Articles

MetaCarvel: linking assembly graph motifs to biological variants

Reconstructing genomic segments from metagenomics data is a highly complex task. In addition to general challenges, such as repeats and sequencing errors, metagenomic assembly needs to tolerate the uneven dept...

Authors: Jay Ghurye, Todd Treangen, Marcus Fedarko, W. Judson Hervey IV and Mihai Pop

Maturation of the infant rhesus macaque gut microbiome and its role in the development of diarrheal disease

Diarrhea is the second leading cause of death in children under 5 years of age. Enhanced understanding of causal pathways, pathogenesis, and sequelae of diarrhea is urgently needed. Although the gut microbiota...

Authors: Nicholas Rhoades, Tasha Barr, Sara Hendrickson, Kamm Prongay, Andrew Haertel, Leanne Gill, Laura Garzel, Katrine Whiteson, Mark Slifka and Ilhem Messaoudi

Regulation of rumen development in neonatal ruminants through microbial metagenomes and host transcriptomes

In ruminants, early rumen development is vital for efficient fermentation that converts plant materials to human edible food such as milk and meat. Here, we investigate the extent and functional basis of host-...

Authors: Nilusha Malmuthuge, Guanxiang Liang and Le Luo Guan

Diurnal regulation of SDG2 and JMJ14 by circadian clock oscillators orchestrates histone modification rhythms in Arabidopsis

Circadian rhythms modulate growth and development in all organisms through interlocking transcriptional-translational feedback loops. The transcriptional loop involves chromatin modifications of central circad...

Authors: Qingxin Song, Tien-Yu Huang, Helen H. Yu, Atsumi Ando, Paloma Mas, Misook Ha and Z. Jeffrey Chen

Benchmarking software tools for detecting and quantifying selection in evolve and resequencing studies

The combination of experimental evolution with whole-genome resequencing of pooled individuals, also called evolve and resequence (E&R) is a powerful approach to study the selection processes and to infer the ...

Authors: Christos Vlachos, Claire Burny, Marta Pelizzola, Rui Borges, Andreas Futschik, Robert Kofler and Christian Schlötterer

An enhanced genetic model of colorectal cancer progression history

The classical genetic model of colorectal cancer presents APC mutations as the earliest genomic alterations, followed by KRAS and TP53 mutations. However, the timing and relative order of clonal expansion and oth...

Authors: Lixing Yang, Su Wang, Jake June-Koo Lee, Semin Lee, Eunjung Lee, Eve Shinbrot, David A. Wheeler, Raju Kucherlapati and Peter J. Park

AlleleAnalyzer: a tool for personalized and allele-specific sgRNA design

The CRISPR/Cas system is a highly specific genome editing tool capable of distinguishing alleles differing by even a single base pair. Target sites might carry genetic variations that are not distinguishable b...

Authors: Kathleen C. Keough, Svetlana Lyalina, Michael P. Olvera, Sean Whalen, Bruce R. Conklin and Katherine S. Pollard

scAlign: a tool for alignment, integration, and rare cell identification from scRNA-seq data

scRNA-seq dataset integration occurs in different contexts, such as the identification of cell type-specific differences in gene expression across conditions or species, or batch effect correction. We present ...

Authors: Nelson Johansen and Gerald Quon

Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1

Epigenetic clocks are mathematical models that predict the biological age of an individual using DNA methylation data and have emerged in the last few years as the most accurate biomarkers of the aging process...

Authors: Daniel E. Martin-Herranz, Erfan Aref-Eshghi, Marc Jan Bonder, Thomas M. Stubbs, Sanaa Choufani, Rosanna Weksberg, Oliver Stegle, Bekim Sadikovic, Wolf Reik and Janet M. Thornton

BERMUDA: a novel deep transfer learning method for single-cell RNA sequencing batch correction reveals hidden high-resolution cellular subtypes

To fully utilize the power of single-cell RNA sequencing (scRNA-seq) technologies for identifying cell lineages and bona fide transcriptional signals, it is necessary to combine data from multiple experiments....

Authors: Tongxin Wang, Travis S. Johnson, Wei Shao, Zixiao Lu, Bryan R. Helm, Jie Zhang and Kun Huang

The bio.tools registry of software tools and data resources for the life sciences

Bioinformaticians and biologists rely increasingly upon workflows for the flexible utilization of the many life science tools that are needed to optimally convert data into knowledge. We outline a pan-European...

