Articles

Machine learning and complex biological data

Machine learning has demonstrated potential in analyzing large, complex biological data. In practice, however, biological information is required in addition to machine learning for successful application.

Authors: Chunming Xu and Scott A. Jackson

DegNorm: normalization of generalized transcript degradation improves accuracy in RNA-seq analysis

RNA degradation affects RNA-seq quality when profiling transcriptional activities in cells. Here, we show that transcript degradation is both gene- and sample-specific and is a common and significant factor th...

Authors: Bin Xiong, Yiben Yang, Frank R. Fineis and Ji-Ping Wang

Analysis of the recombination landscape of hexaploid bread wheat reveals genes controlling recombination and gene conversion frequency

Sequence exchange between homologous chromosomes through crossing over and gene conversion is highly conserved among eukaryotes, contributing to genome stability and genetic diversity. A lack of recombination ...

Authors: Laura-Jayne Gardiner, Luzie U. Wingen, Paul Bailey, Ryan Joynson, Thomas Brabbs, Jonathan Wright, James D. Higgins, Neil Hall, Simon Griffiths, Bernardo J. Clavijo and Anthony Hall

Comparative analysis of sequencing technologies for single-cell transcriptomics

Single-cell RNA-seq technologies require library preparation prior to sequencing. Here, we present the first report to compare the cheaper BGISEQ-500 platform to the Illumina HiSeq platform for scRNA-seq. We g...

Authors: Kedar Nath Natarajan, Zhichao Miao, Miaomiao Jiang, Xiaoyun Huang, Hongpo Zhou, Jiarui Xie, Chunqing Wang, Shishang Qin, Zhikun Zhao, Liang Wu, Naibo Yang, Bo Li, Yong Hou, Shiping Liu and Sarah A. Teichmann

Correction to: Comprehensive benchmarking and ensemble approaches for metagenomic classifiers

Following publication of the original article [1], the authors would like to highlight the following two corrections.

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…

Molecular evolutionary trends and feeding ecology diversification in the Hemiptera, anchored by the milkweed bug genome

The Hemiptera (aphids, cicadas, and true bugs) are a key insect order, with high diversity for feeding ecology and excellent experimental tractability for molecular genetics. Building upon recent sequencing of...

Authors: Kristen A. Panfilio, Iris M. Vargas Jentzsch, Joshua B. Benoit, Deniz Erezyilmaz, Yuichiro Suzuki, Stefano Colella, Hugh M. Robertson, Monica F. Poelchau, Robert M. Waterhouse, Panagiotis Ioannidis, Matthew T. Weirauch, Daniel S. T. Hughes, Shwetha C. Murali, John H. Werren, Chris G. C. Jacobs, Elizabeth J. Duncan…

Conbase: a software for unsupervised discovery of clonal somatic mutations in single cells through read phasing

Accurate variant calling and genotyping represent major limiting factors for downstream applications of single-cell genomics. Here, we report Conbase for the identification of somatic mutations in single-cell ...

Authors: Joanna Hård, Ezeddin Al Hakim, Marie Kindblom, Åsa K. Björklund, Bengt Sennblad, Ilke Demirci, Marta Paterlini, Pedro Reu, Erik Borgström, Patrik L. Ståhl, Jakob Michaelsson, Jeff E. Mold and Jonas Frisén

Topconfects: a package for confident effect sizes in differential expression analysis provides a more biologically useful ranked gene list

Differential gene expression analysis may discover a set of genes too large to easily investigate, so a means of ranking genes by biological interest level is desired. p values are frequently abused for this purp...

Authors: Paul F. Harrison, Andrew D. Pattison, David R. Powell and Traude H. Beilharz

All models are wrong, but some organoids may be useful

Authors: Benjamin E. Mead and Jeffrey M. Karp

Alevin efficiently estimates accurate gene abundances from dscRNA-seq data

We introduce alevin, a fast end-to-end pipeline to process droplet-based single-cell RNA sequencing data, performing cell barcode detection, read mapping, unique molecular identifier (UMI) deduplication, gene ...

