Articles

CellPhy: accurate and fast probabilistic inference of single-cell phylogenies from scDNA-seq data

We introduce CellPhy, a maximum likelihood framework for inferring phylogenetic trees from somatic single-cell single-nucleotide variants. CellPhy leverages a finite-site Markov genotype model with 16 diploid ...

Authors: Alexey Kozlov, Joao M. Alves, Alexandros Stamatakis and David Posada

Species-resolved sequencing of low-biomass or degraded microbiomes using 2bRAD-M

Microbiome samples with low microbial biomass or severe DNA degradation remain challenging for amplicon-based or whole-metagenome sequencing approaches. Here, we introduce 2bRAD-M, a highly reduced and cost-ef...

Authors: Zheng Sun, Shi Huang, Pengfei Zhu, Lam Tzehau, Helen Zhao, Jia Lv, Rongchao Zhang, Lisha Zhou, Qianya Niu, Xiuping Wang, Meng Zhang, Gongchao Jing, Zhenmin Bao, Jiquan Liu, Shi Wang and Jian Xu

Comparative assessment of genes driving cancer and somatic evolution in non-cancer tissues: an update of the Network of Cancer Genes (NCG) resource

Genetic alterations of somatic cells can drive non-malignant clone formation and promote cancer initiation. However, the link between these processes remains unclear and hampers our understanding of tissue hom...

Authors: Lisa Dressler, Michele Bortolomeazzi, Mohamed Reda Keddar, Hrvoje Misetic, Giulia Sartini, Amelia Acha-Sagredo, Lucia Montorsi, Neshika Wijewardhane, Dimitra Repana, Joel Nulsen, Jacki Goldman, Marc Pollitt, Patrick Davis, Amy Strange, Karen Ambrose and Francesca D. Ciccarelli

Open chromatin interaction maps reveal functional regulatory elements and chromatin architecture variations during wheat evolution

Bread wheat (Triticum aestivum) is an allohexaploid that is generated by two subsequent allopolyploidization events. The large genome size (16 Gb) and polyploid complexity impede our understanding of how regulato...

Authors: Jingya Yuan, Haojie Sun, Yijin Wang, Lulu Li, Shiting Chen, Wu Jiao, Guanghong Jia, Longfei Wang, Junrong Mao, Zhongfu Ni, Xiue Wang and Qingxin Song

IDEAS: individual level differential expression analysis for single-cell RNA-seq data

We consider an increasingly popular study design where single-cell RNA-seq data are collected from multiple individuals and the question of interest is to find genes that are differentially expressed between t...

Authors: Mengqi Zhang, Si Liu, Zhen Miao, Fang Han, Raphael Gottardo and Wei Sun

sPLINK: a hybrid federated tool as a robust alternative to meta-analysis in genome-wide association studies

Meta-analysis has been established as an effective approach to combining summary statistics of several genome-wide association studies (GWAS). However, the accuracy of meta-analysis can be attenuated in the pr...

Authors: Reza Nasirigerdeh, Reihaneh Torkzadehmahani, Julian Matschinske, Tobias Frisch, Markus List, Julian Späth, Stefan Weiss, Uwe Völker, Esa Pitkänen, Dominik Heider, Nina Kerstin Wenke, Georgios Kaissis, Daniel Rueckert, Tim Kacprowski and Jan Baumbach

Nanopore adaptive sampling: a tool for enrichment of low abundance species in metagenomic samples

Adaptive sampling is a method of software-controlled enrichment unique to nanopore sequencing platforms. To test its potential for enrichment of rarer species within metagenomic samples, we create a synthetic ...

Authors: Samuel Martin, Darren Heavens, Yuxuan Lan, Samuel Horsfield, Matthew D. Clark and Richard M. Leggett

Statistics or biology: the zero-inflation controversy about scRNA-seq data

Researchers view vast zeros in single-cell RNA-seq data differently: some regard zeros as biological signals representing no or low gene expression, while others regard zeros as missing data to be corrected. T...

Authors: Ruochen Jiang, Tianyi Sun, Dongyuan Song and Jingyi Jessica Li

Bacon: a comprehensive computational benchmarking framework for evaluating targeted chromatin conformation capture-specific methodologies

Chromatin conformation capture (3C)-based technologies have enabled the accurate detection of topological genomic interactions, and the adoption of ChIP techniques to 3C-based protocols makes it possible to id...

Authors: Li Tang, Matthew C. Hill, Patrick T. Ellinor and Min Li

Strainline: full-length de novo viral haplotype reconstruction from noisy long reads

Haplotype-resolved de novo assembly of highly diverse virus genomes is critical in prevention, control and treatment of viral diseases. Current methods either can handle only relatively accurate short read dat...

Authors: Xiao Luo, Xiongbin Kang and Alexander Schönhuth

Genome-wide analysis and functional annotation of chromatin-enriched noncoding RNAs in rice during somatic cell regeneration

Plants have the remarkable ability to generate callus, a pluripotent cell mass that acquires competence for subsequent tissue regeneration. Global chromatin remodeling is required for this cell fate transition...

Authors: Yu-Chan Zhang, Yan-Fei Zhou, Yu Cheng, Jia-Hui Huang, Jian-Ping Lian, Lu Yang, Rui-Rui He, Meng-Qi Lei, Yu-Wei Liu, Chao Yuan, Wen-Long Zhao, Shi Xiao and Yue-Qin Chen

Comparison and evaluation of statistical error models for scRNA-seq

Heterogeneity in single-cell RNA-seq (scRNA-seq) data is driven by multiple sources, including biological variation in cellular state as well as technical variation introduced during experimental processing. D...

Authors: Saket Choudhary and Rahul Satija

Blood-based epigenome-wide analyses of cognitive abilities

Blood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia.

Authors: Daniel L. McCartney, Robert F. Hillary, Eleanor L. S. Conole, Daniel Trejo Banos, Danni A. Gadd, Rosie M. Walker, Cliff Nangle, Robin Flaig, Archie Campbell, Alison D. Murray, Susana Muñoz Maniega, María del C. Valdés-Hernández, Mathew A. Harris, Mark E. Bastin, Joanna M. Wardlaw, Sarah E. Harris…

DENA: training an authentic neural network model using Nanopore sequencing data of Arabidopsis transcripts for detection and quantification of N⁶-methyladenosine on RNA

Models developed using Nanopore direct RNA sequencing data from in vitro synthetic RNA with all adenosine replaced by N⁶-methyladenosine (m⁶A) are likely distorted due to superimposed signals from saturated m⁶A r...

Authors: Hang Qin, Liang Ou, Jian Gao, Longxian Chen, Jia-Wei Wang, Pei Hao and Xuan Li

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 active regulatory elements in tissues and cell types relevant to disease aetiology. Further ...

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

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