Articles

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

Crowdfunding science

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

Correlation of homologous recombination deficiency induced mutational signatures with sensitivity to PARP inhibitors and cytotoxic agents

Homologous recombination (HR) repair deficiency arising from defects in BRCA1 or BRCA2 is associated with characteristic patterns of somatic mutations. In this genetic study, we ask whether inactivating mutati...

Authors: Ádám Póti, Hella Gyergyák, Eszter Németh, Orsolya Rusz, Szilárd Tóth, Csenger Kovácsházi, Dan Chen, Bernadett Szikriszt, Sándor Spisák, Shunichi Takeda, Gergely Szakács, Zoltan Szallasi, Andrea L. Richardson and Dávid Szüts

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

OrthoFinder: phylogenetic orthology inference for comparative genomics

Here, we present a major advance of the OrthoFinder method. This extends OrthoFinder’s high accuracy orthogroup inference to provide phylogenetic inference of orthologs, rooted gene trees, gene duplication eve...

Authors: David M. Emms and Steven Kelly

Evaluating nanopore sequencing data processing pipelines for structural variation identification

Structural variations (SVs) account for about 1% of the differences among human genomes and play a significant role in phenotypic variation and disease susceptibility. The emerging nanopore sequencing technolo...

Authors: Anbo Zhou, Timothy Lin and Jinchuan Xing

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

Correction to: Identifying significantly impacted pathways: a comprehensive review and assessment

Following publication of the original paper [1], the authors reported the following update to the competing interests declaration.

Authors: Tuan-Minh Nguyen, Adib Shafi, Tin Nguyen and Sorin Draghici

Impact of mouse contamination in genomic profiling of patient-derived models and best practice for robust analysis

Patient-derived xenograft and cell line models are popular models for clinical cancer research. However, the inevitable inclusion of a mouse genome in a patient-derived model is a remaining concern in the anal...

Authors: Se-Young Jo, Eunyoung Kim and Sangwoo Kim

CRUP: a comprehensive framework to predict condition-specific regulatory units

We present the software Condition-specific Regulatory Units Prediction (CRUP) to infer from epigenetic marks a list of regulatory units consisting of dynamically changing enhancers with their target genes. The...

Authors: Anna Ramisch, Verena Heinrich, Laura V. Glaser, Alisa Fuchs, Xinyi Yang, Philipp Benner, Robert Schöpflin, Na Li, Sarah Kinkley, Anja Römer-Hillmann, John Longinotto, Steffen Heyne, Beate Czepukojc, Sonja M. Kessler, Alexandra K. Kiemer, Cristina Cadenas…

DESE: estimating driver tissues by selective expression of genes associated with complex diseases or traits

The driver tissues or cell types in which susceptibility genes initiate diseases remain elusive. We develop a unified framework to detect the causal tissues of complex diseases or traits according to selective...

Authors: Lin Jiang, Chao Xue, Sheng Dai, Shangzhen Chen, Peikai Chen, Pak Chung Sham, Haijun Wang and Miaoxin Li

Mash Screen: high-throughput sequence containment estimation for genome discovery

The MinHash algorithm has proven effective for rapidly estimating the resemblance of two genomes or metagenomes. However, this method cannot reliably estimate the containment of a genome within a metagenome. H...

Authors: Brian D. Ondov, Gabriel J. Starrett, Anna Sappington, Aleksandra Kostic, Sergey Koren, Christopher B. Buck and Adam M. Phillippy

Genetic regulation of gene expression and splicing during a 10-year period of human aging

Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splic...

Authors: Brunilda Balliu, Matthew Durrant, Olivia de Goede, Nathan Abell, Xin Li, Boxiang Liu, Michael J. Gloudemans, Naomi L. Cook, Kevin S. Smith, David A. Knowles, Mauro Pala, Francesco Cucca, David Schlessinger, Siddhartha Jaiswal, Chiara Sabatti, Lars Lind…

MaveDB: an open-source platform to distribute and interpret data from multiplexed assays of variant effect

Multiplex assays of variant effect (MAVEs), such as deep mutational scans and massively parallel reporter assays, test thousands of sequence variants in a single experiment. Despite the importance of MAVE data...

Authors: Daniel Esposito, Jochen Weile, Jay Shendure, Lea M. Starita, Anthony T. Papenfuss, Frederick P. Roth, Douglas M. Fowler and Alan F. Rubin

Fueling ab initio folding with marine metagenomics enables structure and function predictions of new protein families

The ocean microbiome represents one of the largest microbiomes and produces nearly half of the primary energy on the planet through photosynthesis or chemosynthesis. Using recent advances in marine genomics, w...

Authors: Yan Wang, Qiang Shi, Pengshuo Yang, Chengxin Zhang, S. M. Mortuza, Zhidong Xue, Kang Ning and Yang Zhang

Scaling computational genomics to millions of individuals with GPUs

Current genomics methods are designed to handle tens to thousands of samples but will need to scale to millions to match the pace of data and hypothesis generation in biomedical science. Here, we show that hig...

Authors: Amaro Taylor-Weiner, François Aguet, Nicholas J. Haradhvala, Sager Gosai, Shankara Anand, Jaegil Kim, Kristin Ardlie, Eliezer M. Van Allen and Gad Getz

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

Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispani...

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…

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewe...

Authors: Jon G. Sanders, Sergey Nurk, Rodolfo A. Salido, Jeremiah Minich, Zhenjiang Z. Xu, Qiyun Zhu, Cameron Martino, Marcus Fedarko, Timothy D. Arthur, Feng Chen, Brigid S. Boland, Greg C. Humphrey, Caitriona Brennan, Karenina Sanders, James Gaffney, Kristen Jepsen…