Authors: Avi Srivastava, Laraib Malik, Tom Smith, Ian Sudbery and Rob Patro

EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data

Droplet-based single-cell RNA sequencing protocols have dramatically increased the throughput of single-cell transcriptomics studies. A key computational challenge when processing these data is to distinguish ...

Authors: Aaron T. L. Lun, Samantha Riesenfeld, Tallulah Andrews, The Phuong Dao, Tomas Gomes and John C. Marioni

Interactive roles of chromatin regulation and circadian clock function in plants

Circadian rhythms in transcription ultimately result in oscillations of key biological processes. Understanding how transcriptional rhythms are generated in plants provides an opportunity for fine-tuning growt...

Authors: Z. Jeffrey Chen and Paloma Mas

Melissa: Bayesian clustering and imputation of single-cell methylomes

Measurements of single-cell methylation are revolutionizing our understanding of epigenetic control of gene expression, yet the intrinsic data sparsity limits the scope for quantitative analysis of such data. ...

Authors: Chantriolnt-Andreas Kapourani and Guido Sanguinetti

TAD fusion score: discovery and ranking the contribution of deletions to genome structure

Deletions that fuse two adjacent topologically associating domains (TADs) can cause severe developmental disorders. We provide a formal method to quantify deletions based on their potential disruption of the t...

Authors: Linh Huynh and Fereydoun Hormozdiari

PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells

Single-cell RNA-seq quantifies biological heterogeneity across both discrete cell types and continuous cell transitions. Partition-based graph abstraction (PAGA) provides an interpretable graph-like map of the...

Authors: F. Alexander Wolf, Fiona K. Hamey, Mireya Plass, Jordi Solana, Joakim S. Dahlin, Berthold Göttgens, Nikolaus Rajewsky, Lukas Simon and Fabian J. Theis

Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads

Tandemly repeated DNA is highly mutable and causes at least 31 diseases, but it is hard to detect pathogenic repeat expansions genome-wide. Here, we report robust detection of human repeat expansions from care...

Authors: Satomi Mitsuhashi, Martin C. Frith, Takeshi Mizuguchi, Satoko Miyatake, Tomoko Toyota, Hiroaki Adachi, Yoko Oma, Yoshihiro Kino, Hiroaki Mitsuhashi and Naomichi Matsumoto

Measuring the reproducibility and quality of Hi-C data

Hi-C is currently the most widely used assay to investigate the 3D organization of the genome and to study its role in gene regulation, DNA replication, and disease. However, Hi-C experiments are costly to per...

Authors: Galip Gürkan Yardımcı, Hakan Ozadam, Michael E. G. Sauria, Oana Ursu, Koon-Kiu Yan, Tao Yang, Abhijit Chakraborty, Arya Kaul, Bryan R. Lajoie, Fan Song, Ye Zhan, Ferhat Ay, Mark Gerstein, Anshul Kundaje, Qunhua Li, James Taylor…

Exploring human host–microbiome interactions in health and disease—how to not get lost in translation

A meeting report on the 7th Wellcome Trust conference on Exploring Human Host–Microbiome Interactions in Health and Disease, held at Hinxton, UK, 5–7 December 2018.

Authors: Sarah Lebeer and Irina Spacova

RnBeads 2.0: comprehensive analysis of DNA methylation data

DNA methylation is a widely investigated epigenetic mark with important roles in development and disease. High-throughput assays enable genome-scale DNA methylation analysis in large numbers of samples. Here, ...

Authors: Fabian Müller, Michael Scherer, Yassen Assenov, Pavlo Lutsik, Jörn Walter, Thomas Lengauer and Christoph Bock

Analysis of error profiles in deep next-generation sequencing data

Sequencing errors are key confounding factors for detecting low-frequency genetic variants that are important for cancer molecular diagnosis, treatment, and surveillance using deep next-generation sequencing (...

Authors: Xiaotu Ma, Ying Shao, Liqing Tian, Diane A. Flasch, Heather L. Mulder, Michael N. Edmonson, Yu Liu, Xiang Chen, Scott Newman, Joy Nakitandwe, Yongjin Li, Benshang Li, Shuhong Shen, Zhaoming Wang, Sheila Shurtleff, Leslie L. Robison…

clonealign: statistical integration of independent single-cell RNA and DNA sequencing data from human cancers

Measuring gene expression of tumor clones at single-cell resolution links functional consequences to somatic alterations. Without scalable methods to simultaneously assay DNA and RNA from the same single cell,...

