Articles

GraphAligner: rapid and versatile sequence-to-graph alignment

Genome graphs can represent genetic variation and sequence uncertainty. Aligning sequences to genome graphs is key to many applications, including error correction, genome assembly, and genotyping of variants in ...

Authors: Mikko Rautiainen and Tobias Marschall

Haplotype threading: accurate polyploid phasing from long reads

Resolving genomes at haplotype level is crucial for understanding the evolutionary history of polyploid species and for designing advanced breeding strategies. Polyploid phasing still presents considerable cha...

Authors: Sven D. Schrinner, Rebecca Serra Mari, Jana Ebler, Mikko Rautiainen, Lancelot Seillier, Julia J. Reimer, Björn Usadel, Tobias Marschall and Gunnar W. Klau

Chromatin regulates expression of small RNAs to help maintain transposon methylome homeostasis in Arabidopsis

Eukaryotic genomes are partitioned into euchromatic and heterochromatic domains to regulate gene expression and other fundamental cellular processes. However, chromatin is dynamic during growth and development...

Authors: Ranjith K. Papareddy, Katalin Páldi, Subramanian Paulraj, Ping Kao, Stefan Lutzmayer and Michael D. Nodine

Removing reference bias and improving indel calling in ancient DNA data analysis by mapping to a sequence variation graph

During the last decade, the analysis of ancient DNA (aDNA) sequence has become a powerful tool for the study of past human populations. However, the degraded nature of aDNA means that aDNA molecules are short ...

Authors: Rui Martiniano, Erik Garrison, Eppie R. Jones, Andrea Manica and Richard Durbin

Bifrost: highly parallel construction and indexing of colored and compacted de Bruijn graphs

Memory consumption of de Bruijn graphs is often prohibitive. Most de Bruijn graph-based assemblers reduce the complexity by compacting paths into single vertices, but this is challenging as it requires the unc...

Authors: Guillaume Holley and Páll Melsted

Ultrasensitive deletion detection links mitochondrial DNA replication, disease, and aging

Acquired human mitochondrial genome (mtDNA) deletions are symptoms and drivers of focal mitochondrial respiratory deficiency, a pathological hallmark of aging and late-onset mitochondrial disease.

Authors: Scott A. Lujan, Matthew J. Longley, Margaret H. Humble, Christopher A. Lavender, Adam Burkholder, Emma L. Blakely, Charlotte L. Alston, Grainne S. Gorman, Doug M. Turnbull, Robert McFarland, Robert W. Taylor, Thomas A. Kunkel and William C. Copeland

Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation

The three-dimensional genome organization is critical for gene regulation and can malfunction in diseases like cancer. As a key regulator of genome organization, CCCTC-binding factor (CTCF) has been characteri...

Authors: Celestia Fang, Zhenjia Wang, Cuijuan Han, Stephanie L. Safgren, Kathryn A. Helmin, Emmalee R. Adelman, Valentina Serafin, Giuseppe Basso, Kyle P. Eagen, Alexandre Gaspar-Maia, Maria E. Figueroa, Benjamin D. Singer, Aakrosh Ratan, Panagiotis Ntziachristos and Chongzhi Zang

AuthentiCT: a model of ancient DNA damage to estimate the proportion of present-day DNA contamination

Contamination from present-day DNA is a fundamental issue when studying ancient DNA from historical or archaeological material, and quantifying the amount of contamination is essential for downstream analyses....

Authors: Stéphane Peyrégne and Benjamin M. Peter

Merqury: reference-free quality, completeness, and phasing assessment for genome assemblies

Recent long-read assemblies often exceed the quality and completeness of available reference genomes, making validation challenging. Here we present Merqury, a novel tool for reference-free assembly evaluation...

Authors: Arang Rhie, Brian P. Walenz, Sergey Koren and Adam M. Phillippy

Primo: integration of multiple GWAS and omics QTL summary statistics for elucidation of molecular mechanisms of trait-associated SNPs and detection of pleiotropy in complex traits

To provide a comprehensive mechanistic interpretation of how known trait-associated SNPs affect complex traits, we propose a method, Primo, for integrative analysis of GWAS summary statistics with multiple set...

