Articles

Abundant expression of somatic transposon-derived piRNAs throughout Tribolium castaneum embryogenesis

Piwi-interacting RNAs (piRNAs) are a class of short (~26–31-nucleotide) non-protein-coding RNAs expressed in the metazoan germline. The piRNA pathway in arthropods is best understood in the ovary of Drosophila me...

Authors: Maria Ninova, Sam Griffiths-Jones and Matthew Ronshaugen

From structure to function, how bioinformatics help to reveal functions of our genomes

A report on the 13th International Bioinformatics Workshop held in Harbin, China, 5–6 August 2017.

Authors: Xiaoqi Zheng and Sheng Zhong

DNA methylation dynamics during early plant life

Cytosine methylation is crucial for gene regulation and silencing of transposable elements in mammals and plants. While this epigenetic mark is extensively reprogrammed in the germline and early embryos of mam...

Authors: Daniel Bouyer, Amira Kramdi, Mohamed Kassam, Maren Heese, Arp Schnittger, François Roudier and Vincent Colot

Comprehensive benchmarking and ensemble approaches for metagenomic classifiers

One of the main challenges in metagenomics is the identification of microorganisms in clinical and environmental samples. While an extensive and heterogeneous set of computational tools is available to classif...

Authors: Alexa B. R. McIntyre, Rachid Ounit, Ebrahim Afshinnekoo, Robert J. Prill, Elizabeth Hénaff, Noah Alexander, Samuel S. Minot, David Danko, Jonathan Foox, Sofia Ahsanuddin, Scott Tighe, Nur A. Hasan, Poorani Subramanian, Kelly Moffat, Shawn Levy, Stefano Lonardi…

DESMAN: a new tool for de novo extraction of strains from metagenomes

We introduce DESMAN for De novo Extraction of Strains from Metagenomes. Large multi-sample metagenomes are being generated but strain variation results in fragmentary co-assemblies. Current algorithms can bin ...

Authors: Christopher Quince, Tom O. Delmont, Sébastien Raguideau, Johannes Alneberg, Aaron E. Darling, Gavin Collins and A. Murat Eren

Topological organization and dynamic regulation of human tRNA genes during macrophage differentiation

The human genome is hierarchically organized into local and long-range structures that help shape cell-type-specific transcription patterns. Transfer RNA (tRNA) genes (tDNAs), which are transcribed by RNA poly...

Authors: Kevin Van Bortle, Douglas H. Phanstiel and Michael P. Snyder

SiFit: inferring tumor trees from single-cell sequencing data under finite-sites models

Single-cell sequencing enables the inference of tumor phylogenies that provide insights on intra-tumor heterogeneity and evolutionary trajectories. Recently introduced methods perform this task under the infin...

Authors: Hamim Zafar, Anthony Tzen, Nicholas Navin, Ken Chen and Luay Nakhleh

Genomic imprinting beyond DNA methylation: a role for maternal histones

Inheritance of DNA methylation states from gametes determines genomic imprinting in mammals. A new study shows that repressive chromatin in oocytes can also confer imprinting.

Authors: Courtney W. Hanna and Gavin Kelsey

DNA epigenome editing using CRISPR-Cas SunTag-directed DNMT3A

DNA methylation has widespread effects on gene expression during development. However, our ability to assign specific function to regions of DNA methylation is limited by the poor correlation between global pa...

Authors: Yung-Hsin Huang, Jianzhong Su, Yong Lei, Lorenzo Brunetti, Michael C. Gundry, Xiaotian Zhang, Mira Jeong, Wei Li and Margaret A. Goodell

Dynamic DNA methylation reconfiguration during seed development and germination

Unlike animals, plants can pause their life cycle as dormant seeds. In both plants and animals, DNA methylation is involved in the regulation of gene expression and genome integrity. In animals, reprogramming ...

