Articles

Insulator-based loops mediate the spreading of H3K27me3 over distant micro-domains repressing euchromatin genes

Chromosomes are subdivided spatially to delimit long-range interactions into topologically associating domains (TADs). TADs are often flanked by chromatin insulators and transcription units that may participat...

Authors: Alexandre Heurteau, Charlène Perrois, David Depierre, Olivier Fosseprez, Jonathan Humbert, Stéphane Schaak and Olivier Cuvier

Assessment of statistical methods from single cell, bulk RNA-seq, and metagenomics applied to microbiome data

The correct identification of differentially abundant microbial taxa between experimental conditions is a methodological and computational challenge. Recent work has produced methods to deal with the high spar...

Authors: Matteo Calgaro, Chiara Romualdi, Levi Waldron, Davide Risso and Nicola Vitulo

Knowledge-primed neural networks enable biologically interpretable deep learning on single-cell sequencing data

Deep learning has emerged as a versatile approach for predicting complex biological phenomena. However, its utility for biological discovery has so far been limited, given that generic deep neural networks pro...

Authors: Nikolaus Fortelny and Christoph Bock

GMM-Demux: sample demultiplexing, multiplet detection, experiment planning, and novel cell-type verification in single cell sequencing

Identifying and removing multiplets are essential to improving the scalability and the reliability of single cell RNA sequencing (scRNA-seq). Multiplets create artificial cell types in the dataset. We propose ...

Authors: Hongyi Xin, Qiuyu Lian, Yale Jiang, Jiadi Luo, Xinjun Wang, Carla Erb, Zhongli Xu, Xiaoyi Zhang, Elisa Heidrich-O’Hare, Qi Yan, Richard H. Duerr, Kong Chen and Wei Chen

Population variation in miRNAs and isomiRs and their impact on human immunity to infection

MicroRNAs (miRNAs) are key regulators of the immune system, yet their variation and contribution to intra- and inter-population differences in immune responses is poorly characterized.

Authors: Maxime Rotival, Katherine J. Siddle, Martin Silvert, Julien Pothlichet, Hélène Quach and Lluis Quintana-Murci

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

Glioma is the most common intrinsic brain tumor and also occurs in the spinal cord. Activating EGFR mutations are common in IDH1 wild-type gliomas. However, the cooperative partners of EGFR driving gliomagenesis ...

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…

RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins

RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant prioritization me...

Authors: Jing Zhang, Jason Liu, Donghoon Lee, Jo-Jo Feng, Lucas Lochovsky, Shaoke Lou, Michael Rutenberg-Schoenberg and Mark Gerstein

Splicing-accessible coding 3′UTRs control protein stability and interaction networks

3′-Untranslated regions (3′UTRs) play crucial roles in mRNA metabolism, such as by controlling mRNA stability, translation efficiency, and localization. Intriguingly, in some genes the 3′UTR is longer than the...

Authors: Marco Preussner, Qingsong Gao, Eliot Morrison, Olga Herdt, Florian Finkernagel, Michael Schumann, Eberhard Krause, Christian Freund, Wei Chen and Florian Heyd

Polymorphic mobile element insertions contribute to gene expression and alternative splicing in human tissues

Mobile elements are a major source of structural variants in the human genome, and some mobile elements can regulate gene expression and transcript splicing. However, the impact of polymorphic mobile element i...

Authors: Xiaolong Cao, Yeting Zhang, Lindsay M. Payer, Hannah Lords, Jared P. Steranka, Kathleen H. Burns and Jinchuan Xing

Bovine breed-specific augmented reference graphs facilitate accurate sequence read mapping and unbiased variant discovery

The current bovine genomic reference sequence was assembled from a Hereford cow. The resulting linear assembly lacks diversity because it does not contain allelic variation, a drawback of linear references tha...

Authors: Danang Crysnanto and Hubert Pausch

Bayesian model selection reveals biological origins of zero inflation in single-cell transcriptomics

Single-cell RNA sequencing is a powerful tool for characterizing cellular heterogeneity in gene expression. However, high variability and a large number of zero counts present challenges for analysis and inter...

Authors: Kwangbom Choi, Yang Chen, Daniel A. Skelly and Gary A. Churchill

DNA methylation repels binding of hypoxia-inducible transcription factors to maintain tumor immunotolerance

Hypoxia is pervasive in cancer and other diseases. Cells sense and adapt to hypoxia by activating hypoxia-inducible transcription factors (HIFs), but it is still an outstanding question why cell types differ i...

