Articles

Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets ...

Authors: Eric L. Van Nostrand, Gabriel A. Pratt, Brian A. Yee, Emily C. Wheeler, Steven M. Blue, Jasmine Mueller, Samuel S. Park, Keri E. Garcia, Chelsea Gelboin-Burkhart, Thai B. Nguyen, Ines Rabano, Rebecca Stanton, Balaji Sundararaman, Ruth Wang, Xiang-Dong Fu, Brenton R. Graveley…

The preceding root system drives the composition and function of the rhizosphere microbiome

The soil environment is responsible for sustaining most terrestrial plant life, yet we know surprisingly little about the important functions carried out by diverse microbial communities in soil. Soil microbes...

Authors: Yi Zhou, David R. Coventry, Vadakattu V. S. R. Gupta, David Fuentes, Andrew Merchant, Brent N. Kaiser, Jishun Li, Yanli Wei, Huan Liu, Yayu Wang, Shuheng Gan and Matthew D. Denton

Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing

Epigenome-wide association studies (EWAS), which seek the association between epigenetic marks and an outcome or exposure, involve multiple hypothesis testing. False discovery rate (FDR) control has been widel...

Authors: Jinyan Huang, Ling Bai, Bowen Cui, Liang Wu, Liwen Wang, Zhiyin An, Shulin Ruan, Yue Yu, Xianyang Zhang and Jun Chen

Lamina-associated domains: peripheral matters and internal affairs

At the nuclear periphery, associations of chromatin with the nuclear lamina through lamina-associated domains (LADs) aid functional organization of the genome. We review the organization of LADs and provide ev...

Authors: Nolwenn Briand and Philippe Collas

TADsplimer reveals splits and mergers of topologically associating domains for epigenetic regulation of transcription

We present TADsplimer, the first computational tool to systematically detect topologically associating domain (TAD) splits and mergers across the genome between Hi-C samples. TADsplimer recaptures splits and m...

Authors: Guangyu Wang, Qingshu Meng, Bo Xia, Shuo Zhang, Jie Lv, Dongyu Zhao, Yanqiang Li, Xin Wang, Lili Zhang, John P. Cooke, Qi Cao and Kaifu Chen

Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome

Epigenetic modifications, including DNA methylation, play an important role in gene silencing and genome stability. Consequently, epigenetic dysregulation can cause several diseases, such as cancer, obesity, d...

Authors: Takuro Horii, Sumiyo Morita, Shinjiro Hino, Mika Kimura, Yuko Hino, Hiroshi Kogo, Mitsuyoshi Nakao and Izuho Hatada

CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma

Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not ...

Authors: S. John Liu, Martina Malatesta, Brian V. Lien, Parna Saha, Shivani S. Thombare, Sung Jun Hong, Leslie Pedraza, Mark Koontz, Kyounghee Seo, Max A. Horlbeck, Daniel He, Harjus S. Birk, Miten Jain, Hugh E. Olsen, Mark Akeson, Jonathan S. Weissman…

Completing the ENCODE3 compendium yields accurate imputations across a variety of assays and human biosamples

Recent efforts to describe the human epigenome have yielded thousands of epigenomic and transcriptomic datasets. However, due primarily to cost, the total number of such assays that can be performed is limited...

Authors: Jacob Schreiber, Jeffrey Bilmes and William Stafford Noble

Avocado: a multi-scale deep tensor factorization method learns a latent representation of the human epigenome

The human epigenome has been experimentally characterized by thousands of measurements for every basepair in the human genome. We propose a deep neural network tensor factorization method, Avocado, that compre...

Authors: Jacob Schreiber, Timothy Durham, Jeffrey Bilmes and William Stafford Noble

Characterisation of genetic regulatory effects for osteoporosis risk variants in human osteoclasts

Osteoporosis is a complex disease with a strong genetic contribution. A recently published genome-wide association study (GWAS) for estimated bone mineral density (eBMD) identified 1103 independent genome-wide...

Authors: Benjamin H. Mullin, Jennifer Tickner, Kun Zhu, Jacob Kenny, Shelby Mullin, Suzanne J. Brown, Frank Dudbridge, Nathan J. Pavlos, Edward S. Mocarski, John P. Walsh, Jiake Xu and Scott G. Wilson

DeepMILO: a deep learning approach to predict the impact of non-coding sequence variants on 3D chromatin structure

Non-coding variants have been shown to be related to disease by alteration of 3D genome structures. We propose a deep learning method, DeepMILO, to predict the effects of variants on CTCF/cohesin-mediated insu...

