Articles

Terminating contamination: large-scale search identifies more than 2,000,000 contaminated entries in GenBank

Genomic analyses are sensitive to contamination in public databases caused by incorrectly labeled reference sequences. Here, we describe Conterminator, an efficient method to detect and remove incorrectly labe...

Authors: Martin Steinegger and Steven L. Salzberg

Insights gained from a comprehensive all-against-all transcription factor binding motif benchmarking study

Positional weight matrix (PWM) is a de facto standard model to describe transcription factor (TF) DNA binding specificities. PWMs inferred from in vivo or in vitro data are stored in many databases and used in...

Authors: Giovanna Ambrosini, Ilya Vorontsov, Dmitry Penzar, Romain Groux, Oriol Fornes, Daria D. Nikolaeva, Benoit Ballester, Jan Grau, Ivo Grosse, Vsevolod Makeev, Ivan Kulakovskiy and Philipp Bucher

Effects of the COVID-19 pandemic on life scientists

Authors: Jan O. Korbel and Oliver Stegle

Sampling time-dependent artifacts in single-cell genomics studies

Robust protocols and automation now enable large-scale single-cell RNA and ATAC sequencing experiments and their application on biobank and clinical cohorts. However, technical biases introduced during sample ...

Authors: Ramon Massoni-Badosa, Giovanni Iacono, Catia Moutinho, Marta Kulis, Núria Palau, Domenica Marchese, Javier Rodríguez-Ubreva, Esteban Ballestar, Gustavo Rodriguez-Esteban, Sara Marsal, Marta Aymerich, Dolors Colomer, Elias Campo, Antonio Julià, José Ignacio Martín-Subero and Holger Heyn

MOFA+: a statistical framework for comprehensive integration of multi-modal single-cell data

Technological advances have enabled the profiling of multiple molecular layers at single-cell resolution, assaying cells from multiple samples or conditions. Consequently, there is a growing need for computati...

Authors: Ricard Argelaguet, Damien Arnol, Danila Bredikhin, Yonatan Deloro, Britta Velten, John C. Marioni and Oliver Stegle

Chromatin topology reorganization and transcription repression by PML-RARα in acute promyeloid leukemia

Acute promyeloid leukemia (APL) is characterized by the oncogenic fusion protein PML-RARα, a major etiological agent in APL. However, the molecular mechanisms underlying the role of PML-RARα in leukemogenesis ...

Authors: Ping Wang, Zhonghui Tang, Byoungkoo Lee, Jacqueline Jufen Zhu, Liuyang Cai, Przemyslaw Szalaj, Simon Zhongyuan Tian, Meizhen Zheng, Dariusz Plewczynski, Xiaoan Ruan, Edison T. Liu, Chia-Lin Wei and Yijun Ruan

Compressing gene expression data using multiple latent space dimensionalities learns complementary biological representations

Unsupervised compression algorithms applied to gene expression data extract latent or hidden signals representing technical and biological sources of variation. However, these algorithms require a user to sele...

Authors: Gregory P. Way, Michael Zietz, Vincent Rubinetti, Daniel S. Himmelstein and Casey S. Greene

Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation

Ubiquitously expressed CTCF is involved in numerous cellular functions, such as organizing chromatin into TAD structures. In contrast, its paralog, CTCFL, is normally only present in the testis. However, it is...

Authors: Mayilaadumveettil Nishana, Caryn Ha, Javier Rodriguez-Hernaez, Ali Ranjbaran, Erica Chio, Elphege P. Nora, Sana B. Badri, Andreas Kloetgen, Benoit G. Bruneau, Aristotelis Tsirigos and Jane A. Skok

A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk

Tumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions betwee...