Authors: Flora D’Anna, Laurien Van Dyck, Jieyi Xiong, Hui Zhao, Rebecca V. Berrens, Junbin Qian, Pawel Bieniasz-Krzywiec, Vikas Chandra, Luc Schoonjans, Jason Matthews, Julie De Smedt, Liesbeth Minnoye, Ricardo Amorim, Sepideh Khorasanizadeh, Qian Yu, Liyun Zhao…

Computational inference of cancer-specific vulnerabilities in clinical samples

Systematic in vitro loss-of-function screens provide valuable resources that can facilitate the discovery of drugs targeting cancer vulnerabilities.

Authors: Kiwon Jang, Min Ji Park, Jae Soon Park, Haeun Hwangbo, Min Kyung Sung, Sinae Kim, Jaeyun Jung, Jong Won Lee, Sei-Hyun Ahn, Suhwan Chang and Jung Kyoon Choi

Producing polished prokaryotic pangenomes with the Panaroo pipeline

Population-level comparisons of prokaryotic genomes must take into account the substantial differences in gene content resulting from horizontal gene transfer, gene duplication and gene loss. However, the auto...

Authors: Gerry Tonkin-Hill, Neil MacAlasdair, Christopher Ruis, Aaron Weimann, Gal Horesh, John A. Lees, Rebecca A. Gladstone, Stephanie Lo, Christopher Beaudoin, R. Andres Floto, Simon D.W. Frost, Jukka Corander, Stephen D. Bentley and Julian Parkhill

Author Correction: Feature selection and dimension reduction for single-cell RNA-Seq based on a multinomial model

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

Authors: F. William Townes, Stephanie C. Hicks, Martin J. Aryee and Rafael A. Irizarry

Single-cell RNA-seq analysis reveals ploidy-dependent and cell-specific transcriptome changes in Arabidopsis female gametophytes

Polyploidy provides new genetic material that facilitates evolutionary novelty, species adaptation, and crop domestication. Polyploidy often leads to an increase in cell or organism size, which may affect tran...

Authors: Qingxin Song, Atsumi Ando, Ning Jiang, Yoko Ikeda and Z. Jeffrey Chen

Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients

Sputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heteroge...

Authors: Daniel Spakowicz, Shaoke Lou, Brian Barron, Jose L. Gomez, Tianxiao Li, Qing Liu, Nicole Grant, Xiting Yan, Rebecca Hoyd, George Weinstock, Geoffrey L. Chupp and Mark Gerstein

The origins and genomic diversity of American Civil War Era smallpox vaccine strains

Vaccination has transformed public health, most notably including the eradication of smallpox. Despite its profound historical importance, little is known of the origins and diversity of the viruses used in sm...

Authors: Ana T. Duggan, Jennifer Klunk, Ashleigh F. Porter, Anna N. Dhody, Robert Hicks, Geoffrey L. Smith, Margaret Humphreys, Andrea M. McCollum, Whitni B. Davidson, Kimberly Wilkins, Yu Li, Amanda Burke, Hanna Polasky, Lowell Flanders, Debi Poinar, Amogelang R. Raphenya…

Assembly of the threespine stickleback Y chromosome reveals convergent signatures of sex chromosome evolution

Heteromorphic sex chromosomes have evolved repeatedly across diverse species. Suppression of recombination between X and Y chromosomes leads to degeneration of the Y chromosome. The progression of degeneration...

Authors: Catherine L. Peichel, Shaugnessy R. McCann, Joseph A. Ross, Alice F. S. Naftaly, James R. Urton, Jennifer N. Cech, Jane Grimwood, Jeremy Schmutz, Richard M. Myers, David M. Kingsley and Michael A. White

Differential chromatin accessibility landscape reveals structural and functional features of the allopolyploid wheat chromosomes

Our understanding of how the complexity of the wheat genome influences the distribution of chromatin states along the homoeologous chromosomes is limited. Using a differential nuclease sensitivity assay, we in...

Authors: Katherine W. Jordan, Fei He, Monica Fernandez de Soto, Alina Akhunova and Eduard Akhunov

Single-cell lineage analysis reveals genetic and epigenetic interplay in glioblastoma drug resistance

Tumors can evolve and adapt to therapeutic pressure by acquiring genetic and epigenetic alterations that may be transient or stable. A precise understanding of how such events contribute to intratumoral hetero...