Authors: Jon Ison, Hans Ienasescu, Piotr Chmura, Emil Rydza, Hervé Ménager, Matúš Kalaš, Veit Schwämmle, Björn Grüning, Niall Beard, Rodrigo Lopez, Severine Duvaud, Heinz Stockinger, Bengt Persson, Radka Svobodová Vařeková, Tomáš Raček, Jiří Vondrášek…

Analysis of Vibrio cholerae genomes identifies new type VI secretion system gene clusters

Like many bacteria, Vibrio cholerae deploys a harpoon-like type VI secretion system (T6SS) to compete against other microbes in environmental and host settings. The T6SS punctures adjacent cells and delivers toxi...

Authors: Cristian V. Crisan, Aroon T. Chande, Kenneth Williams, Vishnu Raghuram, Lavanya Rishishwar, Gabi Steinbach, Samit S. Watve, Peter Yunker, I. King Jordan and Brian K. Hammer

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes

General translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These eleme...

Authors: Jingyi Jessica Li, Guo-Liang Chew and Mark Douglas Biggin

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

Following publication of the original article [1], the authors reported that the Availability of data and materials section required updating. The updated text reads as follows:

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

Correction to: Identification of novel Y chromosome encoded transcripts by testis transcriptome analysis of mice with deletions of the Y chromosome long arm

Following publication of the original article [1], the following error was reported: The actin control panel in Fig. 3 of this paper is reproduced from Fig. 7 of Touré et al, 2004 [2] by kind permission of the...

Authors: Aminata Touré, Emily J. Clemente, Peter J. I. Ellis, Shantha K. Mahadevaiah, Obah A. Ojarikre, Penny A. F. Ball, Louise Reynard, Kate L. Loveland, Paul S. Burgoyne and Nabeel A. Affara

Is it time to change the reference genome?

The use of the human reference genome has shaped methods and data across modern genomics. This has offered many benefits while creating a few constraints. In the following opinion, we outline the history, prop...

Authors: Sara Ballouz, Alexander Dobin and Jesse A. Gillis

A systematic assessment of current genome-scale metabolic reconstruction tools

Several genome-scale metabolic reconstruction software platforms have been developed and are being continuously updated. These tools have been widely applied to reconstruct metabolic models for hundreds of mic...

Authors: Sebastián N. Mendoza, Brett G. Olivier, Douwe Molenaar and Bas Teusink

Linker histones are fine-scale chromatin architects modulating developmental decisions in Arabidopsis

Chromatin provides a tunable platform for gene expression control. Besides the well-studied core nucleosome, H1 linker histones are abundant chromatin components with intrinsic potential to influence chromatin...

Authors: Kinga Rutowicz, Maciej Lirski, Benoît Mermaz, Gianluca Teano, Jasmin Schubert, Imen Mestiri, Magdalena A. Kroteń, Tohnyui Ndinyanka Fabrice, Simon Fritz, Stefan Grob, Christoph Ringli, Lusik Cherkezyan, Fredy Barneche, Andrzej Jerzmanowski and Célia Baroux

RNA methylomes reveal the m⁶A-mediated regulation of DNA demethylase gene SlDML2 in tomato fruit ripening

Methylation of nucleotides, notably in the forms of 5-methylcytosine (5mC) in DNA and N⁶-methyladenosine (m⁶A) in mRNA, carries important information for gene regulation. 5mC has been elucidated to participate in...

Authors: Leilei Zhou, Shiping Tian and Guozheng Qin

BART-Seq: cost-effective massively parallelized targeted sequencing for genomics, transcriptomics, and single-cell analysis

We describe a highly sensitive, quantitative, and inexpensive technique for targeted sequencing of transcript cohorts or genomic regions from thousands of bulk samples or single cells in parallel. Multiplexing...

Authors: Fatma Uzbas, Florian Opperer, Can Sönmezer, Dmitry Shaposhnikov, Steffen Sass, Christian Krendl, Philipp Angerer, Fabian J. Theis, Nikola S. Mueller and Micha Drukker

MicroPro: using metagenomic unmapped reads to provide insights into human microbiota and disease associations

We develop a metagenomic data analysis pipeline, MicroPro, that takes into account all reads from known and unknown microbial organisms and associates viruses with complex diseases. We utilize MicroPro to anal...

Authors: Zifan Zhu, Jie Ren, Sonia Michail and Fengzhu Sun

Assignment of virus and antimicrobial resistance genes to microbial hosts in a complex microbial community by combined long-read assembly and proximity ligation

We describe a method that adds long-read sequencing to a mix of technologies used to assemble a highly complex cattle rumen microbial community, and provide a comparison to short read-based methods. Long-read ...

