Articles

Comparative genomics identifies thousands of candidate structured RNAs in human microbiomes

Structured RNAs play varied bioregulatory roles within microbes. To date, hundreds of candidate structured RNAs have been predicted using informatic approaches that search for motif structures in genomic seque...

Authors: Brayon J. Fremin and Ami S. Bhatt

ACME dissociation: a versatile cell fixation-dissociation method for single-cell transcriptomics

Single-cell sequencing technologies are revolutionizing biology, but they are limited by the need to dissociate live samples. Here, we present ACME (ACetic-MEthanol), a dissociation approach for single-cell tr...

Authors: Helena García-Castro, Nathan J. Kenny, Marta Iglesias, Patricia Álvarez-Campos, Vincent Mason, Anamaria Elek, Anna Schönauer, Victoria A. Sleight, Jakke Neiro, Aziz Aboobaker, Jon Permanyer, Manuel Irimia, Arnau Sebé-Pedrós and Jordi Solana

Response to correspondence on “Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation”

Authors: Channabasavaiah B. Gurumurthy, Aidan R. O’Brien, Rolen M. Quadros, John Adams Jr, Pilar Alcaide, Shinya Ayabe, Johnathan Ballard, Surinder K. Batra, Marie-Claude Beauchamp, Kathleen A. Becker, Guillaume Bernas, David Brough, Francisco Carrillo-Salinas, Wesley Chan, Hanying Chen, Ruby Dawson…

Response to “Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation”

Authors: Hui Yang, Haoyi Wang and Rudolf Jaenisch

PCIP-seq: simultaneous sequencing of integrated viral genomes and their insertion sites with long reads

The integration of a viral genome into the host genome has a major impact on the trajectory of the infected cell. Integration location and variation within the associated viral genome can influence both clonal...

Authors: Maria Artesi, Vincent Hahaut, Basiel Cole, Laurens Lambrechts, Fereshteh Ashrafi, Ambroise Marçais, Olivier Hermine, Philip Griebel, Natasa Arsic, Frank van der Meer, Arsène Burny, Dominique Bron, Elettra Bianchi, Philippe Delvenne, Vincent Bours, Carole Charlier…

Simplitigs as an efficient and scalable representation of de Bruijn graphs

de Bruijn graphs play an essential role in bioinformatics, yet they lack a universal scalable representation. Here, we introduce simplitigs as a compact, efficient, and scalable representation, and ProphAsm, a...

Authors: Karel Břinda, Michael Baym and Gregory Kucherov

Homopolish: a method for the removal of systematic errors in nanopore sequencing by homologous polishing

Nanopore sequencing has been widely used for the reconstruction of microbial genomes. Owing to higher error rates, errors on the genome are corrected via neural networks trained by Nanopore reads. However, the...

Authors: Yao-Ting Huang, Po-Yu Liu and Pei-Wen Shih

MTSplice predicts effects of genetic variants on tissue-specific splicing

We develop the free and open-source model Multi-tissue Splicing (MTSplice) to predict the effects of genetic variants on splicing of cassette exons in 56 human tissues. MTSplice combines MMSplice, which models...

Authors: Jun Cheng, Muhammed Hasan Çelik, Anshul Kundaje and Julien Gagneur

Microbiome meta-analysis and cross-disease comparison enabled by the SIAMCAT machine learning toolbox

The human microbiome is increasingly mined for diagnostic and therapeutic biomarkers using machine learning (ML). However, metagenomics-specific software is scarce, and overoptimistic evaluation and limited cr...

Authors: Jakob Wirbel, Konrad Zych, Morgan Essex, Nicolai Karcher, Ece Kartal, Guillem Salazar, Peer Bork, Shinichi Sunagawa and Georg Zeller

Comprehensive identification of somatic nucleotide variants in human brain tissue

Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. How...