Authors: Taiji Kawakatsu, Joseph R. Nery, Rosa Castanon and Joseph R. Ecker

Extensive transcriptomic and epigenomic remodelling occurs during Arabidopsis thaliana germination

Seed germination involves progression from complete metabolic dormancy to a highly active, growing seedling. Many factors regulate germination and these interact extensively, forming a complex network of input...

Authors: Reena Narsai, Quentin Gouil, David Secco, Akanksha Srivastava, Yuliya V. Karpievitch, Lim Chee Liew, Ryan Lister, Mathew G. Lewsey and James Whelan

Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy

Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases.

Authors: Matthias Heinig, Michiel E. Adriaens, Sebastian Schafer, Hanneke W. M. van Deutekom, Elisabeth M. Lodder, James S. Ware, Valentin Schneider, Leanne E. Felkin, Esther E. Creemers, Benjamin Meder, Hugo A. Katus, Frank Rühle, Monika Stoll, François Cambien, Eric Villard, Philippe Charron…

Genome build information is an essential part of genomic track files

Genomic locations are represented as coordinates on a specific genome build version, but the build information is frequently missing when coordinates are provided. We show that this information is essential to...

Authors: Chakravarthi Kanduri, Diana Domanska, Eivind Hovig and Geir Kjetil Sandve

Splatter: simulation of single-cell RNA sequencing data

As single-cell RNA sequencing (scRNA-seq) technologies have rapidly developed, so have analysis methods. Many methods have been tested, developed, and validated using simulated datasets. Unfortunately, current...

Authors: Luke Zappia, Belinda Phipson and Alicia Oshlack

Trialing transparent peer review

Authors: Andrew Cosgrove and Louisa Flintoft

Identification of high-confidence RNA regulatory elements by combinatorial classification of RNA–protein binding sites

Crosslinking immunoprecipitation sequencing (CLIP-seq) technologies have enabled researchers to characterize transcriptome-wide binding sites of RNA-binding protein (RBP) with high resolution. We apply a soft-...

Authors: Yang Eric Li, Mu Xiao, Binbin Shi, Yu-Cheng T. Yang, Dong Wang, Fei Wang, Marco Marcia and Zhi John Lu

Non-base-contacting residues enable kaleidoscopic evolution of metazoan C2H2 zinc finger DNA binding

The C2H2 zinc finger (C2H2-ZF) is the most numerous protein domain in many metazoans, but is not as frequent or diverse in other eukaryotes. The biochemical and evolutionary mechanisms that underlie the divers...

Authors: Hamed S. Najafabadi, Michael Garton, Matthew T. Weirauch, Sanie Mnaimneh, Ally Yang, Philip M. Kim and Timothy R. Hughes

Zinc-finger domains in metazoans: evolution gone wild

Authors: M. Mar Albà

Protein recoding by ADAR1-mediated RNA editing is not essential for normal development and homeostasis

Adenosine-to-inosine (A-to-I) editing of dsRNA by ADAR proteins is a pervasive epitranscriptome feature. Tens of thousands of A-to-I editing events are defined in the mouse, yet the functional impact of most i...

Authors: Jacki E. Heraud-Farlow, Alistair M. Chalk, Sandra E. Linder, Qin Li, Scott Taylor, Joshua M. White, Lokman Pang, Brian J. Liddicoat, Ankita Gupte, Jin Billy Li and Carl R. Walkley

BayFish: Bayesian inference of transcription dynamics from population snapshots of single-molecule RNA FISH in single cells

Single-molecule RNA fluorescence in situ hybridization (smFISH) provides unparalleled resolution in the measurement of the abundance and localization of nascent and mature RNA transcripts in fixed, single cell...

Authors: Mariana Gómez-Schiavon, Liang-Fu Chen, Anne E. West and Nicolas E. Buchler

Chromosome contacts in activated T cells identify autoimmune disease candidate genes

Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4⁺ T cells. Linking such regulatory regions to gene promoters in disease-relevant cell context...

