Articles

Genetic variation and microRNA targeting of A-to-I RNA editing fine tune human tissue transcriptomes

A-to-I RNA editing diversifies the transcriptome and has multiple downstream functional effects. Genetic variation contributes to RNA editing variability between individuals and has the potential to impact phe...

Authors: Eddie Park, Yan Jiang, Lili Hao, Jingyi Hui and Yi Xing

riboCIRC: a comprehensive database of translatable circRNAs

riboCIRC is a translatome data-oriented circRNA database specifically designed for hosting, exploring, analyzing, and visualizing translatable circRNAs from multi-species. The database provides a comprehensive...

Authors: Huihui Li, Mingzhe Xie, Yan Wang, Ludong Yang, Zhi Xie and Hongwei Wang

Giotto: a toolbox for integrative analysis and visualization of spatial expression data

Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive and open-source toolbox for spat...

Authors: Ruben Dries, Qian Zhu, Rui Dong, Chee-Huat Linus Eng, Huipeng Li, Kan Liu, Yuntian Fu, Tianxiao Zhao, Arpan Sarkar, Feng Bao, Rani E. George, Nico Pierson, Long Cai and Guo-Cheng Yuan

Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells

The discovery that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) has provided a foundation for in vitro human disease modelling, drug development and population genetics studies. ...

Authors: Drew Neavin, Quan Nguyen, Maciej S. Daniszewski, Helena H. Liang, Han Sheng Chiu, Yong Kiat Wee, Anne Senabouth, Samuel W. Lukowski, Duncan E. Crombie, Grace E. Lidgerwood, Damián Hernández, James C. Vickers, Anthony L. Cook, Nathan J. Palpant, Alice Pébay, Alex W. Hewitt…

seqQscorer: automated quality control of next-generation sequencing data using machine learning

Controlling quality of next-generation sequencing (NGS) data files is a necessary but complex task. To address this problem, we statistically characterize common NGS quality features and develop a novel qualit...

Authors: Steffen Albrecht, Maximilian Sprang, Miguel A. Andrade-Navarro and Jean-Fred Fontaine

simATAC: a single-cell ATAC-seq simulation framework

Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) identifies regulated chromatin accessibility modules at the single-cell resolution. Robust evaluation is critical to the developme...

Authors: Zeinab Navidi, Lin Zhang and Bo Wang

Pluripotent stem cell-derived models of neurological diseases reveal early transcriptional heterogeneity

Many neurodegenerative diseases develop only later in life, when cells in the nervous system lose their structure or function. In many forms of neurodegenerative diseases, this late-onset phenomenon remains la...

Authors: Matan Sorek, Walaa Oweis, Malka Nissim-Rafinia, Moria Maman, Shahar Simon, Cynthia C. Hession, Xian Adiconis, Sean K. Simmons, Neville E. Sanjana, Xi Shi, Congyi Lu, Jen Q. Pan, Xiaohong Xu, Mahmoud A. Pouladi, Lisa M. Ellerby, Feng Zhang…

2passtools: two-pass alignment using machine-learning-filtered splice junctions increases the accuracy of intron detection in long-read RNA sequencing

Transcription of eukaryotic genomes involves complex alternative processing of RNAs. Sequencing of full-length RNAs using long reads reveals the true complexity of processing. However, the relatively high erro...

Authors: Matthew T. Parker, Katarzyna Knop, Geoffrey J. Barton and Gordon G. Simpson

Re-evaluating experimental validation in the Big Data Era: a conceptual argument

Authors: Mohieddin Jafari, Yuanfang Guan, David C. Wedge and Naser Ansari-Pour

MEDALT: single-cell copy number lineage tracing enabling gene discovery

We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine...

Authors: Fang Wang, Qihan Wang, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jincheng Han, Darlan Conterno Minussi, Ruli Gao, Li Ding, Nicholas Navin and Ken Chen

scSorter: assigning cells to known cell types according to marker genes

On single-cell RNA-sequencing data, we consider the problem of assigning cells to known cell types, assuming that the identities of cell-type-specific marker genes are given but their exact expression levels a...