Authors: Andrew J. Gentles, Angela Bik-Yu Hui, Weiguo Feng, Armon Azizi, Ramesh V. Nair, Gina Bouchard, David A. Knowles, Alice Yu, Youngtae Jeong, Alborz Bejnood, Erna Forgó, Sushama Varma, Yue Xu, Amanda Kuong, Viswam S. Nair, Rob West…

Integrative analyses of the RNA modification machinery reveal tissue- and cancer-specific signatures

RNA modifications play central roles in cellular fate and differentiation. However, the machinery responsible for placing, removing, and recognizing more than 170 RNA modifications remains largely uncharacteri...

Authors: Oguzhan Begik, Morghan C. Lucas, Huanle Liu, Jose Miguel Ramirez, John S. Mattick and Eva Maria Novoa

Single-cell RNA-seq with spike-in cells enables accurate quantification of cell-specific drug effects in pancreatic islets

Single-cell RNA-seq (scRNA-seq) is emerging as a powerful tool to dissect cell-specific effects of drug treatment in complex tissues. This application requires high levels of precision, robustness, and quantit...

Authors: Brenda Marquina-Sanchez, Nikolaus Fortelny, Matthias Farlik, Andhira Vieira, Patrick Collombat, Christoph Bock and Stefan Kubicek

What are innovations in peer review and editorial assessment for?

Authors: Willem Halffman and Serge P.J.M Horbach

Open access, open data and peer review

Authors: Jernej Ule

In memory of James Taylor: the birth of Galaxy

Authors: Anton Nekrutenko and Michael C. Schatz

Wheat chromatin architecture is organized in genome territories and transcription factories

Polyploidy is ubiquitous in eukaryotic plant and fungal lineages, and it leads to the co-existence of several copies of similar or related genomes in one nucleus. In plants, polyploidy is considered a major fa...

Authors: Lorenzo Concia, Alaguraj Veluchamy, Juan S. Ramirez-Prado, Azahara Martin-Ramirez, Ying Huang, Magali Perez, Severine Domenichini, Natalia Y. Rodriguez Granados, Soonkap Kim, Thomas Blein, Susan Duncan, Clement Pichot, Deborah Manza-Mianza, Caroline Juery, Etienne Paux, Graham Moore…

CCMetagen: comprehensive and accurate identification of eukaryotes and prokaryotes in metagenomic data

There is an increasing demand for accurate and fast metagenome classifiers that can not only identify bacteria, but all members of a microbial community. We used a recently developed concept in read mapping to...

Authors: Vanessa R. Marcelino, Philip T. L. C. Clausen, Jan P. Buchmann, Michelle Wille, Jonathan R. Iredell, Wieland Meyer, Ole Lund, Tania C. Sorrell and Edward C. Holmes

ExpansionHunter Denovo: a computational method for locating known and novel repeat expansions in short-read sequencing data

Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat expansions remain to be discovered. Existing methods for detecting repeat expansions in short-read sequ...

Authors: Egor Dolzhenko, Mark F. Bennett, Phillip A. Richmond, Brett Trost, Sai Chen, Joke J. F. A. van Vugt, Charlotte Nguyen, Giuseppe Narzisi, Vladimir G. Gainullin, Andrew M. Gross, Bryan R. Lajoie, Ryan J. Taft, Wyeth W. Wasserman, Stephen W. Scherer, Jan H. Veldink, David R. Bentley…

CircAtlas: an integrated resource of one million highly accurate circular RNAs from 1070 vertebrate transcriptomes

Existing circular RNA (circRNA) databases have become essential for transcriptomics. However, most are unsuitable for mining in-depth information for candidate circRNA prioritization. To address this, we integ...

Authors: Wanying Wu, Peifeng Ji and Fangqing Zhao

REPIC: a database for exploring the N⁶-methyladenosine methylome

The REPIC (RNA EPItranscriptome Collection) database records about 10 million peaks called from publicly available m⁶A-seq and MeRIP-seq data using our unified pipeline. These data were collected from 672 samples...

Authors: Shun Liu, Allen Zhu, Chuan He and Mengjie Chen

Influenza infection elicits an expansion of gut population of endogenous Bifidobacterium animalis which protects mice against infection

Influenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanis...

