Articles

Elevated retrotransposon activity and genomic instability in primed pluripotent stem cells

Naïve and primed pluripotent stem cells (PSCs) represent two different pluripotent states. Primed PSCs following in vitro culture exhibit lower developmental potency as evidenced by failure in germline chimera...

Authors: Haifeng Fu, Weiyu Zhang, Niannian Li, Jiao Yang, Xiaoying Ye, Chenglei Tian, Xinyi Lu and Lin Liu

The evolving gene regulatory landscape—a tinkerer of complex creatures

Authors: Geoffrey J. Faulkner

Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors.

Authors: Xiaojing Chu, Martin Jaeger, Joep Beumer, Olivier B. Bakker, Raul Aguirre-Gamboa, Marije Oosting, Sanne P. Smeekens, Simone Moorlag, Vera P. Mourits, Valerie A. C. M. Koeken, Charlotte de Bree, Trees Jansen, Ian T. Mathews, Khoi Dao, Mahan Najhawan, Jeramie D. Watrous…

Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation

Single-cell technologies are transforming biomedical research, including the recent demonstration that unspliced pre-mRNA present in single-cell RNA-Seq permits prediction of future expression states. Here we ...

Authors: Melania Barile, Ivan Imaz-Rosshandler, Isabella Inzani, Shila Ghazanfar, Jennifer Nichols, John C. Marioni, Carolina Guibentif and Berthold Göttgens

CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strateg...

Authors: Samuel M. Nicholls, Radoslaw Poplawski, Matthew J. Bull, Anthony Underwood, Michael Chapman, Khalil Abu-Dahab, Ben Taylor, Rachel M. Colquhoun, Will P. M. Rowe, Ben Jackson, Verity Hill, Áine O’Toole, Sara Rey, Joel Southgate, Roberto Amato, Rich Livett…

SMOOTH-seq: single-cell genome sequencing of human cells on a third-generation sequencing platform

There is no effective way to detect structure variations (SVs) and extra-chromosomal circular DNAs (ecDNAs) at single-cell whole-genome level. Here, we develop a novel third-generation sequencing platform-base...

Authors: Xiaoying Fan, Cheng Yang, Wen Li, Xiuzhen Bai, Xin Zhou, Haoling Xie, Lu Wen and Fuchou Tang

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation i...

Authors: Daniel L. McCartney, Josine L. Min, Rebecca C. Richmond, Ake T. Lu, Maria K. Sobczyk, Gail Davies, Linda Broer, Xiuqing Guo, Ayoung Jeong, Jeesun Jung, Silva Kasela, Seyma Katrinli, Pei-Lun Kuo, Pamela R. Matias-Garcia, Pashupati P. Mishra, Marianne Nygaard…

Evolution of mouse circadian enhancers from transposable elements

Transposable elements are increasingly recognized as a source of cis-regulatory variation. Previous studies have revealed that transposons are often bound by transcription factors and some have been co-opted into...

Authors: Julius Judd, Hayley Sanderson and Cédric Feschotte

mbImpute: an accurate and robust imputation method for microbiome data

A critical challenge in microbiome data analysis is the existence of many non-biological zeros, which distort taxon abundance distributions, complicate data analysis, and jeopardize the reliability of scientif...

Authors: Ruochen Jiang, Wei Vivian Li and Jingyi Jessica Li

A trans locus causes a ribosomopathy in hypertrophic hearts that affects mRNA translation in a protein length-dependent fashion

Little is known about the impact of trans-acting genetic variation on the rates with which proteins are synthesized by ribosomes. Here, we investigate the influence of such distant genetic loci on the efficien...

Authors: Franziska Witte, Jorge Ruiz-Orera, Camilla Ciolli Mattioli, Susanne Blachut, Eleonora Adami, Jana Felicitas Schulz, Valentin Schneider-Lunitz, Oliver Hummel, Giannino Patone, Michael Benedikt Mücke, Jan Šilhavý, Matthias Heinig, Leonardo Bottolo, Daniel Sanchis, Martin Vingron, Marina Chekulaeva…

Direct long-read RNA sequencing identifies a subset of questionable exitrons likely arising from reverse transcription artifacts

Resistance to CD19-directed immunotherapies in lymphoblastic leukemia has been attributed, among other factors, to several aberrant CD19 pre-mRNA splicing events, including recently reported excision of a cryptic...

