Articles

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

Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression

Single-cell RNA-seq (scRNA-seq) data exhibits significant cell-to-cell variation due to technical factors, including the number of molecules detected in each cell, which can confound biological heterogeneity w...

Authors: Christoph Hafemeister and Rahul Satija

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

PIRCh-seq: functional classification of non-coding RNAs associated with distinct histone modifications

We develop PIRCh-seq, a method which enables a comprehensive survey of chromatin-associated RNAs in a histone modification-specific manner. We identify hundreds of chromatin-associated RNAs in several cell typ...

Authors: Jingwen Fang, Qing Ma, Ci Chu, Beibei Huang, Lingjie Li, Pengfei Cai, Pedro J. Batista, Karen Erisse Martin Tolentino, Jin Xu, Rui Li, Pengcheng Du, Kun Qu and Howard Y. Chang

Paragraph: a graph-based structural variant genotyper for short-read sequence data

Accurate detection and genotyping of structural variations (SVs) from short-read data is a long-standing area of development in genomics research and clinical sequencing pipelines. We introduce Paragraph, an a...

Authors: Sai Chen, Peter Krusche, Egor Dolzhenko, Rachel M. Sherman, Roman Petrovski, Felix Schlesinger, Melanie Kirsche, David R. Bentley, Michael C. Schatz, Fritz J. Sedlazeck and Michael A. Eberle

Genotype-free demultiplexing of pooled single-cell RNA-seq

A variety of methods have been developed to demultiplex pooled samples in a single cell RNA sequencing (scRNA-seq) experiment which either require hashtag barcodes or sample genotypes prior to pooling. We intr...

Authors: Jun Xu, Caitlin Falconer, Quan Nguyen, Joanna Crawford, Brett D. McKinnon, Sally Mortlock, Anne Senabouth, Stacey Andersen, Han Sheng Chiu, Longda Jiang, Nathan J. Palpant, Jian Yang, Michael D. Mueller, Alex W. Hewitt, Alice Pébay, Grant W. Montgomery…

What is the question?

Authors: Itai Yanai and Martin Lercher

Quantifying the benefit offered by transcript assembly with Scallop-LR on single-molecule long reads

Single-molecule long-read sequencing has been used to improve mRNA isoform identification. However, not all single-molecule long reads represent full transcripts due to incomplete cDNA synthesis and sequencing...

Authors: Laura H. Tung, Mingfu Shao and Carl Kingsford

Within-species contamination of bacterial whole-genome sequence data has a greater influence on clustering analyses than between-species contamination

Although it is assumed that contamination in bacterial whole-genome sequencing causes errors, the influences of contamination on clustering analyses, such as single-nucleotide polymorphism discovery, phylogene...

Authors: Arthur W. Pightling, James B. Pettengill, Yu Wang, Hugh Rand and Errol Strain

Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type

The lifelong accumulation of somatic mutations underlies age-related phenotypes and cancer. Mutagenic forces are thought to shape the genome of aging cells in a tissue-specific way. Whole genome analyses of so...

Authors: Irene Franco, Hafdis T. Helgadottir, Aldo Moggio, Malin Larsson, Peter Vrtačnik, Anna Johansson, Nina Norgren, Pär Lundin, David Mas-Ponte, Johan Nordström, Torbjörn Lundgren, Peter Stenvinkel, Lars Wennberg, Fran Supek and Maria Eriksson

TRITEX: chromosome-scale sequence assembly of Triticeae genomes with open-source tools

Chromosome-scale genome sequence assemblies underpin pan-genomic studies. Recent genome assembly efforts in the large-genome Triticeae crops wheat and barley have relied on the commercial closed-source assembl...

Authors: Cécile Monat, Sudharsan Padmarasu, Thomas Lux, Thomas Wicker, Heidrun Gundlach, Axel Himmelbach, Jennifer Ens, Chengdao Li, Gary J. Muehlbauer, Alan H. Schulman, Robbie Waugh, Ilka Braumann, Curtis Pozniak, Uwe Scholz, Klaus F. X. Mayer, Manuel Spannagl…

OnTAD: hierarchical domain structure reveals the divergence of activity among TADs and boundaries

The spatial organization of chromatin in the nucleus has been implicated in regulating gene expression. Maps of high-frequency interactions between different segments of chromatin have revealed topologically a...

Authors: Lin An, Tao Yang, Jiahao Yang, Johannes Nuebler, Guanjue Xiang, Ross C. Hardison, Qunhua Li and Yu Zhang

Systematic underestimation of the epigenetic clock and age acceleration in older subjects

The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues...

Authors: Louis Y. El Khoury, Tyler Gorrie-Stone, Melissa Smart, Amanda Hughes, Yanchun Bao, Alexandria Andrayas, Joe Burrage, Eilis Hannon, Meena Kumari, Jonathan Mill and Leonard C. Schalkwyk

Guidelines for benchmarking of optimization-based approaches for fitting mathematical models

Insufficient performance of optimization-based approaches for the fitting of mathematical models is still a major bottleneck in systems biology. In this article, the reasons and methodological challenges are s...

