Articles

Landscape of transcription termination in Arabidopsis revealed by single-molecule nascent RNA sequencing

The dynamic process of transcription termination produces transient RNA intermediates that are difficult to distinguish from each other via short-read sequencing methods.

Authors: Weipeng Mo, Bo Liu, Hong Zhang, Xianhao Jin, Dongdong Lu, Yiming Yu, Yuelin Liu, Jinbu Jia, Yanping Long, Xian Deng, Xiaofeng Cao, Hongwei Guo and Jixian Zhai

Roadblock: improved annotations do not necessarily translate into new functional insights

Authors: Nicola A. L. Hall, Becky C. Carlyle, Wilfried Haerty and Elizabeth M. Tunbridge

Transcriptional landscape of highly lignified poplar stems at single-cell resolution

Plant secondary growth depends on the activity of the vascular cambium, which produces xylem and phloem. Wood derived from xylem is the most abundant form of biomass globally and has played key socio-economic ...

Authors: Yang Chen, Shaofei Tong, Yuanzhong Jiang, Fandi Ai, Yanlin Feng, Junlin Zhang, Jue Gong, Jiajia Qin, Yuanyuan Zhang, Yingying Zhu, Jianquan Liu and Tao Ma

Promotech: a general tool for bacterial promoter recognition

Promoters are genomic regions where the transcription machinery binds to initiate the transcription of specific genes. Computational tools for identifying bacterial promoters have been around for decades. Howe...

Authors: Ruben Chevez-Guardado and Lourdes Peña-Castillo

NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome

Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and tha...

Authors: Tatsuaki Kurosaki, Hitomi Sakano, Christoph Pröschel, Jason Wheeler, Alexander Hewko and Lynne E. Maquat

Resequencing of 388 cassava accessions identifies valuable loci and selection for variation in heterozygosity

Heterozygous genomes are widespread in outcrossing and clonally propagated crops. However, the variation in heterozygosity underlying key agronomic traits and crop domestication remains largely unknown. Cassav...

Authors: Wei Hu, Changmian Ji, Zhe Liang, Jianqiu Ye, Wenjun Ou, Zehong Ding, Gang Zhou, Weiwei Tie, Yan Yan, Jinghao Yang, Liming Ma, Xiaoying Yang, Yunxie Wei, Zhiqiang Jin, Jianghui Xie, Ming Peng…

Chromatin spatial organization of wild type and mutant peanuts reveals high-resolution genomic architecture and interaction alterations

Three-dimensional (3D) chromatin organization provides a critical foundation to investigate gene expression regulation and cellular homeostasis.

Authors: Xingguo Zhang, Manish K. Pandey, Jianping Wang, Kunkun Zhao, Xingli Ma, Zhongfeng Li, Kai Zhao, Fangping Gong, Baozhu Guo, Rajeev K. Varshney and Dongmei Yin

Correction: Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist

Authors: Hong Mei, Zhao Zha, Wei Wang, Yusang Xie, Yuege Huang, Wenping Li, Dong Wei, Xinxin Zhang, Jieming Qu and Jia Liu

Lamin C is required to establish genome organization after mitosis

The dynamic 3D organization of the genome is central to gene regulation and development. The nuclear lamina influences genome organization through the tethering of lamina-associated domains (LADs) to the nucle...

Authors: Xianrong Wong, Victoria E. Hoskins, Ashley J. Melendez-Perez, Jennifer C. Harr, Molly Gordon and Karen L. Reddy

A systems genetics approach reveals PbrNSC as a regulator of lignin and cellulose biosynthesis in stone cells of pear fruit

Stone cells in fruits of pear (Pyrus pyrifolia) negatively influence fruit quality because their lignified cell walls impart a coarse and granular texture to the fruit flesh.

Authors: Runze Wang, Yongsong Xue, Jing Fan, Jia-Long Yao, Mengfan Qin, Tao Lin, Qun Lian, Mingyue Zhang, Xiaolong Li, Jiaming Li, Manyi Sun, Bobo Song, Jiaying Zhang, Kejiao Zhao, Xu Chen, Hongju Hu…

Accurate long-read de novo assembly evaluation with Inspector

Long-read de novo genome assembly continues to advance rapidly. However, there is a lack of effective tools to accurately evaluate the assembly results, especially for structural errors. We present Inspector, ...