Authors: Laura Schulz, Manuel Torres-Diz, Mariela Cortés-López, Katharina E. Hayer, Mukta Asnani, Sarah K. Tasian, Yoseph Barash, Elena Sotillo, Kathi Zarnack, Julian König and Andrei Thomas-Tikhonenko

The dynamics of N⁶-methyladenine RNA modification in interactions between rice and plant viruses

N⁶-methyladenosine (m⁶A) is the most common RNA modification in eukaryotes and has been implicated as a novel epigenetic marker that is involved in various biological processes. The pattern and functional dissect...

Authors: Kun Zhang, Xinjian Zhuang, Zhuozhuo Dong, Kai Xu, Xijun Chen, Fang Liu and Zhen He

Optimizing expression quantitative trait locus mapping workflows for single-cell studies

Single-cell RNA sequencing (scRNA-seq) has enabled the unbiased, high-throughput quantification of gene expression specific to cell types and states. With the cost of scRNA-seq decreasing and techniques for sa...

Authors: Anna S. E. Cuomo, Giordano Alvari, Christina B. Azodi, Davis J. McCarthy and Marc Jan Bonder

Using high-throughput multiple optical phenotyping to decipher the genetic architecture of maize drought tolerance

Drought threatens the food supply of the world population. Dissecting the dynamic responses of plants to drought will be beneficial for breeding drought-tolerant crops, as the genetic controls of these respons...

Authors: Xi Wu, Hui Feng, Di Wu, Shijuan Yan, Pei Zhang, Wenbin Wang, Jun Zhang, Junli Ye, Guoxin Dai, Yuan Fan, Weikun Li, Baoxing Song, Zedong Geng, Wanli Yang, Guoxin Chen, Feng Qin…

Detection of cell-free microbial DNA using a contaminant-controlled analysis framework

The human microbiome plays an important role in cancer. Accumulating evidence indicates that commensal microbiome-derived DNA may be represented in minute quantities in the cell-free DNA of human blood and cou...

Authors: Enrique Zozaya-Valdés, Stephen Q. Wong, Jeanette Raleigh, Athena Hatzimihalis, Sarah Ftouni, Anthony T. Papenfuss, Shahneen Sandhu, Mark A. Dawson and Sarah-Jane Dawson

Roles of TET and TDG in DNA demethylation in proliferating and non-proliferating immune cells

TET enzymes mediate DNA demethylation by oxidizing 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Since these oxidized methylcytosines (...

Authors: Atsushi Onodera, Edahí González-Avalos, Chan-Wang Jerry Lio, Romain O. Georges, Alfonso Bellacosa, Toshinori Nakayama and Anjana Rao

SPARK-X: non-parametric modeling enables scalable and robust detection of spatial expression patterns for large spatial transcriptomic studies

Spatial transcriptomic studies are becoming increasingly common and large, posing important statistical and computational challenges for many analytic tasks. Here, we present SPARK-X, a non-parametric method f...

Authors: Jiaqiang Zhu, Shiquan Sun and Xiang Zhou

GxEsum: a novel approach to estimate the phenotypic variance explained by genome-wide GxE interaction based on GWAS summary statistics for biobank-scale data

Genetic variation in response to the environment, that is, genotype-by-environment interaction (GxE), is fundamental in the biology of complex traits and diseases. However, existing methods are computationally...

Authors: Jisu Shin and Sang Hong Lee

LIQA: long-read isoform quantification and analysis

Long-read RNA sequencing (RNA-seq) technologies can sequence full-length transcripts, facilitating the exploration of isoform-specific gene expression over short-read RNA-seq. We present LIQA to quantify isofo...

Authors: Yu Hu, Li Fang, Xuelian Chen, Jiang F. Zhong, Mingyao Li and Kai Wang

Author Correction: Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation

Authors: Nisha Padmanabhan, Huang Kie Kyon, Arnoud Boot, Kevin Lim, Supriya Srivastava, Shuwen Chen, Zhiyuan Wu, Hyung-Ok Lee, Vineeth T. Mukundan, Charlene Chan, Yarn Kit Chan, Ong Xuewen, Jason J. Pitt, Zul Fazreen Adam Isa, Manjie Xing, Ming Hui Lee…

Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes

Canonical nonsense-mediated decay (NMD) is an important splicing-dependent process for mRNA surveillance in mammals. However, processed pseudogenes are not able to trigger NMD due to their lack of introns. It ...