Authors: Tuan Trieu, Alexander Martinez-Fundichely and Ekta Khurana

Diverse genetic mechanisms underlie worldwide convergent rice feralization

Worldwide feralization of crop species into agricultural weeds threatens global food security. Weedy rice is a feral form of rice that infests paddies worldwide and aggressively outcompetes cultivated varietie...

Authors: Jie Qiu, Lei Jia, Dongya Wu, Xifang Weng, Lijuan Chen, Jian Sun, Meihong Chen, Lingfeng Mao, Bowen Jiang, Chuyu Ye, Guilherme Menegol Turra, Longbiao Guo, Guoyou Ye, Qian-Hao Zhu, Toshiyuki Imaizumi, Beng-Kah Song…

A Cas12a ortholog with stringent PAM recognition followed by low off-target editing rates for genome editing

AsCas12a and LbCas12a nucleases are reported to be promising tools for genome engineering with protospacer adjacent motif (PAM) TTTV as the optimal. However, the C-containing PAM (CTTV, TCTV, TTCV, etc.) recog...

Authors: Peng Chen, Jin Zhou, Yibin Wan, Huan Liu, Yongzheng Li, Zhaoxin Liu, Hongjian Wang, Jun Lei, Kai Zhao, Yiliang Zhang, Yan Wang, Xinghua Zhang and Lei Yin

High-resolution Repli-Seq defines the temporal choreography of initiation, elongation and termination of replication in mammalian cells

DNA replication in mammalian cells occurs in a defined temporal order during S phase, known as the replication timing (RT) programme. Replication timing is developmentally regulated and correlated with chromat...

Authors: Peiyao A. Zhao, Takayo Sasaki and David M. Gilbert

Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection

CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem.

Authors: Zhilian Jia, Jingwei Li, Xiao Ge, Yonghu Wu, Ya Guo and Qiang Wu

Obstacles to detecting isoforms using full-length scRNA-seq data

Early single-cell RNA-seq (scRNA-seq) studies suggested that it was unusual to see more than one isoform being produced from a gene in a single cell, even when multiple isoforms were detected in matched bulk R...

Authors: Jennifer Westoby, Pavel Artemov, Martin Hemberg and Anne Ferguson-Smith

HiNT: a computational method for detecting copy number variations and translocations from Hi-C data

The three-dimensional conformation of a genome can be profiled using Hi-C, a technique that combines chromatin conformation capture with high-throughput sequencing. However, structural variations often yield f...

Authors: Su Wang, Soohyun Lee, Chong Chu, Dhawal Jain, Peter Kerpedjiev, Geoffrey M. Nelson, Jennifer M. Walsh, Burak H. Alver and Peter J. Park

Decode-seq: a practical approach to improve differential gene expression analysis

Many differential gene expression analyses are conducted with an inadequate number of biological replicates. We describe an easy and effective RNA-seq approach using molecular barcoding to enable profiling of ...

Authors: Yingshu Li, Hang Yang, Hujun Zhang, Yongjie Liu, Hanqiao Shang, Herong Zhao, Ting Zhang and Qiang Tu

VALOR2: characterization of large-scale structural variants using linked-reads

Most existing methods for structural variant detection focus on discovery and genotyping of deletions, insertions, and mobile elements. Detection of balanced structural variants with no gain or loss of genomic...

Authors: Fatih Karaoğlanoğlu, Camir Ricketts, Ezgi Ebren, Marzieh Eslami Rasekh, Iman Hajirasouliha and Can Alkan

Benchmarking of computational error-correction methods for next-generation sequencing data

Recent advancements in next-generation sequencing have rapidly improved our ability to study genomic material at an unprecedented scale. Despite substantial improvements in sequencing technologies, errors pres...

Authors: Keith Mitchell, Jaqueline J. Brito, Igor Mandric, Qiaozhen Wu, Sergey Knyazev, Sei Chang, Lana S. Martin, Aaron Karlsberg, Ekaterina Gerasimov, Russell Littman, Brian L. Hill, Nicholas C. Wu, Harry Taegyun Yang, Kevin Hsieh, Linus Chen, Eli Littman…

BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty

Alternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we p...

Authors: Simone Tiberi and Mark D. Robinson

Ultraplexing: increasing the efficiency of long-read sequencing for hybrid assembly with k-mer-based multiplexing

Hybrid genome assembly has emerged as an important technique in bacterial genomics, but cost and labor requirements limit large-scale application. We present Ultraplexing, a method to improve per-sample sequen...

Authors: Alexander T. Dilthey, Sebastian A. Meyer and Achim J. Kaasch

Renaissance minds in 21st century science

Authors: Itai Yanai and Martin Lercher

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