Authors: Yu Chen, Yixin Zhang, Amy Y. Wang, Min Gao and Zechen Chong

ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma

Recent single-cell transcriptomic studies report that IDH-mutant gliomas share a common hierarchy of cellular phenotypes, independent of genetic subtype. However, the genetic differences between IDH-mutant gli...

Authors: Husam Babikir, Lin Wang, Karin Shamardani, Francisca Catalan, Sweta Sudhir, Manish K. Aghi, David R. Raleigh, Joanna J. Phillips and Aaron A. Diaz

Comprehensive characterization of single-cell full-length isoforms in human and mouse with long-read sequencing

A modified Chromium 10x droplet-based protocol that subsamples cells for both short-read and long-read (nanopore) sequencing together with a new computational pipeline (FLAMES) is developed to enable isoform disc...

Authors: Luyi Tian, Jafar S. Jabbari, Rachel Thijssen, Quentin Gouil, Shanika L. Amarasinghe, Oliver Voogd, Hasaru Kariyawasam, Mei R. M. Du, Jakob Schuster, Changqing Wang, Shian Su, Xueyi Dong, Charity W. Law, Alexis Lucattini, Yair David Joseph Prawer, Coralina Collar-Fernández…

TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations

Topologically associating domains (TADs) are important building blocks of three-dimensional genome architectures. The formation of TADs has been shown to depend on cohesin in a loop-extrusion mechanism. Recent...

Authors: Yubao Cheng, Miao Liu, Mengwei Hu and Siyuan Wang

An explainable artificial intelligence approach for decoding the enhancer histone modifications code and identification of novel enhancers in Drosophila

Enhancers are non-coding regions of the genome that control the activity of target genes. Recent efforts to identify active enhancers experimentally and in silico have proven effective. While these tools can p...

Authors: Jareth C. Wolfe, Liudmila A. Mikheeva, Hani Hagras and Nicolae Radu Zabet

IRFinder-S: a comprehensive suite to discover and explore intron retention

Accurate quantification and detection of intron retention levels require specialized software. Building on our previous software, we create a suite of tools called IRFinder-S, to analyze and explore intron ret...

Authors: Claudio Lorenzi, Sylvain Barriere, Katharina Arnold, Reini F. Luco, Andrew J. Oldfield and William Ritchie

The Sequencing Quality Control 2 study: establishing community standards for sequencing in precision medicine

Authors: Tim R. Mercer, Joshua Xu, Christopher E. Mason and Weida Tong

High-quality reference genome sequences of two coconut cultivars provide insights into evolution of monocot chromosomes and differentiation of fiber content and plant height

Coconut is an important tropical oil and fruit crop whose evolutionary position renders it a fantastic species for the investigation of the evolution of monocot chromosomes and the subsequent differentiation o...

Authors: Shouchuang Wang, Yong Xiao, Zhi-Wei Zhou, Jiaqing Yuan, Hao Guo, Zhuang Yang, Jun Yang, Pengchuan Sun, Lisong Sun, Yuan Deng, Wen-Zhao Xie, Jia-Ming Song, Muhammad Tahir ul Qamar, Wei Xia, Rui Liu, Shufang Gong…

Sex without crossing over in the yeast Saccharomycodes ludwigii

Intermixing of genomes through meiotic reassortment and recombination of homologous chromosomes is a unifying theme of sexual reproduction in eukaryotic organisms and is considered crucial for their adaptive e...

Authors: Ioannis A. Papaioannou, Fabien Dutreux, France A. Peltier, Hiromi Maekawa, Nicolas Delhomme, Amit Bardhan, Anne Friedrich, Joseph Schacherer and Michael Knop

Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals

Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chrom...

