Articles

Functional genomics analysis identifies T and NK cell activation as a driver of epigenetic clock progression

Epigenetic clocks use DNA methylation (DNAm) levels of specific sets of CpG dinucleotides to accurately predict individual chronological age. A popular application of these clocks is to explore whether the dev...

Authors: Thomas H. Jonkman, Koen F. Dekkers, Roderick C. Slieker, Crystal D. Grant, M. Arfan Ikram, Marleen M. J. van Greevenbroek, Lude Franke, Jan H. Veldink, Dorret I. Boomsma, P. Eline Slagboom, B. I. O. S. Consortium and Bastiaan T. Heijmans

Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries

Polygenic risk scores (PRS) are valuable to translate the results of genome-wide association studies (GWAS) into clinical practice. To date, most GWAS have been based on individuals of European-ancestry leadin...

Authors: Yanyu Liang, Milton Pividori, Ani Manichaikul, Abraham A. Palmer, Nancy J. Cox, Heather E. Wheeler and Hae Kyung Im

The blooming of long-read sequencing reforms biomedical research

Authors: Kin Fai Au

A deep generative model for multi-view profiling of single-cell RNA-seq and ATAC-seq data

Here, we present a multi-modal deep generative model, the single-cell Multi-View Profiler (scMVP), which is designed for handling sequencing data that simultaneously measure gene expression and chromatin acces...

Authors: Gaoyang Li, Shaliu Fu, Shuguang Wang, Chenyu Zhu, Bin Duan, Chen Tang, Xiaohan Chen, Guohui Chuai, Ping Wang and Qi Liu

Using synthetic chromosome controls to evaluate the sequencing of difficult regions within the human genome

Next-generation sequencing (NGS) can identify mutations in the human genome that cause disease and has been widely adopted in clinical diagnosis. However, the human genome contains many polymorphic, low-comple...

Authors: Andre L. M. Reis, Ira W. Deveson, Bindu Swapna Madala, Ted Wong, Chris Barker, Joshua Xu, Niall Lennon, Weida Tong and Tim R. Mercer

Phiclust: a clusterability measure for single-cell transcriptomics reveals phenotypic subpopulations

The ability to discover new cell phenotypes by unsupervised clustering of single-cell transcriptomes has revolutionized biology. Currently, there is no principled way to decide whether a cluster of cells conta...

Authors: Maria Mircea, Mazène Hochane, Xueying Fan, Susana M. Chuva de Sousa Lopes, Diego Garlaschelli and Stefan Semrau

Evolution of the repression mechanisms in circadian clocks

Circadian (daily) timekeeping is essential to the survival of many organisms. An integral part of all circadian timekeeping systems is negative feedback between an activator and repressor. However, the role of...

Authors: Jonathan Tyler, Yining Lu, Jay Dunlap and Daniel B. Forger

Knockout of circRNAs by base editing back-splice sites of circularized exons

Many circular RNAs (circRNAs) are produced from back-splicing of exons of precursor mRNAs and are generally co-expressed with cognate linear RNAs. Methods for circRNA-specific knockout are lacking, largely due...

Authors: Xiang Gao, Xu-Kai Ma, Xiang Li, Guo-Wei Li, Chu-Xiao Liu, Jun Zhang, Ying Wang, Jia Wei, Jia Chen, Ling-Ling Chen and Li Yang

Systematic identification of ACE2 expression modulators reveals cardiomyopathy as a risk factor for mortality in COVID-19 patients

Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2. It plays critical roles in both the transmission and the pathogenesis of COVID-19. Comprehensive profiling of ACE2 expression p...

Authors: Navchetan Kaur, Boris Oskotsky, Atul J. Butte and Zicheng Hu

The genome of oil-Camellia and population genomics analysis provide insights into seed oil domestication

As a perennial crop, oil-Camellia possesses a long domestication history and produces high-quality seed oil that is beneficial to human health. Camellia oleifera Abel. is a sister species to the tea plant, which ...

Authors: Ping Lin, Kailiang Wang, Yupeng Wang, Zhikang Hu, Chao Yan, Hu Huang, Xianjin Ma, Yongqing Cao, Wei Long, Weixin Liu, Xinlei Li, Zhengqi Fan, Jiyuan Li, Ning Ye, Huadong Ren, Xiaohua Yao…

Integrative analysis of 3604 GWAS reveals multiple novel cell type-specific regulatory associations

Genome-wide association study (GWAS) single nucleotide polymorphisms (SNPs) are known to preferentially co-locate to act...