Authors: Christine E. Eyler, Hironori Matsunaga, Volker Hovestadt, Samantha J. Vantine, Peter van Galen and Bradley E. Bernstein

PWAS: proteome-wide association study—linking genes and phenotypes by functional variation in proteins

We introduce Proteome-Wide Association Study (PWAS), a new method for detecting gene-phenotype associations mediated by protein function alterations. PWAS aggregates the signal of all variants jointly affectin...

Authors: Nadav Brandes, Nathan Linial and Michal Linial

Cell type-specific genome scans of DNA methylation divergence indicate an important role for transposable elements

In population genomics, genetic diversity measures play an important role in genome scans for divergent sites. In population epigenomics, comparable tools are rare although the epigenome can vary at several le...

Authors: Önder Kartal, Marc W. Schmid and Ueli Grossniklaus

HBA-DEALS: accurate and simultaneous identification of differential expression and splicing using hierarchical Bayesian analysis

We present Hierarchical Bayesian Analysis of Differential Expression and ALternative Splicing (HBA-DEALS), which simultaneously characterizes differential expression and splicing in cohorts. HBA-DEALS attains ...

Authors: Guy Karlebach, Peter Hansen, Diogo FT Veiga, Robin Steinhaus, Daniel Danis, Sheng Li, Olga Anczukow and Peter N Robinson

DISC: a highly scalable and accurate inference of gene expression and structure for single-cell transcriptomes using semi-supervised deep learning

Dropouts distort gene expression and misclassify cell types in single-cell transcriptome. Although imputation may improve gene expression and downstream analysis to some degree, it also inevitably introduces f...

Authors: Yao He, Hao Yuan, Cheng Wu and Zhi Xie

Genome-wide studies reveal the essential and opposite roles of ARID1A in controlling human cardiogenesis and neurogenesis from pluripotent stem cells

Early human heart and brain development simultaneously occur during embryogenesis. Notably, in human newborns, congenital heart defects strongly associate with neurodevelopmental abnormalities, suggesting a co...

Authors: Juli Liu, Sheng Liu, Hongyu Gao, Lei Han, Xiaona Chu, Yi Sheng, Weinian Shou, Yue Wang, Yunlong Liu, Jun Wan and Lei Yang

Genes adapt to outsmart gene-targeting strategies in mutant mouse strains by skipping exons to reinitiate transcription and translation

Gene disruption in mouse embryonic stem cells or zygotes is a conventional genetics approach to identify gene function in vivo. However, because different gene disruption strategies use different mechanisms to...

Authors: Vishnu Hosur, Benjamin E. Low, Daniel Li, Grace A. Stafford, Vivek Kohar, Leonard D. Shultz and Michael V. Wiles

Sierra: discovery of differential transcript usage from polyA-captured single-cell RNA-seq data

High-throughput single-cell RNA-seq (scRNA-seq) is a powerful tool for studying gene expression in single cells. Most current scRNA-seq bioinformatics tools focus on analysing overall expression levels, largel...

Authors: Ralph Patrick, David T. Humphreys, Vaibhao Janbandhu, Alicia Oshlack, Joshua W.K. Ho, Richard P. Harvey and Kitty K. Lo

Dysregulation of cancer genes by recurrent intergenic fusions

Gene fusions have been studied extensively, as frequent drivers of tumorigenesis as well as potential therapeutic targets. In many well-known cases, breakpoints occur at two intragenic positions, leading to in...

Authors: Jae Won Yun, Lixing Yang, Hye-Young Park, Chang-Woo Lee, Hongui Cha, Hyun-Tae Shin, Ka-Won Noh, Yoon-La Choi, Woong-Yang Park and Peter J. Park

The regulatory landscape of early maize inflorescence development

The functional genome of agronomically important plant species remains largely unexplored, yet presents a virtually untapped resource for targeted crop improvement. Functional elements of regulatory DNA reveal...

Authors: Rajiv K. Parvathaneni, Edoardo Bertolini, Md Shamimuzzaman, Daniel L. Vera, Pei-Yau Lung, Brian R. Rice, Jinfeng Zhang, Patrick J. Brown, Alexander E. Lipka, Hank W. Bass and Andrea L. Eveland

Exploring neighborhoods in large metagenome assembly graphs using spacegraphcats reveals hidden sequence diversity

Genomes computationally inferred from large metagenomic data sets are often incomplete and may be missing functionally important content and strain variation. We introduce an information retrieval system for l...