Authors: Irene Talon, Adrian Janiszewski, Bart Theeuwes, Thomas Lefevre, Juan Song, Greet Bervoets, Lotte Vanheer, Natalie De Geest, Suresh Poovathingal, Ryan Allsop, Jean-Christophe Marine, Florian Rambow, Thierry Voet and Vincent Pasque

Over 1000 tools reveal trends in the single-cell RNA-seq analysis landscape

Recent years have seen a revolution in single-cell RNA-sequencing (scRNA-seq) technologies, datasets, and analysis methods. Since 2016, the scRNA-tools database has cataloged software tools for analyzing scRNA...

Authors: Luke Zappia and Fabian J. Theis

A genome variation map provides insights into the genetics of walnut adaptation and agronomic traits

Common walnut (Juglans regia L.) is one of the top four most consumed nuts in the world due to its health benefits and pleasant taste. Despite its economic importance, the evolutionary history and genetic control...

Authors: Feiyang Ji, Qingguo Ma, Wenting Zhang, Jie Liu, Yu Feng, Peng Zhao, Xiaobo Song, Jiaxin Chen, Junpei Zhang, Xin Wei, Ye Zhou, Yingying Chang, Pu Zhang, Xuehui Huang, Jie Qiu and Dong Pei

phasebook: haplotype-aware de novo assembly of diploid genomes from long reads

Haplotype-aware diploid genome assembly is crucial in genomics, precision medicine, and many other disciplines. Long-read sequencing technologies have greatly improved genome assembly. However, current long-re...

Authors: Xiao Luo, Xiongbin Kang and Alexander Schönhuth

SquiggleNet: real-time, direct classification of nanopore signals

We present SquiggleNet, the first deep-learning model that can classify nanopore reads directly from their electrical signals. SquiggleNet operates faster than DNA passes through the pore, allowing real-time c...

Authors: Yuwei Bao, Jack Wadden, John R. Erb-Downward, Piyush Ranjan, Weichen Zhou, Torrin L. McDonald, Ryan E. Mills, Alan P. Boyle, Robert P. Dickson, David Blaauw and Joshua D. Welch

Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist

Rhinoviruses (RVs) cause more than half of common colds and, in some cases, more severe diseases. Functional genomics analyses of RVs using siRNA or genome-wide CRISPR screen uncovered a limited set of host fa...

Authors: Hong Mei, Zhao Zha, Wei Wang, Yusang Xie, Yuege Huang, Wenping Li, Dong Wei, Xinxin Zhang, Jieming Qu and Jia Liu

MINTIE: identifying novel structural and splice variants in transcriptomes using RNA-seq data

Calling fusion genes from RNA-seq data is well established, but other transcriptional variants are difficult to detect using existing approaches. To identify all types of variants in transcriptomes we develope...

Authors: Marek Cmero, Breon Schmidt, Ian J. Majewski, Paul G. Ekert, Alicia Oshlack and Nadia M. Davidson

DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation

Nanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylati...

Authors: Yang Liu, Wojciech Rosikiewicz, Ziwei Pan, Nathaniel Jillette, Ping Wang, Aziz Taghbalout, Jonathan Foox, Christopher Mason, Martin Carroll, Albert Cheng and Sheng Li

The chromatin remodeler Ino80 mediates RNAPII pausing site determination

Promoter-proximal pausing of RNA polymerase II (RNAPII) is a critical step for the precise regulation of gene expression. Despite the apparent close relationship between promoter-proximal pausing and nucleosom...

Authors: Youngseo Cheon, Sungwook Han, Taemook Kim, Daehee Hwang and Daeyoup Lee

Effects of sequence motifs in the yeast 3′ untranslated region determined from massively parallel assays of random sequences

The 3′ untranslated region (UTR) plays critical roles in determining the level of gene expression through effects on activities such as mRNA stability and translation. Functional elements within this region ha...

Authors: Andrew Savinov, Benjamin M. Brandsen, Brooke E. Angell, Josh T. Cuperus and Stanley Fields

Gut bacterial metabolites modulate endoplasmic reticulum stress

The endoplasmic reticulum (ER) is a membranous organelle that maintains proteostasis and cellular homeostasis, controlling the fine balance between health and disease. Dysregulation of the ER stress response h...