Authors: Derek M. Bickhart, Mick Watson, Sergey Koren, Kevin Panke-Buisse, Laura M. Cersosimo, Maximilian O. Press, Curtis P. Van Tassell, Jo Ann S. Van Kessel, Bradd J. Haley, Seon Woo Kim, Cheryl Heiner, Garret Suen, Kiranmayee Bakshy, Ivan Liachko, Shawn T. Sullivan, Phillip R. Myer…

A statistical and biological response to an informatics appraisal of healthy aging gene signatures

Jacob and Speed did not identify even a single example of a ‘150-gene-set’ that was statistically significant at classifying Alzheimer’s disease (AD) samples, or age in independent studies. We attempt to clari...

Authors: James A. Timmons, Iain J. Gallagher, Sanjana Sood, Bethan Phillips, Hannah Crossland, Robert Howard, William E. Kraus and Philip J. Atherton

Alternative splicing is required for stage differentiation in malaria parasites

In multicellular organisms, alternative splicing is central to tissue differentiation and identity. Unicellular protists lack multicellular tissue but differentiate into variable cell types during their life c...

Authors: Lee M. Yeoh, Christopher D. Goodman, Vanessa Mollard, Emma McHugh, V. Vern Lee, Angelika Sturm, Anton Cozijnsen, Geoffrey I. McFadden and Stuart A. Ralph

Population dynamics of the human gut microbiome: change is the only constant

Characterization of the temporal dynamics of the human gut microbiome is crucial for understanding its role in modulating host health. Two recent studies explored the genetic diversity of gut microbes and unra...

Authors: Sambhawa Priya and Ran Blekhman

HUPAN: a pan-genome analysis pipeline for human genomes

The human reference genome is still incomplete, especially for those population-specific or individual-specific regions, which may have important functions. Here, we developed a HUman Pan-genome ANalysis (HUPA...

Authors: Zhongqu Duan, Yuyang Qiao, Jinyuan Lu, Huimin Lu, Wenmin Zhang, Fazhe Yan, Chen Sun, Zhiqiang Hu, Zhen Zhang, Guichao Li, Hongzhuan Chen, Zhen Xiang, Zhenggang Zhu, Hongyu Zhao, Yingyan Yu and Chaochun Wei

Spatial chromatin architecture alteration by structural variations in human genomes at the population scale

The number of reported examples of chromatin architecture alterations involved in the regulation of gene transcription and in disease is increasing. However, no genome-wide testing has been performed to assess...

Authors: Michal Sadowski, Agnieszka Kraft, Przemyslaw Szalaj, Michal Wlasnowolski, Zhonghui Tang, Yijun Ruan and Dariusz Plewczynski

Challenges in funding and developing genomic software: roots and remedies

The computer software used for genomic analysis has become a crucial component of the infrastructure for life sciences. However, genomic software is still typically developed in an ad hoc manner, with inadequa...

Authors: Adam Siepel

Modulating chromatin accessibility by transactivation and targeting proximal dsgRNAs enhances Cas9 editing efficiency in vivo

The CRISPR/Cas9 system is unable to edit all targetable genomic sites with full efficiency in vivo. We show that Cas9-mediated editing is more efficient in open chromatin regions than in closed chromatin regio...

Authors: Guanwen Liu, Kangquan Yin, Qianwei Zhang, Caixia Gao and Jin-Long Qiu

Benchmarking of alignment-free sequence comparison methods

Alignment-free (AF) sequence comparison is attracting persistent interest driven by data-intensive applications. Hence, many AF procedures have been proposed in recent years, but a lack of a clearly defined be...

Authors: Andrzej Zielezinski, Hani Z. Girgis, Guillaume Bernard, Chris-Andre Leimeister, Kujin Tang, Thomas Dencker, Anna Katharina Lau, Sophie Röhling, Jae Jin Choi, Michael S. Waterman, Matteo Comin, Sung-Hou Kim, Susana Vinga, Jonas S. Almeida, Cheong Xin Chan, Benjamin T. James…

RaPID: ultra-fast, powerful, and accurate detection of segments identical by descent (IBD) in biobank-scale cohorts

While genetic relatedness, usually manifested as segments identical by descent (IBD), is ubiquitous in modern large biobanks, current IBD detection methods are not efficient at such a scale. Here, we describe ...

Authors: Ardalan Naseri, Xiaoming Liu, Kecong Tang, Shaojie Zhang and Degui Zhi

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