Articles

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…

Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues

Genomic imprinting is an epigenetic phenomenon that allows a subset of genes to be expressed mono-allelically based on the parent of origin and is typically regulated by differential DNA methylation inherited ...

Authors: Courtney W. Hanna, Raquel Pérez-Palacios, Lenka Gahurova, Michael Schubert, Felix Krueger, Laura Biggins, Simon Andrews, Maria Colomé-Tatché, Deborah Bourc’his, Wendy Dean and Gavin Kelsey

RaGOO: fast and accurate reference-guided scaffolding of draft genomes

We present RaGOO, a reference-guided contig ordering and orienting tool that leverages the speed and sensitivity of Minimap2 to accurately achieve chromosome-scale assemblies in minutes. After the pseudomolecu...

Authors: Michael Alonge, Sebastian Soyk, Srividya Ramakrishnan, Xingang Wang, Sara Goodwin, Fritz J. Sedlazeck, Zachary B. Lippman and Michael C. Schatz

HOPS: a quantitative score reveals pervasive horizontal pleiotropy in human genetic variation is driven by extreme polygenicity of human traits and diseases

Horizontal pleiotropy, where one variant has independent effects on multiple traits, is important for our understanding of the genetic architecture of human phenotypes. We develop a method to quantify horizont...

Authors: Daniel M. Jordan, Marie Verbanck and Ron Do

Soil domestication by rice cultivation results in plant-soil feedback through shifts in soil microbiota

Soils are a key component of agricultural productivity, and soil microbiota determine the availability of many essential plant nutrients. Agricultural domestication of soils, that is, the conversion of previou...

Authors: Joseph Edwards, Christian Santos-Medellín, Bao Nguyen, John Kilmer, Zachary Liechty, Esteban Veliz, Jiadong Ni, Gregory Phillips and Venkatesan Sundaresan

IMAGE: high-powered detection of genetic effects on DNA methylation using integrated methylation QTL mapping and allele-specific analysis

Identifying genetic variants that are associated with methylation variation—an analysis commonly referred to as methylation quantitative trait locus (mQTL) mapping—is important for understanding the epigenetic...

Authors: Yue Fan, Tauras P. Vilgalys, Shiquan Sun, Qinke Peng, Jenny Tung and Xiang Zhou

Comparison of cytosine base editors and development of the BEable-GPS database for targeting pathogenic SNVs

A variety of base editors have been developed to achieve C-to-T editing in different genomic contexts. Here, we compare a panel of five base editors on their C-to-T editing efficiencies and product purity at c...

Authors: Ying Wang, Runze Gao, Jing Wu, Yi-Chun Xiong, Jia Wei, Sipin Zhang, Bei Yang, Jia Chen and Li Yang

Robust taxonomic classification of uncharted microbial sequences and bins with CAT and BAT

Current-day metagenomics analyses increasingly involve de novo taxonomic classification of long DNA sequences and metagenome-assembled genomes. Here, we show that the conventional best-hit approach often leads...

Authors: F. A. Bastiaan von Meijenfeldt, Ksenia Arkhipova, Diego D. Cambuy, Felipe H. Coutinho and Bas E. Dutilh

The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation

Cells have evolved quality control mechanisms to ensure protein homeostasis by detecting and degrading aberrant mRNAs and proteins. A common source of aberrant mRNAs is premature polyadenylation, which can res...

Authors: Andrea Hildebrandt, Mirko Brüggemann, Cornelia Rücklé, Susan Boerner, Jan B. Heidelberger, Anke Busch, Heike Hänel, Andrea Voigt, Martin M. Möckel, Stefanie Ebersberger, Anica Scholz, Annabelle Dold, Tobias Schmid, Ingo Ebersberger, Jean-Yves Roignant, Kathi Zarnack…

PGG.SNV: understanding the evolutionary and medical implications of human single nucleotide variations in diverse populations

Despite the tremendous growth of the DNA sequencing data in the last decade, our understanding of the human genome is still in its infancy. To understand the implications of genetic variants in the light of po...

Authors: Chao Zhang, Yang Gao, Zhilin Ning, Yan Lu, Xiaoxi Zhang, Jiaojiao Liu, Bo Xie, Zhe Xue, Xiaoji Wang, Kai Yuan, Xueling Ge, Yuwen Pan, Chang Liu, Lei Tian, Yuchen Wang, Dongsheng Lu…

Correction to: MicroPro: using metagenomic unmapped reads to provide insights into human microbiota and disease associations

Following publication of the original paper [1], Dr. Nayfach kindly pointed out an error and the authors would like to report the following correction.