Authors: C. Titus Brown, Dominik Moritz, Michael P. O’Brien, Felix Reidl, Taylor Reiter and Blair D. Sullivan

Mapping regulatory variants controlling gene expression in drought response and tolerance in maize

Gene expression is a key determinant of cellular response. Natural variation in gene expression bridges genetic variation to phenotypic alteration. Identification of the regulatory variants controlling the gen...

Authors: Shengxue Liu, Cuiping Li, Hongwei Wang, Shuhui Wang, Shiping Yang, Xiaohu Liu, Jianbing Yan, Bailin Li, Mary Beatty, Gina Zastrow-Hayes, Shuhui Song and Feng Qin

Decoding the evolutionary response to prostate cancer therapy by plasma genome sequencing

Investigating genome evolution in response to therapy is difficult in human tissue samples. To address this challenge, we develop an unbiased whole-genome plasma DNA sequencing approach that concurrently measu...

Authors: Naveen Ramesh, Emi Sei, Pei Ching Tsai, Shanshan Bai, Yuehui Zhao, Patricia Troncoso, Paul G. Corn, Christopher Logothetis, Amado J. Zurita and Nicholas E. Navin

Single-cell ATAC-seq signal extraction and enhancement with SCATE

Single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) is the state-of-the-art technology for analyzing genome-wide regulatory landscapes in single cells. Single-cell ATAC-seq data are ...

Authors: Zhicheng Ji, Weiqiang Zhou, Wenpin Hou and Hongkai Ji

Quantile normalization of single-cell RNA-seq read counts without unique molecular identifiers

Single-cell RNA-seq (scRNA-seq) profiles gene expression of individual cells. Unique molecular identifiers (UMIs) remove duplicates in read counts resulting from polymerase chain reaction, a major source of no...

Authors: F. William Townes and Rafael A. Irizarry

Genomic analysis of the domestication and post-Spanish conquest evolution of the llama and alpaca

Despite their regional economic importance and being increasingly reared globally, the origins and evolution of the llama and alpaca remain poorly understood. Here we report reference genomes for the llama, an...

Authors: Ruiwen Fan, Zhongru Gu, Xuanmin Guang, Juan Carlos Marín, Valeria Varas, Benito A. González, Jane C. Wheeler, Yafei Hu, Erli Li, Xiaohui Sun, Xukui Yang, Chi Zhang, Wenjun Gao, Junping He, Kasper Munch, Russel Corbett-Detig…

Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II, and Pol III

The relationship between transcription and the 3D chromatin structure is debated. Multiple studies have shown that transcription affects global Cohesin binding and 3D genome structures. However, several other ...

Authors: Yongpeng Jiang, Jie Huang, Kehuan Lun, Boyuan Li, Haonan Zheng, Yuanjun Li, Rong Zhou, Wenjia Duan, Chenlu Wang, Yuanqing Feng, Hong Yao, Cheng Li and Xiong Ji

Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation

Haematopoietic stem cells (HSCs) first arise during development in the aorta-gonad-mesonephros (AGM) region of the embryo from a population of haemogenic endothelial cells which undergo endothelial-to-haematop...

Authors: Giovanni Canu, Emmanouil Athanasiadis, Rodrigo A. Grandy, Jose Garcia-Bernardo, Paulina M. Strzelecka, Ludovic Vallier, Daniel Ortmann and Ana Cvejic

Identification of cell type-specific methylation signals in bulk whole genome bisulfite sequencing data

The traditional approach to studying the epigenetic mechanism CpG methylation in tissue samples is to identify regions of concordant differential methylation spanning multiple CpG sites (differentially methyla...

Authors: C. Anthony Scott, Jack D. Duryea, Harry MacKay, Maria S. Baker, Eleonora Laritsky, Chathura J. Gunasekara, Cristian Coarfa and Robert A. Waterland

Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs

Mapping of allele-specific DNA methylation (ASM) can be a post-GWAS strategy for localizing regulatory sequence polymorphisms (rSNPs). The advantages of this approach, and the mechanisms underlying ASM in norm...