Authors: Kieran R. Campbell, Adi Steif, Emma Laks, Hans Zahn, Daniel Lai, Andrew McPherson, Hossein Farahani, Farhia Kabeer, Ciara O’Flanagan, Justina Biele, Jazmine Brimhall, Beixi Wang, Pascale Walters, IMAXT Consortium, Alexandre Bouchard-Côté, Samuel Aparicio…

Correction to: DNA copy number evolution in Drosophila cell lines

Following publication of the original article [1], the authors reported the following errors.

Authors: Hangnoh Lee, C. Joel McManus, Dong-Yeon Cho, Matthew Eaton, Fioranna Renda, Maria Patrizia Somma, Lucy Cherbas, Gemma May, Sara Powell, Dayu Zhang, Lijun Zhan, Alissa Resch, Justen Andrews, Susan E. Celniker, Peter Cherbas, Teresa M. Przytycka…

I-Boost: an integrative boosting approach for predicting survival time with multiple genomics platforms

We propose a statistical boosting method, termed I-Boost, to integrate multiple types of high-dimensional genomics data with clinical data for predicting survival time. I-Boost provides substantially higher pr...

Authors: Kin Yau Wong, Cheng Fan, Maki Tanioka, Joel S. Parker, Andrew B. Nobel, Donglin Zeng, Dan-Yu Lin and Charles M. Perou

Assessing taxonomic metagenome profilers with OPAL

The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment too...

Authors: Fernando Meyer, Andreas Bremges, Peter Belmann, Stefan Janssen, Alice C. McHardy and David Koslicki

Genome-scale network model of metabolism and histone acetylation reveals metabolic dependencies of histone deacetylase inhibitors

Histone acetylation plays a central role in gene regulation and is sensitive to the levels of metabolic intermediates. However, predicting the impact of metabolic alterations on acetylation in pathological con...

Authors: Fangzhou Shen, Luigi Boccuto, Rini Pauly, Sujata Srikanth and Sriram Chandrasekaran

MMSplice: modular modeling improves the predictions of genetic variant effects on splicing

Predicting the effects of genetic variants on splicing is highly relevant for human genetics. We describe the framework MMSplice (modular modeling of splicing) with which we built the winning model of the CAGI...

Authors: Jun Cheng, Thi Yen Duong Nguyen, Kamil J. Cygan, Muhammed Hasan Çelik, William G. Fairbrother, žiga Avsec and Julien Gagneur

Improving the usability and archival stability of bioinformatics software

Implementation of bioinformatics software involves numerous unique challenges; a rigorous standardized approach is needed to examine software tools prior to their publication.

Authors: Serghei Mangul, Lana S. Martin, Eleazar Eskin and Ran Blekhman

bin3C: exploiting Hi-C sequencing data to accurately resolve metagenome-assembled genomes

Most microbes cannot be easily cultured, and metagenomics provides a means to study them. Current techniques aim to resolve individual genomes from metagenomes, so-called metagenome-assembled genomes (MAGs). L...

Authors: Matthew Z. DeMaere and Aaron E. Darling

Identification of transcription factor binding sites using ATAC-seq

Transposase-Accessible Chromatin followed by sequencing (ATAC-seq) is a simple protocol for detection of open chromatin. Computational footprinting, the search for regions with depletion of cleavage events due...

Authors: Zhijian Li, Marcel H. Schulz, Thomas Look, Matthias Begemann, Martin Zenke and Ivan G. Costa

Correction to: Rapid turnover of life-cycle-related genes in the brown algae

Following publication of the original article [1], it was noticed that the author names were published with initials instead of full names. The article [1] has been updated.

