Articles

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…

A curated benchmark of enhancer-gene interactions for evaluating enhancer-target gene prediction methods

Many genome-wide collections of candidate cis-regulatory elements (cCREs) have been defined using genomic and epigenomic data, but it remains a major challenge to connect these elements to their target genes.

Authors: Jill E. Moore, Henry E. Pratt, Michael J. Purcaro and Zhiping Weng

Benchmarking principal component analysis for large-scale single-cell RNA-sequencing

Principal component analysis (PCA) is an essential method for analyzing single-cell RNA-seq (scRNA-seq) datasets, but for large-scale scRNA-seq datasets, computation time is long and consumes large amounts of ...

Authors: Koki Tsuyuzaki, Hiroyuki Sato, Kenta Sato and Itoshi Nikaido

Performance difference of graph-based and alignment-based hybrid error correction methods for error-prone long reads

The error-prone third-generation sequencing (TGS) long reads can be corrected by the high-quality second-generation sequencing (SGS) short reads, which is referred to as hybrid error correction. We here invest...

Authors: Anqi Wang and Kin Fai Au

cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel

Resistance to enteric pathogens is a complex trait at the crossroads of multiple biological processes. We have previously shown in the Drosophila Genetic Reference Panel (DGRP) that resistance to infection is hig...

Authors: Michael V. Frochaux, Maroun Bou Sleiman, Vincent Gardeux, Riccardo Dainese, Brian Hollis, Maria Litovchenko, Virginie S. Braman, Tommaso Andreani, Dani Osman and Bart Deplancke

Enteric infection induces Lark-mediated intron retention at the 5′ end of Drosophila genes

RNA splicing is a key post-transcriptional mechanism that generates protein diversity and contributes to the fine-tuning of gene expression, which may facilitate adaptation to environmental challenges. Here, w...

Authors: Maroun Bou Sleiman, Michael Vincent Frochaux, Tommaso Andreani, Dani Osman, Roderic Guigo and Bart Deplancke

CHROMATIX: computing the functional landscape of many-body chromatin interactions in transcriptionally active loci from deconvolved single cells

Chromatin interactions are important for gene regulation and cellular specialization. Emerging evidence suggests many-body spatial interactions play important roles in condensing super-enhancer regions into a ...

Authors: Alan Perez-Rathke, Qiu Sun, Boshen Wang, Valentina Boeva, Zhifeng Shao and Jie Liang

A benchmark of batch-effect correction methods for single-cell RNA sequencing data

Large-scale single-cell transcriptomic datasets generated using different technologies contain batch-specific systematic variations that present a challenge to batch-effect removal and data integration. With c...

Authors: Hoa Thi Nhu Tran, Kok Siong Ang, Marion Chevrier, Xiaomeng Zhang, Nicole Yee Shin Lee, Michelle Goh and Jinmiao Chen

HIFI: estimating DNA-DNA interaction frequency from Hi-C data at restriction-fragment resolution

Hi-C is a popular technique to map three-dimensional chromosome conformation. In principle, Hi-C’s resolution is only limited by the size of restriction fragments. However, insufficient sequencing depth forces...

Authors: Christopher JF Cameron, Josée Dostie and Mathieu Blanchette

DENDRO: genetic heterogeneity profiling and subclone detection by single-cell RNA sequencing

Although scRNA-seq is now ubiquitously adopted in studies of intratumor heterogeneity, detection of somatic mutations and inference of clonal membership from scRNA-seq is currently unreliable. We propose DENDR...

Authors: Zilu Zhou, Bihui Xu, Andy Minn and Nancy R. Zhang

Chromatin interactome mapping at 139 independent breast cancer risk signals

Genome-wide association studies have identified 196 high confidence independent signals associated with breast cancer susceptibility. Variants within these signals frequently fall in distal regulatory DNA elem...

Authors: Jonathan Beesley, Haran Sivakumaran, Mahdi Moradi Marjaneh, Luize G. Lima, Kristine M. Hillman, Susanne Kaufmann, Natasha Tuano, Nehal Hussein, Sunyoung Ham, Pamela Mukhopadhyay, Stephen Kazakoff, Jason S. Lee, Kyriaki Michailidou, Daniel R. Barnes, Antonis C. Antoniou, Laura Fachal…

Non-coding RNAs underlie genetic predisposition to breast cancer

Genetic variants identified through genome-wide association studies (GWAS) are predominantly non-coding and typically attributed to altered regulatory elements such as enhancers and promoters. However, the con...

