of sequence variations for phenotype prediction. We have developed a prediction machine for quantitative phenotypes (WhoGEM) t...

Authors: Laurent Gentzbittel, Cécile Ben, Mélanie Mazurier, Min-Gyoung Shin, Todd Lorenz, Martina Rickauer, Paul Marjoram, Sergey V. Nuzhdin and Tatiana V. Tatarinova

One reference genome is not enough

A recent study on human structural variation indicates insufficiencies and errors in the human reference genome, GRCh38, and argues for the construction of a human pan-genome.

Authors: Xiaofei Yang, Wan-Ping Lee, Kai Ye and Charles Lee

The inherited variations of a p53-responsive enhancer in 13q12.12 confer lung cancer risk by attenuating TNFRSF19 expression

Inherited factors contribute to lung cancer risk, but the mechanism is not well understood. Defining the biological consequence of GWAS hits in cancers is a promising strategy to elucidate the inherited mechan...

Authors: Lipei Shao, Xianglin Zuo, Yin Yang, Yu Zhang, Nan Yang, Bin Shen, Jianying Wang, Xuchun Wang, Ruilei Li, Guangfu Jin, Dawei Yu, Yuan Chen, Luan Sun, Zhen Li, Qiaofen Fu, Zhibin Hu…

ChiCMaxima: a robust and simple pipeline for detection and visualization of chromatin looping in Capture Hi-C

Capture Hi-C (CHi-C) is a new technique for assessing genome organization based on chromosome conformation capture coupled to oligonucleotide capture of regions of interest, such as gene promoters. Chromatin l...

Authors: Yousra Ben Zouari, Anne M. Molitor, Natalia Sikorska, Vera Pancaldi and Tom Sexton

Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors

Base editing installs a precise nucleotide change in specific gene loci without causing a double-strand break. Its efficiency in human embryos is generally low, limiting its utility in functional genetic studi...

Authors: Meiling Zhang, Changyang Zhou, Yu Wei, Chunlong Xu, Hong Pan, Wenqin Ying, Yidi Sun, Yun Sun, Qingquan Xiao, Ning Yao, Wanxia Zhong, Yun Li, Keliang Wu, Gao Yuan, Shoukhrat Mitalipov, Zi-jiang Chen…

Arabidopsis S2Lb links AtCOMPASS-like and SDG2 activity in H3K4me3 independently from histone H2B monoubiquitination

The functional determinants of H3K4me3, their potential dependency on histone H2B monoubiquitination, and their contribution to defining transcriptional regimes are poorly defined in plant systems. Unlike in Sacc...

Authors: Anne-Sophie Fiorucci, Clara Bourbousse, Lorenzo Concia, Martin Rougée, Anne-Flore Deton-Cabanillas, Gérald Zabulon, Elodie Layat, David Latrasse, Soon Kap Kim, Nicole Chaumont, Bérangère Lombard, David Stroebel, Sophie Lemoine, Ammara Mohammad, Corinne Blugeon, Damarys Loew…

Detection of circular RNA expression and related quantitative trait loci in the human dorsolateral prefrontal cortex

Circular RNAs (circRNAs) are implicated in various biological processes. As a layer of the gene regulatory network, circRNA expression is also an intermediate phenotype bridging genetic variation and phenotypi...

Authors: Zelin Liu, Yuan Ran, Changyu Tao, Sichen Li, Jian Chen and Ence Yang

Systematic analysis of dark and camouflaged genes reveals disease-relevant genes hiding in plain sight

The human genome contains “dark” gene regions that cannot be adequately assembled or aligned using standard short-read sequencing technologies, preventing researchers from identifying mutations within these ge...

Authors: Mark T. W. Ebbert, Tanner D. Jensen, Karen Jansen-West, Jonathon P. Sens, Joseph S. Reddy, Perry G. Ridge, John S. K. Kauwe, Veronique Belzil, Luc Pregent, Minerva M. Carrasquillo, Dirk Keene, Eric Larson, Paul Crane, Yan W. Asmann, Nilufer Ertekin-Taner, Steven G. Younkin…

Genomic signatures accompanying the dietary shift to phytophagy in polyphagan beetles

The diversity and evolutionary success of beetles (Coleoptera) are proposed to be related to the diversity of plants on which they feed. Indeed, the largest beetle suborder, Polyphaga, mostly includes plant ea...

Authors: Mathieu Seppey, Panagiotis Ioannidis, Brent C. Emerson, Camille Pitteloud, Marc Robinson-Rechavi, Julien Roux, Hermes E. Escalona, Duane D. McKenna, Bernhard Misof, Seunggwan Shin, Xin Zhou, Robert M. Waterhouse and Nadir Alvarez

Isolation of novel gut bifidobacteria using a combination of metagenomic and cultivation approaches

Whole metagenome shotgun (WMGS) sequencing is a method that provides insights into the genomic composition and arrangement of complex microbial consortia. Here, we report how WMGS coupled with a cultivation ap...