Authors: Agnieszka P. Lipinska, Martha L. Serrano-Serrano, Alexandre Cormier, Akira F. Peters, Kazuhiro Kogame, J. Mark Cock and Susana M. Coelho

Correction to: Comparison of whole-genome bisulfite sequencing library preparation strategies identifies sources of biases affecting DNA methylation data

Following publication of the original article [1], it was reported that the incorrect “Additional file 3” was published. The correct additional file is given below.

Authors: Nelly Olova, Felix Krueger, Simon Andrews, David Oxley, Rebecca V. Berrens, Miguel R. Branco and Wolf Reik

Reproducible inference of transcription factor footprints in ATAC-seq and DNase-seq datasets using protocol-specific bias modeling

DNase-seq and ATAC-seq are broadly used methods to assay open chromatin regions genome-wide. The single nucleotide resolution of DNase-seq has been further exploited to infer transcription factor binding sites...

Authors: Aslıhan Karabacak Calviello, Antje Hirsekorn, Ricardo Wurmus, Dilmurat Yusuf and Uwe Ohler

Epigenetic signatures associated with imprinted paternally expressed genes in the Arabidopsis endosperm

Imprinted genes are epigenetically modified during gametogenesis and maintain the established epigenetic signatures after fertilization, causing parental-specific gene expression.

Authors: Jordi Moreno-Romero, Gerardo Del Toro-De León, Vikash Kumar Yadav, Juan Santos-González and Claudia Köhler

dStruct: identifying differentially reactive regions from RNA structurome profiling data

RNA biology is revolutionized by recent developments of diverse high-throughput technologies for transcriptome-wide profiling of molecular RNA structures. RNA structurome profiling data can be used to identify...

Authors: Krishna Choudhary, Yu-Hsuan Lai, Elizabeth J. Tran and Sharon Aviran

Fragile DNA contributes to repeated evolution

Sequence features that affect DNA fragility might facilitate fast, repeated evolution by elevating mutation rates at genomic hotspots.

Authors: Claudius F. Kratochwil and Axel Meyer

Gene duplication and evolution in recurring polyploidization–diploidization cycles in plants

The sharp increase of plant genome and transcriptome data provide valuable resources to investigate evolutionary consequences of gene duplication in a range of taxa, and unravel common principles underlying du...

Authors: Xin Qiao, Qionghou Li, Hao Yin, Kaijie Qi, Leiting Li, Runze Wang, Shaoling Zhang and Andrew H. Paterson

Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Protein recoding by RNA editing is required for normal health and evolutionary adaptation. However, de novo induction of RNA editing in response to environmental factors is an uncommon phenomenon. While APOBEC...

Authors: Shraddha Sharma, Jianmin Wang, Emad Alqassim, Scott Portwood, Eduardo Cortes Gomez, Orla Maguire, Per H. Basse, Eunice S. Wang, Brahm H. Segal and Bora E. Baysal

Genomic analyses of an extensive collection of wild and cultivated accessions provide new insights into peach breeding history

Human selection has a long history of transforming crop genomes. Peach (Prunus persica) has undergone more than 5000 years of domestication that led to remarkable changes in a series of agronomically important tr...

Authors: Yong Li, Ke Cao, Gengrui Zhu, Weichao Fang, Changwen Chen, Xinwei Wang, Pei Zhao, Jian Guo, Tiyu Ding, Liping Guan, Qian Zhang, Wenwu Guo, Zhangjun Fei and Lirong Wang

Rapid turnover of life-cycle-related genes in the brown algae

Sexual life cycles in eukaryotes involve a cyclic alternation between haploid and diploid phases. While most animals possess a diploid life cycle, many plants and algae alternate between multicellular haploid ...

Authors: Agnieszka P. Lipinska, Martha L. Serrano-Serrano, Alexandre Cormier, Akira F. Peters, Kazuhiro Kogame, J. Mark Cock and Susana M. Coelho

Skmer: assembly-free and alignment-free sample identification using genome skims

The ability to inexpensively describe taxonomic diversity is critical in this era of rapid climate and biodiversity changes. The recent genome-skimming approach extends current barcoding practices beyond short...