Authors: Hongyu Guo and Jun Li

Megabase-scale methylation phasing using nanopore long reads and NanoMethPhase

The ability of nanopore sequencing to simultaneously detect modified nucleotides while producing long reads makes it ideal for detecting and phasing allele-specific methylation. However, there is currently no ...

Authors: Vahid Akbari, Jean-Michel Garant, Kieran O’Neill, Pawan Pandoh, Richard Moore, Marco A. Marra, Martin Hirst and Steven J. M. Jones

ReSeq simulates realistic Illumina high-throughput sequencing data

In high-throughput sequencing data, performance comparisons between computational tools are essential for making informed decisions at each step of a project. Simulations are a critical part of method comparis...

Authors: Stephan Schmeing and Mark D. Robinson

FlsnRNA-seq: protoplasting-free full-length single-nucleus RNA profiling in plants

The broad application of single-cell RNA profiling in plants has been hindered by the prerequisite of protoplasting that requires digesting the cell walls from different types of plant tissues. Here, we presen...

Authors: Yanping Long, Zhijian Liu, Jinbu Jia, Weipeng Mo, Liang Fang, Dongdong Lu, Bo Liu, Hong Zhang, Wei Chen and Jixian Zhai

Promoting reproducibility with Code Ocean

Authors: Barbara Cheifet

Addressing uncertainty in genome-scale metabolic model reconstruction and analysis

The reconstruction and analysis of genome-scale metabolic models constitutes a powerful systems biology approach, with applications ranging from basic understanding of genotype-phenotype mapping to solving bio...

Authors: David B. Bernstein, Snorre Sulheim, Eivind Almaas and Daniel Segrè

iMAP: integration of multiple single-cell datasets by adversarial paired transfer networks

The integration of single-cell RNA-sequencing datasets from multiple sources is critical for deciphering cell-to-cell heterogeneities and interactions in complex biological systems. We present a novel unsuperv...

Authors: Dongfang Wang, Siyu Hou, Lei Zhang, Xiliang Wang, Baolin Liu and Zemin Zhang

LINE retrotransposons characterize mammalian tissue-specific and evolutionarily dynamic regulatory regions

To investigate the mechanisms driving regulatory evolution across tissues, we experimentally mapped promoters, enhancers, and gene expression in the liver, brain, muscle, and testis from ten diverse mammals.

Authors: Maša Roller, Ericca Stamper, Diego Villar, Osagie Izuogu, Fergal Martin, Aisling M. Redmond, Raghavendra Ramachanderan, Louise Harewood, Duncan T. Odom and Paul Flicek

CellWalker integrates single-cell and bulk data to resolve regulatory elements across cell types in complex tissues

Single-cell and bulk genomics assays have complementary strengths and weaknesses, and alone neither strategy can fully capture regulatory elements across the diversity of cells in complex tissues. We present C...

Authors: Pawel F. Przytycki and Katherine S. Pollard

Author Correction: Assembly of hundreds of novel bacterial genomes from the chicken caecum

An amendment to this paper has been published and can be accessed via the original article.

Authors: Laura Glendinning, Robert D. Stewart, Mark J. Pallen, Kellie A. Watson and Mick Watson

Data bias

Authors: Teppo Felin, Jan Koenderink, Joachim I. Krueger, Denis Noble and George F. R. Ellis

The data-hypothesis conversation

Authors: Itai Yanai and Martin Lercher

The data-hypothesis relationship

Authors: Teppo Felin, Jan Koenderink, Joachim I. Krueger, Denis Noble and George F.R. Ellis

3 ^′-5 ^′ crosstalk contributes to transcriptional bursting

Transcription in mammalian cells is a complex stochastic process involving shuttling of polymerase between genes and phase-separated liquid condensates. It occurs in bursts, which results in vastly different n...

Authors: Massimo Cavallaro, Mark D. Walsh, Matt Jones, James Teahan, Simone Tiberi, Bärbel Finkenstädt and Daniel Hebenstreit

GeneWalk identifies relevant gene functions for a biological context using network representation learning

A bottleneck in high-throughput functional genomics experiments is identifying the most important genes and their relevant functions from a list of gene hits. Gene Ontology (GO) enrichment methods provide insi...

