Articles

Sfaira accelerates data and model reuse in single cell genomics

Single-cell RNA-seq datasets are often first analyzed independently without harnessing model fits from previous studies, and are then contextualized with public data sets, requiring time-consuming data wrangli...

Authors: David S. Fischer, Leander Dony, Martin König, Abdul Moeed, Luke Zappia, Lukas Heumos, Sophie Tritschler, Olle Holmberg, Hananeh Aliee and Fabian J. Theis

Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability

Genome-wide association studies have reported more than 100 risk loci for rheumatoid arthritis (RA). These loci are shown to be enriched in immune cell-specific enhancers, but the analysis so far has excluded ...

Authors: Xiangyu Ge, Mojca Frank-Bertoncelj, Kerstin Klein, Amanda McGovern, Tadeja Kuret, Miranda Houtman, Blaž Burja, Raphael Micheroli, Chenfu Shi, Miriam Marks, Andrew Filer, Christopher D. Buckley, Gisela Orozco, Oliver Distler, Andrew P. Morris, Paul Martin…

Author Correction: Community-wide hackathons to identify central themes in single-cell multi-omics

Authors: Kim-Anh Lê Cao, Al J. Abadi, Emily F. Davis-Marcisak, Lauren Hsu, Arshi Arora, Alexis Coullomb, Atul Deshpande, Yuzhou Feng, Pratheepa Jeganathan, Melanie Loth, Chen Meng, Wancen Mu, Vera Pancaldi, Kris Sankaran, Dario Righelli, Amrit Singh…

Absent from DNA and protein: genomic characterization of nullomers and nullpeptides across functional categories and evolution

Nullomers and nullpeptides are short DNA or amino acid sequences that are absent from a genome or proteome, respectively. One potential cause for their absence could be their having a detrimental impact on an ...

Authors: Ilias Georgakopoulos-Soares, Ofer Yizhar-Barnea, Ioannis Mouratidis, Martin Hemberg and Nadav Ahituv

Acute depletion of CTCF rewires genome-wide chromatin accessibility

The transcription factor CTCF appears indispensable in defining topologically associated domain boundaries and maintaining chromatin loop structures within these domains, supported by numerous functional studi...

Authors: Beisi Xu, Hong Wang, Shaela Wright, Judith Hyle, Yang Zhang, Ying Shao, Mingming Niu, Yiping Fan, Wojciech Rosikiewicz, Mohamed Nadhir Djekidel, Junmin Peng, Rui Lu and Chunliang Li

Deterministic transition of enterotypes shapes the infant gut microbiome at an early age

The succession of the gut microbiota during the first few years plays a vital role in human development. We elucidate the characteristics and alternations of the infant gut microbiota to better understand the ...

Authors: Liwen Xiao, Jinfeng Wang, Jiayong Zheng, Xiaoqing Li and Fangqing Zhao

Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus

To date, the locus with the most robust human genetic association to COVID-19 severity is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to...

Authors: Silva Kasela, Zharko Daniloski, Sailalitha Bollepalli, Tristan X. Jordan, Benjamin R. tenOever, Neville E. Sanjana and Tuuli Lappalainen

INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants

Genome-wide association studies reveal many non-coding variants associated with complex traits. However, model organism studies largely remain as an untapped resource for unveiling the effector genes of non-co...

Authors: Chenyang Dong, Shane P. Simonett, Sunyoung Shin, Donnie S. Stapleton, Kathryn L. Schueler, Gary A. Churchill, Leina Lu, Xiaoxiao Liu, Fulai Jin, Yan Li, Alan D. Attie, Mark P. Keller and Sündüz Keleş

Systematic functional interrogation of human pseudogenes using CRISPRi

The human genome encodes over 14,000 pseudogenes that are evolutionary relics of protein-coding genes and commonly considered as nonfunctional. Emerging evidence suggests that some pseudogenes may exert import...

Authors: Ming Sun, Yunfei Wang, Caishang Zheng, Yanjun Wei, Jiakai Hou, Peng Zhang, Wei He, Xiangdong Lv, Yao Ding, Han Liang, Chung-Chau Hon, Xi Chen, Han Xu and Yiwen Chen

ExOrthist: a tool to infer exon orthologies at any evolutionary distance

Several bioinformatic tools have been developed for genome-wide identification of orthologous and paralogous genes. However, no corresponding tool allows the detection of exon homology relationships. Here, we ...