Authors: Kevin J. Gleason, Fan Yang, Brandon L. Pierce, Xin He and Lin S. Chen

sn-spMF: matrix factorization informs tissue-specific genetic regulation of gene expression

Genetic regulation of gene expression, revealed by expression quantitative trait loci (eQTLs), exhibits complex patterns of tissue-specific effects. Characterization of these patterns may allow us to better un...

Authors: Yuan He, Surya B. Chhetri, Marios Arvanitis, Kaushik Srinivasan, François Aguet, Kristin G. Ardlie, Alvaro N. Barbeira, Rodrigo Bonazzola, Hae Kyung Im, Christopher D. Brown and Alexis Battle

A vast resource of allelic expression data spanning human tissues

Allele expression (AE) analysis robustly measures cis-regulatory effects. Here, we present and demonstrate the utility of a vast AE resource generated from the GTEx v8 release, containing 15,253 samples spanning ...

Authors: Stephane E. Castel, François Aguet, Pejman Mohammadi, Kristin G. Ardlie and Tuuli Lappalainen

Impact of admixture and ancestry on eQTL analysis and GWAS colocalization in GTEx

Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings. The Genotype-Tissue Expression (GTEx) project largely contains i...

Authors: Nicole R. Gay, Michael Gloudemans, Margaret L. Antonio, Nathan S. Abell, Brunilda Balliu, YoSon Park, Alicia R. Martin, Shaila Musharoff, Abhiram S. Rao, François Aguet, Alvaro N. Barbeira, Rodrigo Bonazzola, Farhad Hormozdiari, Kristin G. Ardlie, Christopher D. Brown, Hae Kyung Im…

PTWAS: investigating tissue-relevant causal molecular mechanisms of complex traits using probabilistic TWAS analysis

We propose a new computational framework, probabilistic transcriptome-wide association study (PTWAS), to investigate causal relationships between gene expressions and complex traits. PTWAS applies the establis...

Authors: Yuhua Zhang, Corbin Quick, Ketian Yu, Alvaro Barbeira, Francesca Luca, Roger Pique-Regi, Hae Kyung Im and Xiaoquan Wen

Estimating the quality of eukaryotic genomes recovered from metagenomic analysis with EukCC

Microbial eukaryotes constitute a significant fraction of biodiversity and have recently gained more attention, but the recovery of high-quality metagenomic assembled eukaryotic genomes is limited by the curre...

Authors: Paul Saary, Alex L. Mitchell and Robert D. Finn

STARR-seq identifies active, chromatin-masked, and dormant enhancers in pluripotent mouse embryonic stem cells

Enhancers are distal regulators of gene expression that shape cell identity and control cell fate transitions. In mouse embryonic stem cells (mESCs), the pluripotency network is maintained by the function of a...

Authors: Tianran Peng, Yanan Zhai, Yaser Atlasi, Menno ter Huurne, Hendrik Marks, Hendrik G. Stunnenberg and Wout Megchelenbrink

Metalign: efficient alignment-based metagenomic profiling via containment min hash

Metagenomic profiling, predicting the presence and relative abundances of microbes in a sample, is a critical first step in microbiome analysis. Alignment-based approaches are often considered accurate yet com...

Authors: Nathan LaPierre, Mohammed Alser, Eleazar Eskin, David Koslicki and Serghei Mangul

GetOrganelle: a fast and versatile toolkit for accurate de novo assembly of organelle genomes

GetOrganelle is a state-of-the-art toolkit to accurately assemble organelle genomes from whole genome sequencing data. It recruits organelle-associated reads using a modified “baiting and iterative mapping” ap...

Authors: Jian-Jun Jin, Wen-Bin Yu, Jun-Bo Yang, Yu Song, Claude W. dePamphilis, Ting-Shuang Yi and De-Zhu Li

Natural display of nuclear-encoded RNA on the cell surface and its impact on cell interaction

Compared to proteins, glycans, and lipids, much less is known about RNAs on the cell surface. We develop a series of technologies to test for any nuclear-encoded RNAs that are stably attached to the cell surfa...

Authors: Norman Huang, Xiaochen Fan, Kathia Zaleta-Rivera, Tri C. Nguyen, Jiarong Zhou, Yingjun Luo, Jie Gao, Ronnie H. Fang, Zhangming Yan, Zhen Bouman Chen, Liangfang Zhang and Sheng Zhong

COCOA: coordinate covariation analysis of epigenetic heterogeneity

A key challenge in epigenetics is to determine the biological significance of epigenetic variation among individuals. We present Coordinate Covariation Analysis (COCOA), a computational framework that uses cov...