Authors: Charles E. Breeze, Eric Haugen, Alex Reynolds, Andrew Teschendorff, Jenny van Dongen, Qing Lan, Nathaniel Rothman, Guillaume Bourque, Ian Dunham, Stephan Beck, John Stamatoyannopoulos, Nora Franceschini and Sonja I. Berndt

Achieving robust somatic mutation detection with deep learning models derived from reference data sets of a cancer sample

Accurate detection of somatic mutations is challenging but critical in understanding cancer formation, progression, and treatment. We recently proposed NeuSomatic, the first deep convolutional neural network-b...

Authors: Sayed Mohammad Ebrahim Sahraeian, Li Tai Fang, Konstantinos Karagiannis, Malcolm Moos, Sean Smith, Luis Santana-Quintero, Chunlin Xiao, Michael Colgan, Huixiao Hong, Marghoob Mohiyuddin and Wenming Xiao

JAFFAL: detecting fusion genes with long-read transcriptome sequencing

In cancer, fusions are important diagnostic markers and targets for therapy. Long-read transcriptome sequencing allows the discovery of fusions with their full-length isoform structure. However, due to higher ...

Authors: Nadia M. Davidson, Ying Chen, Teresa Sadras, Georgina L. Ryland, Piers Blombery, Paul G. Ekert, Jonathan Göke and Alicia Oshlack

Universal annotation of the human genome through integration of over a thousand epigenomic datasets

Genome-wide maps of chromatin marks such as histone modifications and open chromatin sites provide valuable information for annotating the non-coding genome, including identifying regulatory elements. Computat...

Authors: Ha Vu and Jason Ernst

scDALI: modeling allelic heterogeneity in single cells reveals context-specific genetic regulation

While it is established that the functional impact of genetic variation can vary across cell types and states, capturing this diversity remains challenging. Current studies using bulk sequencing either ignore ...

Authors: Tobias Heinen, Stefano Secchia, James P. Reddington, Bingqing Zhao, Eileen E. M. Furlong and Oliver Stegle

Diurnal RNAPII-tethered chromatin interactions are associated with rhythmic gene expression in rice

The daily cycling of plant physiological processes is speculated to arise from the coordinated rhythms of gene expression. However, the dynamics of diurnal 3D genome architecture and their potential functions ...

Authors: Li Deng, Baibai Gao, Lun Zhao, Ying Zhang, Qing Zhang, Minrong Guo, Yongqing Yang, Shuangqi Wang, Liang Xie, Hao Lou, Meng Ma, Wei Zhang, Zhilin Cao, Qinghua Zhang, C. Robertson McClung, Guoliang Li…

CRISPR guides induce gene silencing in plants in the absence of Cas

RNA-targeting CRISPR-Cas can provide potential advantages over DNA editing, such as avoiding pleiotropic effects of genome editing, providing precise spatiotemporal regulation, and expanded function including ...

Authors: Veerendra Kumar Sharma, Sandeep Marla, Wenguang Zheng, Divya Mishra, Jun Huang, Wei Zhang, Geoffrey Preston Morris and David Edward Cook

N⁴-acetyldeoxycytosine DNA modification marks euchromatin regions in Arabidopsis thaliana

Direct analogs of chemically modified bases that carry important epigenetic information, such as 5-methylcytosine (m5C)/5-methyldeoxycytosine (5mC), 5-hydroxymethylcytosine (hm5C)/5-hydroxymethyldeoxycytosine ...

Authors: Shuai Wang, Hairong Xie, Fei Mao, Haiyan Wang, Shu Wang, Zhenglin Chen, Yuxia Zhang, Zhihui Xu, Jinming Xing, Zhaokang Cui, Xiquan Gao, Hongmei Jin, Jian Hua, Bo Xiong and Yufeng Wu

Improvisational science

Authors: Itai Yanai and Martin Lercher

The Agricultural Genome to Phenome Initiative (AG2PI): creating a shared vision across crop and livestock research communities

Authors: Christopher K. Tuggle, Jennifer Clarke, Jack C. M. Dekkers, David Ertl, Carolyn J. Lawrence-Dill, Eric Lyons, Brenda M. Murdoch, Nicole M. Scott and Patrick S. Schnable

Assessing reproducibility of inherited variants detected with short-read whole genome sequencing

Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call qualit...

