Articles

CHOP: haplotype-aware path indexing in population graphs

The practical use of graph-based reference genomes depends on the ability to align reads to them. Performing substring queries to paths through these graphs lies at the core of this task. The combination of in...

Authors: Tom Mokveld, Jasper Linthorst, Zaid Al-Ars, Henne Holstege and Marcel Reinders

Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium

How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly und...

Authors: Juri Kazakevych, Jérémy Denizot, Anke Liebert, Mariana Portovedo, Mia Mosavie, Payal Jain, Claudia Stellato, Claire Fraser, Renan Oliveira Corrêa, Marina Célestine, Raphaël Mattiuz, Hanneke Okkenhaug, J. Ross Miller, Marco Aurélio Ramirez Vinolo, Marc Veldhoen and Patrick Varga-Weisz

High-resolution modeling of the selection on local mRNA folding strength in coding sequences across the tree of life

mRNA can form local secondary structure within the protein-coding sequence, and the strength of this structure is thought to influence gene expression regulation. Previous studies suggest that secondary struct...

Authors: Michael Peeri and Tamir Tuller

A benchmark of algorithms for the analysis of pooled CRISPR screens

Genome-wide pooled CRISPR-Cas-mediated knockout, activation, and repression screens are powerful tools for functional genomic investigations. Despite their increasing importance, there is currently little guid...

Authors: Sunil Bodapati, Timothy P. Daley, Xueqiu Lin, James Zou and Lei S. Qi

Hemispheric asymmetry in the human brain and in Parkinson’s disease is linked to divergent epigenetic patterns in neurons

Hemispheric asymmetry in neuronal processes is a fundamental feature of the human brain and drives symptom lateralization in Parkinson’s disease (PD), but its molecular determinants are unknown. Here, we ident...

Authors: Peipei Li, Elizabeth Ensink, Sean Lang, Lee Marshall, Meghan Schilthuis, Jared Lamp, Irving Vega and Viviane Labrie

The genome evolution and domestication of tropical fruit mango

Mango is one of the world’s most important tropical fruits. It belongs to the family Anacardiaceae, which includes several other economically important species, notably cashew, sumac and pistachio from other g...

Authors: Peng Wang, Yingfeng Luo, Jianfeng Huang, Shenghan Gao, Guopeng Zhu, Zhiguo Dang, Jiangtao Gai, Meng Yang, Min Zhu, Huangkai Zhang, Xiuxu Ye, Aiping Gao, Xinyu Tan, Sen Wang, Shuangyang Wu, Edgar B. Cahoon…

Multiplexed capture of spatial configuration and temporal dynamics of locus-specific 3D chromatin by biotinylated dCas9

The spatiotemporal control of 3D genome is fundamental for gene regulation, yet it remains challenging to profile high-resolution chromatin structure at cis-regulatory elements (CREs). Using C-terminally biotinyl...

Authors: Xin Liu, Yong Chen, Yuannyu Zhang, Yuxuan Liu, Nan Liu, Giovanni A. Botten, Hui Cao, Stuart H. Orkin, Michael Q. Zhang and Jian Xu

WhatsGNU: a tool for identifying proteomic novelty

To understand diversity in enormous collections of genome sequences, we need computationally scalable tools that can quickly contextualize individual genomes based on their similarities and identify features o...

Authors: Ahmed M. Moustafa and Paul J. Planet

Decontamination of ambient RNA in single-cell RNA-seq with DecontX

Droplet-based microfluidic devices have become widely used to perform single-cell RNA sequencing (scRNA-seq). However, ambient RNA present in the cell suspension can be aberrantly counted along with a cell’s n...

Authors: Shiyi Yang, Sean E. Corbett, Yusuke Koga, Zhe Wang, W Evan Johnson, Masanao Yajima and Joshua D. Campbell

NanoVar: accurate characterization of patients’ genomic structural variants using low-depth nanopore sequencing

The recent advent of third-generation sequencing technologies brings promise for better characterization of genomic structural variants by virtue of having longer reads. However, long-read applications are sti...

Authors: Cheng Yong Tham, Roberto Tirado-Magallanes, Yufen Goh, Melissa J. Fullwood, Bryan T.H. Koh, Wilson Wang, Chin Hin Ng, Wee Joo Chng, Alexandre Thiery, Daniel G. Tenen and Touati Benoukraf

Longitudinal survey of microbiome associated with particulate matter in a megacity

While the physical and chemical properties of airborne particulate matter (PM) have been extensively studied, their associated microbiome remains largely unexplored. Here, we performed a longitudinal metagenom...