Authors: Yamile Márquez, Federica Mantica, Luca Cozzuto, Demian Burguera, Antonio Hermoso-Pulido, Julia Ponomarenko, Scott W. Roy and Manuel Irimia

Bedshift: perturbation of genomic interval sets

Functional genomics experiments, like ChIP-Seq or ATAC-Seq, produce results that are summarized as a region set. There is no way to objectively evaluate the effectiveness of region set similarity metrics. We p...

Authors: Aaron Gu, Hyun Jae Cho and Nathan C. Sheffield

Megabase-scale presence-absence variation with Tripsacum origin was under selection during maize domestication and adaptation

Structural variants (SVs) significantly drive genome diversity and environmental adaptation for diverse species. Unlike the prevalent small SVs (< kilobase-scale) in higher eukaryotes, large-size SVs rarely ex...

Authors: Yumin Huang, Wei Huang, Zhuang Meng, Guilherme Tomaz Braz, Yunfei Li, Kai Wang, Hai Wang, Jinsheng Lai, Jiming Jiang, Zhaobin Dong and Weiwei Jin

Effective control of large deletions after double-strand breaks by homology-directed repair and dsODN insertion

After repairing double-strand breaks (DSBs) caused by CRISPR-Cas9 cleavage, genomic damage, such as large deletions, may have pathogenic consequences.

Authors: Wei Wen, Zi-Jun Quan, Si-Ang Li, Zhi-Xue Yang, Ya-Wen Fu, Feng Zhang, Guo-Hua Li, Mei Zhao, Meng-Di Yin, Jing Xu, Jian-Ping Zhang, Tao Cheng and Xiao-Bing Zhang

Easy-Prime: a machine learning–based prime editor design tool

Prime editing is a revolutionary genome-editing technology that can make a wide range of precise edits in DNA. However, designing highly efficient prime editors (PEs) remains challenging. We develop Easy-Prime...

Authors: Yichao Li, Jingjing Chen, Shengdar Q. Tsai and Yong Cheng

Keeping your lab together in the COVID-19 era

Authors: Timothy R. Sands

Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network

A specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate...

Authors: Zhonghua Du, Xue Wen, Yichen Wang, Lin Jia, Shilin Zhang, Yudi Liu, Lei Zhou, Hui Li, Wang Yang, Cong Wang, Jingcheng Chen, Yajing Hao, Daniela Salgado Figueroa, Huiling Chen, Dan Li, Naifei Chen…

MultiK: an automated tool to determine optimal cluster numbers in single-cell RNA sequencing data

Single-cell RNA sequencing (scRNA-seq) provides new opportunities to characterize cell populations, typically accomplished through some type of clustering analysis. Estimation of the optimal cluster number (K) is...

Authors: Siyao Liu, Aatish Thennavan, Joseph P. Garay, J. S. Marron and Charles M. Perou

VariantStore: an index for large-scale genomic variant search

Efficiently scaling genomic variant search indexes to thousands of samples is computationally challenging due to the presence of multiple coordinate systems to avoid reference biases. We present VariantStore, ...

Authors: Prashant Pandey, Yinjie Gao and Carl Kingsford

Time-dependent effect of 1,6-hexanediol on biomolecular condensates and 3D chromatin organization

Biomolecular condensates have been implicated in multiple cellular processes. However, the global role played by condensates in 3D chromatin organization remains unclear. At present, 1,6-hexanediol (1,6-HD) is...

Authors: Xinyi Liu, Shaoshuai Jiang, Lin Ma, Jiale Qu, Longying Zhao, Xing Zhu and Junjun Ding

Quantifying the phase separation property of chromatin-associated proteins under physiological conditions using an anti-1,6-hexanediol index

Liquid-liquid phase separation (LLPS) is an important organizing principle for biomolecular condensation and chromosome compartmentalization. However, while many proteins have been reported to undergo LLPS, qu...