Authors: Xiaobo Ke, Kwontae You, Matthieu Pichaud, Henry J. Haiser, Daniel B. Graham, Hera Vlamakis, Jeffrey A. Porter and Ramnik J. Xavier

Benchmarking sequencing methods and tools that facilitate the study of alternative polyadenylation

Alternative cleavage and polyadenylation (APA), an RNA processing event, occurs in over 70% of human protein-coding genes. APA results in mRNA transcripts with distinct 3′ ends. Most APA occurs within 3′ UTRs,...

Authors: Ankeeta Shah, Briana E. Mittleman, Yoav Gilad and Yang I. Li

A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation

Cellular RNA-binding proteins (RBPs) have multiple roles in post-transcriptional control, and some are shown to bind DNA. However, the global localization and the general chromatin-binding ability of RBPs are ...

Authors: Yue Ren, Yue Huo, Weiqian Li, Manman He, Siqi Liu, Jiabin Yang, Hongmei Zhao, Lingjie Xu, Yuehong Guo, Yanmin Si, Hualu Zhao, Shuan Rao, Jing Wang, Yanni Ma, Xiaoshuang Wang, Jia Yu…

Kras^G12D induces changes in chromatin territories that differentially impact early nuclear reprogramming in pancreatic cells

Pancreatic ductal adenocarcinoma initiation is most frequently caused by Kras mutations.

Authors: Angela J. Mathison, Romica Kerketta, Thiago Milech de Assuncao, Elise Leverence, Atefeh Zeighami, Guillermo Urrutia, Timothy J. Stodola, Marina Pasca di Magliano, Juan L. Iovanna, Michael T. Zimmermann, Gwen Lomberk and Raul Urrutia

Clipper: p-value-free FDR control on high-throughput data from two conditions

High-throughput biological data analysis commonly involves identifying features such as genes, genomic regions, and proteins, whose values differ between two conditions, from numerous features measured simulta...

Authors: Xinzhou Ge, Yiling Elaine Chen, Dongyuan Song, MeiLu McDermott, Kyla Woyshner, Antigoni Manousopoulou, Ning Wang, Wei Li, Leo D. Wang and Jingyi Jessica Li

Network propagation-based prioritization of long tail genes in 17 cancer types

The diversity of genomic alterations in cancer poses challenges to fully understanding the etiologies of the disease. Recent interest in infrequent mutations, in genes that reside in the “long tail” of the mut...

Authors: Hussein Mohsen, Vignesh Gunasekharan, Tao Qing, Montrell Seay, Yulia Surovtseva, Sahand Negahban, Zoltan Szallasi, Lajos Pusztai and Mark B. Gerstein

Mapping and modeling the genomic basis of differential RNA isoform expression at single-cell resolution with LR-Split-seq

The rise in throughput and quality of long-read sequencing should allow unambiguous identification of full-length transcript isoforms. However, its application to single-cell RNA-seq has been limited by throug...

Authors: Elisabeth Rebboah, Fairlie Reese, Katherine Williams, Gabriela Balderrama-Gutierrez, Cassandra McGill, Diane Trout, Isaryhia Rodriguez, Heidi Liang, Barbara J. Wold and Ali Mortazavi

Global properties of regulatory sequences are predicted by transcription factor recognition mechanisms

Mammalian genomes contain millions of putative regulatory sequences, which are delineated by binding of multiple transcription factors. The degree to which spacing and orientation constraints among transcripti...

Authors: Zain M. Patel and Timothy R. Hughes

Differential regulation of mRNA fate by the human Ccr4-Not complex is driven by coding sequence composition and mRNA localization

Regulation of protein output at the level of translation allows for a rapid adaptation to dynamic changes to the cell’s requirements. This precise control of gene expression is achieved by complex and interlin...

Authors: Sarah L. Gillen, Chiara Giacomelli, Kelly Hodge, Sara Zanivan, Martin Bushell and Ania Wilczynska

Genomic insight into balancing high yield, good quality, and blast resistance of japonica rice

Balancing the yield, quality and resistance to disease is a daunting challenge in crop breeding due to the negative relationship among these traits. Large-scale genomic landscape analysis of germplasm resource...