Authors: John T. Lawson, Jason P. Smith, Stefan Bekiranov, Francine E. Garrett-Bakelman and Nathan C. Sheffield

Alignment and mapping methodology influence transcript abundance estimation

The accuracy of transcript quantification using RNA-seq data depends on many factors, such as the choice of alignment or mapping method and the quantification model being adopted. While the choice of quantific...

Authors: Avi Srivastava, Laraib Malik, Hirak Sarkar, Mohsen Zakeri, Fatemeh Almodaresi, Charlotte Soneson, Michael I. Love, Carl Kingsford and Rob Patro

Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease

Viral load is a major contributor to outcome in patients with Ebola virus disease (EVD), with high values leading to a fatal outcome. Evidence from the 2013–2016 Ebola virus (EBOV) outbreak indicated that diff...

Authors: Xiaofeng Dong, Jordana Munoz-Basagoiti, Natasha Y. Rickett, Georgios Pollakis, William A. Paxton, Stephan Günther, Romy Kerber, Lisa F. P. Ng, Michael J. Elmore, N’faly Magassouba, Miles W. Carroll, David A. Matthews and Julian A. Hiscox

The Tug1 lncRNA locus is essential for male fertility

Several long noncoding RNAs (lncRNAs) have been shown to function as components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has grea...

Authors: Jordan P. Lewandowski, Gabrijela Dumbović, Audrey R. Watson, Taeyoung Hwang, Emily Jacobs-Palmer, Nydia Chang, Christian Much, Kyle M. Turner, Christopher Kirby, Nimrod D. Rubinstein, Abigail F. Groff, Steve C. Liapis, Chiara Gerhardinger, Assaf Bester, Pier Paolo Pandolfi, John G. Clohessy…

The wild grape genome sequence provides insights into the transition from dioecy to hermaphroditism during grape domestication

A key step in domestication of the grapevine was the transition from separate sexes (dioecy) in wild Vitis vinifera ssp. sylvestris (V. sylvestris) to hermaphroditism in cultivated Vitis vinifera ssp. sativa (V. ...

Authors: Hélène Badouin, Amandine Velt, François Gindraud, Timothée Flutre, Vincent Dumas, Sonia Vautrin, William Marande, Jonathan Corbi, Erika Sallet, Jérémy Ganofsky, Sylvain Santoni, Dominique Guyot, Eugenia Ricciardelli, Kristen Jepsen, Jos Käfer, Hélène Berges…

EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data

Cell type heterogeneity presents a challenge to the interpretation of epigenome data, compounded by the difficulty in generating reliable single-cell DNA methylomes for large numbers of cells and samples. We p...

Authors: Andrew E. Teschendorff, Tianyu Zhu, Charles E. Breeze and Stephan Beck

A hypothesis is a liability

Authors: Itai Yanai and Martin Lercher

Fine-tuning sugar content in strawberry

Fine-tuning quantitative traits for continuous subtle phenotypes is highly advantageous. We engineer the highly conserved upstream open reading frame (uORF) of FvebZIPs1.1 in strawberry (Fragaria vesca), using ba...

Authors: Sinian Xing, Kunling Chen, Haocheng Zhu, Rui Zhang, Huawei Zhang, Bingbing Li and Caixia Gao

1200 high-quality metagenome-assembled genomes from the rumen of African cattle and their relevance in the context of sub-optimal feeding

The Boran (Bos indicus), indigenous Zebu cattle breed from sub-Saharan Africa, is remarkably well adapted to harsh tropical environments. Due to financial constraints and low-quality forage, African livestock are...

Authors: Toby Wilkinson, Daniel Korir, Moses Ogugo, Robert D. Stewart, Mick Watson, Edith Paxton, John Goopy and Christelle Robert

A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation

The central nervous system (CNS) is vulnerable to viral infection, yet few host factors in the CNS are known to defend against invasion by neurotropic viruses. Long noncoding RNAs (lncRNAs) have been revealed ...