Authors: Liqiang Tan, Weisheng Cheng, Fang Liu, Dan Ohtan Wang, Linwei Wu, Nan Cao and Jinkai Wang

Leveraging breeding programs and genomic data in Norway spruce (Picea abies L. Karst) for GWAS analysis

Genome-wide association studies (GWAS) identify loci underlying the variation of complex traits. One of the main limitations of GWAS is the availability of reliable phenotypic data, particularly for long-lived...

Authors: Zhi-Qiang Chen, Yanjun Zan, Pascal Milesi, Linghua Zhou, Jun Chen, Lili Li, BinBin Cui, Shihui Niu, Johan Westin, Bo Karlsson, Maria Rosario García-Gil, Martin Lascoux and Harry X. Wu

GUNC: detection of chimerism and contamination in prokaryotic genomes

Genomes are critical units in microbiology, yet ascertaining quality in prokaryotic genome assemblies remains a formidable challenge. We present GUNC (the Genome UNClutterer), a tool that accurately detects an...

Authors: Askarbek Orakov, Anthony Fullam, Luis Pedro Coelho, Supriya Khedkar, Damian Szklarczyk, Daniel R. Mende, Thomas S. B. Schmidt and Peer Bork

Publisher Correction: scDesign2: a transparent simulator that generates high-fidelity single-cell gene expression count data with gene correlations captured

Authors: Tianyi Sun, Dongyuan Song, Wei Vivian Li and Jingyi Jessica Li

Transcription shapes DNA replication initiation to preserve genome integrity

Early DNA replication occurs within actively transcribed chromatin compartments in mammalian cells, raising the immediate question of how early DNA replication coordinates with transcription to avoid collision...

Authors: Yang Liu, Chen Ai, Tingting Gan, Jinchun Wu, Yongpeng Jiang, Xuhao Liu, Rusen Lu, Ning Gao, Qing Li, Xiong Ji and Jiazhi Hu

Chromosome-level genome assembly of a regenerable maize inbred line A188

The maize inbred line A188 is an attractive model for elucidation of gene function and improvement due to its high embryogenic capacity and many contrasting traits to the first maize reference genome, B73, and...

Authors: Guifang Lin, Cheng He, Jun Zheng, Dal-Hoe Koo, Ha Le, Huakun Zheng, Tej Man Tamang, Jinguang Lin, Yan Liu, Mingxia Zhao, Yangfan Hao, Frank McFraland, Bo Wang, Yang Qin, Haibao Tang, Donald R. McCarty…

BUTTERFLY: addressing the pooled amplification paradox with unique molecular identifiers in single-cell RNA-seq

The incorporation of unique molecular identifiers (UMIs) in single-cell RNA-seq assays makes possible the identification of duplicated molecules, thereby facilitating the counting of distinct molecules from se...

Authors: Johan Gustafsson, Jonathan Robinson, Jens Nielsen and Lior Pachter

Gene set enrichment analysis for genome-wide DNA methylation data

DNA methylation is one of the most commonly studied epigenetic marks, due to its role in disease and development. Illumina methylation arrays have been extensively used to measure methylation across the human ...

Authors: Jovana Maksimovic, Alicia Oshlack and Belinda Phipson

The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle

Circadian gene expression is essential for organisms to adjust their physiology and anticipate daily changes in the environment. The molecular mechanisms controlling circadian gene transcription are still unde...

Authors: Mayra Furlan-Magaril, Masami Ando-Kuri, Rodrigo G. Arzate-Mejía, Jörg Morf, Jonathan Cairns, Abraham Román-Figueroa, Luis Tenorio-Hernández, A. César Poot-Hernández, Simon Andrews, Csilla Várnai, Boo Virk, Steven W. Wingett and Peter Fraser

Annotation of snoRNA abundance across human tissues reveals complex snoRNA-host gene relationships

Small nucleolar RNAs (snoRNAs) are mid-size non-coding RNAs required for ribosomal RNA modification, implying a ubiquitous tissue distribution linked to ribosome synthesis. However, increasing numbers of studi...

Authors: Étienne Fafard-Couture, Danny Bergeron, Sonia Couture, Sherif Abou-Elela and Michelle S. Scott

Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1

Somatic cell reprogramming is the process that allows differentiated cells to revert to a pluripotent state. In contrast to the extensively studied rewiring of epigenetic and transcriptional programs required ...