Authors: Shahab Sarmashghi, Kristine Bohmann, M. Thomas P. Gilbert, Vineet Bafna and Siavash Mirarab

Dynamic inosinome profiles reveal novel patient stratification and gender-specific differences in glioblastoma

Adenosine-to-inosine (A-to-I) RNA editing is an essential post-transcriptional mechanism mediated by ADAR enzymes that have been recently associated with cancer.

Authors: Domenico Alessandro Silvestris, Ernesto Picardi, Valeriana Cesarini, Bruno Fosso, Nicolò Mangraviti, Luca Massimi, Maurizio Martini, Graziano Pesole, Franco Locatelli and Angela Gallo

NCBoost classifies pathogenic non-coding variants in Mendelian diseases through supervised learning on purifying selection signals in humans

State-of-the-art methods assessing pathogenic non-coding variants have mostly been characterized on common disease-associated polymorphisms, yet with modest accuracy and strong positional biases. In this study...

Authors: Barthélémy Caron, Yufei Luo and Antonio Rausell

CellFishing.jl: an ultrafast and scalable cell search method for single-cell RNA sequencing

Recent technical improvements in single-cell RNA sequencing (scRNA-seq) have enabled massively parallel profiling of transcriptomes, thereby promoting large-scale studies encompassing a wide range of cell type...

Authors: Kenta Sato, Koki Tsuyuzaki, Kentaro Shimizu and Itoshi Nikaido

Combined single-cell profiling of expression and DNA methylation reveals splicing regulation and heterogeneity

Alternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied ...

Authors: Stephanie M. Linker, Lara Urban, Stephen J. Clark, Mariya Chhatriwala, Shradha Amatya, Davis J. McCarthy, Ingo Ebersberger, Ludovic Vallier, Wolf Reik, Oliver Stegle and Marc Jan Bonder

Paleogenomics: reconstruction of plant evolutionary trajectories from modern and ancient DNA

How contemporary plant genomes originated and evolved is a fascinating question. One approach uses reference genomes from extant species to reconstruct the sequence and structure of their common ancestors over...

Authors: Caroline Pont, Stefanie Wagner, Antoine Kremer, Ludovic Orlando, Christophe Plomion and Jerome Salse

Modeling double strand break susceptibility to interrogate structural variation in cancer

Structural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. Many SVs are thought to emerge from errors in the...

Authors: Tracy J. Ballinger, Britta A. M. Bouwman, Reza Mirzazadeh, Silvano Garnerone, Nicola Crosetto and Colin A. Semple

Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects

CRISPR-Cas9 genome editing is widely used to study gene function, from basic biology to biomedical research. Structural rearrangements are a ubiquitous feature of cancer cells and their impact on the functiona...

Authors: Emanuel Gonçalves, Fiona M. Behan, Sandra Louzada, Damien Arnol, Euan A. Stronach, Fengtang Yang, Kosuke Yusa, Oliver Stegle, Francesco Iorio and Mathew J. Garnett

Enhanced mammalian genome editing by new Cas12a orthologs with optimized crRNA scaffolds

CRISPR-Cas12a/Cpf1, a single RNA-guided endonuclease system, provides a promising tool for genome engineering. However, only three Cas12a orthologs have been employed for mammalian genome editing, and the edit...

Authors: Fei Teng, Jing Li, Tongtong Cui, Kai Xu, Lu Guo, Qingqin Gao, Guihai Feng, Chuanyuan Chen, Dali Han, Qi Zhou and Wei Li

A comparative evaluation of hybrid error correction methods for error-prone long reads

Third-generation sequencing technologies have advanced the progress of the biological research by generating reads that are substantially longer than second-generation sequencing technologies. However, their n...

Authors: Shuhua Fu, Anqi Wang and Kin Fai Au

Evolutionarily significant A-to-I RNA editing events originated through G-to-A mutations in primates

Recent studies have revealed thousands of A-to-I RNA editing events in primates, but the origination and general functions of these events are not well addressed.

Authors: Ni A. An, Wanqiu Ding, Xin-Zhuang Yang, Jiguang Peng, Bin Z. He, Qing Sunny Shen, Fujian Lu, Aibin He, Yong E. Zhang, Bertrand Chin-Ming Tan, Jia-Yu Chen and Chuan-Yun Li