Articles

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…

Half a century of the reverse transcriptase—happy birthday!

Authors: Karin Moelling

BlastFrost: fast querying of 100,000s of bacterial genomes in Bifrost graphs

BlastFrost is a highly efficient method for querying 100,000s of genome assemblies, building on Bifrost, a dynamic data structure for compacted and colored de Bruijn graphs. BlastFrost queries a Bifrost data s...

Authors: Nina Luhmann, Guillaume Holley and Mark Achtman

Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences

Animal genomes contain thousands of long noncoding RNA (lncRNA) genes, a growing subset of which are thought to be functionally important. This functionality is often mediated by short sequence elements scatte...

Authors: Caroline Jane Ross, Aviv Rom, Amit Spinrad, Dikla Gelbard-Solodkin, Neta Degani and Igor Ulitsky

Ratatosk: hybrid error correction of long reads enables accurate variant calling and assembly

A major challenge to long read sequencing data is their high error rate of up to 15%. We present Ratatosk, a method to correct long reads with short read data. We demonstrate on 5 human genome trios that Ratat...

Authors: Guillaume Holley, Doruk Beyter, Helga Ingimundardottir, Peter L. Møller, Snædis Kristmundsdottir, Hannes P. Eggertsson and Bjarni V. Halldorsson

Roles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs

PIWI proteins, a subfamily of PAZ/PIWI Domain family RNA-binding proteins, are best known for their function in silencing transposons and germline development by partnering with small noncoding RNAs called PIW...

Authors: Chen Wang and Haifan Lin

Homology-mediated inter-chromosomal interactions in hexaploid wheat lead to specific subgenome territories following polyploidization and introgression

Polyploidization and introgression are major events driving plant genome evolution and influencing crop breeding. However, the mechanisms underlying the higher-order chromatin organization of subgenomes and al...

Authors: Jizeng Jia, Yilin Xie, Jingfei Cheng, Chuizheng Kong, Meiyue Wang, Lifeng Gao, Fei Zhao, Jingyu Guo, Kai Wang, Guangwei Li, Dangqun Cui, Tiezhu Hu, Guangyao Zhao, Daowen Wang, Zhengang Ru and Yijing Zhang

Evolution of regulatory networks associated with traits under selection in cichlids

Seminal studies of vertebrate protein evolution speculated that gene regulatory changes can drive anatomical innovations. However, very little is known about gene regulatory network (GRN) evolution associated ...

Authors: Tarang K. Mehta, Christopher Koch, Will Nash, Sara A. Knaack, Padhmanand Sudhakar, Marton Olbei, Sarah Bastkowski, Luca Penso-Dolfin, Tamas Korcsmaros, Wilfried Haerty, Sushmita Roy and Federica Di-Palma

Quantitative profiling of N⁶-methyladenosine at single-base resolution in stem-differentiating xylem of Populus trichocarpa using Nanopore direct RNA sequencing

There are no comprehensive methods to identify N⁶-methyladenosine (m⁶A) at single-base resolution for every single transcript, which is necessary for the estimation of m⁶A abundance. We develop a new pipeline cal...

Authors: Yubang Gao, Xuqing Liu, Bizhi Wu, Huihui Wang, Feihu Xi, Markus V. Kohnen, Anireddy S. N. Reddy and Lianfeng Gu

HiDeF: identifying persistent structures in multiscale ‘omics data

In any ‘omics study, the scale of analysis can dramatically affect the outcome. For instance, when clustering single-cell transcriptomes, is the analysis tuned to discover broad or specific cell types? Likewis...

Authors: Fan Zheng, She Zhang, Christopher Churas, Dexter Pratt, Ivet Bahar and Trey Ideker

An interpretable bimodal neural network characterizes the sequence and preexisting chromatin predictors of induced transcription factor binding

Transcription factor (TF) binding specificity is determined via a complex interplay between the transcription factor’s DNA binding preference and cell type-specific chromatin environments. The chromatin featur...