Authors: Clemens Kreutz

HOPS: automated detection and authentication of pathogen DNA in archaeological remains

High-throughput DNA sequencing enables large-scale metagenomic analyses of complex biological systems. Such analyses are not restricted to present-day samples and can also be applied to molecular data from arc...

Authors: Ron Hübler, Felix M. Key, Christina Warinner, Kirsten I. Bos, Johannes Krause and Alexander Herbig

PASTMUS: mapping functional elements at single amino acid resolution in human cells

Identification of functional elements for a protein of interest is important for achieving a mechanistic understanding. However, it remains cumbersome to assess each and every amino acid of a given protein in ...

Authors: Xinyi Zhang, Di Yue, Yinan Wang, Yuexin Zhou, Ying Liu, Yeting Qiu, Feng Tian, Ying Yu, Zhuo Zhou and Wensheng Wei

Transcriptome assembly from long-read RNA-seq alignments with StringTie2

RNA sequencing using the latest single-molecule sequencing instruments produces reads that are thousands of nucleotides long. The ability to assemble these long reads can greatly improve the sensitivity of lon...

Authors: Sam Kovaka, Aleksey V. Zimin, Geo M. Pertea, Roham Razaghi, Steven L. Salzberg and Mihaela Pertea

SyRI: finding genomic rearrangements and local sequence differences from whole-genome assemblies

Genomic differences range from single nucleotide differences to complex structural variations. Current methods typically annotate sequence differences ranging from SNPs to large indels accurately but do not un...

Authors: Manish Goel, Hequan Sun, Wen-Biao Jiao and Korbinian Schneeberger

Curing hemophilia A by NHEJ-mediated ectopic F8 insertion in the mouse

Hemophilia A, a bleeding disorder resulting from F8 mutations, can only be cured by gene therapy. A promising strategy is CRISPR-Cas9-mediated precise insertion of F8 in hepatocytes at highly expressed gene loci,...

Authors: Jian-Ping Zhang, Xin-Xin Cheng, Mei Zhao, Guo-Hua Li, Jing Xu, Feng Zhang, Meng-Di Yin, Fei-Ying Meng, Xin-Yue Dai, Ya-Wen Fu, Zhi-Xue Yang, Cameron Arakaki, Ruijun Jeanna Su, Wei Wen, Wen-Tian Wang, Wanqiu Chen…

Benchmarking transposable element annotation methods for creation of a streamlined, comprehensive pipeline

Sequencing technology and assembly algorithms have matured to the point that high-quality de novo assembly is possible for large, repetitive genomes. Current assemblies traverse transposable elements (TEs) and...

Authors: Shujun Ou, Weija Su, Yi Liao, Kapeel Chougule, Jireh R. A. Agda, Adam J. Hellinga, Carlos Santiago Blanco Lugo, Tyler A. Elliott, Doreen Ware, Thomas Peterson, Ning Jiang, Candice N. Hirsch and Matthew B. Hufford

deSALT: fast and accurate long transcriptomic read alignment with de Bruijn graph-based index

The alignment of long-read RNA sequencing reads is non-trivial due to high sequencing errors and complicated gene structures. We propose deSALT, a tailored two-pass alignment approach, which constructs graph-b...

Authors: Bo Liu, Yadong Liu, Junyi Li, Hongzhe Guo, Tianyi Zang and Yadong Wang

Vireo: Bayesian demultiplexing of pooled single-cell RNA-seq data without genotype reference

Multiplexed single-cell RNA-seq analysis of multiple samples using pooling is a promising experimental design, offering increased throughput while allowing to overcome batch variation. To reconstruct the sampl...

Authors: Yuanhua Huang, Davis J. McCarthy and Oliver Stegle

CTCF modulates allele-specific sub-TAD organization and imprinted gene activity at the mouse Dlk1-Dio3 and Igf2-H19 domains

Genomic imprinting is essential for mammalian development and provides a unique paradigm to explore intra-cellular differences in chromatin configuration. So far, the detailed allele-specific chromatin organiz...

Authors: David Llères, Benoît Moindrot, Rakesh Pathak, Vincent Piras, Mélody Matelot, Benoît Pignard, Alice Marchand, Mallory Poncelet, Aurélien Perrin, Virgile Tellier, Robert Feil and Daan Noordermeer

From Hawaii to PECASE award: tips of success from a female bioinformatician

Authors: Lana X. Garmire

scPred: accurate supervised method for cell-type classification from single-cell RNA-seq data

Single-cell RNA sequencing has enabled the characterization of highly specific cell types in many tissues, as well as both primary and stem cell-derived cell lines. An important facet of these studies is the a...

Authors: Jose Alquicira-Hernandez, Anuja Sathe, Hanlee P. Ji, Quan Nguyen and Joseph E. Powell

Accuracy, robustness and scalability of dimensionality reduction methods for single-cell RNA-seq analysis

Dimensionality reduction is an indispensable analytic component for many areas of single-cell RNA sequencing (scRNA-seq) data analysis. Proper dimensionality reduction can allow for effective noise removal and...

Authors: Shiquan Sun, Jiaqiang Zhu, Ying Ma and Xiang Zhou