Authors: Catherine Do, Emmanuel L. P. Dumont, Martha Salas, Angelica Castano, Huthayfa Mujahed, Leonel Maldonado, Arunjot Singh, Sonia C. DaSilva-Arnold, Govind Bhagat, Soren Lehman, Angela M. Christiano, Subha Madhavan, Peter L. Nagy, Peter H. R. Green, Rena Feinman, Cornelia Trimble…

Sustainable agriculture in the era of omics: knowledge-driven crop breeding

Authors: Qing Li and Jianbing Yan

Single-cell transcriptome and antigen-immunoglobin analysis reveals the diversity of B cells in non-small cell lung cancer

Malignant transformation and progression of cancer are driven by the co-evolution of cancer cells and their dysregulated tumor microenvironment (TME). Recent studies on immunotherapy demonstrate the efficacy i...

Authors: Jian Chen, Yun Tan, Fenghuan Sun, Likun Hou, Chi Zhang, Tao Ge, Huansha Yu, Chunxiao Wu, Yuming Zhu, Liang Duan, Liang Wu, Nan Song, Liping Zhang, Wei Zhang, Di Wang, Chang Chen…

Enhanced Integrated Gradients: improving interpretability of deep learning models using splicing codes as a case study

Despite the success and fast adaptation of deep learning models in biomedical domains, their lack of interpretability remains an issue. Here, we introduce Enhanced Integrated Gradients (EIG), a method to ident...

Authors: Anupama Jha, Joseph K. Aicher, Matthew R. Gazzara, Deependra Singh and Yoseph Barash

instaGRAAL: chromosome-level quality scaffolding of genomes using a proximity ligation-based scaffolder

Hi-C exploits contact frequencies between pairs of loci to bridge and order contigs during genome assembly, resulting in chromosome-level assemblies. Because few robust programs are available for this type of ...

Authors: Lyam Baudry, Nadège Guiglielmoni, Hervé Marie-Nelly, Alexandre Cormier, Martial Marbouty, Komlan Avia, Yann Loe Mie, Olivier Godfroy, Lieven Sterck, J. Mark Cock, Christophe Zimmer, Susana M. Coelho and Romain Koszul

The two languages of science

Authors: Itai Yanai and Martin Lercher

KAML: improving genomic prediction accuracy of complex traits using machine learning determined parameters

Advances in high-throughput sequencing technologies have reduced the cost of genotyping dramatically and led to genomic prediction being widely used in animal and plant breeding, and increasingly in human gene...

Authors: Lilin Yin, Haohao Zhang, Xiang Zhou, Xiaohui Yuan, Shuhong Zhao, Xinyun Li and Xiaolei Liu

Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics

At least 50% of patients with suspected Mendelian disorders remain undiagnosed after whole-exome sequencing (WES), and the extent to which non-coding variants that are not captured by WES contribute to this fr...

Authors: Sateesh Maddirevula, Hiroyuki Kuwahara, Nour Ewida, Hanan E. Shamseldin, Nisha Patel, Fatema Alzahrani, Tarfa AlSheddi, Eman AlObeid, Mona Alenazi, Hessa S. Alsaif, Maha Alqahtani, Maha AlAli, Hatoon Al Ali, Rana Helaby, Niema Ibrahim, Firdous Abdulwahab…

Removal of H2Aub1 by ubiquitin-specific proteases 12 and 13 is required for stable Polycomb-mediated gene repression in Arabidopsis

Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and ...

Authors: Lejon E. M. Kralemann, Shujing Liu, Minerva S. Trejo-Arellano, Rafael Muñoz-Viana, Claudia Köhler and Lars Hennig

Repeat-induced point mutation in Neurospora crassa causes the highest known mutation rate and mutational burden of any cellular life

Repeat-induced point (RIP) mutation in Neurospora crassa degrades transposable elements by targeting repeats with C→T mutations. Whether RIP affects core genomic sequence in important ways is unknown.

Authors: Long Wang, Yingying Sun, Xiaoguang Sun, Luyao Yu, Lan Xue, Zhen He, Ju Huang, Dacheng Tian, Laurence D. Hurst and Sihai Yang

SWISS: multiplexed orthogonal genome editing in plants with a Cas9 nickase and engineered CRISPR RNA scaffolds

We describe here a CRISPR simultaneous and wide-editing induced by a single system (SWISS), in which RNA aptamers engineered in crRNA scaffold recruit their cognate binding proteins fused with cytidine deamina...

Authors: Chao Li, Yuan Zong, Shuai Jin, Haocheng Zhu, Dexing Lin, Shengnan Li, Jin-Long Qiu, Yanpeng Wang and Caixia Gao