Authors: Divyanshi Srivastava, Begüm Aydin, Esteban O. Mazzoni and Shaun Mahony

An integrated multi-omics approach to identify regulatory mechanisms in cancer metastatic processes

Metastatic progress is the primary cause of death in most cancers, yet the regulatory dynamics driving the cellular changes necessary for metastasis remain poorly understood. Multi-omics approaches hold great ...

Authors: Saba Ghaffari, Casey Hanson, Remington E. Schmidt, Kelly J. Bouchonville, Steven M. Offer and Saurabh Sinha

Equivalent DNA methylation variation between monozygotic co-twins and unrelated individuals reveals universal epigenetic inter-individual dissimilarity

Although the genomes of monozygotic twins are practically identical, their methylomes may evolve divergently throughout their lifetime as a consequence of factors such as the environment or aging. Particularly...

Authors: Benjamin Planterose Jiménez, Fan Liu, Amke Caliebe, Diego Montiel González, Jordana T. Bell, Manfred Kayser and Athina Vidaki

N6-methyladenosine dynamics in neurodevelopment and aging, and its potential role in Alzheimer’s disease

N6-methyladenosine (m⁶A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain.

Authors: Andrew M. Shafik, Feiran Zhang, Zhenxing Guo, Qing Dai, Kinga Pajdzik, Yangping Li, Yunhee Kang, Bing Yao, Hao Wu, Chuan He, Emily G. Allen, Ranhui Duan and Peng Jin

Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding

The folding of proteins is challenging in the highly crowded and sticky environment of a cell. Regulation of translation elongation may play a crucial role in ensuring the correct folding of proteins. Much of ...

Authors: Taolan Zhao, Yan-Ming Chen, Yu Li, Jia Wang, Siyu Chen, Ning Gao and Wenfeng Qian

Widespread occurrence of microRNA-mediated target cleavage on membrane-bound polysomes

Small RNAs (sRNAs) including microRNAs (miRNAs) and small interfering RNAs (siRNAs) serve as core players in gene silencing at transcriptional and post-transcriptional levels in plants, but their subcellular l...

Authors: Xiaoyu Yang, Chenjiang You, Xufeng Wang, Lei Gao, Beixin Mo, Lin Liu and Xuemei Chen

Crosstalk between codon optimality and cis-regulatory elements dictates mRNA stability

The regulation of messenger RNA (mRNA) stability has a profound impact on gene expression dynamics during embryogenesis. For example, in animals, maternally deposited mRNAs are degraded after fertilization to ...

Authors: Santiago Gerardo Medina-Muñoz, Gopal Kushawah, Luciana Andrea Castellano, Michay Diez, Michelle Lynn DeVore, María José Blanco Salazar and Ariel Alejandro Bazzini

Genome structure variation analyses of peach reveal population dynamics and a 1.67 Mb causal inversion for fruit shape

Structural variations (SVs), a major resource of genomic variation, can have profound consequences on phenotypic variation, yet the impacts of SVs remain largely unexplored in crops.

Authors: Jiantao Guan, Yaoguang Xu, Yang Yu, Jun Fu, Fei Ren, Jiying Guo, Jianbo Zhao, Quan Jiang, Jianhua Wei and Hua Xie

Histone modifications during the life cycle of the brown alga Ectocarpus

Brown algae evolved complex multicellularity independently of the animal and land plant lineages and are the third most developmentally complex phylogenetic group on the planet. An understanding of development...

Authors: Simon Bourdareau, Leila Tirichine, Bérangère Lombard, Damarys Loew, Delphine Scornet, Yue Wu, Susana M. Coelho and J. Mark Cock

In vivo nuclear RNA structurome reveals RNA-structure regulation of mRNA processing in plants

mRNA processing is critical for gene expression. A challenge in regulating mRNA processing is how to recognize the actual mRNA processing sites, such as splice and polyadenylation sites, when the sequence cont...