Authors: Qiang Zhang, Jin Hu, Jia-Wu Feng, Xiao-Tong Hu, Ting Wang, Wen-Xiao Gong, Kun Huang, Yi-Xiong Guo, Zhong Zou, Xian Lin, Run Zhou, Yu-Qi Yuan, An-Ding Zhang, Hong Wei, Gang Cao, Chen Liu…

Varlociraptor: enhancing sensitivity and controlling false discovery rate in somatic indel discovery

Accurate discovery of somatic variants is of central importance in cancer research. However, count statistics on discovered somatic insertions and deletions (indels) indicate that large amounts of discoveries ...

Authors: Johannes Köster, Louis J. Dijkstra, Tobias Marschall and Alexander Schönhuth

Open data in a deeply connected world

Authors: Barbara Cheifet

Hi-D: nanoscale mapping of nuclear dynamics in single living cells

Bulk chromatin motion has not been analyzed at high resolution. We present Hi-D, a method to quantitatively map dynamics of chromatin and abundant nuclear proteins for every pixel simultaneously over the entir...

Authors: Haitham A. Shaban, Roman Barth, Ludmila Recoules and Kerstin Bystricky

scATAC-pro: a comprehensive workbench for single-cell chromatin accessibility sequencing data

Single-cell chromatin accessibility sequencing has become a powerful technology for understanding epigenetic heterogeneity of complex tissues. However, there is a lack of open-source software for comprehensive...

Authors: Wenbao Yu, Yasin Uzun, Qin Zhu, Changya Chen and Kai Tan

Reverse-genetics studies of lncRNAs—what we have learnt and paths forward

Long non-coding RNAs (lncRNAs) represent a major fraction of the transcriptome in multicellular organisms. Although a handful of well-studied lncRNAs are broadly recognized as biologically meaningful, the frac...

Authors: Fan Gao, Ye Cai, Philipp Kapranov and Dongyang Xu

Inference of single-cell phylogenies from lineage tracing data using Cassiopeia

The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpace...

Authors: Matthew G Jones, Alex Khodaverdian, Jeffrey J Quinn, Michelle M Chan, Jeffrey A Hussmann, Robert Wang, Chenling Xu, Jonathan S Weissman and Nir Yosef

A multidimensional systems biology analysis of cellular senescence in aging and disease

Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescenc...

Authors: Roberto A. Avelar, Javier Gómez Ortega, Robi Tacutu, Eleanor J. Tyler, Dominic Bennett, Paolo Binetti, Arie Budovsky, Kasit Chatsirisupachai, Emily Johnson, Alex Murray, Samuel Shields, Daniela Tejada-Martinez, Daniel Thornton, Vadim E. Fraifeld, Cleo L. Bishop and João Pedro de Magalhães

Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets ...

Authors: Eric L. Van Nostrand, Gabriel A. Pratt, Brian A. Yee, Emily C. Wheeler, Steven M. Blue, Jasmine Mueller, Samuel S. Park, Keri E. Garcia, Chelsea Gelboin-Burkhart, Thai B. Nguyen, Ines Rabano, Rebecca Stanton, Balaji Sundararaman, Ruth Wang, Xiang-Dong Fu, Brenton R. Graveley…

The preceding root system drives the composition and function of the rhizosphere microbiome

The soil environment is responsible for sustaining most terrestrial plant life, yet we know surprisingly little about the important functions carried out by diverse microbial communities in soil. Soil microbes...

Authors: Yi Zhou, David R. Coventry, Vadakattu V. S. R. Gupta, David Fuentes, Andrew Merchant, Brent N. Kaiser, Jishun Li, Yanli Wei, Huan Liu, Yayu Wang, Shuheng Gan and Matthew D. Denton

Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing

Epigenome-wide association studies (EWAS), which seek the association between epigenetic marks and an outcome or exposure, involve multiple hypothesis testing. False discovery rate (FDR) control has been widel...