Authors: Bohu Pan, Luyao Ren, Vitor Onuchic, Meijian Guan, Rebecca Kusko, Steve Bruinsma, Len Trigg, Andreas Scherer, Baitang Ning, Chaoyang Zhang, Christine Glidewell-Kenney, Chunlin Xiao, Eric Donaldson, Fritz J. Sedlazeck, Gary Schroth, Gokhan Yavas…

Robust normalization and transformation techniques for constructing gene coexpression networks from RNA-seq data

Constructing gene coexpression networks is a powerful approach for analyzing high-throughput gene expression data towards module identification, gene function prediction, and disease-gene prioritization. While...

Authors: Kayla A. Johnson and Arjun Krishnan

Cobolt: integrative analysis of multimodal single-cell sequencing data

A growing number of single-cell sequencing platforms enable joint profiling of multiple omics from the same cells. We present Cobolt, a novel method that not only allows for analyzing the data from joint-modality...

Authors: Boying Gong, Yun Zhou and Elizabeth Purdom

Author Correction: The SEQC2 epigenomics quality control (EpiQC) study

Authors: Jonathan Foox, Jessica Nordlund, Claudia Lalancette, Ting Gong, Michelle Lacey, Samantha Lent, Bradley W. Langhorst, V. K. Chaithanya Ponnaluri, Louise Williams, Karthik Ramaswamy Padmanabhan, Raymond Cavalcante, Anders Lundmark, Daniel Butler, Christopher Mozsary, Justin Gurvitch, John M. Greally…

An accessible, efficient and global approach for the large-scale sequencing of bacterial genomes

We have developed an efficient and inexpensive pipeline for streamlining large-scale collection and genome sequencing of bacterial isolates. Evaluation of this method involved a worldwide research collaboratio...

Authors: Blanca M. Perez-Sepulveda, Darren Heavens, Caisey V. Pulford, Alexander V. Predeus, Ross Low, Hermione Webster, Gregory F. Dykes, Christian Schudoma, Will Rowe, James Lipscombe, Chris Watkins, Benjamin Kumwenda, Neil Shearer, Karl Costigan, Kate S. Baker, Nicholas A. Feasey…

Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue

Understanding the contributions of transcription factor DNA binding sites to transcriptional enhancers is a significant challenge. We developed Quantitative enhancer-FACS-Seq for highly parallel quantification...

Authors: Colin T. Waters, Stephen S. Gisselbrecht, Yuliya A. Sytnikova, Tiziana M. Cafarelli, David E. Hill and Martha L. Bulyk

Hidden biases in germline structural variant detection

Genomic structural variations (SV) are important determinants of genotypic and phenotypic changes in many organisms. However, the detection of SV from next-generation sequencing data remains challenging.

Authors: Michael M. Khayat, Sayed Mohammad Ebrahim Sahraeian, Samantha Zarate, Andrew Carroll, Huixiao Hong, Bohu Pan, Leming Shi, Richard A. Gibbs, Marghoob Mohiyuddin, Yuanting Zheng and Fritz J. Sedlazeck

MultiMAP: dimensionality reduction and integration of multimodal data

Multimodal data is rapidly growing in many fields of science and engineering, including single-cell biology. We introduce MultiMAP, a novel algorithm for dimensionality reduction and integration. MultiMAP can ...

Authors: Mika Sarkin Jain, Krzysztof Polanski, Cecilia Dominguez Conde, Xi Chen, Jongeun Park, Lira Mamanova, Andrew Knights, Rachel A. Botting, Emily Stephenson, Muzlifah Haniffa, Austen Lamacraft, Mirjana Efremova and Sarah A. Teichmann

The economics of organellar gene loss and endosymbiotic gene transfer

The endosymbiosis of the bacterial progenitors of the mitochondrion and the chloroplast are landmark events in the evolution of life on Earth. While both organelles have retained substantial proteomic and bioc...

Authors: Steven Kelly

SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis

Single-cell CRISPR screens are a promising biotechnology for mapping regulatory elements to target genes at genome-wide scale. However, technical factors like sequencing depth impact not only expression measur...