Authors: Zhenshan Liu, Qi Liu, Xiaofei Yang, Yueying Zhang, Matthew Norris, Xiaoxi Chen, Jitender Cheema, Huakun Zhang and Yiliang Ding

scMC learns biological variation through the alignment of multiple single-cell genomics datasets

Distinguishing biological from technical variation is crucial when integrating and comparing single-cell genomics datasets across different experiments. Existing methods lack the capability in explicitly disti...

Authors: Lihua Zhang and Qing Nie

Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer

Long-read sequencing of full-length cDNAs enables the detection of structures of aberrant splicing isoforms in cancer cells. These isoforms are occasionally translated, presented by HLA molecules, and recogniz...

Authors: Miho Oka, Liu Xu, Toshihiro Suzuki, Toshiaki Yoshikawa, Hiromi Sakamoto, Hayato Uemura, Akiyasu C. Yoshizawa, Yutaka Suzuki, Tetsuya Nakatsura, Yasushi Ishihama, Ayako Suzuki and Masahide Seki

Reference flow: reducing reference bias using multiple population genomes

Most sequencing data analyses start by aligning sequencing reads to a linear reference genome, but failure to account for genetic variation leads to reference bias and confounding of results downstream. Other ...

Authors: Nae-Chyun Chen, Brad Solomon, Taher Mun, Sheila Iyer and Ben Langmead

Comprehensive integrative profiling of upper tract urothelial carcinomas

Crosstalk between genetic, epigenetic, and immune alterations in upper tract urothelial carcinomas and their role in shaping muscle invasiveness and patient outcome are poorly understood.

Authors: Xiaoping Su, Xiaofan Lu, Sehrish Khan Bazai, Eva Compérat, Roger Mouawad, Hui Yao, Morgan Rouprêt, Jean-Philippe Spano, David Khayat, Irwin Davidson, Nizar N. Tannir, Fangrong Yan and Gabriel G. Malouf

SpRY greatly expands the genome editing scope in rice with highly flexible PAM recognition

Plant genome engineering mediated by various CRISPR-based tools requires specific protospacer adjacent motifs (PAMs), such as the well-performed NGG, NG, and NNG, to initiate target recognition, which notably ...

Authors: Ziyan Xu, Yongjie Kuang, Bin Ren, Daqi Yan, Fang Yan, Carl Spetz, Wenxian Sun, Guirong Wang, Xueping Zhou and Huanbin Zhou

Compacting a synthetic yeast chromosome arm

Redundancy is a common feature of genomes, presumably to ensure robust growth under different and changing conditions. Genome compaction, removing sequences nonessential for given conditions, provides a novel ...

Authors: Zhouqing Luo, Kang Yu, Shangqian Xie, Marco Monti, Daniel Schindler, Yuan Fang, Shijun Zhao, Zhenzhen Liang, Shuangying Jiang, Meiwei Luan, Chuanle Xiao, Yizhi Cai and Junbiao Dai

Integrated genomic and transcriptomic analysis reveals unique characteristics of hepatic metastases and pro-metastatic role of complement C1q in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high metastasis rate in the liver. However, little is known about the molecular features of hepatic metastases due to diffic...

Authors: Jianyu Yang, Ping Lin, Minwei Yang, Wei Liu, Xueliang Fu, Dejun Liu, Lingye Tao, Yanmiao Huo, Junfeng Zhang, Rong Hua, Zhigang Zhang, Yixue Li, Liwei Wang, Jing Xue, Hong Li and Yongwei Sun

How the pan-genome is changing crop genomics and improvement

Crop genomics has seen dramatic advances in recent years due to improvements in sequencing technology, assembly methods, and computational resources. These advances have led to the development of new tools to ...