Authors: Nan Qin, Peng Liang, Chunyan Wu, Guanqun Wang, Qian Xu, Xiao Xiong, Tingting Wang, Moreno Zolfo, Nicola Segata, Huanlong Qin, Rob Knight, Jack A. Gilbert and Ting F. Zhu

Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS

We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compati...

Authors: Yibin Liu, Jingfei Cheng, Paulina Siejka-Zielińska, Carika Weldon, Hannah Roberts, Maria Lopopolo, Andrea Magri, Valentina D’Arienzo, James M. Harris, Jane A. McKeating and Chun-Xiao Song

gscreend: modelling asymmetric count ratios in CRISPR screens to decrease experiment size and improve phenotype detection

Pooled CRISPR screens are a powerful tool to probe genotype-phenotype relationships at genome-wide scale. However, criteria for optimal design are missing, and it remains unclear how experimental parameters af...

Authors: Katharina Imkeller, Giulia Ambrosi, Michael Boutros and Wolfgang Huber

Regenerating zebrafish fin epigenome is characterized by stable lineage-specific DNA methylation and dynamic chromatin accessibility

Zebrafish can faithfully regenerate injured fins through the formation of a blastema, a mass of proliferative cells that can grow and develop into the lost body part. After amputation, various cell types contr...

Authors: Hyung Joo Lee, Yiran Hou, Yujie Chen, Zea Z. Dailey, Aiyana Riddihough, Hyo Sik Jang, Ting Wang and Stephen L. Johnson

A rare codon-based translational program of cell proliferation

The speed of translation elongation is primarily determined by the abundance of tRNAs. Thus, the codon usage influences the rate with which individual mRNAs are translated. As the nature of tRNA pools and modi...

Authors: Joao C. Guimaraes, Nitish Mittal, Alexandra Gnann, Dominik Jedlinski, Andrea Riba, Katarzyna Buczak, Alexander Schmidt and Mihaela Zavolan

Allosteric inhibition of CRISPR-Cas9 by bacteriophage-derived peptides

CRISPR-Cas9 has been developed as a therapeutic agent for various infectious and genetic diseases. In many clinically relevant applications, constitutively active CRISPR-Cas9 is delivered into human cells with...

Authors: Yan-ru Cui, Shao-jie Wang, Jun Chen, Jie Li, Wenzhang Chen, Shuyue Wang, Bing Meng, Wei Zhu, Zhuhong Zhang, Bei Yang, Biao Jiang, Guang Yang, Peixiang Ma and Jia Liu

Author Correction: Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity

Following publication of the original paper [1], an error was reported in the third paragraph in the section “Analysis of GMB composition and its correlates” (page 3 of the PDF). The first sentence of the text sh...

Authors: Robert C. Kaplan, Zheng Wang, Mykhaylo Usyk, Daniela Sotres-Alvarez, Martha L. Daviglus, Neil Schneiderman, Gregory A. Talavera, Marc D. Gellman, Bharat Thyagarajan, Jee-Young Moon, Yoshiki Vázquez-Baeza, Daniel McDonald, Jessica S. Williams-Nguyen, Michael C. Wu, Kari E. North, Justin Shaffer…

Linked optical and gene expression profiling of single cells at high-throughput

Single-cell RNA sequencing has emerged as a powerful tool for characterizing cells, but not all phenotypes of interest can be observed through changes in gene expression. Linking sequencing with optical analys...

Authors: Jesse Q. Zhang, Christian A. Siltanen, Leqian Liu, Kai-Chun Chang, Zev J. Gartner and Adam R. Abate

ncHMR detector: a computational framework to systematically reveal non-classical functions of histone modification regulators

Recently, several non-classical functions of histone modification regulators (HMRs), independent of their known histone modification substrates and products, have been reported to be essential for specific cel...

Authors: Shengen Hu, Dawei Huo, Zhaowei Yu, Yujie Chen, Jing Liu, Lin Liu, Xudong Wu and Yong Zhang

Carnelian uncovers hidden functional patterns across diverse study populations from whole metagenome sequencing reads

Microbial populations exhibit functional changes in response to different ambient environments. Although whole metagenome sequencing promises enough raw data to study those changes, existing tools are limited ...

Authors: Sumaiya Nazeen, Yun William Yu and Bonnie Berger

Author Correction: 547 transcriptomes from 44 brain areas reveal features of the aging brain in non-human primates

Following publication of the original paper [1], the authors reported an error in the affiliation of Xin-Tian Hu, who is also affiliated with “Kunming Primate Research Center, Kunming Institute of Zoology, Chi...

