Articles

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

The Pseudomonas aeruginosa accessory genome elements influence virulence towards Caenorhabditis elegans

Multicellular animals and bacteria frequently engage in predator-prey and host-pathogen interactions, such as the well-studied relationship between Pseudomonas aeruginosa and the nematode Caenorhabditis elegans. ...

Authors: Alejandro Vasquez-Rifo, Isana Veksler-Lublinsky, Zhenyu Cheng, Frederick M. Ausubel and Victor Ambros

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

The majority of A-to-I RNA editing is not required for mammalian homeostasis

Adenosine-to-inosine (A-to-I) RNA editing, mediated by ADAR1 and ADAR2, occurs at tens of thousands to millions of sites across mammalian transcriptomes. A-to-I editing can change the protein coding potential ...

Authors: Alistair M. Chalk, Scott Taylor, Jacki E. Heraud-Farlow and Carl R. Walkley

Chromosome-level genome assembly for giant panda provides novel insights into Carnivora chromosome evolution

Chromosome evolution is an important driver of speciation and species evolution. Previous studies have detected chromosome rearrangement events among different Carnivora species using chromosome painting strat...

Authors: Huizhong Fan, Qi Wu, Fuwen Wei, Fengtang Yang, Bee Ling Ng and Yibo Hu

Afann: bias adjustment for alignment-free sequence comparison based on sequencing data using neural network regression

Alignment-free methods, more time and memory efficient than alignment-based methods, have been widely used for comparing genome sequences or raw sequencing samples without assembly. However, in this study, we ...

Authors: Kujin Tang, Jie Ren and Fengzhu Sun

Dashing: fast and accurate genomic distances with HyperLogLog

Dashing is a fast and accurate software tool for estimating similarities of genomes or sequencing datasets. It uses the HyperLogLog sketch together with cardinality estimation methods that are specialized for ...

Authors: Daniel N. Baker and Ben Langmead

CRISPR-Cas13d mediates robust RNA virus interference in plants

CRISPR-Cas systems endow bacterial and archaeal species with adaptive immunity mechanisms to fend off invading phages and foreign genetic elements. CRISPR-Cas9 has been harnessed to confer virus interference a...

Authors: Ahmed Mahas, Rashid Aman and Magdy Mahfouz

eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5′UTR

Regulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of act...

Authors: Ania Wilczynska, Sarah L. Gillen, Tobias Schmidt, Hedda A. Meijer, Rebekah Jukes-Jones, Claudia Langlais, Kari Kopra, Wei-Ting Lu, Jack D. Godfrey, Benjamin R. Hawley, Kelly Hodge, Sara Zanivan, Kelvin Cain, John Le Quesne and Martin Bushell

methylCC: technology-independent estimation of cell type composition using differentially methylated regions

A major challenge in the analysis of DNA methylation (DNAm) data is variability introduced from intra-sample cellular heterogeneity, such as whole blood which is a convolution of DNAm profiles across a unique ...

Authors: Stephanie C. Hicks and Rafael A. Irizarry

ReorientExpress: reference-free orientation of nanopore cDNA reads with deep learning

We describe ReorientExpress, a method to perform reference-free orientation of transcriptomic long sequencing reads. ReorientExpress uses deep learning to correctly predict the orientation of the majority of r...

Authors: Angel Ruiz-Reche, Akanksha Srivastava, Joel A. Indi, Ivan de la Rubia and Eduardo Eyras

Characterizing the interplay between gene nucleotide composition bias and splicing

Nucleotide composition bias plays an important role in the 1D and 3D organization of the human genome. Here, we investigate the potential interplay between nucleotide composition bias and the regulation of exo...

Authors: Sébastien Lemaire, Nicolas Fontrodona, Fabien Aubé, Jean-Baptiste Claude, Hélène Polvèche, Laurent Modolo, Cyril F. Bourgeois, Franck Mortreux and Didier Auboeuf

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

Brain aging is a complex process that depends on the precise regulation of multiple brain regions; however, the underlying molecular mechanisms behind this process remain to be clarified in non-human primates.

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

Improved metagenomic analysis with Kraken 2

Although Kraken’s k-mer-based approach provides a fast taxonomic classification of metagenomic sequence data, its large memory requirements can be limiting for some applications. Kraken 2 improves upon Kraken 1 b...