Authors: Ning Xiao, Cunhong Pan, Yuhong Li, Yunyu Wu, Yue Cai, Yue Lu, Ruyi Wang, Ling Yu, Wei Shi, Houxiang Kang, Zhaobing Zhu, Niansheng Huang, Xiaoxiang Zhang, Zichun Chen, Jianju Liu, Zefeng Yang…

Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish

Zebrafish pigment cell differentiation provides an attractive model for studying cell fate progression as a neural crest progenitor engenders diverse cell types, including two morphologically distinct pigment ...

Authors: Hyo Sik Jang, Yujie Chen, Jiaxin Ge, Alicia N. Wilkening, Yiran Hou, Hyung Joo Lee, You Rim Choi, Rebecca F. Lowdon, Xiaoyun Xing, Daofeng Li, Charles K. Kaufman, Stephen L. Johnson and Ting Wang

PAM-repeat associations and spacer selection preferences in single and co-occurring CRISPR-Cas systems

The adaptive CRISPR-Cas immune system stores sequences from past invaders as spacers in CRISPR arrays and thereby provides direct evidence that links invaders to hosts. Mapping CRISPR spacers has revealed many...

Authors: Jochem N. A. Vink, Jan H. L. Baijens and Stan J. J. Brouns

Biologically relevant transfer learning improves transcription factor binding prediction

Deep learning has proven to be a powerful technique for transcription factor (TF) binding prediction but requires large training datasets. Transfer learning can reduce the amount of data required for deep lear...

Authors: Gherman Novakovsky, Manu Saraswat, Oriol Fornes, Sara Mostafavi and Wyeth W. Wasserman

Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation

Mammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentia...

Authors: Giancarlo Bonora, Vijay Ramani, Ritambhara Singh, He Fang, Dana L. Jackson, Sanjay Srivatsan, Ruolan Qiu, Choli Lee, Cole Trapnell, Jay Shendure, Zhijun Duan, Xinxian Deng, William S. Noble and Christine M. Disteche

ACE: a probabilistic model for characterizing gene-level essentiality in CRISPR screens

High-throughput CRISPR-Cas9 knockout screens are widely used to evaluate gene essentiality in cancer research. Here we introduce a probabilistic modeling framework, Analysis of CRISPR-based Essentiality (ACE),...

Authors: Elizabeth R. Hutton, Christopher R. Vakoc and Adam Siepel

SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs

Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs fo...

Authors: Avigayel Rabin, Michela Zaffagni, Reut Ashwal-Fluss, Ines Lucia Patop, Aarti Jajoo, Shlomo Shenzis, Liran Carmel and Sebastian Kadener

Genome and metabolome: chance and necessity

Authors: Emanuel Gonçalves and Christian Frezza

The influence of the gut microbiome on BCG-induced trained immunity

The bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in specific and nonspecific, or trained, immune responses. While...

Authors: Martin Stražar, Vera P. Mourits, Valerie A. C. M. Koeken, L. Charlotte J. de Bree, Simone J. C. F. M. Moorlag, Leo A. B. Joosten, Reinout van Crevel, Hera Vlamakis, Mihai G. Netea and Ramnik J. Xavier

Revisiting genetic artifacts on DNA methylation microarrays exposes novel biological implications

Illumina DNA methylation microarrays enable epigenome-wide analysis vastly used for the discovery of novel DNA methylation variation in health and disease. However, the microarrays’ probe design cannot fully c...

Authors: Benjamin Planterose Jiménez, Manfred Kayser and Athina Vidaki

Chromatin accessibility and regulatory vocabulary across indicine cattle tissues

Spatiotemporal changes in the chromatin accessibility landscape are essential to cell differentiation, development, health, and disease. The quest of identifying regulatory elements in open chromatin regions a...

Authors: Pâmela A. Alexandre, Marina Naval-Sánchez, Moira Menzies, Loan T. Nguyen, Laercio R. Porto-Neto, Marina R. S. Fortes and Antonio Reverter

Author Correction: Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network

Authors: Zhonghua Du, Xue Wen, Yichen Wang, Lin Jia, Shilin Zhang, Yudi Liu, Lei Zhou, Hui Li, Wang Yang, Cong Wang, Jingcheng Chen, Yajing Hao, Daniela Salgado Figueroa, Huiling Chen, Dan Li, Naifei Chen…