Authors: Minglei Shi, Kaiqiang You, Taoyu Chen, Chao Hou, Zhengyu Liang, Mingwei Liu, Jifeng Wang, Taotao Wei, Jun Qin, Yang Chen, Michael Q. Zhang and Tingting Li

CoCoA-diff: counterfactual inference for single-cell gene expression analysis

Finding a causal gene is a fundamental problem in genomic medicine. We present a causal inference framework, CoCoA-diff, that prioritizes disease genes by adjusting confounders without prior knowledge of contr...

Authors: Yongjin P. Park and Manolis Kellis

Chromatin interaction neural network (ChINN): a machine learning-based method for predicting chromatin interactions from DNA sequences

Chromatin interactions play important roles in regulating gene expression. However, the availability of genome-wide chromatin interaction data is limited. We develop a computational method, chromatin interacti...

Authors: Fan Cao, Yu Zhang, Yichao Cai, Sambhavi Animesh, Ying Zhang, Semih Can Akincilar, Yan Ping Loh, Xinya Li, Wee Joo Chng, Vinay Tergaonkar, Chee Keong Kwoh and Melissa J. Fullwood

Retrotransposons as pathogenicity factors of the plant pathogenic fungus Botrytis cinerea

Retrotransposons are genetic elements inducing mutations in all domains of life. Despite their detrimental effect, retrotransposons can become temporarily active during epigenetic reprogramming and cellular st...

Authors: Antoine Porquier, Constance Tisserant, Francisco Salinas, Carla Glassl, Lucas Wange, Wolfgang Enard, Andreas Hauser, Matthias Hahn and Arne Weiberg

Straglr: discovering and genotyping tandem repeat expansions using whole genome long-read sequences

Tandem repeat (TR) expansion is the underlying cause of over 40 neurological disorders. Long-read sequencing offers an exciting avenue over conventional technologies for detecting TR expansions. Here, we prese...

Authors: Readman Chiu, Indhu-Shree Rajan-Babu, Jan M. Friedman and Inanc Birol

Nanopore sequencing reveals endogenous NMD-targeted isoforms in human cells

Nonsense-mediated mRNA decay (NMD) is a eukaryotic, translation-dependent degradation pathway that targets mRNAs with premature termination codons and also regulates the expression of some mRNAs that encode fu...

Authors: Evangelos D. Karousis, Foivos Gypas, Mihaela Zavolan and Oliver Mühlemann

MAAPER: model-based analysis of alternative polyadenylation using 3′ end-linked reads

Most eukaryotic genes express alternative polyadenylation (APA) isoforms. A growing number of RNA sequencing methods, especially those used for single-cell transcriptome analysis, generate reads close to the p...

Authors: Wei Vivian Li, Dinghai Zheng, Ruijia Wang and Bin Tian

SCAPTURE: a deep learning-embedded pipeline that captures polyadenylation information from 3′ tag-based RNA-seq of single cells

Single-cell RNA-seq (scRNA-seq) profiles gene expression with high resolution. Here, we develop a stepwise computational method-called SCAPTURE to identify, evaluate, and quantify cleavage and polyadenylation ...

Authors: Guo-Wei Li, Fang Nan, Guo-Hua Yuan, Chu-Xiao Liu, Xindong Liu, Ling-Ling Chen, Bin Tian and Li Yang

Genetic and phylogeographic evidence for Jewish Holocaust victims at the Sobibór death camp

Six million Jews were killed by Nazi Germany and its collaborators during World War II. Archaeological excavations in the area of the death camp in Sobibór, Poland, revealed ten sets of human skeletal remains ...

Authors: Marta Diepenbroek, Christina Amory, Harald Niederstätter, Bettina Zimmermann, Maria Szargut, Grażyna Zielińska, Arne Dür, Iwona Teul, Wojciech Mazurek, Krzysztof Persak, Andrzej Ossowski and Walther Parson

Community-wide hackathons to identify central themes in single-cell multi-omics

Authors: Kim-Anh Lê Cao, Al J. Abadi, Emily F. Davis-Marcisak, Lauren Hsu, Arshi Arora, Alexis Coullomb, Atul Deshpande, Yuzhou Feng, Pratheepa Jeganathan, Melanie Loth, Chen Meng, Wancen Mu, Vera Pancaldi, Kris Sankaran, Dario Righelli, Amrit Singh…

Specific splice junction detection in single cells with SICILIAN

Precise splice junction calls are currently unavailable in scRNA-seq pipelines such as the 10x Chromium platform but are critical for understanding single-cell biology. Here, we introduce SICILIAN, a new metho...