Authors: Baokun Sui, Dong Chen, Wei Liu, Qiong Wu, Bin Tian, Yingying Li, Jing Hou, Shiyong Liu, Juan Xie, Hao Jiang, Zhaochen Luo, Lei Lv, Fei Huang, Ruiming Li, Chengguang Zhang, Yuling Tian…

pipeComp, a general framework for the evaluation of computational pipelines, reveals performant single cell RNA-seq preprocessing tools

We present pipeComp (https://​github.​com/​plger/​pipeComp), a flexible R framework for pipeline comparison handling interactions between analysis steps and relying on multi-level evaluation metrics. We apply it t...

Authors: Pierre-Luc Germain, Anthony Sonrel and Mark D. Robinson

RNA G-quadruplex structures exist and function in vivo in plants

Guanine-rich sequences are able to form complex RNA structures termed RNA G-quadruplexes in vitro. Because of their high stability, RNA G-quadruplexes are proposed to exist in vivo and are suggested to be asso...

Authors: Xiaofei Yang, Jitender Cheema, Yueying Zhang, Hongjing Deng, Susan Duncan, Mubarak Ishaq Umar, Jieyu Zhao, Qi Liu, Xiaofeng Cao, Chun Kit Kwok and Yiliang Ding

CSS: cluster similarity spectrum integration of single-cell genomics data

It is a major challenge to integrate single-cell sequencing data across experiments, conditions, batches, time points, and other technical considerations. New computational methods are required that can integr...

Authors: Zhisong He, Agnieska Brazovskaja, Sebastian Ebert, J. Gray Camp and Barbara Treutlein

sgBE: a structure-guided design of sgRNA architecture specifies base editing window and enables simultaneous conversion of cytosine and adenosine

We present a base editing system, in which base editors are attached to different sites of sgRNA scaffold (sgBE). Each independent sgBE has its own specific editing pattern for a given target site. Among teste...

Authors: Yanhong Wang, Lifang Zhou, Rui Tao, Nan Liu, Jie Long, Fengming Qin, Wenling Tang, Yang Yang, Qiang Chen and Shaohua Yao

Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference

DNA methylation is a key epigenetic modification in human development and disease, yet there is limited understanding of its highly coordinated regulation. Here, we identify 818 genes that affect DNA methylati...

Authors: Paul J. Hop, René Luijk, Lucia Daxinger, Maarten van Iterson, Koen F. Dekkers, Rick Jansen, Joyce B. J. van Meurs, Peter A. C. ’t Hoen, M. Arfan Ikram, Marleen M. J. van Greevenbroek, Dorret I. Boomsma, P. Eline Slagboom, Jan H. Veldink, Erik W. van Zwet and Bastiaan T. Heijmans

3DeFDR: statistical methods for identifying cell type-specific looping interactions in 5C and Hi-C data

An important unanswered question in chromatin biology is the extent to which long-range looping interactions change across developmental models, genetic perturbations, drug treatments, and disease states. Comp...

Authors: Lindsey R. Fernandez, Thomas G. Gilgenast and Jennifer E. Phillips-Cremins

A systematic evaluation of single-cell RNA-sequencing imputation methods

The rapid development of single-cell RNA-sequencing (scRNA-seq) technologies has led to the emergence of many methods for removing systematic technical noises, including imputation methods, which aim to addres...

Authors: Wenpin Hou, Zhicheng Ji, Hongkai Ji and Stephanie C. Hicks

PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection

Germline disease-causing variants are generally more spatially clustered in protein 3-dimensional structures than benign variants. Motivated by this tendency, we develop a fast and powerful protein-structure-b...

Authors: Zheng-Zheng Tang, Gregory R. Sliwoski, Guanhua Chen, Bowen Jin, William S. Bush, Bingshan Li and John A. Capra

Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma

Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype up...

Authors: Jason K. Sa, Nakho Chang, Hye Won Lee, Hee Jin Cho, Michele Ceccarelli, Luigi Cerulo, Jinlong Yin, Sung Soo Kim, Francesca P. Caruso, Mijeong Lee, Donggeon Kim, Young Taek Oh, Yeri Lee, Nam-Gu Her, Byeongkwi Min, Hye-Jin Kim…

Improved reference genome of the arboviral vector Aedes albopictus

The Asian tiger mosquito Aedes albopictus is globally expanding and has become the main vector for human arboviruses in Europe. With limited antiviral drugs and vaccines available, vector control is the primary a...