Authors: Timothy Barry, Xuran Wang, John A. Morris, Kathryn Roeder and Eugene Katsevich

Chronos: a cell population dynamics model of CRISPR experiments that improves inference of gene fitness effects

CRISPR loss of function screens are powerful tools to interrogate biology but exhibit a number of biases and artifacts that can confound the results. Here, we introduce Chronos, an algorithm for inferring gene...

Authors: Joshua M. Dempster, Isabella Boyle, Francisca Vazquez, David E. Root, Jesse S. Boehm, William C. Hahn, Aviad Tsherniak and James M. McFarland

A benchmark of structural variation detection by long reads through a realistic simulated model

Accurate simulations of structural variation distributions and sequencing data are crucial for the development and benchmarking of new tools. We develop Sim-it, a straightforward tool for the simulation of bot...

Authors: Nicolas Dierckxsens, Tong Li, Joris R. Vermeesch and Zhi Xie

splatPop: simulating population scale single-cell RNA sequencing data

Population-scale single-cell RNA sequencing (scRNA-seq) is now viable, enabling finer resolution functional genomics studies and leading to a rush to adapt bulk methods and develop new single-cell-specific met...

Authors: Christina B. Azodi, Luke Zappia, Alicia Oshlack and Davis J. McCarthy

Reprogramming of RNA silencing triggered by cucumber mosaic virus infection in Arabidopsis

RNA silencing has an important role mediating sequence-specific virus resistance in plants. The complex interaction of viruses with RNA silencing involves the loading of viral small interfering RNAs (vsiRNAs) ...

Authors: Maria Luz Annacondia and German Martinez

A cis-regulatory-directed pipeline for the identification of genes involved in cardiac development and disease

Congenital heart diseases are the major cause of death in newborns, but the genetic etiology of this developmental disorder is not fully known. The conventional approach to identify the disease-causing genes f...

Authors: Hieu T. Nim, Louis Dang, Harshini Thiyagarajah, Daniel Bakopoulos, Michael See, Natalie Charitakis, Tennille Sibbritt, Michael P. Eichenlaub, Stuart K. Archer, Nicolas Fossat, Richard E. Burke, Patrick P. L. Tam, Coral G. Warr, Travis K. Johnson and Mirana Ramialison

Benchmarking UMI-based single-cell RNA-seq preprocessing workflows

Single-cell RNA-sequencing (scRNA-seq) technologies and associated analysis methods have rapidly developed in recent years. This includes preprocessing methods, which assign sequencing reads to genes to create...

Authors: Yue You, Luyi Tian, Shian Su, Xueyi Dong, Jafar S. Jabbari, Peter F. Hickey and Matthew E. Ritchie

Flimma: a federated and privacy-aware tool for differential gene expression analysis

Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted by privacy...

Authors: Olga Zolotareva, Reza Nasirigerdeh, Julian Matschinske, Reihaneh Torkzadehmahani, Mohammad Bakhtiari, Tobias Frisch, Julian Späth, David B. Blumenthal, Amir Abbasinejad, Paolo Tieri, Georgios Kaissis, Daniel Rückert, Nina K. Wenke, Markus List and Jan Baumbach

CIDER: an interpretable meta-clustering framework for single-cell RNA-seq data integration and evaluation

Clustering of joint single-cell RNA-Seq (scRNA-Seq) data is often challenged by confounding factors, such as batch effects and biologically relevant variability. Existing batch effect removal methods typically...

Authors: Zhiyuan Hu, Ahmed A. Ahmed and Christopher Yau

Microbial co-occurrence complicates associations of gut microbiome with US immigration, dietary intake and obesity

Obesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut microbiome feat...

Authors: Zheng Wang, Mykhaylo Usyk, Yoshiki Vázquez-Baeza, Guo-Chong Chen, Carmen R. Isasi, Jessica S. Williams-Nguyen, Simin Hua, Daniel McDonald, Bharat Thyagarajan, Martha L. Daviglus, Jianwen Cai, Kari E. North, Tao Wang, Rob Knight, Robert D. Burk, Robert C. Kaplan…

Programmed genomic instability regulates neural transdifferentiation of human brain microvascular pericytes

Transdifferentiation describes transformation in vivo of specialized cells from one lineage into another. While there is extensive literature on forced induction of lineage reprogramming in vitro, endogenous m...