Authors: Roozbeh Dehghannasiri, Julia Eve Olivieri, Ana Damljanovic and Julia Salzman

Host adaptation in gut Firmicutes is associated with sporulation loss and altered transmission cycle

Human-to-human transmission of symbiotic, anaerobic bacteria is a fundamental evolutionary adaptation essential for membership of the human gut microbiota. However, despite its importance, the genomic and biol...

Authors: Hilary P. Browne, Alexandre Almeida, Nitin Kumar, Kevin Vervier, Anne T. Adoum, Elisa Viciani, Nicholas J. R. Dawson, Samuel C. Forster, Claire Cormie, David Goulding and Trevor D. Lawley

Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers

Spatial interactions and insulation of chromatin regions are associated with transcriptional regulation. Domains of frequent chromatin contacts are proposed as functional units, favoring and delimiting gene re...

Authors: Marie Zufferey, Yuanlong Liu, Daniele Tavernari, Marco Mina and Giovanni Ciriello

DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell

Topologically associating domains (TAD) are a key structure of the 3D mammalian genomes. However, the prevalence and dynamics of TAD-like domains in single cells remain elusive. Here we develop a new algorithm...

Authors: Xiao Li, Guangjie Zeng, Angsheng Li and Zhihua Zhang

Dissecting indirect genetic effects from peers in laboratory mice

The phenotype of an individual can be affected not only by the individual’s own genotypes, known as direct genetic effects (DGE), but also by genotypes of interacting partners, indirect genetic effects (IGE). ...

Authors: Amelie Baud, Francesco Paolo Casale, Amanda M. Barkley-Levenson, Nilgoun Farhadi, Charlotte Montillot, Binnaz Yalcin, Jerome Nicod, Abraham A. Palmer and Oliver Stegle

Enabling reproducible re-analysis of single-cell data

Authors: Michael A. Skinnider, Jordan W. Squair and Grégoire Courtine

STRONG: metagenomics strain resolution on assembly graphs

We introduce STrain Resolution ON assembly Graphs (STRONG), which identifies strains de novo, from multiple metagenome samples. STRONG performs coassembly, and binning into metagenome assembled genomes (MAGs),...

Authors: Christopher Quince, Sergey Nurk, Sebastien Raguideau, Robert James, Orkun S. Soyer, J. Kimberly Summers, Antoine Limasset, A. Murat Eren, Rayan Chikhi and Aaron E. Darling

MegaLMM: Mega-scale linear mixed models for genomic predictions with thousands of traits

Large-scale phenotype data can enhance the power of genomic prediction in plant and animal breeding, as well as human genetics. However, the statistical foundation of multi-trait genomic prediction is based on...

Authors: Daniel E. Runcie, Jiayi Qu, Hao Cheng and Lorin Crawford

Haploflow: strain-resolved de novo assembly of viral genomes

With viral infections, multiple related viral strains are often present due to coinfection or within-host evolution. We describe Haploflow, a deBruijn graph-based assembler for de novo genome assembly of viral...

Authors: Adrian Fritz, Andreas Bremges, Zhi-Luo Deng, Till Robin Lesker, Jasper Götting, Tina Ganzenmueller, Alexander Sczyrba, Alexander Dilthey, Frank Klawonn and Alice Carolyn McHardy

The genetic architecture of temperature adaptation is shaped by population ancestry and not by selection regime

Understanding the genetic architecture of temperature adaptation is key for characterizing and predicting the effect of climate change on natural populations. One particularly promising approach is Evolve and ...

Authors: Kathrin A. Otte, Viola Nolte, François Mallard and Christian Schlötterer

Publisher Correction: Leveraging breeding programs and genomic data in Norway spruce (Picea abies L. Karst) for GWAS analysis

Authors: Zhi-Qiang Chen, Yanjun Zan, Pascal Milesi, Linghua Zhou, Jun Chen, Lili Li, BinBin Cui, Shihui Niu, Johan Westin, Bo Karlsson, Maria Rosario García-Gil, Martin Lascoux and Harry X. Wu

Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly

Akkermansia muciniphila is a human gut microbe with a key role in the physiology of the intestinal mucus layer and reported associations with decreased body mass and increased gut barrier function and health. Des...