Authors: Claudia Vivori, Panagiotis Papasaikas, Ralph Stadhouders, Bruno Di Stefano, Anna Ribó Rubio, Clara Berenguer Balaguer, Serena Generoso, Anna Mallol, José Luis Sardina, Bernhard Payer, Thomas Graf and Juan Valcárcel

Targeted mutagenesis in mouse cells and embryos using an enhanced prime editor

Prime editors, novel genome-editing tools consisting of a CRISPR-Cas9 nickase and an engineered reverse transcriptase, can induce targeted mutagenesis. Nevertheless, much effort is required to optimize and imp...

Authors: Soo-Ji Park, Tae Yeong Jeong, Seung Kyun Shin, Da Eun Yoon, Soo-Yeon Lim, Sol Pin Kim, Jungmin Choi, Hyunji Lee, Jeong-Im Hong, Jinhee Ahn, Je Kyung Seong and Kyoungmi Kim

Detection of SARS-CoV-2 RNA using RT-LAMP and molecular beacons

Rapid spread of SARS-CoV-2 has led to a global pandemic, resulting in the need for rapid assays to allow diagnosis and prevention of transmission. Reverse transcription-polymerase chain reaction (RT-PCR) provi...

Authors: Scott Sherrill-Mix, Young Hwang, Aoife M. Roche, Abigail Glascock, Susan R. Weiss, Yize Li, Leila Haddad, Peter Deraska, Caitlin Monahan, Andrew Kromer, Jevon Graham-Wooten, Louis J. Taylor, Benjamin S. Abella, Arupa Ganguly, Ronald G. Collman, Gregory D. Van Duyne…

N⁶-methyladenosine RNA modification regulates strawberry fruit ripening in an ABA-dependent manner

Epigenetic mark such as DNA methylation plays pivotal roles in regulating ripening of both climacteric and non-climacteric fruits. However, it remains unclear whether mRNA m⁶A methylation, which has been shown to...

Authors: Leilei Zhou, Renkun Tang, Xiaojing Li, Shiping Tian, Bingbing Li and Guozheng Qin

Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation

CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumor suppressors. Currently, for most cancers inclu...

Authors: Nisha Padmanabhan, Huang Kie Kyon, Arnoud Boot, Kevin Lim, Supriya Srivastava, Shuwen Chen, Zhiyuan Wu, Hyung-Ok Lee, Vineeth T. Mukundan, Charlene Chan, Yarn Kit Chan, Ong Xuewen, Jason J. Pitt, Zul Fazreen Adam Isa, Manjie Xing, Ming Hui Lee…

Impacts of allopolyploidization and structural variation on intraspecific diversification in Brassica rapa

Despite the prevalence and recurrence of polyploidization in the speciation of flowering plants, its impacts on crop intraspecific genome diversification are largely unknown. Brassica rapa is a mesopolyploid spec...

Authors: Xu Cai, Lichun Chang, Tingting Zhang, Haixu Chen, Lei Zhang, Runmao Lin, Jianli Liang, Jian Wu, Michael Freeling and Xiaowu Wang

diffBUM-HMM: a robust statistical modeling approach for detecting RNA flexibility changes in high-throughput structure probing data

Advancing RNA structural probing techniques with next-generation sequencing has generated demands for complementary computational tools to robustly extract RNA structural information amidst sampling noise and ...

Authors: Paolo Marangio, Ka Ying Toby Law, Guido Sanguinetti and Sander Granneman

GRiNCH: simultaneous smoothing and detection of topological units of genome organization from sparse chromatin contact count matrices with matrix factorization

High-throughput chromosome conformation capture assays, such as Hi-C, have shown that the genome is organized into organizational units such as topologically associating domains (TADs), which can impact gene r...

Authors: Da-Inn Lee and Sushmita Roy

scDesign2: a transparent simulator that generates high-fidelity single-cell gene expression count data with gene correlations captured

A pressing challenge in single-cell transcriptomics is to benchmark experimental protocols and computational methods. A solution is to use computational simulators, but existing simulators cannot simultaneousl...

Authors: Tianyi Sun, Dongyuan Song, Wei Vivian Li and Jingyi Jessica Li

Samplot: a platform for structural variant visual validation and automated filtering

Visual validation is an important step to minimize false-positive predictions from structural variant (SV) detection. We present Samplot, a tool for creating images that display the read depth and sequence ali...