Authors: Oliver S. Burren, Arcadio Rubio García, Biola-Maria Javierre, Daniel B. Rainbow, Jonathan Cairns, Nicholas J. Cooper, John J. Lambourne, Ellen Schofield, Xaquin Castro Dopico, Ricardo C. Ferreira, Richard Coulson, Frances Burden, Sophia P. Rowlston, Kate Downes, Steven W. Wingett, Mattia Frontini…

Sparse conserved under-methylated CpGs are associated with high-order chromatin structure

Whole-genome bisulfite sequencing (WGBS) is the gold standard for studying landscape DNA methylation. Current computational methods for WGBS are mainly designed for gene regulatory regions with multiple under-...

Authors: Xueqiu Lin, Jianzhong Su, Kaifu Chen, Benjamin Rodriguez and Wei Li

A subset of conserved mammalian long non-coding RNAs are fossils of ancestral protein-coding genes

Only a small portion of human long non-coding RNAs (lncRNAs) appear to be conserved outside of mammals, but the events underlying the birth of new lncRNAs in mammals remain largely unknown. One potential sourc...

Authors: Hadas Hezroni, Rotem Ben-Tov Perry, Zohar Meir, Gali Housman, Yoav Lubelsky and Igor Ulitsky

Genome-wide association studies dissect the genetic networks underlying agronomical traits in soybean

Soybean (Glycine max [L.] Merr.) is one of the most important oil and protein crops. Ever-increasing soybean consumption necessitates the improvement of varieties for more efficient production. However, both corr...

Authors: Chao Fang, Yanming Ma, Shiwen Wu, Zhi Liu, Zheng Wang, Rui Yang, Guanghui Hu, Zhengkui Zhou, Hong Yu, Min Zhang, Yi Pan, Guoan Zhou, Haixiang Ren, Weiguang Du, Hongrui Yan, Yanping Wang…

New skin for the old RNA-Seq ceremony: the age of single-cell multi-omics

New methods for simultaneously quantifying protein and gene expression at the single-cell level have the power to identify cell types and to classify cell populations.

Authors: Maayan Baron and Itai Yanai

Erratum to: SuperTranscripts: a data driven reference for analysis and visualisation of transcriptomes

Authors: Nadia M. Davidson, Anthony D. K. Hawkins and Alicia Oshlack

Conservation and divergence of small RNA pathways and microRNAs in land plants

As key regulators of gene expression in eukaryotes, small RNAs have been characterized in many seed plants, and pathways for their biogenesis, degradation, and action have been defined in model angiosperms. Ho...

Authors: Chenjiang You, Jie Cui, Hui Wang, Xinping Qi, Li-Yaung Kuo, Hong Ma, Lei Gao, Beixin Mo and Xuemei Chen

Altered chromatin compaction and histone methylation drive non-additive gene expression in an interspecific Arabidopsis hybrid

The merging of two diverged genomes can result in hybrid offspring that phenotypically differ greatly from both parents. In plants, interspecific hybridization plays important roles in evolution and speciation...

Authors: Wangsheng Zhu, Bo Hu, Claude Becker, Ezgi Süheyla Doğan, Kenneth Wayne Berendzen, Detlef Weigel and Chang Liu

Stable inheritance of DNA methylation allows creation of epigenotype maps and the study of epiallele inheritance patterns in the absence of genetic variation

Differences in DNA methylation can arise as epialleles, which are loci that differ in chromatin state and are inherited over generations. Epialleles offer an additional source of variation that can affect phen...

Authors: Brigitte T. Hofmeister, Kevin Lee, Nicholas A. Rohr, David W. Hall and Robert J. Schmitz

Erratum to: The advantages of SMRT sequencing

Authors: Richard J. Roberts, Mauricio O. Carneiro and Michael C. Schatz

Erratum to: Insights into the design and interpretation of iCLIP experiments

Authors: Nejc Haberman, Ina Huppertz, Jan Attig, Julian König, Zhen Wang, Christian Hauer, Matthias W. Hentze, Andreas E. Kulozik, Hervé Le Hir, Tomaž Curk, Christopher R. Sibley, Kathi Zarnack and Jernej Ule

Knowledge-guided gene prioritization reveals new insights into the mechanisms of chemoresistance

Identification of genes whose basal mRNA expression predicts the sensitivity of tumor cells to cytotoxic treatments can play an important role in individualized cancer medicine. It enables detailed characteriz...