Authors: Derrick E. Wood, Jennifer Lu and Ben Langmead

The Aquilegia genome reveals a hybrid origin of core eudicots

Whole-genome duplications (WGDs) have dominated the evolutionary history of plants. One consequence of WGD is a dramatic restructuring of the genome as it undergoes diploidization, a process under which deleti...

Authors: Gökçe Aköz and Magnus Nordborg

Common DNA sequence variation influences 3-dimensional conformation of the human genome

The 3-dimensional (3D) conformation of chromatin inside the nucleus is integral to a variety of nuclear processes including transcriptional regulation, DNA replication, and DNA damage repair. Aberrations in 3D...

Authors: David U. Gorkin, Yunjiang Qiu, Ming Hu, Kipper Fletez-Brant, Tristin Liu, Anthony D. Schmitt, Amina Noor, Joshua Chiou, Kyle J. Gaulton, Jonathan Sebat, Yun Li, Kasper D. Hansen and Bing Ren

RegSNPs-intron: a computational framework for predicting pathogenic impact of intronic single nucleotide variants

Single nucleotide variants (SNVs) in intronic regions have yet to be systematically investigated for their disease-causing potential. Using known pathogenic and neutral intronic SNVs (iSNVs) as training data, ...

Authors: Hai Lin, Katherine A. Hargreaves, Rudong Li, Jill L. Reiter, Yue Wang, Matthew Mort, David N. Cooper, Yaoqi Zhou, Chi Zhang, Michael T. Eadon, M. Eileen Dolan, Joseph Ipe, Todd C. Skaar and Yunlong Liu

Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, pro...

Authors: Jason K. Sa, Jae Ryoung Hwang, Young-Jae Cho, Ji-Yoon Ryu, Jung-Joo Choi, Soo Young Jeong, Jihye Kim, Myeong Seon Kim, E. Sun Paik, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Byoung-Gie Kim, Duk-Soo Bae, Yeri Lee, Nam-Gu Her…

Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host

Recent metagenomic analyses have revealed dysbiosis of the gut microbiota of ulcerative colitis (UC) patients. However, the impacts of this dysbiosis are not fully understood, particularly at the strain level.

Authors: Jun Seishima, Noriho Iida, Kazuya Kitamura, Masahiro Yutani, Ziyu Wang, Akihiro Seki, Taro Yamashita, Yoshio Sakai, Masao Honda, Tatsuya Yamashita, Takashi Kagaya, Yukihiro Shirota, Yukako Fujinaga, Eishiro Mizukoshi and Shuichi Kaneko

MIA-Sig: multiplex chromatin interaction analysis by signal processing and statistical algorithms

The single-molecule multiplex chromatin interaction data are generated by emerging 3D genome mapping technologies such as GAM, SPRITE, and ChIA-Drop. These datasets provide insights into high-dimensional chrom...

Authors: Minji Kim, Meizhen Zheng, Simon Zhongyuan Tian, Byoungkoo Lee, Jeffrey H. Chuang and Yijun Ruan

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Authors: Melissa A. Wilson

DNA methylation aging clocks: challenges and recommendations

Epigenetic clocks comprise a set of CpG sites whose DNA methylation levels measure subject age. These clocks are acknowledged as a highly accurate molecular correlate of chronological age in humans and other v...

Authors: Christopher G. Bell, Robert Lowe, Peter D. Adams, Andrea A. Baccarelli, Stephan Beck, Jordana T. Bell, Brock C. Christensen, Vadim N. Gladyshev, Bastiaan T. Heijmans, Steve Horvath, Trey Ideker, Jean-Pierre J. Issa, Karl T. Kelsey, Riccardo E. Marioni, Wolf Reik, Caroline L. Relton…

EpiMethylTag: simultaneous detection of ATAC-seq or ChIP-seq signals with DNA methylation

Activation of regulatory elements is thought to be inversely correlated with DNA methylation levels. However, it is difficult to determine whether DNA methylation is compatible with chromatin accessibility or ...

Authors: Priscillia Lhoumaud, Gunjan Sethia, Franco Izzo, Theodore Sakellaropoulos, Valentina Snetkova, Simon Vidal, Sana Badri, Macintosh Cornwell, Dafne Campigli Di Giammartino, Kyu-Tae Kim, Effie Apostolou, Matthias Stadtfeld, Dan Avi Landau and Jane Skok

Correction to: scBFA: modeling detection patterns to mitigate technical noise in large-scale single-cell genomics data

Following publication of the original article [1], the following two errors were found in formulae:

Authors: Ruoxin Li and Gerald Quon

Structural variant calling: the long and the short of it

Recent research into structural variants (SVs) has established their importance to medicine and molecular biology, elucidating their role in various diseases, regulation of gene expression, ethnic diversity, a...