Authors: Robert Ietswaart, Benjamin M. Gyori, John A. Bachman, Peter K. Sorger and L. Stirling Churchman

A comprehensive enhancer screen identifies TRAM2 as a key and novel mediator of YAP oncogenesis

Frequent activation of the co-transcriptional factor YAP is observed in a large number of solid tumors. Activated YAP associates with enhancer loci via TEAD4-DNA-binding protein and stimulates cancer aggressiv...

Authors: Li Li, Alejandro P. Ugalde, Colinda L. G. J. Scheele, Sebastian M. Dieter, Remco Nagel, Jin Ma, Abhijeet Pataskar, Gozde Korkmaz, Ran Elkon, Miao-Ping Chien, Li You, Pin-Rui Su, Onno B. Bleijerveld, Maarten Altelaar, Lyubomir Momchev, Zohar Manber…

My personal mutanome: a computational genomic medicine platform for searching network perturbing alleles linking genotype to phenotype

Massive genome sequencing data have inspired new challenges in personalized treatments and facilitated oncological drug discovery. We present a comprehensive database, My Personal Mutanome (MPM), for accelerat...

Authors: Yadi Zhou, Junfei Zhao, Jiansong Fang, William Martin, Lang Li, Ruth Nussinov, Timothy A. Chan, Charis Eng and Feixiong Cheng

Evolutionary conservation and divergence of the human brain transcriptome

Mouse models have allowed for the direct interrogation of genetic effects on molecular, physiological, and behavioral brain phenotypes. However, it is unknown to what extent neurological or psychiatric traits ...

Authors: William G. Pembroke, Christopher L. Hartl and Daniel H. Geschwind

ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism

N⁶-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing are two of the most abundant RNA modification events affecting adenosines in mammals. Both these RNA modifications determine mRNA fate and p....

Authors: Valentina Tassinari, Valeriana Cesarini, Sara Tomaselli, Zaira Ianniello, Domenico Alessandro Silvestris, Lavinia Ceci Ginistrelli, Maurizio Martini, Biagio De Angelis, Gabriele De Luca, Lucia Ricci Vitiani, Alessandro Fatica, Franco Locatelli and Angela Gallo

Single-cell proteomic and transcriptomic analysis of macrophage heterogeneity using SCoPE2

Macrophages are innate immune cells with diverse functional and molecular phenotypes. This diversity is largely unexplored at the level of single-cell proteomes because of the limitations of quantitative singl...

Authors: Harrison Specht, Edward Emmott, Aleksandra A. Petelski, R. Gray Huffman, David H. Perlman, Marco Serra, Peter Kharchenko, Antonius Koller and Nikolai Slavov

Exploiting the GTEx resources to decipher the mechanisms at GWAS loci

The resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of the biology of human diseases. Here, we present an in-depth examination of the phenotypic conseq...

Authors: Alvaro N. Barbeira, Rodrigo Bonazzola, Eric R. Gamazon, Yanyu Liang, YoSon Park, Sarah Kim-Hellmuth, Gao Wang, Zhuoxun Jiang, Dan Zhou, Farhad Hormozdiari, Boxiang Liu, Abhiram Rao, Andrew R. Hamel, Milton D. Pividori, François Aguet, Lisa Bastarache…

The evolution of alternative splicing in glioblastoma under therapy

Alternative splicing is a rich source of tumor-specific neoantigen targets for immunotherapy. This holds promise for glioblastomas (GBMs), the most common primary tumors of the adult brain, which are resistant...

Authors: Lin Wang, Karin Shamardani, Husam Babikir, Francisca Catalan, Takahide Nejo, Susan Chang, Joanna J. Phillips, Hideho Okada and Aaron A. Diaz

CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies

Genes contain multiple promoters that can drive the expression of various transcript isoforms. Although transcript isoforms from the same gene could have diverse and non-overlapping functions, current loss-of-...