Authors: Mahdi Moradi Marjaneh, Jonathan Beesley, Tracy A. O’Mara, Pamela Mukhopadhyay, Lambros T. Koufariotis, Stephen Kazakoff, Nehal Hussein, Laura Fachal, Nenad Bartonicek, Kristine M. Hillman, Susanne Kaufmann, Haran Sivakumaran, Chanel E. Smart, Amy E. McCart Reed, Kaltin Ferguson, Jodi M. Saunus…

Clustered CTCF binding is an evolutionary mechanism to maintain topologically associating domains

CTCF binding contributes to the establishment of a higher-order genome structure by demarcating the boundaries of large-scale topologically associating domains (TADs). However, despite the importance and conse...

Authors: Elissavet Kentepozidou, Sarah J. Aitken, Christine Feig, Klara Stefflova, Ximena Ibarra-Soria, Duncan T. Odom, Maša Roller and Paul Flicek

Functional consequences of archaic introgression and their impact on fitness

Authors: Maxime Rotival and Lluis Quintana-Murci

Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis

Tumor-reactive CD8+ tumor-infiltrating lymphocytes (TILs) represent a subtype of T cells that can recognize and destroy tumor specifically. Understanding the regulatory mechanism of tumor-reactive CD8+ T cells...

Authors: Rui Yang, Sijin Cheng, Nan Luo, Ranran Gao, Kezhuo Yu, Boxi Kang, Li Wang, Qiming Zhang, Qiao Fang, Lei Zhang, Chen Li, Aibin He, Xueda Hu, Jirun Peng, Xianwen Ren and Zemin Zhang

scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation

The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an atlas. However,...

Authors: E. Madissoon, A. Wilbrey-Clark, R. J. Miragaia, K. Saeb-Parsy, K. T. Mahbubani, N. Georgakopoulos, P. Harding, K. Polanski, N. Huang, K. Nowicki-Osuch, R. C. Fitzgerald, K. W. Loudon, J. R. Ferdinand, M. R. Clatworthy, A. Tsingene, S. van Dongen…

mRNA structural elements immediately upstream of the start codon dictate dependence upon eIF4A helicase activity

The RNA helicase eIF4A1 is a key component of the translation initiation machinery and is required for the translation of many pro-oncogenic mRNAs. There is increasing interest in targeting eIF4A1 therapeutica...

Authors: Joseph A. Waldron, David C. Tack, Laura E. Ritchey, Sarah L. Gillen, Ania Wilczynska, Ernest Turro, Philip C. Bevilacqua, Sarah M. Assmann, Martin Bushell and John Le Quesne

Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species

Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative...

Authors: Serena Manara, Francesco Asnicar, Francesco Beghini, Davide Bazzani, Fabio Cumbo, Moreno Zolfo, Eleonora Nigro, Nicolai Karcher, Paolo Manghi, Marisa Isabell Metzger, Edoardo Pasolli and Nicola Segata

The somatic mutation landscape of the human body

Somatic mutations in healthy tissues contribute to aging, neurodegeneration, and cancer initiation, yet they remain largely uncharacterized.

Authors: Pablo E. García-Nieto, Ashby J. Morrison and Hunter B. Fraser

A comparison framework and guideline of clustering methods for mass cytometry data

With the expanding applications of mass cytometry in medical research, a wide variety of clustering methods, both semi-supervised and unsupervised, have been developed for data analysis. Selecting the optimal ...

Authors: Xiao Liu, Weichen Song, Brandon Y. Wong, Ting Zhang, Shunying Yu, Guan Ning Lin and Xianting Ding

Feature selection and dimension reduction for single-cell RNA-Seq based on a multinomial model

Single-cell RNA-Seq (scRNA-Seq) profiles gene expression of individual cells. Recent scRNA-Seq datasets have incorporated unique molecular identifiers (UMIs). Using negative controls, we show UMI counts follow...

Authors: F. William Townes, Stephanie C. Hicks, Martin J. Aryee and Rafael A. Irizarry

RADAR: differential analysis of MeRIP-seq data with a random effect model

Epitranscriptome profiling using MeRIP-seq is a powerful technique for in vivo functional studies of reversible RNA modifications. We develop RADAR, a comprehensive analytical tool for detecting differentially...

Authors: Zijie Zhang, Qi Zhan, Mark Eckert, Allen Zhu, Agnieszka Chryplewicz, Dario F. De Jesus, Decheng Ren, Rohit N. Kulkarni, Ernst Lengyel, Chuan He and Mengjie Chen

tmap: an integrative framework based on topological data analysis for population-scale microbiome stratification and association studies

Untangling the complex variations of microbiome associated with large-scale host phenotypes or environment types challenges the currently available analytic methods. Here, we present tmap, an integrative framewor...

Authors: Tianhua Liao, Yuchen Wei, Mingjing Luo, Guo-Ping Zhao and Haokui Zhou