Authors: Medhat Mahmoud, Nastassia Gobet, Diana Ivette Cruz-Dávalos, Ninon Mounier, Christophe Dessimoz and Fritz J. Sedlazeck

Epigenetic modifications of histones in cancer

The epigenetic modifications of histones are versatile marks that are intimately connected to development and disease pathogenesis including human cancers. In this review, we will discuss the many different ty...

Authors: Zibo Zhao and Ali Shilatifard

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.

Authors: Naihui Zhou, Yuxiang Jiang, Timothy R. Bergquist, Alexandra J. Lee, Balint Z. Kacsoh, Alex W. Crocker, Kimberley A. Lewis, George Georghiou, Huy N. Nguyen, Md Nafiz Hamid, Larry Davis, Tunca Dogan, Volkan Atalay, Ahmet S. Rifaioglu, Alperen Dalkıran, Rengul Cetin Atalay…

Population-level analysis reveals the widespread occurrence and phenotypic consequence of DNA methylation variation not tagged by genetic variation in maize

DNA methylation can provide a source of heritable information that is sometimes entirely uncoupled from genetic variation. However, the extent of this uncoupling and the roles of DNA methylation in shaping div...

Authors: Jing Xu, Guo Chen, Peter J. Hermanson, Qiang Xu, Changshuo Sun, Wenqing Chen, Qiuxin Kan, Minqi Li, Peter A. Crisp, Jianbing Yan, Lin Li, Nathan M. Springer and Qing Li

Systematic comparative analysis of single-nucleotide variant detection methods from single-cell RNA sequencing data

Systematic interrogation of single-nucleotide variants (SNVs) is one of the most promising approaches to delineate the cellular heterogeneity and phylogenetic relationships at the single-cell level. While SNV ...

Authors: Fenglin Liu, Yuanyuan Zhang, Lei Zhang, Ziyi Li, Qiao Fang, Ranran Gao and Zemin Zhang

Assessment of computational methods for the analysis of single-cell ATAC-seq data

Recent innovations in single-cell Assay for Transposase Accessible Chromatin using sequencing (scATAC-seq) enable profiling of the epigenetic landscape of thousands of individual cells. scATAC-seq data analysi...

Authors: Huidong Chen, Caleb Lareau, Tommaso Andreani, Michael E. Vinyard, Sara P. Garcia, Kendell Clement, Miguel A. Andrade-Navarro, Jason D. Buenrostro and Luca Pinello

NanoSatellite: accurate characterization of expanded tandem repeat length and sequence through whole genome long-read sequencing on PromethION

Technological limitations have hindered the large-scale genetic investigation of tandem repeats in disease. We show that long-read sequencing with a single Oxford Nanopore Technologies PromethION flow cell per...

Authors: Arne De Roeck, Wouter De Coster, Liene Bossaerts, Rita Cacace, Tim De Pooter, Jasper Van Dongen, Svenn D’Hert, Peter De Rijk, Mojca Strazisar, Christine Van Broeckhoven and Kristel Sleegers

Differential co-expression-based detection of conditional relationships in transcriptional data: comparative analysis and application to breast cancer

Elucidation of regulatory networks, including identification of regulatory mechanisms specific to a given biological context, is a key aim in systems biology. This has motivated the move from co-expression to ...

Authors: Dharmesh D. Bhuva, Joseph Cursons, Gordon K. Smyth and Melissa J. Davis

Evaluation of commonly used analysis strategies for epigenome- and transcriptome-wide association studies through replication of large-scale population studies

A large number of analysis strategies are available for DNA methylation (DNAm) array and RNA-seq datasets, but it is unclear which strategies are best to use. We compare commonly used strategies and report how...

Authors: Jeroen van Rooij, Pooja R. Mandaviya, Annique Claringbould, Janine F. Felix, Jenny van Dongen, Rick Jansen, Lude Franke, Peter A. C. ’t Hoen, Bas Heijmans and Joyce B. J. van Meurs