Authors: Rebecca Davies, Ling Liu, Sheng Taotao, Natasha Tuano, Richa Chaturvedi, Kie Kyon Huang, Catherine Itman, Amit Mandoli, Aditi Qamra, Changyuan Hu, David Powell, Roger J. Daly, Patrick Tan and Joseph Rosenbluh

Author Correction: High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts

An amendment to this paper has been published and can be accessed via the original article.

Authors: Minghao Chia, Cai Li, Sueli Marques, Vicente Pelechano, Nicholas M. Luscombe and Folkert J. van Werven

SuperTAD: robust detection of hierarchical topologically associated domains with optimized structural information

Topologically associating domains (TADs) are the organizational units of chromosome structures. TADs can contain TADs, thus forming a hierarchy. TAD hierarchies can be inferred from Hi-C data through coding tr...

Authors: Yu Wei Zhang, Meng Bo Wang and Shuai Cheng Li

SequencErr: measuring and suppressing sequencer errors in next-generation sequencing data

There is currently no method to precisely measure the errors that occur in the sequencing instrument/sequencer, which is critical for next-generation sequencing applications aimed at discovering the genetic ma...

Authors: Eric M. Davis, Yu Sun, Yanling Liu, Pandurang Kolekar, Ying Shao, Karol Szlachta, Heather L. Mulder, Dongren Ren, Stephen V. Rice, Zhaoming Wang, Joy Nakitandwe, Alexander M. Gout, Bridget Shaner, Salina Hall, Leslie L. Robison, Stanley Pounds…

Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer

Deregulated gene expression is a hallmark of cancer; however, most studies to date have analyzed short-read RNA sequencing data with inherent limitations. Here, we combine PacBio long-read isoform sequencing (...

Authors: Kie Kyon Huang, Jiawen Huang, Jeanie Kar Leng Wu, Minghui Lee, Su Ting Tay, Vikrant Kumar, Kalpana Ramnarayanan, Nisha Padmanabhan, Chang Xu, Angie Lay Keng Tan, Charlene Chan, Dennis Kappei, Jonathan Göke and Patrick Tan

MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development

Microexons, exons that are ≤ 30 nucleotides, are a highly conserved and dynamically regulated set of cassette exons. They have key roles in nervous system development and function, as evidenced by recent resul...

Authors: Guillermo E. Parada, Roberto Munita, Ilias Georgakopoulos-Soares, Hugo J. R. Fernandes, Veronika R. Kedlian, Emmanouil Metzakopian, Maria Estela Andres, Eric A. Miska and Martin Hemberg

tidybulk: an R tidy framework for modular transcriptomic data analysis

Recently, efforts have been made toward the harmonization of transcriptomic data structures and workflows using the concept of data tidiness, to facilitate modularisation. We present tidybulk, a modular framew...

Authors: Stefano Mangiola, Ramyar Molania, Ruining Dong, Maria A. Doyle and Anthony T. Papenfuss

Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying functional circRNAs

Short hairpin RNAs (shRNAs) are used to deplete circRNAs by targeting back-splicing junction (BSJ) sites. However, frequent discrepancies exist between shRNA-mediated circRNA knockdown and the corresponding bi...

Authors: Yang Zhang, Tuan M. Nguyen, Xiao-Ou Zhang, Limei Wang, Tin Phan, John G. Clohessy and Pier Paolo Pandolfi

Minimal genome-wide human CRISPR-Cas9 library

CRISPR guide RNA libraries have been iteratively improved to provide increasingly efficient reagents, although their large size is a barrier for many applications. We design an optimised minimal genome-wide hu...

Authors: Emanuel Gonçalves, Mark Thomas, Fiona M. Behan, Gabriele Picco, Clare Pacini, Felicity Allen, Alessandro Vinceti, Mamta Sharma, David A. Jackson, Stacey Price, Charlotte M. Beaver, Oliver Dovey, David Parry-Smith, Francesco Iorio, Leopold Parts, Kosuke Yusa…

Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes

The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics ap...