Authors: Zifan Zhu, Jie Ren, Sonia Michail and Fengzhu Sun

SEPATH: benchmarking the search for pathogens in human tissue whole genome sequence data leads to template pipelines

Human tissue is increasingly being whole genome sequenced as we transition into an era of genomic medicine. With this arises the potential to detect sequences originating from microorganisms, including pathoge...

Authors: Abraham Gihawi, Ghanasyam Rallapalli, Rachel Hurst, Colin S. Cooper, Richard M. Leggett and Daniel S. Brewer

Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods

Accurate fusion transcript detection is essential for comprehensive characterization of cancer transcriptomes. Over the last decade, multiple bioinformatic tools have been developed to predict fusions from RNA...

Authors: Brian J. Haas, Alexander Dobin, Bo Li, Nicolas Stransky, Nathalie Pochet and Aviv Regev

DNA extraction for human microbiome studies: the issue of standardization

Among the laboratory and bioinformatic processing steps for human microbiome studies, a lack of consistency in DNA extraction methodologies is hindering the ability to compare results between studies and somet...

Authors: K. Leigh Greathouse, Rashmi Sinha and Emily Vogtmann

DeepImpute: an accurate, fast, and scalable deep neural network method to impute single-cell RNA-seq data

Single-cell RNA sequencing (scRNA-seq) offers new opportunities to study gene expression of tens of thousands of single cells simultaneously. We present DeepImpute, a deep neural network-based imputation algor...

Authors: Cédric Arisdakessian, Olivier Poirion, Breck Yunits, Xun Zhu and Lana X. Garmire

Dissociation of solid tumor tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses

Single-cell RNA sequencing (scRNA-seq) is a powerful tool for studying complex biological systems, such as tumor heterogeneity and tissue microenvironments. However, the sources of technical and biological var...

Authors: Ciara H. O’Flanagan, Kieran R. Campbell, Allen W. Zhang, Farhia Kabeer, Jamie L. P. Lim, Justina Biele, Peter Eirew, Daniel Lai, Andrew McPherson, Esther Kong, Cherie Bates, Kelly Borkowski, Matt Wiens, Brittany Hewitson, James Hopkins, Jenifer Pham…

Global impact of somatic structural variation on the DNA methylome of human cancers

Genomic rearrangements exert a heavy influence on the molecular landscape of cancer. New analytical approaches integrating somatic structural variants (SSVs) with altered gene features represent a framework by...

Authors: Yiqun Zhang, Lixing Yang, Melanie Kucherlapati, Angela Hadjipanayis, Angeliki Pantazi, Christopher A. Bristow, Eunjung Alice Lee, Harshad S. Mahadeshwar, Jiabin Tang, Jianhua Zhang, Sahil Seth, Semin Lee, Xiaojia Ren, Xingzhi Song, Huandong Sun, Jonathan Seidman…

Birth, expansion, and death of VCY-containing palindromes on the human Y chromosome

Large palindromes (inverted repeats) make up substantial proportions of mammalian sex chromosomes, often contain genes, and have high rates of structural variation arising via ectopic recombination. As a resul...

Authors: Wentao Shi, Andrea Massaia, Sandra Louzada, Juliet Handsaker, William Chow, Shane McCarthy, Joanna Collins, Pille Hallast, Kerstin Howe, Deanna M. Church, Fengtang Yang, Yali Xue and Chris Tyler-Smith

MetaCell: analysis of single-cell RNA-seq data using K-nn graph partitions

scRNA-seq profiles each represent a highly partial sample of mRNA molecules from a unique cell that can never be resampled, and robust analysis must separate the sampling effect from biological variance. We de...

Authors: Yael Baran, Akhiad Bercovich, Arnau Sebe-Pedros, Yaniv Lubling, Amir Giladi, Elad Chomsky, Zohar Meir, Michael Hoichman, Aviezer Lifshitz and Amos Tanay

Benchmarking comes of age

Authors: Mark D. Robinson and Olga Vitek

Correction to: African evolutionary history inferred from whole genome sequence data of 44 indigenous African populations

Following publication of the original article [1], a typographical error in the formula for calculating d_i in the “Scans for local adaptation” subsection in the Method section, was identified. The correct formula...

Authors: Shaohua Fan, Derek E. Kelly, Marcia H. Beltrame, Matthew E. B. Hansen, Swapan Mallick, Alessia Ranciaro, Jibril Hirbo, Simon Thompson, William Beggs, Thomas Nyambo, Sabah A. Omar, Dawit Wolde Meskel, Gurja Belay, Alain Froment, Nick Patterson, David Reich…

Identifying significantly impacted pathways: a comprehensive review and assessment

Many high-throughput experiments compare two phenotypes such as disease vs. healthy, with the goal of understanding the underlying biological phenomena characterizing the given phenotype. Because of the import...