Authors: Gabriele Andrea Lugli, Christian Milani, Sabrina Duranti, Giulia Alessandri, Francesca Turroni, Leonardo Mancabelli, Danilo Tatoni, Maria Cristina Ossiprandi, Douwe van Sinderen and Marco Ventura

Comments on the model parameters in “SiFit: inferring tumor trees from single-cell sequencing data under finite-sites models”

Authors: Hamim Zafar, Anthony Tzen, Nicholas Navin, Ken Chen and Luay Nakhleh

Addressing confounding artifacts in reconstruction of gene co-expression networks

Gene co-expression networks capture biological relationships between genes and are important tools in predicting gene function and understanding disease mechanisms. We show that technical and biological artifa...

Authors: Princy Parsana, Claire Ruberman, Andrew E. Jaffe, Michael C. Schatz, Alexis Battle and Jeffrey T. Leek

Next-generation genome annotation: we still struggle to get it right

While the genome sequencing revolution has led to the sequencing and assembly of many thousands of new genomes, genome annotation still uses very nearly the same technology that we have used for the past two d...

Authors: Steven L. Salzberg

VULCAN integrates ChIP-seq with patient-derived co-expression networks to identify GRHL2 as a key co-regulator of ERa at enhancers in breast cancer

VirtUaL ChIP-seq Analysis through Networks (VULCAN) infers regulatory interactions of transcription factors by overlaying networks generated from publicly available tumor expression data onto ChIP-seq data. We...

Authors: Andrew N. Holding, Federico M. Giorgi, Amanda Donnelly, Amy E. Cullen, Sankari Nagarajan, Luke A. Selth and Florian Markowetz

CellTag Indexing: genetic barcode-based sample multiplexing for single-cell genomics

High-throughput single-cell assays increasingly require special consideration in experimental design, sample multiplexing, batch effect removal, and data interpretation. Here, we describe a lentiviral barcode-...

Authors: Chuner Guo, Wenjun Kong, Kenji Kamimoto, Guillermo C. Rivera-Gonzalez, Xue Yang, Yuhei Kirita and Samantha A. Morris

Correction to: Functional variation in allelic methylomes underscores a strong genetic contribution and reveals novel epigenetic alterations in the human epigenome

Following publication of the original article [1], the authors reported an error in Additional file 1.

Authors: Warren A. Cheung, Xiaojian Shao, Andréanne Morin, Valérie Siroux, Tony Kwan, Bing Ge, Dylan Aïssi, Lu Chen, Louella Vasquez, Fiona Allum, Frédéric Guénard, Emmanuelle Bouzigon, Marie-Michelle Simon, Elodie Boulier, Adriana Redensek, Stephen Watt…

SCRABBLE: single-cell RNA-seq imputation constrained by bulk RNA-seq data

Single-cell RNA-seq data contain a large proportion of zeros for expressed genes. Such dropout events present a fundamental challenge for various types of data analyses. Here, we describe the SCRABBLE algorith...

Authors: Tao Peng, Qin Zhu, Penghang Yin and Kai Tan

Plant lamin-like proteins mediate chromatin tethering at the nuclear periphery

The nuclear envelope not only serves as a physical barrier separating nuclear content from the cytoplasm but also plays critical roles in modulating the three-dimensional organization of genomic DNA. For both ...

Authors: Bo Hu, Nan Wang, Xiuli Bi, Ezgi Süheyla Karaaslan, Anna-Lena Weber, Wangsheng Zhu, Kenneth Wayne Berendzen and Chang Liu

The tech for the next decade: promises and challenges in genome biology

The 19th Annual Advances in Genome Biology and Technology (AGBT) meeting came back to Marco Island, Florida, and was held in the renovated venue from 27 February to 2 March 2019. The meeting showed a variety o...

Authors: Iman Hajirasouliha and Hagen U. Tilgner

CRISPR enables directed evolution in plants

A proof-of-concept study has demonstrated the application of CRISPR-Cas9 for directed evolution in rice, engineering crops for desired traits.

Authors: Yingxiao Zhang and Yiping Qi

CRISPR directed evolution of the spliceosome for resistance to splicing inhibitors

Increasing genetic diversity via directed evolution holds great promise to accelerate trait development and crop improvement. We developed a CRISPR/Cas-based directed evolution platform in plants to evolve the...

Authors: Haroon Butt, Ayman Eid, Afaque A. Momin, Jeremie Bazin, Martin Crespi, Stefan T. Arold and Magdy M. Mahfouz

Measuring sequencer size bias using REcount: a novel method for highly accurate Illumina sequencing-based quantification

Quantification of DNA sequence tags from engineered constructs such as plasmids, transposons, or other transgenes underlies many functional genomics measurements. Typically, such measurements rely on PCR follo...