Authors: Amin Emad, Junmei Cairns, Krishna R. Kalari, Liewei Wang and Saurabh Sinha

A tandem simulation framework for predicting mapping quality

Read alignment is the first step in most sequencing data analyses. Because a read’s point of origin can be ambiguous, aligners report a mapping quality, which is the probability that the reported alignment is ...

Authors: Ben Langmead

A statistical framework for analyzing deep mutational scanning data

Deep mutational scanning is a widely used method for multiplex measurement of functional consequences of protein variants. We developed a new deep mutational scanning statistical model that generates error est...

Authors: Alan F. Rubin, Hannah Gelman, Nathan Lucas, Sandra M. Bajjalieh, Anthony T. Papenfuss, Terence P. Speed and Douglas M. Fowler

stageR: a general stage-wise method for controlling the gene-level false discovery rate in differential expression and differential transcript usage

RNA sequencing studies with complex designs and transcript-resolution analyses involve multiple hypotheses per gene; however, conventional approaches fail to control the false discovery rate (FDR) at gene leve...

Authors: Koen Van den Berge, Charlotte Soneson, Mark D. Robinson and Lieven Clement

Large scale genomic reorganization of topological domains at the HoxD locus

The transcriptional activation of HoxD genes during mammalian limb development involves dynamic interactions with two topologically associating domains (TADs) flanking the HoxD cluster. In particular, the activat...

Authors: Pierre J. Fabre, Marion Leleu, Benjamin H. Mormann, Lucille Lopez-Delisle, Daan Noordermeer, Leonardo Beccari and Denis Duboule

SuperTranscripts: a data driven reference for analysis and visualisation of transcriptomes

Numerous methods have been developed to analyse RNA sequencing (RNA-seq) data, but most rely on the availability of a reference genome, making them unsuitable for non-model organisms. Here we present superTran...

Authors: Nadia M. Davidson, Anthony D. K. Hawkins and Alicia Oshlack

Searching for cancer vulnerabilities amid genetic chaos

A meeting report on the Third European Association for Cancer Research Conference on Cancer Genomics, held at Churchill College, Cambridge, UK, 25–28 June 2017.

Authors: Michael R. Speicher

An interaction map of circulating metabolites, immune gene networks, and their genetic regulation

Immunometabolism plays a central role in many cardiometabolic diseases. However, a robust map of immune-related gene networks in circulating human cells, their interactions with metabolites, and their genetic ...

Authors: Artika P. Nath, Scott C. Ritchie, Sean G. Byars, Liam G. Fearnley, Aki S. Havulinna, Anni Joensuu, Antti J. Kangas, Pasi Soininen, Annika Wennerström, Lili Milani, Andres Metspalu, Satu Männistö, Peter Würtz, Johannes Kettunen, Emma Raitoharju, Mika Kähönen…

Selection plays the hand it was dealt: evidence that human adaptation commonly targets standing genetic variation

Using a powerful machine learning approach, a recent study of human genomes has revealed widespread footprints of recent positive selection on standing genetic variation.

Authors: Rajiv C. McCoy and Joshua M. Akey

The three-dimensional genome organization of Drosophila melanogaster through data integration

Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize the accuracy and coverage of three-dimensional genome structural models, it is important to integrate a...

Authors: Qingjiao Li, Harianto Tjong, Xiao Li, Ke Gong, Xianghong Jasmine Zhou, Irene Chiolo and Frank Alber

A novel mechanism for variable phenotypic expressivity in Mendelian diseases uncovered by an AU-rich element (ARE)-creating mutation

Variable expressivity is a well-known phenomenon in which patients with mutations in one gene display varying degrees of clinical severity, potentially displaying only subsets of the clinical manifestations as...