Authors: Jinyan Huang, Ling Bai, Bowen Cui, Liang Wu, Liwen Wang, Zhiyin An, Shulin Ruan, Yue Yu, Xianyang Zhang and Jun Chen

Lamina-associated domains: peripheral matters and internal affairs

At the nuclear periphery, associations of chromatin with the nuclear lamina through lamina-associated domains (LADs) aid functional organization of the genome. We review the organization of LADs and provide ev...

Authors: Nolwenn Briand and Philippe Collas

TADsplimer reveals splits and mergers of topologically associating domains for epigenetic regulation of transcription

We present TADsplimer, the first computational tool to systematically detect topologically associating domain (TAD) splits and mergers across the genome between Hi-C samples. TADsplimer recaptures splits and m...

Authors: Guangyu Wang, Qingshu Meng, Bo Xia, Shuo Zhang, Jie Lv, Dongyu Zhao, Yanqiang Li, Xin Wang, Lili Zhang, John P. Cooke, Qi Cao and Kaifu Chen

Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome

Epigenetic modifications, including DNA methylation, play an important role in gene silencing and genome stability. Consequently, epigenetic dysregulation can cause several diseases, such as cancer, obesity, d...

Authors: Takuro Horii, Sumiyo Morita, Shinjiro Hino, Mika Kimura, Yuko Hino, Hiroshi Kogo, Mitsuyoshi Nakao and Izuho Hatada

CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma

Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not ...

Authors: S. John Liu, Martina Malatesta, Brian V. Lien, Parna Saha, Shivani S. Thombare, Sung Jun Hong, Leslie Pedraza, Mark Koontz, Kyounghee Seo, Max A. Horlbeck, Daniel He, Harjus S. Birk, Miten Jain, Hugh E. Olsen, Mark Akeson, Jonathan S. Weissman…

Completing the ENCODE3 compendium yields accurate imputations across a variety of assays and human biosamples

Recent efforts to describe the human epigenome have yielded thousands of epigenomic and transcriptomic datasets. However, due primarily to cost, the total number of such assays that can be performed is limited...

Authors: Jacob Schreiber, Jeffrey Bilmes and William Stafford Noble

Avocado: a multi-scale deep tensor factorization method learns a latent representation of the human epigenome

The human epigenome has been experimentally characterized by thousands of measurements for every basepair in the human genome. We propose a deep neural network tensor factorization method, Avocado, that compre...

Authors: Jacob Schreiber, Timothy Durham, Jeffrey Bilmes and William Stafford Noble

Characterisation of genetic regulatory effects for osteoporosis risk variants in human osteoclasts

Osteoporosis is a complex disease with a strong genetic contribution. A recently published genome-wide association study (GWAS) for estimated bone mineral density (eBMD) identified 1103 independent genome-wide...

Authors: Benjamin H. Mullin, Jennifer Tickner, Kun Zhu, Jacob Kenny, Shelby Mullin, Suzanne J. Brown, Frank Dudbridge, Nathan J. Pavlos, Edward S. Mocarski, John P. Walsh, Jiake Xu and Scott G. Wilson

DeepMILO: a deep learning approach to predict the impact of non-coding sequence variants on 3D chromatin structure

Non-coding variants have been shown to be related to disease by alteration of 3D genome structures. We propose a deep learning method, DeepMILO, to predict the effects of variants on CTCF/cohesin-mediated insu...

Authors: Tuan Trieu, Alexander Martinez-Fundichely and Ekta Khurana

Diverse genetic mechanisms underlie worldwide convergent rice feralization

Worldwide feralization of crop species into agricultural weeds threatens global food security. Weedy rice is a feral form of rice that infests paddies worldwide and aggressively outcompetes cultivated varietie...

Authors: Jie Qiu, Lei Jia, Dongya Wu, Xifang Weng, Lijuan Chen, Jian Sun, Meihong Chen, Lingfeng Mao, Bowen Jiang, Chuyu Ye, Guilherme Menegol Turra, Longbiao Guo, Guoyou Ye, Qian-Hao Zhu, Toshiyuki Imaizumi, Beng-Kah Song…

A Cas12a ortholog with stringent PAM recognition followed by low off-target editing rates for genome editing

AsCas12a and LbCas12a nucleases are reported to be promising tools for genome engineering with protospacer adjacent motif (PAM) TTTV as the optimal. However, the C-containing PAM (CTTV, TCTV, TTCV, etc.) recog...

