Articles

CellSIUS provides sensitive and specific detection of rare cell populations from complex single-cell RNA-seq data

We develop CellSIUS (Cell Subtype Identification from Upregulated gene Sets) to fill a methodology gap for rare cell population identification for scRNA-seq data. CellSIUS outperforms existing algorithms for s...

Authors: Rebekka Wegmann, Marilisa Neri, Sven Schuierer, Bilada Bilican, Huyen Hartkopf, Florian Nigsch, Felipa Mapa, Annick Waldt, Rachel Cuttat, Max R. Salick, Joe Raymond, Ajamete Kaykas, Guglielmo Roma and Caroline Gubser Keller

Multilayered control of exon acquisition permits the emergence of novel forms of regulatory control

The long introns of mammals are pools of evolutionary potential due to the multiplicity of sequences that permit the acquisition of novel exons. However, the permissibility of genes to this type of acquisition...

Authors: Nesli Avgan, Juli I. Wang, Javier Fernandez-Chamorro and Robert J. Weatheritt

Stable enhancers are active in development, and fragile enhancers are associated with evolutionary adaptation

Despite continual progress in the identification and characterization of trait- and disease-associated variants that disrupt transcription factor (TF)-DNA binding, little is known about the distribution of TF ...

Authors: Shan Li, Evgeny Z. Kvon, Axel Visel, Len A. Pennacchio and Ivan Ovcharenko

The bread wheat epigenomic map reveals distinct chromatin architectural and evolutionary features of functional genetic elements

Bread wheat is an allohexaploid species with a 16-Gb genome that has large intergenic regions, which presents a big challenge for pinpointing regulatory elements and further revealing the transcriptional regul...

Authors: Zijuan Li, Meiyue Wang, Kande Lin, Yilin Xie, Jingyu Guo, Luhuan Ye, Yili Zhuang, Wan Teng, Xiaojuan Ran, Yiping Tong, Yongbiao Xue, Wenli Zhang and Yijing Zhang

CONFINED: distinguishing biological from technical sources of variation by leveraging multiple methylation datasets

Methylation datasets are affected by innumerable sources of variability, both biological (cell-type composition, genetics) and technical (batch effects). Here, we propose a reference-free method based on spars...

Authors: Mike Thompson, Zeyuan Johnson Chen, Elior Rahmani and Eran Halperin

GEMINI: a variational Bayesian approach to identify genetic interactions from combinatorial CRISPR screens

Systems for CRISPR-based combinatorial perturbation of two or more genes are emerging as powerful tools for uncovering genetic interactions. However, systematic identification of these relationships is complic...

Authors: Mahdi Zamanighomi, Sidharth S. Jain, Takahiro Ito, Debjani Pal, Timothy P. Daley and William R. Sellers

Frequent intra- and inter-species introgression shapes the landscape of genetic variation in bread wheat

Bread wheat is one of the most important and broadly studied crops. However, due to the complexity of its genome and incomplete genome collection of wild populations, the bread wheat genome landscape and domes...

Authors: Hong Cheng, Jing Liu, Jia Wen, Xiaojun Nie, Luohao Xu, Ningbo Chen, Zhongxing Li, Qilin Wang, Zhuqing Zheng, Ming Li, Licao Cui, Zihua Liu, Jianxin Bian, Zhonghua Wang, Shengbao Xu, Qin Yang…

Cell type-specific epigenetic links to schizophrenia risk in the brain

The importance of cell type-specific epigenetic variation of non-coding regions in neuropsychiatric disorders is increasingly appreciated, yet data from disease brains are conspicuously lacking. We generate ce...

Authors: Isabel Mendizabal, Stefano Berto, Noriyoshi Usui, Kazuya Toriumi, Paramita Chatterjee, Connor Douglas, Iksoo Huh, Hyeonsoo Jeong, Thomas Layman, Carol A. Tamminga, Todd M. Preuss, Genevieve Konopka and Soojin V. Yi

SMURF-seq: efficient copy number profiling on long-read sequencers

We present SMURF-seq, a protocol to efficiently sequence short DNA molecules on a long-read sequencer by randomly ligating them to form long molecules. Applying SMURF-seq using the Oxford Nanopore MinION yield...

Authors: Rishvanth K. Prabakar, Liya Xu, James Hicks and Andrew D. Smith

Integrative analysis of vascular endothelial cell genomic features identifies AIDA as a coronary artery disease candidate gene

Genome-wide association studies (GWAS) have identified hundreds of loci associated with coronary artery disease (CAD) and blood pressure (BP) or hypertension. Many of these loci are not linked to traditional r...

Authors: Simon Lalonde, Valérie-Anne Codina-Fauteux, Sébastian Méric de Bellefon, Francis Leblanc, Mélissa Beaudoin, Marie-Michelle Simon, Rola Dali, Tony Kwan, Ken Sin Lo, Tomi Pastinen and Guillaume Lettre

Emerging technologies towards enhancing privacy in genomic data sharing

As the scale of genomic and health-related data explodes and our understanding of these data matures, the privacy of the individuals behind the data is increasingly at stake. Traditional approaches to protect ...

Authors: Bonnie Berger and Hyunghoon Cho

CDetection: CRISPR-Cas12b-based DNA detection with sub-attomolar sensitivity and single-base specificity

CRISPR-based nucleic acid detection methods are reported to facilitate rapid and sensitive DNA detection. However, precise DNA detection at the single-base resolution and its wide applications including high-f...