Authors: Ming-Li Li, Shi-Hao Wu, Jin-Jin Zhang, Hang-Yu Tian, Yong Shao, Zheng-Bo Wang, David M. Irwin, Jia-Li Li, Xin-Tian Hu and Dong-Dong Wu

Histone H3K27 acetylation is dispensable for enhancer activity in mouse embryonic stem cells

H3K27ac is well recognized as a marker for active enhancers and a great indicator of enhancer activity. However, its functional impact on transcription has not been characterized. By substituting lysine 27 in ...

Authors: Tiantian Zhang, Zhuqiang Zhang, Qiang Dong, Jun Xiong and Bing Zhu

Comprehensive assessment of computational algorithms in predicting cancer driver mutations

The initiation and subsequent evolution of cancer are largely driven by a relatively small number of somatic mutations with critical functional impacts, so-called driver mutations. Identifying driver mutations...

Authors: Hu Chen, Jun Li, Yumeng Wang, Patrick Kwok-Shing Ng, Yiu Huen Tsang, Kenna R. Shaw, Gordon B. Mills and Han Liang

A framework for transcriptome-wide association studies in breast cancer in diverse study populations

The relationship between germline genetic variation and breast cancer survival is largely unknown, especially in understudied minority populations who often have poorer survival. Genome-wide association studie...

Authors: Arjun Bhattacharya, Montserrat García-Closas, Andrew F. Olshan, Charles M. Perou, Melissa A. Troester and Michael I. Love

Author Correction: Interaction between the microbiome and TP53 in human lung cancer

Following publication of the original paper [1], the authors submitted a new Additional file 5 to replace the one containing formatting issues. The updated Additional file 5 is published in this correction.

Authors: K. Leigh Greathouse, James R. White, Ashely J. Vargas, Valery V. Bliskovsky, Jessica A. Beck, Natalia von Muhlinen, Eric C. Polley, Elise D. Bowman, Mohammed A. Khan, Ana I. Robles, Tomer Cooks, Bríd M. Ryan, Noah Padgett, Amiran H. Dzutsev, Giorgio Trinchieri, Marbin A. Pineda…

Publisher Correction: Host-associated microbiomes are predicted by immune system complexity and climate

Following publication of the original paper [1], it was reported that an error in the processing of Fig. 8 occurred. In the online HTML version of the article, Fig. 8 was presented as a duplication of Fig. 7. ...

Authors: Douglas C. Woodhams, Molly C. Bletz, C. Guilherme Becker, Hayden A. Bender, Daniel Buitrago-Rosas, Hannah Diebboll, Roger Huynh, Patrick J. Kearns, Jordan Kueneman, Emmi Kurosawa, Brandon C. LaBumbard, Casandra Lyons, Kerry McNally, Klaus Schliep, Nachiket Shankar, Amanda G. Tokash-Peters…

Protein velocity and acceleration from single-cell multiomics experiments

The simultaneous quantification of protein and RNA makes possible the inference of past, present, and future cell states from single experimental snapshots. To enable such temporal analysis from multimodal sin...

Authors: Gennady Gorin, Valentine Svensson and Lior Pachter

A willow sex chromosome reveals convergent evolution of complex palindromic repeats

Sex chromosomes have arisen independently in a wide variety of species, yet they share common characteristics, including the presence of suppressed recombination surrounding sex determination loci. Mammalian s...

Authors: Ran Zhou, David Macaya-Sanz, Craig H. Carlson, Jeremy Schmutz, Jerry W. Jenkins, David Kudrna, Aditi Sharma, Laura Sandor, Shengqiang Shu, Kerrie Barry, Gerald A. Tuskan, Tao Ma, Jianquan Liu, Matthew Olson, Lawrence B. Smart and Stephen P. DiFazio

Mutational signatures: experimental design and analytical framework

Mutational signatures provide a powerful alternative for understanding the pathophysiology of cancer. Currently, experimental efforts aimed at validating and understanding the etiologies of cancer-derived muta...

Authors: Gene Koh, Xueqing Zou and Serena Nik-Zainal

Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data

Many functional analysis tools have been developed to extract functional and mechanistic insight from bulk transcriptome data. With the advent of single-cell RNA sequencing (scRNA-seq), it is in principle poss...

Authors: Christian H. Holland, Jovan Tanevski, Javier Perales-Patón, Jan Gleixner, Manu P. Kumar, Elisabetta Mereu, Brian A. Joughin, Oliver Stegle, Douglas A. Lauffenburger, Holger Heyn, Bence Szalai and Julio Saez-Rodriguez

Genotyping structural variants in pangenome graphs using the vg toolkit

Structural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide a...