Authors: Nicolai Karcher, Eleonora Nigro, Michal Punčochář, Aitor Blanco-Míguez, Matteo Ciciani, Paolo Manghi, Moreno Zolfo, Fabio Cumbo, Serena Manara, Davide Golzato, Anna Cereseto, Manimozhiyan Arumugam, Thi Phuong Nam Bui, Hanne L. P. Tytgat, Mireia Valles-Colomer, Willem M. de Vos…

2dFDR: a new approach to confounder adjustment substantially increases detection power in omics association studies

One challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted...

Authors: Sangyoon Yi, Xianyang Zhang, Lu Yang, Jinyan Huang, Yuanhang Liu, Chen Wang, Daniel J. Schaid and Jun Chen

Revealing the full biosphere structure and versatile metabolic functions in the deepest ocean sediment of the Challenger Deep

The full biosphere structure and functional exploration of the microbial communities of the Challenger Deep of the Mariana Trench, the deepest known hadal zone on Earth, lag far behind that of other marine rea...

Authors: Ping Chen, Hui Zhou, Yanyan Huang, Zhe Xie, Mengjie Zhang, Yuli Wei, Jia Li, Yuewei Ma, Min Luo, Wenmian Ding, Junwei Cao, Tao Jiang, Peng Nan, Jiasong Fang and Xuan Li

Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency

Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication st...

Authors: Yongzheng Li, Boxin Xue, Mengling Zhang, Liwei Zhang, Yingping Hou, Yizhi Qin, Haizhen Long, Qian Peter Su, Yao Wang, Xiaodong Guan, Yanyan Jin, Yuan Cao, Guohong Li and Yujie Sun

Author Correction: Improved reference genome of the arboviral vector Aedes albopictus

Authors: Umberto Palatini, Reem A. Masri, Luciano V. Cosme, Sergey Koren, Françoise Thibaud-Nissen, James K. Biedler, Flavia Krsticevic, J. Spencer Johnston, Rebecca Halbach, Jacob E. Crawford, Igor Antoshechkin, Anna-Bella Failloux, Elisa Pischedda, Michele Marconcini, Jay Ghurye, Arang Rhie…

Telomere-to-telomere assembly of a fish Y chromosome reveals the origin of a young sex chromosome pair

The origin of sex chromosomes requires the establishment of recombination suppression between the proto-sex chromosomes. In many fish species, the sex chromosome pair is homomorphic with a recent origin, provi...

Authors: Lingzhan Xue, Yu Gao, Meiying Wu, Tian Tian, Haiping Fan, Yongji Huang, Zhen Huang, Dapeng Li and Luohao Xu

GRIDSS2: comprehensive characterisation of somatic structural variation using single breakend variants and structural variant phasing

GRIDSS2 is the first structural variant caller to explicitly report single breakends—breakpoints in which only one side can be unambiguously determined. By treating single breakends as a fundamental genomic re...

Authors: Daniel L. Cameron, Jonathan Baber, Charles Shale, Jose Espejo Valle-Inclan, Nicolle Besselink, Arne van Hoeck, Roel Janssen, Edwin Cuppen, Peter Priestley and Anthony T. Papenfuss

Elevated retrotransposon activity and genomic instability in primed pluripotent stem cells

Naïve and primed pluripotent stem cells (PSCs) represent two different pluripotent states. Primed PSCs following in vitro culture exhibit lower developmental potency as evidenced by failure in germline chimera...

Authors: Haifeng Fu, Weiyu Zhang, Niannian Li, Jiao Yang, Xiaoying Ye, Chenglei Tian, Xinyi Lu and Lin Liu

The evolving gene regulatory landscape—a tinkerer of complex creatures

Authors: Geoffrey J. Faulkner

Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors.

Authors: Xiaojing Chu, Martin Jaeger, Joep Beumer, Olivier B. Bakker, Raul Aguirre-Gamboa, Marije Oosting, Sanne P. Smeekens, Simone Moorlag, Vera P. Mourits, Valerie A. C. M. Koeken, Charlotte de Bree, Trees Jansen, Ian T. Mathews, Khoi Dao, Mahan Najhawan, Jeramie D. Watrous…