Authors: Nisha Patel, Arif O. Khan, Maher Al-Saif, Walid N. Moghrabi, Balsam M. AlMaarik, Niema Ibrahim, Firdous Abdulwahab, Mais Hashem, Tarfa Alshidi, Eman Alobeid, Rana A. Alomar, Saad Al-Harbi, Mohamed Abouelhoda, Khalid S. A. Khabar and Fowzan S. Alkuraya

Population and allelic variation of A-to-I RNA editing in human transcriptomes

A-to-I RNA editing is an important step in RNA processing in which specific adenosines in some RNA molecules are post-transcriptionally modified to inosines. RNA editing has emerged as a widespread mechanism f...

Authors: Eddie Park, Jiguang Guo, Shihao Shen, Levon Demirdjian, Ying Nian Wu, Lan Lin and Yi Xing

ReMixT: clone-specific genomic structure estimation in cancer

Somatic evolution of malignant cells produces tumors composed of multiple clonal populations, distinguished in part by rearrangements and copy number changes affecting chromosomal segments. Whole genome sequen...

Authors: Andrew W. McPherson, Andrew Roth, Gavin Ha, Cedric Chauve, Adi Steif, Camila P. E. de Souza, Peter Eirew, Alexandre Bouchard-Côté, Sam Aparicio, S. Cenk Sahinalp and Sohrab P. Shah

Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis

The assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence show...

Authors: Chengping Wen, Zhijun Zheng, Tiejuan Shao, Lin Liu, Zhijun Xie, Emmanuelle Le Chatelier, Zhixing He, Wendi Zhong, Yongsheng Fan, Linshuang Zhang, Haichang Li, Chunyan Wu, Changfeng Hu, Qian Xu, Jia Zhou, Shunfeng Cai…

Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network

We report a novel computational method, RegNetDriver, to identify tumorigenic drivers using the combined effects of coding and non-coding single nucleotide variants, structural variants, and DNA methylation ch...

Authors: Priyanka Dhingra, Alexander Martinez-Fundichely, Adeline Berger, Franklin W. Huang, Andre Neil Forbes, Eric Minwei Liu, Deli Liu, Andrea Sboner, Pablo Tamayo, David S. Rickman, Mark A. Rubin and Ekta Khurana

MATCHER: manifold alignment reveals correspondence between single cell transcriptome and epigenome dynamics

Single cell experimental techniques reveal transcriptomic and epigenetic heterogeneity among cells, but how these are related is unclear. We present MATCHER, an approach for integrating multiple types of singl...

Authors: Joshua D. Welch, Alexander J. Hartemink and Jan F. Prins

Characterization of background noise in capture-based targeted sequencing data

Targeted deep sequencing is increasingly used to detect low-allelic fraction variants; it is therefore essential that errors that constitute baseline noise and impose a practical limit on detection are charact...

Authors: Gahee Park, Joo Kyung Park, Seung-Ho Shin, Hyo-Jeong Jeon, Nayoung K. D. Kim, Yeon Jeong Kim, Hyun-Tae Shin, Eunjin Lee, Kwang Hyuck Lee, Dae-Soon Son, Woong-Yang Park and Donghyun Park

Genome-wide mapping of transcriptional enhancer candidates using DNA and chromatin features in maize

While most cells in multicellular organisms carry the same genetic information, in each cell type only a subset of genes is being transcribed. Such differentiation in gene expression depends, for a large part,...

Authors: Rurika Oka, Johan Zicola, Blaise Weber, Sarah N. Anderson, Charlie Hodgman, Jonathan I. Gent, Jan-Jaap Wesselink, Nathan M. Springer, Huub C. J. Hoefsloot, Franziska Turck and Maike Stam

Understanding the genetics behind complex human disease with large-scale iPSC collections

Three recent studies analyzing large-scale collections of human induced pluripotent stem cell lines provide valuable insight into how genetic regulatory variation affects cellular and molecular traits.

Authors: Amanda E. Yamasaki, Athanasia D. Panopoulos and Juan Carlos Izpisua Belmonte