Authors: Rafael Della Coletta, Yinjie Qiu, Shujun Ou, Matthew B. Hufford and Candice N. Hirsch

Mentorship is not co-authorship: a revisit to mentorship

Authors: Lana X. Garmire

Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual

Bone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this d...

Authors: Diana L. Cousminer, Yadav Wagley, James A. Pippin, Ahmed Elhakeem, Gregory P. Way, Matthew C. Pahl, Shana E. McCormack, Alessandra Chesi, Jonathan A. Mitchell, Joseph M. Kindler, Denis Baird, April Hartley, Laura Howe, Heidi J. Kalkwarf, Joan M. Lappe, Sumei Lu…

Gamete binning: chromosome-level and haplotype-resolved genome assembly enabled by high-throughput single-cell sequencing of gamete genomes

Generating chromosome-level, haplotype-resolved assemblies of heterozygous genomes remains challenging. To address this, we developed gamete binning, a method based on single-cell sequencing of haploid gametes...

Authors: José A. Campoy, Hequan Sun, Manish Goel, Wen-Biao Jiao, Kat Folz-Donahue, Nan Wang, Manuel Rubio, Chang Liu, Christian Kukat, David Ruiz, Bruno Huettel and Korbinian Schneeberger

Author Correction: Stairway Plot 2: demographic history inference with folded SNP frequency spectra

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

Authors: Xiaoming Liu and Yun-Xin Fu

Potentially adaptive SARS-CoV-2 mutations discovered with novel spatiotemporal and explainable AI models

A mechanistic understanding of the spread of SARS-CoV-2 and diligent tracking of ongoing mutagenesis are of key importance to plan robust strategies for confining its transmission. Large numbers of available s...

Authors: Michael R. Garvin, Erica T. Prates, Mirko Pavicic, Piet Jones, B. Kirtley Amos, Armin Geiger, Manesh B. Shah, Jared Streich, Joao Gabriel Felipe Machado Gazolla, David Kainer, Ashley Cliff, Jonathon Romero, Nathan Keith, James B. Brown and Daniel Jacobson

FAN-C: a feature-rich framework for the analysis and visualisation of chromosome conformation capture data

Chromosome conformation capture data, particularly from high-throughput approaches such as Hi-C, are typically very complex to analyse. Existing analysis tools are often single-purpose, or limited in compatibi...

Authors: Kai Kruse, Clemens B. Hug and Juan M. Vaquerizas

Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity

The increasing availability of microbial genomes and environmental shotgun metagenomes provides unprecedented access to the genomic differences within related bacteria. The human oral microbiome with its diver...

Authors: Daniel R. Utter, Gary G. Borisy, A. Murat Eren, Colleen M. Cavanaugh and Jessica L. Mark Welch

Functional and genetic markers of niche partitioning among enigmatic members of the human oral microbiome

Microbial residents of the human oral cavity have long been a major focus of microbiology due to their influence on host health and intriguing patterns of site specificity amidst the lack of dispersal limitati...

Authors: Alon Shaiber, Amy D. Willis, Tom O. Delmont, Simon Roux, Lin-Xing Chen, Abigail C. Schmid, Mahmoud Yousef, Andrea R. Watson, Karen Lolans, Özcan C. Esen, Sonny T. M. Lee, Nora Downey, Hilary G. Morrison, Floyd E. Dewhirst, Jessica L. Mark Welch and A. Murat Eren

Convergent network effects along the axis of gene expression during prostate cancer progression

Tumor-specific genomic aberrations are routinely determined by high-throughput genomic measurements. It remains unclear how complex genome alterations affect molecular networks through changing protein levels ...

Authors: Konstantina Charmpi, Tiannan Guo, Qing Zhong, Ulrich Wagner, Rui Sun, Nora C. Toussaint, Christine E. Fritz, Chunhui Yuan, Hao Chen, Niels J. Rupp, Ailsa Christiansen, Dorothea Rutishauser, Jan H. Rüschoff, Christian Fankhauser, Karim Saba, Cedric Poyet…