Authors: Daryl M. Gohl, Alessandro Magli, John Garbe, Aaron Becker, Darrell M. Johnson, Shea Anderson, Benjamin Auch, Bradley Billstein, Elyse Froehling, Shana L. McDevitt and Kenneth B. Beckman

Translation of the circular RNA circβ-catenin promotes liver cancer cell growth through activation of the Wnt pathway

Circular RNAs are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. In the current study, we evaluate the function of a novel circRNA derived from the β-catenin gene locus,...

Authors: Wei-Cheng Liang, Cheuk-Wa Wong, Pu-Ping Liang, Mai Shi, Ye Cao, Shi-Tao Rao, Stephen Kwok-Wing Tsui, Mary Miu-Yee Waye, Qi Zhang, Wei-Ming Fu and Jin-Fang Zhang

African evolutionary history inferred from whole genome sequence data of 44 indigenous African populations

Africa is the origin of modern humans within the past 300 thousand years. To infer the complex demographic history of African populations and adaptation to diverse environments, we sequenced the genomes of 92 ...

Authors: Shaohua Fan, Derek E. Kelly, Marcia H. Beltrame, Matthew E. B. Hansen, Swapan Mallick, Alessia Ranciaro, Jibril Hirbo, Simon Thompson, William Beggs, Thomas Nyambo, Sabah A. Omar, Dawit Wolde Meskel, Gurja Belay, Alain Froment, Nick Patterson, David Reich…

Whole-genome sequence analysis of a Pan African set of samples reveals archaic gene flow from an extinct basal population of modern humans into sub-Saharan populations

Population demography and gene flow among African groups, as well as the putative archaic introgression of ancient hominins, have been poorly explored at the genome level.

Authors: Belen Lorente-Galdos, Oscar Lao, Gerard Serra-Vidal, Gabriel Santpere, Lukas F. K. Kuderna, Lara R. Arauna, Karima Fadhlaoui-Zid, Ville N. Pimenoff, Himla Soodyall, Pierre Zalloua, Tomas Marques-Bonet and David Comas

Linking CRISPR-Cas9 interference in cassava to the evolution of editing-resistant geminiviruses

Geminiviruses cause damaging diseases in several important crop species. However, limited progress has been made in developing crop varieties resistant to these highly diverse DNA viruses. Recently, the bacter...

Authors: Devang Mehta, Alessandra Stürchler, Ravi B. Anjanappa, Syed Shan-e-Ali Zaidi, Matthias Hirsch-Hoffmann, Wilhelm Gruissem and Hervé Vanderschuren

Genome-wide nucleotide patterns and potential mechanisms of genome divergence following domestication in maize and soybean

Plant domestication provides a unique model to study genome evolution. Many studies have been conducted to examine genes, genetic diversity, genome structure, and epigenome changes associated with domesticatio...

Authors: Jinyu Wang, Xianran Li, Kyung Do Kim, Michael J. Scanlon, Scott A. Jackson, Nathan M. Springer and Jianming Yu

TransLiG: a de novo transcriptome assembler that uses line graph iteration

We present TransLiG, a new de novo transcriptome assembler, which is able to integrate the sequence depth and pair-end information into the assembling procedure by phasing paths and iteratively constructing li...

Authors: Juntao Liu, Ting Yu, Zengchao Mu and Guojun Li

BRB-seq: ultra-affordable high-throughput transcriptomics enabled by bulk RNA barcoding and sequencing

Despite its widespread use, RNA-seq is still too laborious and expensive to replace RT-qPCR as the default gene expression analysis method. We present a novel approach, BRB-seq, which uses early multiplexing t...

Authors: Daniel Alpern, Vincent Gardeux, Julie Russeil, Bastien Mangeat, Antonio C. A. Meireles-Filho, Romane Breysse, David Hacker and Bart Deplancke

Whole genomes and transcriptomes reveal adaptation and domestication of pistachio

Pistachio (Pistacia vera), one of the most important commercial nut crops worldwide, is highly adaptable to abiotic stresses and is tolerant to drought and salt stresses.

Authors: Lin Zeng, Xiao-Long Tu, He Dai, Feng-Ming Han, Bing-She Lu, Ming-Shan Wang, Hojjat Asadollahpour Nanaei, Ali Tajabadipour, Mehdi Mansouri, Xiao-Long Li, Li-Li Ji, David M. Irwin, Hong Zhou, Min Liu, Hong-Kun Zheng, Ali Esmailizadeh…

Bazam: a rapid method for read extraction and realignment of high-throughput sequencing data

The vast quantities of short-read sequencing data being generated are often exchanged and stored as aligned reads. However, aligned data becomes outdated as new reference genomes and alignment methods become a...