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

Benchmark of computational methods for predicting microRNA-disease associations

A series of miRNA-disease association prediction methods have been proposed to prioritize potential disease-associated miRNAs. Independent benchmarking of these methods is warranted to assess their effectivene...

Authors: Zhou Huang, Leibo Liu, Yuanxu Gao, Jiangcheng Shi, Qinghua Cui, Jianwei Li and Yuan Zhou

Convergence of human and Old World monkey gut microbiomes demonstrates the importance of human ecology over phylogeny

Comparative data from non-human primates provide insight into the processes that shaped the evolution of the human gut microbiome and highlight microbiome traits that differentiate humans from other primates. ...

Authors: Katherine R. Amato, Elizabeth K. Mallott, Daniel McDonald, Nathaniel J. Dominy, Tony Goldberg, Joanna E. Lambert, Larissa Swedell, Jessica L. Metcalf, Andres Gomez, Gillian A. O. Britton, Rebecca M. Stumpf, Steven R. Leigh and Rob Knight

Divergent neuronal DNA methylation patterns across human cortical development reveal critical periods and a unique role of CpH methylation

DNA methylation (DNAm) is a critical regulator of both development and cellular identity and shows unique patterns in neurons. To better characterize maturational changes in DNAm patterns in these cells, we pr...

Authors: Amanda J. Price, Leonardo Collado-Torres, Nikolay A. Ivanov, Wei Xia, Emily E. Burke, Joo Heon Shin, Ran Tao, Liang Ma, Yankai Jia, Thomas M. Hyde, Joel E. Kleinman, Daniel R. Weinberger and Andrew E. Jaffe

How to meet your ‘silent partner’: tips for approaching editors at conferences

Authors: Yixin Yao

When the levee breaks: a practical guide to sketching algorithms for processing the flood of genomic data

Considerable advances in genomics over the past decade have resulted in vast amounts of data being generated and deposited in global archives. The growth of these archives exceeds our ability to process their ...

Authors: Will P. M. Rowe

Quantitative MNase-seq accurately maps nucleosome occupancy levels

Micrococcal nuclease (MNase) is widely used to map nucleosomes. However, its aggressive endo-/exo-nuclease activities make MNase-seq unreliable for determining nucleosome occupancies, because cleavages within ...

Authors: Răzvan V. Chereji, Terri D. Bryson and Steven Henikoff

The first enhancer in an enhancer chain safeguards subsequent enhancer-promoter contacts from a distance

Robustness and evolutionary stability of gene expression in the human genome are established by an array of redundant enhancers.

Authors: Wei Song, Roded Sharan and Ivan Ovcharenko

Reproducible biomedical benchmarking in the cloud: lessons from crowd-sourced data challenges

Challenges are achieving broad acceptance for addressing many biomedical questions and enabling tool assessment. But ensuring that the methods evaluated are reproducible and reusable is complicated by the dive...

Authors: Kyle Ellrott, Alex Buchanan, Allison Creason, Michael Mason, Thomas Schaffter, Bruce Hoff, James Eddy, John M. Chilton, Thomas Yu, Joshua M. Stuart, Julio Saez-Rodriguez, Gustavo Stolovitzky, Paul C. Boutros and Justin Guinney

A comparison of automatic cell identification methods for single-cell RNA sequencing data

Single-cell transcriptomics is rapidly advancing our understanding of the cellular composition of complex tissues and organisms. A major limitation in most analysis pipelines is the reliance on manual annotati...

Authors: Tamim Abdelaal, Lieke Michielsen, Davy Cats, Dylan Hoogduin, Hailiang Mei, Marcel J. T. Reinders and Ahmed Mahfouz

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

Technical variation in feature measurements, such as gene expression and locus accessibility, is a key challenge of large-scale single-cell genomic datasets. We show that this technical variation in both scRNA...

Authors: Ruoxin Li and Gerald Quon

CUT&RUNTools: a flexible pipeline for CUT&RUN processing and footprint analysis

We introduce CUT&RUNTools as a flexible, general pipeline for facilitating the identification of chromatin-associated protein binding and genomic footprinting analysis from antibody-targeted CUT&RUN primary cl...

Authors: Qian Zhu, Nan Liu, Stuart H. Orkin and Guo-Cheng Yuan

Expanding the scope and scale of microbiome research

Authors: Rob Knight, Ruth E. Ley, Jeroen Raes and Elizabeth A. Grice