Authors: Umberto Palatini, Reem A. Masri, Luciano V. Cosme, Sergey Koren, Françoise Thibaud-Nissen, James K. Biedler, Flavia Krsticevic, J. Spencer Johnston, Rebecca Halbach, Jacob E. Crawford, Igor Antoshechkin, Anna-Bella Failloux, Elisa Pischedda, Michele Marconcini, Jay Ghurye, Arang Rhie…

Author Correction: SMURF-seq: efficient copy number profiling on long-read sequencers

An amendment to this paper has been published and can be accessed via the original article.

Authors: Rishvanth K. Prabakar, Liya Xu, James Hicks and Andrew D. Smith

Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs

Quantifying the genetic heterogeneity of a cell population is essential to understanding of biological systems. We develop a universal method to label individual DNA molecules for single-base-resolution haplot...

Authors: Chongwei Bi, Lin Wang, Baolei Yuan, Xuan Zhou, Yu Li, Sheng Wang, Yuhong Pang, Xin Gao, Yanyi Huang and Mo Li

Tuning parameters of dimensionality reduction methods for single-cell RNA-seq analysis

Many computational methods have been developed recently to analyze single-cell RNA-seq (scRNA-seq) data. Several benchmark studies have compared these methods on their ability for dimensionality reduction, clu...

Authors: Felix Raimundo, Celine Vallot and Jean-Philippe Vert

GBAT: a gene-based association test for robust detection of trans-gene regulation

The observation that disease-associated genetic variants typically reside outside of exons has inspired widespread investigation into the genetic basis of transcriptional regulation. While associations between...

Authors: Xuanyao Liu, Joel A. Mefford, Andrew Dahl, Yuan He, Meena Subramaniam, Alexis Battle, Alkes L. Price and Noah Zaitlen

DNA polymerase stalling at structured DNA constrains the expansion of short tandem repeats

Short tandem repeats (STRs) contribute significantly to de novo mutagenesis, driving phenotypic diversity and genetic disease. Although highly diverse, their repetitive sequences induce DNA polymerase slippage...

Authors: Pierre Murat, Guillaume Guilbaud and Julian E. Sale

Cis and trans effects differentially contribute to the evolution of promoters and enhancers

Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects are caused by genetic variants located on the same DNA molecule as the target gene, trans effects are due ...

Authors: Kaia Mattioli, Winona Oliveros, Chiara Gerhardinger, Daniel Andergassen, Philipp G. Maass, John L. Rinn and Marta Melé

CRISPR and transposon in vivo screens for cancer drivers and therapeutic targets

Human cancers harbor substantial genetic, epigenetic, and transcriptional changes, only some of which drive oncogenesis at certain times during cancer evolution. Identifying the cancer-driver alterations among...

Authors: Imran Noorani, Allan Bradley and Jorge de la Rosa

Methods for copy number aberration detection from single-cell DNA-sequencing data

Copy number aberrations (CNAs), which are pathogenic copy number variations (CNVs), play an important role in the initiation and progression of cancer. Single-cell DNA-sequencing (scDNAseq) technologies produc...

Authors: Xian F. Mallory, Mohammadamin Edrisi, Nicholas Navin and Luay Nakhleh

DiMSum: an error model and pipeline for analyzing deep mutational scanning data and diagnosing common experimental pathologies

Deep mutational scanning (DMS) enables multiplexed measurement of the effects of thousands of variants of proteins, RNAs, and regulatory elements. Here, we present a customizable pipeline, DiMSum, that represe...

Authors: Andre J. Faure, Jörn M. Schmiedel, Pablo Baeza-Centurion and Ben Lehner

Correction to: PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas

An amendment to this paper has been published and can be accessed via the original article.

Authors: Imran Noorani, Jorge de la Rosa, Yoon Ha Choi, Alexander Strong, Hannes Ponstingl, M. S. Vijayabaskar, Jusung Lee, Eunmin Lee, Angela Richard-Londt, Mathias Friedrich, Federica Furlanetto, Rocio Fuente, Ruby Banerjee, Fengtang Yang, Frances Law, Colin Watts…

Sc3.0: revamping and minimizing the yeast genome

Authors: Junbiao Dai, Jef D. Boeke, Zhouqing Luo, Shuangying Jiang and Yizhi Cai