Authors: Glenn Hickey, David Heller, Jean Monlong, Jonas A. Sibbesen, Jouni Sirén, Jordan Eizenga, Eric T. Dawson, Erik Garrison, Adam M. Novak and Benedict Paten

Assembly of hundreds of novel bacterial genomes from the chicken caecum

Chickens are a highly important source of protein for a large proportion of the human population. The caecal microbiota plays a crucial role in chicken nutrition through the production of short-chain fatty aci...

Authors: Laura Glendinning, Robert D. Stewart, Mark J. Pallen, Kellie A. Watson and Mick Watson

A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells

Quiescence (G0) is a transient, cell cycle-arrested state. By entering G0, cancer cells survive unfavorable conditions such as chemotherapy and cause relapse. While G0 cells have been studied at the transcript...

Authors: Sooncheol Lee, Douglas Micalizzi, Samuel S. Truesdell, Syed I. A. Bukhari, Myriam Boukhali, Jennifer Lombardi-Story, Yasutaka Kato, Min-Kyung Choo, Ipsita Dey-Guha, Fei Ji, Benjamin T. Nicholson, David T. Myers, Dongjun Lee, Maria A. Mazzola, Radhika Raheja, Adam Langenbucher…

Lisa: inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data

We developed Lisa (http://​lisa.​cistrome.​org/​) to predict the transcriptional regulators (TRs) of differentially expressed or co-expressed gene sets. Based on the input gene sets, Lisa first uses histone mark ChIP...

Authors: Qian Qin, Jingyu Fan, Rongbin Zheng, Changxin Wan, Shenglin Mei, Qiu Wu, Hanfei Sun, Myles Brown, Jing Zhang, Clifford A. Meyer and X. Shirley Liu

Eleven grand challenges in single-cell data science

The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands—or even millions—of cells analyzed in a si...

Authors: David Lähnemann, Johannes Köster, Ewa Szczurek, Davis J. McCarthy, Stephanie C. Hicks, Mark D. Robinson, Catalina A. Vallejos, Kieran R. Campbell, Niko Beerenwinkel, Ahmed Mahfouz, Luca Pinello, Pavel Skums, Alexandros Stamatakis, Camille Stephan-Otto Attolini, Samuel Aparicio, Jasmijn Baaijens…

Opportunities and challenges in long-read sequencing data analysis

Long-read technologies are overcoming early limitations in accuracy and throughput, broadening their application domains in genomics. Dedicated analysis tools that take into account the characteristics of long...

Authors: Shanika L. Amarasinghe, Shian Su, Xueyi Dong, Luke Zappia, Matthew E. Ritchie and Quentin Gouil

Admixture-enabled selection for rapid adaptive evolution in the Americas

Admixture occurs when previously isolated populations come together and exchange genetic material. We hypothesize that admixture can enable rapid adaptive evolution in human populations by introducing novel ge...

Authors: Emily T. Norris, Lavanya Rishishwar, Aroon T. Chande, Andrew B. Conley, Kaixiong Ye, Augusto Valderrama-Aguirre and I. King Jordan

Publisher Correction: Co-opted transposons help perpetuate conserved higher-order chromosomal structures

Following publication of the original paper [1], an error was reported in the processing of Fig. 2. The correct Fig. 2 is supplied below and the original article [1] has been corrected. The publishers apologiz...

Authors: Mayank N. K. Choudhary, Ryan Z. Friedman, Julia T. Wang, Hyo Sik Jang, Xiaoyu Zhuo and Ting Wang

Systematic functional identification of cancer multi-drug resistance genes

Drug resistance is a major obstacle in cancer therapy. To elucidate the genetic factors that regulate sensitivity to anti-cancer drugs, we performed CRISPR-Cas9 knockout screens for resistance to a spectrum of...

Authors: Man-Tat Lau, Shila Ghazanfar, Ashleigh Parkin, Angela Chou, Jourdin R. Rouaen, Jamie B. Littleboy, Danielle Nessem, Thang M. Khuong, Damien Nevoltris, Peter Schofield, David Langley, Daniel Christ, Jean Yang, Marina Pajic and G. Gregory Neely

Purifying selection of long dsRNA is the first line of defense against false activation of innate immunity

Mobile elements comprise a large fraction of metazoan genomes. Accumulation of mobile elements is bound to produce multiple putative double-stranded RNA (dsRNA) structures within the transcriptome. These endog...

Authors: Michal Barak, Hagit T. Porath, Gilad Finkelstein, Binyamin A. Knisbacher, Ilana Buchumenski, Shalom Hillel Roth, Erez Y. Levanon and Eli Eisenberg

Nanopore sequencing-based genome assembly and evolutionary genomics of circum-basmati rice

The circum-basmati group of cultivated Asian rice (Oryza sativa) contains many iconic varieties and is widespread in the Indian subcontinent. Despite its economic and cultural importance, a high-quality reference...