Authors: Saba Rezaei-Lotfi, Filip Vujovic, Mary Simonian, Neil Hunter and Ramin M. Farahani

geneBasis: an iterative approach for unsupervised selection of targeted gene panels from scRNA-seq

scRNA-seq datasets are increasingly used to identify gene panels that can be probed using alternative technologies, such as spatial transcriptomics, where choosing the best subset of genes is vital. Existing m...

Authors: Alsu Missarova, Jaison Jain, Andrew Butler, Shila Ghazanfar, Tim Stuart, Maigan Brusko, Clive Wasserfall, Harry Nick, Todd Brusko, Mark Atkinson, Rahul Satija and John C. Marioni

The SEQC2 epigenomics quality control (EpiQC) study

Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other dis...

Authors: Jonathan Foox, Jessica Nordlund, Claudia Lalancette, Ting Gong, Michelle Lacey, Samantha Lent, Bradley W. Langhorst, V. K. Chaithanya Ponnaluri, Louise Williams, Karthik Ramaswamy Padmanabhan, Raymond Cavalcante, Anders Lundmark, Daniel Butler, Christopher Mozsary, Justin Gurvitch, John M. Greally…

Single-cell characterization of CRISPR-modified transcript isoforms with nanopore sequencing

We developed a single-cell approach to detect CRISPR-modified mRNA transcript structures. This method assesses how genetic variants at splicing sites and splicing factors contribute to alternative mRNA isoform...

Authors: Heon Seok Kim, Susan M. Grimes, Anna C. Hooker, Billy T. Lau and Hanlee P. Ji

Interferon inducible pseudouridine modification in human mRNA by quantitative nanopore profiling

Pseudouridine (Ψ) is an abundant mRNA modification in mammalian transcriptome, but its functions have remained elusive due to the difficulty of transcriptome-wide mapping. We develop a nanopore native RNA sequ...

Authors: Sihao Huang, Wen Zhang, Christopher D. Katanski, Devin Dersh, Qing Dai, Karen Lolans, Jonathan Yewdell, A. Murat Eren and Tao Pan

Heterochromatin: did H3K9 methylation evolve to tame transposons?

Authors: Manisha Kabi and Guillaume J. Filion

DropletQC: improved identification of empty droplets and damaged cells in single-cell RNA-seq data

Advances in droplet-based single-cell RNA-sequencing (scRNA-seq) have dramatically increased throughput, allowing tens of thousands of cells to be routinely sequenced in a single experiment. In addition to cel...

Authors: Walter Muskovic and Joseph E. Powell

Malignancy and NF-κB signalling strengthen coordination between expression of mitochondrial and nuclear-encoded oxidative phosphorylation genes

Mitochondria are ancient endosymbiotic organelles crucial to eukaryotic growth and metabolism. The mammalian mitochondrial genome encodes for 13 mitochondrial proteins, and the remaining mitochondrial proteins...

Authors: Marcos Francisco Perez and Peter Sarkies

Functional enrichment of alternative splicing events with NEASE reveals insights into tissue identity and diseases

Alternative splicing (AS) is an important aspect of gene regulation. Nevertheless, its role in molecular processes and pathobiology is far from understood. A roadblock is that tools for the functional analysis...

Authors: Zakaria Louadi, Maria L. Elkjaer, Melissa Klug, Chit Tong Lio, Amit Fenn, Zsolt Illes, Dario Bongiovanni, Jan Baumbach, Tim Kacprowski, Markus List and Olga Tsoy

Feature selection revisited in the single-cell era

Recent advances in single-cell biotechnologies have resulted in high-dimensional datasets with increased complexity, making feature selection an essential technique for single-cell data analysis. Here, we revi...

Authors: Pengyi Yang, Hao Huang and Chunlei Liu

Wheat in vivo RNA structure landscape reveals a prevalent role of RNA structure in modulating translational subgenome expression asymmetry

Polyploidy, especially allopolyploidy, which entails merging divergent genomes via hybridization and whole-genome duplication (WGD), is a major route to speciation in plants. The duplication among the parental...

Authors: Xiaofei Yang, Haopeng Yu, Wenqing Sun, Ling Ding, Ji Li, Jitender Cheema, Ricardo Ramirez-Gonzalez, Xuebo Zhao, Azahara C. Martín, Fei Lu, Bao Liu, Cristobal Uauy, Yiliang Ding and Huakun Zhang