Authors: Jonathan R. Belyeu, Murad Chowdhury, Joseph Brown, Brent S. Pedersen, Michael J. Cormier, Aaron R. Quinlan and Ryan M. Layer

Genome-wide DNA mutations in Arabidopsis plants after multigenerational exposure to high temperatures

Elevated temperatures can cause physiological, biochemical, and molecular responses in plants that can greatly affect their growth and development. Mutations are the most fundamental force driving biological e...

Authors: Zhaogeng Lu, Jiawen Cui, Li Wang, Nianjun Teng, Shoudong Zhang, Hon-Ming Lam, Yingfang Zhu, Siwei Xiao, Wensi Ke, Jinxing Lin, Chenwu Xu and Biao Jin

Characterization of structural variation in Tibetans reveals new evidence of high-altitude adaptation and introgression

Structural variation (SV) acts as an essential mutational force shaping the evolution and function of the human genome. However, few studies have examined the role of SVs in high-altitude adaptation and little...

Authors: Cheng Quan, Yuanfeng Li, Xinyi Liu, Yahui Wang, Jie Ping, Yiming Lu and Gangqiao Zhou

MichiGAN: sampling from disentangled representations of single-cell data using generative adversarial networks

Deep generative models such as variational autoencoders (VAEs) and generative adversarial networks (GANs) generate and manipulate high-dimensional images. We systematically assess the complementary strengths a...

Authors: Hengshi Yu and Joshua D. Welch

treeclimbR pinpoints the data-dependent resolution of hierarchical hypotheses

treeclimbR is for analyzing hierarchical trees of entities, such as phylogenies or cell types, at different resolutions. It proposes multiple candidates that capture the latent signal and pinpoints branches or le...

Authors: Ruizhu Huang, Charlotte Soneson, Pierre-Luc Germain, Thomas S.B. Schmidt, Christian Von Mering and Mark D. Robinson

A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks

Lung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the ...

Authors: Chongze Yuan, Haojie Chen, Shiqi Tu, Hsin-Yi Huang, Yunjian Pan, Xiuqi Gui, Muyu Kuang, Xuxia Shen, Qiang Zheng, Yang Zhang, Chao Cheng, Hui Hong, Xiaoting Tao, Yizhou Peng, Xingxin Yao, Feilong Meng…

PEPPRO: quality control and processing of nascent RNA profiling data

Nascent RNA profiling is growing in popularity; however, there is no standard analysis pipeline to uniformly process the data and assess quality. Here, we introduce PEPPRO, a comprehensive, scalable workflow f...

Authors: Jason P. Smith, Arun B. Dutta, Kizhakke Mattada Sathyan, Michael J. Guertin and Nathan C. Sheffield

Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune regulatory pathways

The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed at the metastatic stage, and standard therapies have limited activity with a dismal 5-year survival rate of only 8%. The liver and lung ar...

Authors: Won Jin Ho, Rossin Erbe, Ludmila Danilova, Zaw Phyo, Emma Bigelow, Genevieve Stein-O’Brien, Dwayne L. Thomas II, Soren Charmsaz, Nicole Gross, Skylar Woolman, Kayla Cruz, Rebecca M. Munday, Neeha Zaidi, Todd D. Armstrong, Marcelo B. Sztein, Mark Yarchoan…

Novel predictions arise from contradictions

Authors: Itai Yanai and Martin Lercher

On the optimistic performance evaluation of newly introduced bioinformatic methods

Most research articles presenting new data analysis methods claim that “the new method performs better than existing methods,” but the veracity of such statements is questionable. Our manuscript discusses and ...

Authors: Stefan Buchka, Alexander Hapfelmeier, Paul P. Gardner, Rory Wilson and Anne-Laure Boulesteix

Functional mapping of androgen receptor enhancer activity

Androgen receptor (AR) is critical to the initiation, growth, and progression of prostate cancer. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there ...

Authors: Chia-Chi Flora Huang, Shreyas Lingadahalli, Tunc Morova, Dogancan Ozturan, Eugene Hu, Ivan Pak Lok Yu, Simon Linder, Marlous Hoogstraat, Suzan Stelloo, Funda Sar, Henk van der Poel, Umut Berkay Altintas, Mohammadali Saffarzadeh, Stephane Le Bihan, Brian McConeghy, Bengul Gokbayrak…