Authors: Peng Chen, Jin Zhou, Yibin Wan, Huan Liu, Yongzheng Li, Zhaoxin Liu, Hongjian Wang, Jun Lei, Kai Zhao, Yiliang Zhang, Yan Wang, Xinghua Zhang and Lei Yin

High-resolution Repli-Seq defines the temporal choreography of initiation, elongation and termination of replication in mammalian cells

DNA replication in mammalian cells occurs in a defined temporal order during S phase, known as the replication timing (RT) programme. Replication timing is developmentally regulated and correlated with chromat...

Authors: Peiyao A. Zhao, Takayo Sasaki and David M. Gilbert

Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection

CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem.

Authors: Zhilian Jia, Jingwei Li, Xiao Ge, Yonghu Wu, Ya Guo and Qiang Wu

Obstacles to detecting isoforms using full-length scRNA-seq data

Early single-cell RNA-seq (scRNA-seq) studies suggested that it was unusual to see more than one isoform being produced from a gene in a single cell, even when multiple isoforms were detected in matched bulk R...

Authors: Jennifer Westoby, Pavel Artemov, Martin Hemberg and Anne Ferguson-Smith

HiNT: a computational method for detecting copy number variations and translocations from Hi-C data

The three-dimensional conformation of a genome can be profiled using Hi-C, a technique that combines chromatin conformation capture with high-throughput sequencing. However, structural variations often yield f...

Authors: Su Wang, Soohyun Lee, Chong Chu, Dhawal Jain, Peter Kerpedjiev, Geoffrey M. Nelson, Jennifer M. Walsh, Burak H. Alver and Peter J. Park

Decode-seq: a practical approach to improve differential gene expression analysis

Many differential gene expression analyses are conducted with an inadequate number of biological replicates. We describe an easy and effective RNA-seq approach using molecular barcoding to enable profiling of ...

Authors: Yingshu Li, Hang Yang, Hujun Zhang, Yongjie Liu, Hanqiao Shang, Herong Zhao, Ting Zhang and Qiang Tu

VALOR2: characterization of large-scale structural variants using linked-reads

Most existing methods for structural variant detection focus on discovery and genotyping of deletions, insertions, and mobile elements. Detection of balanced structural variants with no gain or loss of genomic...

Authors: Fatih Karaoğlanoğlu, Camir Ricketts, Ezgi Ebren, Marzieh Eslami Rasekh, Iman Hajirasouliha and Can Alkan

Benchmarking of computational error-correction methods for next-generation sequencing data

Recent advancements in next-generation sequencing have rapidly improved our ability to study genomic material at an unprecedented scale. Despite substantial improvements in sequencing technologies, errors pres...

Authors: Keith Mitchell, Jaqueline J. Brito, Igor Mandric, Qiaozhen Wu, Sergey Knyazev, Sei Chang, Lana S. Martin, Aaron Karlsberg, Ekaterina Gerasimov, Russell Littman, Brian L. Hill, Nicholas C. Wu, Harry Taegyun Yang, Kevin Hsieh, Linus Chen, Eli Littman…

BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty

Alternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we p...

Authors: Simone Tiberi and Mark D. Robinson

Ultraplexing: increasing the efficiency of long-read sequencing for hybrid assembly with k-mer-based multiplexing

Hybrid genome assembly has emerged as an important technique in bacterial genomics, but cost and labor requirements limit large-scale application. We present Ultraplexing, a method to improve per-sample sequen...

Authors: Alexander T. Dilthey, Sebastian A. Meyer and Achim J. Kaasch

Renaissance minds in 21st century science

Authors: Itai Yanai and Martin Lercher