Authors: Yifan Wang, Taejeong Bae, Jeremy Thorpe, Maxwell A. Sherman, Attila G. Jones, Sean Cho, Kenneth Daily, Yanmei Dou, Javier Ganz, Alon Galor, Irene Lobon, Reenal Pattni, Chaggai Rosenbluh, Simone Tomasi, Livia Tomasini, Xiaoxu Yang…

Utilizing genomics to understand and respond to global climate change

Authors: Justin Borevitz

Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders

People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm...

Authors: Marta F. Nabais, Simon M. Laws, Tian Lin, Costanza L. Vallerga, Nicola J. Armstrong, Ian P. Blair, John B. Kwok, Karen A. Mather, George D. Mellick, Perminder S. Sachdev, Leanne Wallace, Anjali K. Henders, Ramona A. J. Zwamborn, Paul J. Hop, Katie Lunnon, Ehsan Pishva…

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

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

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

Unraveling the cartography of the cancer ecosystem

Authors: Roy Rabbie, Doreen Lau, Richard M. White and David J. Adams

Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing

Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new...

Authors: Xi Gu, Daqi Wang, Zhijiao Xu, Jinghan Wang, Luo Guo, Renjie Chai, Genglin Li, Yilai Shu and Huawei Li

Histone lactylation drives oncogenesis by facilitating m⁶A reader protein YTHDF2 expression in ocular melanoma

Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in...

Authors: Jie Yu, Peiwei Chai, Minyue Xie, Shengfang Ge, Jing Ruan, Xianqun Fan and Renbing Jia

Kssd: sequence dimensionality reduction by k-mer substring space sampling enables real-time large-scale datasets analysis

Here, we develop k -mer substring space decomposition (Kssd), a sketching technique which is significantly faster and more accurate than current sketching methods. We show that it is the only method that can b...

Authors: Huiguang Yi, Yanling Lin, Chengqi Lin and Wenfei Jin

Prime editing in mice reveals the essentiality of a single base in driving tissue-specific gene expression

Most single nucleotide variants (SNVs) occur in noncoding sequence where millions of transcription factor binding sites (TFBS) reside. Here, a comparative analysis of CRISPR-mediated homology-directed repair (...

Authors: Pan Gao, Qing Lyu, Amr R. Ghanam, Cicera R. Lazzarotto, Gregory A. Newby, Wei Zhang, Mihyun Choi, Orazio J. Slivano, Kevin Holden, John A. Walker II, Anastasia P. Kadina, Rob J. Munroe, Christian M. Abratte, John C. Schimenti, David R. Liu, Shengdar Q. Tsai…

SRSF3 and SRSF7 modulate 3′UTR length through suppression or activation of proximal polyadenylation sites and regulation of CFIm levels

Alternative polyadenylation (APA) refers to the regulated selection of polyadenylation sites (PASs) in transcripts, which determines the length of their 3′ untranslated regions (3′UTRs). We have recently shown...

Authors: Oliver Daniel Schwich, Nicole Blümel, Mario Keller, Marius Wegener, Samarth Thonta Setty, Melinda Elaine Brunstein, Ina Poser, Igor Ruiz De Los Mozos, Beatrix Suess, Christian Münch, François McNicoll, Kathi Zarnack and Michaela Müller-McNicoll

gapseq: informed prediction of bacterial metabolic pathways and reconstruction of accurate metabolic models

Genome-scale metabolic models of microorganisms are powerful frameworks to predict phenotypes from an organism’s genotype. While manual reconstructions are laborious, automated reconstructions often fail to re...

Authors: Johannes Zimmermann, Christoph Kaleta and Silvio Waschina

Identification of pathogenic variants in cancer genes using base editing screens with editing efficiency correction

Millions of nucleotide variants are identified through cancer genome sequencing and it is clinically important to identify the pathogenic variants among them. By introducing base substitutions at guide RNA tar...

Authors: Changcai Huang, Guangyu Li, Jiayu Wu, Junbo Liang and Xiaoyue Wang

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