Authors: Fei Teng, Lu Guo, Tongtong Cui, Xin-Ge Wang, Kai Xu, Qingqin Gao, Qi Zhou and Wei Li

Emphasis on the deep or shallow parts of the tree provides a new characterization of phylogenetic distances

Phylogenetically informed distances are commonly used in the analysis of microbiome data, and analysts have many options to choose from. Although all phylogenetic distances share the goal of incorporating the ...

Authors: Julia Fukuyama

The long walk to African genomics

Authors: Serena Tucci and Joshua M. Akey

Performance of neural network basecalling tools for Oxford Nanopore sequencing

Basecalling, the computational process of translating raw electrical signal to nucleotide sequence, is of critical importance to the sequencing platforms produced by Oxford Nanopore Technologies (ONT). Here, w...

Authors: Ryan R. Wick, Louise M. Judd and Kathryn E. Holt

Trapping a somatic endogenous retrovirus into a germline piRNA cluster immunizes the germline against further invasion

For species survival, the germline must faithfully transmit genetic information to the progeny. Transposable elements (TEs) constitute a significant threat to genome stability due to their mobility. In the met...

Authors: Céline Duc, Marianne Yoth, Silke Jensen, Nolwenn Mouniée, Casey M. Bergman, Chantal Vaury and Emilie Brasset

Ancient polymorphisms contribute to genome-wide variation by long-term balancing selection and divergent sorting in Boechera stricta

Genomic variation is widespread, and both neutral and selective processes can generate similar patterns in the genome. These processes are not mutually exclusive, so it is difficult to infer the evolutionary m...

Authors: Baosheng Wang, Julius P. Mojica, Nadeesha Perera, Cheng-Ruei Lee, John T. Lovell, Aditi Sharma, Catherine Adam, Anna Lipzen, Kerrie Barry, Daniel S. Rokhsar, Jeremy Schmutz and Thomas Mitchell-Olds

Essential guidelines for computational method benchmarking

In computational biology and other sciences, researchers are frequently faced with a choice between several computational methods for performing data analyses. Benchmarking studies aim to rigorously compare th...

Authors: Lukas M. Weber, Wouter Saelens, Robrecht Cannoodt, Charlotte Soneson, Alexander Hapfelmeier, Paul P. Gardner, Anne-Laure Boulesteix, Yvan Saeys and Mark D. Robinson

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

Cold stress induces enhanced chromatin accessibility and bivalent histone modifications H3K4me3 and H3K27me3 of active genes in potato

Cold stress can greatly affect plant growth and development. Plants have developed special systems to respond to and tolerate cold stress. While plant scientists have discovered numerous genes involved in resp...

Authors: Zixian Zeng, Wenli Zhang, Alexandre P. Marand, Bo Zhu, C. Robin Buell and Jiming Jiang

Correction to: 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

Following publication of the original article [1], the authors reported that Figs. 4 and 5 had mistakenly been transposed. Please find the correct Figs. 4 and 5 below. The original article [1] has been corrected.

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

Current status and applications of genome-scale metabolic models

Genome-scale metabolic models (GEMs) computationally describe gene-protein-reaction associations for entire metabolic genes in an organism, and can be simulated to predict metabolic fluxes for various systems-...

Authors: Changdai Gu, Gi Bae Kim, Won Jun Kim, Hyun Uk Kim and Sang Yup Lee

Invasive DNA elements modify the nuclear architecture of their insertion site by KNOT-linked silencing in Arabidopsis thaliana

The three-dimensional (3D) organization of chromosomes is linked to epigenetic regulation and transcriptional activity. However, only few functional features of 3D chromatin architecture have been described to...

Authors: Stefan Grob and Ueli Grossniklaus

Codon usage optimization in pluripotent embryonic stem cells

The uneven use of synonymous codons in the transcriptome regulates the efficiency and fidelity of protein translation rates. Yet, the importance of this codon bias in regulating cell state-specific expression ...

Authors: Susanne Bornelöv, Tommaso Selmi, Sophia Flad, Sabine Dietmann and Michaela Frye

A practical guide to methods controlling false discoveries in computational biology

In high-throughput studies, hundreds to millions of hypotheses are typically tested. Statistical methods that control the false discovery rate (FDR) have emerged as popular and powerful tools for error rate co...

Authors: Keegan Korthauer, Patrick K. Kimes, Claire Duvallet, Alejandro Reyes, Ayshwarya Subramanian, Mingxiang Teng, Chinmay Shukla, Eric J. Alm and Stephanie C. Hicks

Single-cell transcriptomics unveils gene regulatory network plasticity

Single-cell RNA sequencing (scRNA-seq) plays a pivotal role in our understanding of cellular heterogeneity. Current analytical workflows are driven by categorizing principles that consider cells as individual ...

Authors: Giovanni Iacono, Ramon Massoni-Badosa and Holger Heyn

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

Haplotype-aware diplotyping from noisy long reads

Current genotyping approaches for single-nucleotide variations rely on short, accurate reads from second-generation sequencing devices. Presently, third-generation sequencing platforms are rapidly becoming mor...

Authors: Jana Ebler, Marina Haukness, Trevor Pesout, Tobias Marschall and Benedict Paten

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

Collateral damage: benchmarking off-target effects in genome editing

This editorial discusses what levels of off-target effects can be tolerated in genome editing, in the context of various types of applications.

Authors: Dana Carroll

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

Bridging the gap between reference and real transcriptomes

Genetic, transcriptional, and post-transcriptional variations shape the transcriptome of individual cells, rendering establishing an exhaustive set of reference RNAs a complicated matter. Current reference tra...

Authors: Antonin Morillon and Daniel Gautheret

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