Authors: Simon P. Sadedin and Alicia Oshlack

Machine learning and complex biological data

Machine learning has demonstrated potential in analyzing large, complex biological data. In practice, however, biological information is required in addition to machine learning for successful application.

Authors: Chunming Xu and Scott A. Jackson

DegNorm: normalization of generalized transcript degradation improves accuracy in RNA-seq analysis

RNA degradation affects RNA-seq quality when profiling transcriptional activities in cells. Here, we show that transcript degradation is both gene- and sample-specific and is a common and significant factor th...

Authors: Bin Xiong, Yiben Yang, Frank R. Fineis and Ji-Ping Wang

Analysis of the recombination landscape of hexaploid bread wheat reveals genes controlling recombination and gene conversion frequency

Sequence exchange between homologous chromosomes through crossing over and gene conversion is highly conserved among eukaryotes, contributing to genome stability and genetic diversity. A lack of recombination ...

Authors: Laura-Jayne Gardiner, Luzie U. Wingen, Paul Bailey, Ryan Joynson, Thomas Brabbs, Jonathan Wright, James D. Higgins, Neil Hall, Simon Griffiths, Bernardo J. Clavijo and Anthony Hall

Comparative analysis of sequencing technologies for single-cell transcriptomics

Single-cell RNA-seq technologies require library preparation prior to sequencing. Here, we present the first report to compare the cheaper BGISEQ-500 platform to the Illumina HiSeq platform for scRNA-seq. We g...

Authors: Kedar Nath Natarajan, Zhichao Miao, Miaomiao Jiang, Xiaoyun Huang, Hongpo Zhou, Jiarui Xie, Chunqing Wang, Shishang Qin, Zhikun Zhao, Liang Wu, Naibo Yang, Bo Li, Yong Hou, Shiping Liu and Sarah A. Teichmann

Correction to: Comprehensive benchmarking and ensemble approaches for metagenomic classifiers

Following publication of the original article [1], the authors would like to highlight the following two corrections.

Authors: Alexa B. R. McIntyre, Rachid Ounit, Ebrahim Afshinnekoo, Robert J. Prill, Elizabeth Hénaff, Noah Alexander, Samuel S. Minot, David Danko, Jonathan Foox, Sofia Ahsanuddin, Scott Tighe, Nur A. Hasan, Poorani Subramanian, Kelly Moffat, Shawn Levy, Stefano Lonardi…

Molecular evolutionary trends and feeding ecology diversification in the Hemiptera, anchored by the milkweed bug genome

The Hemiptera (aphids, cicadas, and true bugs) are a key insect order, with high diversity for feeding ecology and excellent experimental tractability for molecular genetics. Building upon recent sequencing of...

Authors: Kristen A. Panfilio, Iris M. Vargas Jentzsch, Joshua B. Benoit, Deniz Erezyilmaz, Yuichiro Suzuki, Stefano Colella, Hugh M. Robertson, Monica F. Poelchau, Robert M. Waterhouse, Panagiotis Ioannidis, Matthew T. Weirauch, Daniel S. T. Hughes, Shwetha C. Murali, John H. Werren, Chris G. C. Jacobs, Elizabeth J. Duncan…

Conbase: a software for unsupervised discovery of clonal somatic mutations in single cells through read phasing

Accurate variant calling and genotyping represent major limiting factors for downstream applications of single-cell genomics. Here, we report Conbase for the identification of somatic mutations in single-cell ...

Authors: Joanna Hård, Ezeddin Al Hakim, Marie Kindblom, Åsa K. Björklund, Bengt Sennblad, Ilke Demirci, Marta Paterlini, Pedro Reu, Erik Borgström, Patrik L. Ståhl, Jakob Michaelsson, Jeff E. Mold and Jonas Frisén

Topconfects: a package for confident effect sizes in differential expression analysis provides a more biologically useful ranked gene list

Differential gene expression analysis may discover a set of genes too large to easily investigate, so a means of ranking genes by biological interest level is desired. p values are frequently abused for this purp...

Authors: Paul F. Harrison, Andrew D. Pattison, David R. Powell and Traude H. Beilharz

All models are wrong, but some organoids may be useful

Authors: Benjamin E. Mead and Jeffrey M. Karp

Alevin efficiently estimates accurate gene abundances from dscRNA-seq data

We introduce alevin, a fast end-to-end pipeline to process droplet-based single-cell RNA sequencing data, performing cell barcode detection, read mapping, unique molecular identifier (UMI) deduplication, gene ...

Authors: Avi Srivastava, Laraib Malik, Tom Smith, Ian Sudbery and Rob Patro