Authors: Leandro Balzano-Nogueira, Ricardo Ramirez, Tatyana Zamkovaya, Jordan Dailey, Alexandria N. Ardissone, Srikar Chamala, Joan Serrano-Quílez, Teresa Rubio, Michael J. Haller, Patrick Concannon, Mark A. Atkinson, Desmond A. Schatz, Eric W. Triplett and Ana Conesa

Pair consensus decoding improves accuracy of neural network basecallers for nanopore sequencing

We develop a general computational approach for improving the accuracy of basecalling with Oxford Nanopore’s 1D² and related sequencing protocols. Our software PoreOver (

Authors: Jordi Silvestre-Ryan and Ian Holmes

MethylationToActivity: a deep-learning framework that reveals promoter activity landscapes from DNA methylomes in individual tumors

Although genome-wide DNA methylomes have demonstrated their clinical value as reliable biomarkers for tumor detection, subtyping, and classification, their direct biological impacts at the individual gene leve...

Authors: Justin Williams, Beisi Xu, Daniel Putnam, Andrew Thrasher, Chunliang Li, Jun Yang and Xiang Chen

SPIN reveals genome-wide landscape of nuclear compartmentalization

We report SPIN, an integrative computational method to reveal genome-wide intranuclear chromosome positioning and nuclear compartmentalization relative to multiple nuclear structures, which are pivotal for mod...

Authors: Yuchuan Wang, Yang Zhang, Ruochi Zhang, Tom van Schaik, Liguo Zhang, Takayo Sasaki, Daniel Peric-Hupkes, Yu Chen, David M. Gilbert, Bas van Steensel, Andrew S. Belmont and Jian Ma

Alternative splicing landscapes in Arabidopsis thaliana across tissues and stress conditions highlight major functional differences with animals

Alternative splicing (AS) is a widespread regulatory mechanism in multicellular organisms. Numerous transcriptomic and single-gene studies in plants have investigated AS in response to specific conditions, esp...

Authors: Guiomar Martín, Yamile Márquez, Federica Mantica, Paula Duque and Manuel Irimia

High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts

The start and end sites of messenger RNAs (TSSs and TESs) are highly regulated, often in a cell-type-specific manner. Yet the contribution of transcript diversity in regulating gene expression remains largely ...

Authors: Minghao Chia, Cai Li, Sueli Marques, Vicente Pelechano, Nicholas M. Luscombe and Folkert J. van Werven

A novel protein encoded by circular SMO RNA is essential for Hedgehog signaling activation and glioblastoma tumorigenicity

Aberrant activation of the Hedgehog pathway drives tumorigenesis of many cancers, including glioblastoma. However, the sensitization mechanism of the G protein-coupled-like receptor smoothened (SMO), a key com...

Authors: Xujia Wu, Songhua Xiao, Maolei Zhang, Lixuan Yang, Jian Zhong, Bo Li, Fanying Li, Xin Xia, Xixi Li, Huangkai Zhou, Dawei Liu, Nunu Huang, Xuesong Yang, Feizhe Xiao and Nu Zhang

The variant call format provides efficient and robust storage of GWAS summary statistics

GWAS summary statistics are fundamental for a variety of research applications yet no common storage format has been widely adopted. Existing tabular formats ambiguously or incompletely store information about...

Authors: Matthew S. Lyon, Shea J. Andrews, Ben Elsworth, Tom R. Gaunt, Gibran Hemani and Edoardo Marcora

Resequencing of global Tartary buckwheat accessions reveals multiple domestication events and key loci associated with agronomic traits

Tartary buckwheat (Fagopyrum tataricum) is a nutritionally balanced and flavonoid-rich crop plant that has been in cultivation for 4000 years and is now grown globally. Despite its nutraceutical and agricultural ...

Authors: Kaixuan Zhang, Ming He, Yu Fan, Hui Zhao, Bin Gao, Keli Yang, Faliang Li, Yu Tang, Qiang Gao, Tao Lin, Muriel Quinet, Dagmar Janovská, Vladimir Meglič, Jacek Kwiatkowski, Olga Romanova, Nikhil Chrungoo…