Authors: Jae Young Choi, Zoe N. Lye, Simon C. Groen, Xiaoguang Dai, Priyesh Rughani, Sophie Zaaijer, Eoghan D. Harrington, Sissel Juul and Michael D. Purugganan

scAI: an unsupervised approach for the integrative analysis of parallel single-cell transcriptomic and epigenomic profiles

Simultaneous measurements of transcriptomic and epigenomic profiles in the same individual cells provide an unprecedented opportunity to understand cell fates. However, effective approaches for the integrative...

Authors: Suoqin Jin, Lihua Zhang and Qing Nie

Genome-wide MNase hypersensitivity assay unveils distinct classes of open chromatin associated with H3K27me3 and DNA methylation in Arabidopsis thaliana

Regulation of transcription depends on interactions between cis-regulatory elements (CREs) and regulatory proteins. Active CREs are imbedded in open chromatin that are accessible to nucleases. Several techniques,...

Authors: Hainan Zhao, Wenli Zhang, Tao Zhang, Yuan Lin, Yaodong Hu, Chao Fang and Jiming Jiang

Host-associated microbiomes are predicted by immune system complexity and climate

Host-associated microbiomes, the microorganisms occurring inside and on host surfaces, influence evolutionary, immunological, and ecological processes. Interactions between host and microbiome affect metabolis...

Authors: Douglas C. Woodhams, Molly C. Bletz, C. Guilherme Becker, Hayden A. Bender, Daniel Buitrago-Rosas, Hannah Diebboll, Roger Huynh, Patrick J. Kearns, Jordan Kueneman, Emmi Kurosawa, Brandon C. LaBumbard, Casandra Lyons, Kerry McNally, Klaus Schliep, Nachiket Shankar, Amanda G. Tokash-Peters…

From reads to insight: a hitchhiker’s guide to ATAC-seq data analysis

Assay of Transposase Accessible Chromatin sequencing (ATAC-seq) is widely used in studying chromatin biology, but a comprehensive review of the analysis tools has not been completed yet. Here, we discuss the m...

Authors: Feng Yan, David R. Powell, David J. Curtis and Nicholas C. Wong

The Deep Genome Project

Authors: K. C. Kent Lloyd, David J. Adams, Gareth Baynam, Arthur L. Beaudet, Fatima Bosch, Kym M. Boycott, Robert E. Braun, Mark Caulfield, Ronald Cohn, Mary E. Dickinson, Michael S. Dobbie, Ann M. Flenniken, Paul Flicek, Sanjeev Galande, Xiang Gao, Anne Grobler…

CUBIC: an atlas of genetic architecture promises directed maize improvement

Identifying genotype-phenotype links and causative genes from quantitative trait loci (QTL) is challenging for complex agronomically important traits. To accelerate maize gene discovery and breeding, we presen...

Authors: Hai-Jun Liu, Xiaqing Wang, Yingjie Xiao, Jingyun Luo, Feng Qiao, Wenyu Yang, Ruyang Zhang, Yijiang Meng, Jiamin Sun, Shijuan Yan, Yong Peng, Luyao Niu, Liumei Jian, Wei Song, Jiali Yan, Chunhui Li…

scMAGeCK links genotypes with multiple phenotypes in single-cell CRISPR screens

We present scMAGeCK, a computational framework to identify genomic elements associated with multiple expression-based phenotypes in CRISPR/Cas9 functional screening that uses single-cell RNA-seq as readout. sc...

Authors: Lin Yang, Yuqing Zhu, Hua Yu, Xiaolong Cheng, Sitong Chen, Yulan Chu, He Huang, Jin Zhang and Wei Li

Co-opted transposons help perpetuate conserved higher-order chromosomal structures

Transposable elements (TEs) make up half of mammalian genomes and shape genome regulation by harboring binding sites for regulatory factors. These include binding sites for architectural proteins, such as CTCF...

Authors: Mayank NK Choudhary, Ryan Z. Friedman, Julia T. Wang, Hyo Sik Jang, Xiaoyu Zhuo and Ting Wang

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recor...

Authors: Gregg W. C. Thomas, Elias Dohmen, Daniel S. T. Hughes, Shwetha C. Murali, Monica Poelchau, Karl Glastad, Clare A. Anstead, Nadia A. Ayoub, Phillip Batterham, Michelle Bellair, Greta J. Binford, Hsu Chao, Yolanda H. Chen, Christopher Childers, Huyen Dinh, Harsha Vardhan Doddapaneni…