Articles

Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries

Topologically associating domains (TADs) are genomic regions of self-interaction. Additionally, it is known that TAD boundaries are enriched in CTCF binding sites. In turn, CTCF sites are known to be asymmetri...

Authors: Luca Nanni, Stefano Ceri and Colin Logie

The asynchronous establishment of chromatin 3D architecture between in vitro fertilized and uniparental preimplantation pig embryos

Pigs are important animals for agricultural and biomedical research, and improvement is needed for use of the assisted reproductive technologies. Determining underlying mechanisms of epigenetic reprogramming i...

Authors: Feifei Li, Danyang Wang, Ruigao Song, Chunwei Cao, Zhihua Zhang, Yu Wang, Xiaoli Li, Jiaojiao Huang, Qiang Liu, Naipeng Hou, Bingxiang Xu, Xiao Li, Xiaomeng Gao, Yan Jia, Jianguo Zhao and Yanfang Wang

An evolutionary driver of interspersed segmental duplications in primates

The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brai...

Authors: Stuart Cantsilieris, Susan M. Sunkin, Matthew E. Johnson, Fabio Anaclerio, John Huddleston, Carl Baker, Max L. Dougherty, Jason G. Underwood, Arvis Sulovari, PingHsun Hsieh, Yafei Mao, Claudia Rita Catacchio, Maika Malig, AnneMarie E. Welch, Melanie Sorensen, Katherine M. Munson…

A seventeenth-century Mycobacterium tuberculosis genome supports a Neolithic emergence of the Mycobacterium tuberculosis complex

Although tuberculosis accounts for the highest mortality from a bacterial infection on a global scale, questions persist regarding its origin. One hypothesis based on modern Mycobacterium tuberculosis complex (MT...

Authors: Susanna Sabin, Alexander Herbig, Åshild J. Vågene, Torbjörn Ahlström, Gracijela Bozovic, Caroline Arcini, Denise Kühnert and Kirsten I. Bos

The chromosome-level wintersweet (Chimonanthus praecox) genome provides insights into floral scent biosynthesis and flowering in winter

Wintersweet (Chimonanthus praecox), an important ornamental plant, has evolved unique fragrant aroma and winter-flowering properties, which are critical for its successful sexual reproduction. However, the molecu...

Authors: Junzhong Shang, Jingpu Tian, Huihui Cheng, Qiaomu Yan, Lai Li, Abbas Jamal, Zhongping Xu, Lin Xiang, Christopher A. Saski, Shuangxia Jin, Kaige Zhao, Xiuqun Liu and Longqing Chen

ContamLD: estimation of ancient nuclear DNA contamination using breakdown of linkage disequilibrium

We report a method called ContamLD for estimating autosomal ancient DNA (aDNA) contamination by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the introduction of contaminan...

Authors: Nathan Nakatsuka, Éadaoin Harney, Swapan Mallick, Matthew Mah, Nick Patterson and David Reich

Integrative analyses of single-cell transcriptome and regulome using MAESTRO

We present Model-based AnalysEs of Transcriptome and RegulOme (MAESTRO), a comprehensive open-source computational workflow (http://​github.​com/​liulab-dfci/​MAESTRO)...

Authors: Chenfei Wang, Dongqing Sun, Xin Huang, Changxin Wan, Ziyi Li, Ya Han, Qian Qin, Jingyu Fan, Xintao Qiu, Yingtian Xie, Clifford A. Meyer, Myles Brown, Ming Tang, Henry Long, Tao Liu and X. Shirley Liu

Demystifying “drop-outs” in single-cell UMI data

Many existing pipelines for scRNA-seq data apply pre-processing steps such as normalization or imputation to account for excessive zeros or “drop-outs." Here, we extensively analyze diverse UMI data sets to sh...

Authors: Tae Hyun Kim, Xiang Zhou and Mengjie Chen

The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation

RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in RBP expression and function are often observed in cancer and influence critical pathways implicated in tumor initiat...

Authors: Adam Kosti, Patricia Rosa de Araujo, Wei-Qing Li, Gabriela D. A. Guardia, Jennifer Chiou, Caihong Yi, Debashish Ray, Fabiana Meliso, Yi-Ming Li, Talia Delambre, Mei Qiao, Suzanne S. Burns, Franziska K. Lorbeer, Fanny Georgi, Markus Flosbach, Sarah Klinnert…

Contiguous and stochastic CHH methylation patterns of plant DRM2 and CMT2 revealed by single-read methylome analysis

Cytosine methylome data is commonly generated through next-generation sequencing, with analyses averaging methylation states of individual reads. We propose an alternative method of analysing single-read methy...

Authors: Keith D. Harris and Assaf Zemach

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

Elucidating the role of the gastrointestinal microbiota in racial and ethnic health disparities

Authors: Doratha A. Byrd, Tiffany L. Carson, Faustine Williams and Emily Vogtmann

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

Long-read-based human genomic structural variation detection with cuteSV

Long-read sequencing is promising for the comprehensive discovery of structural variations (SVs). However, it is still non-trivial to achieve high yields and performance simultaneously due to the complex SV si...

Authors: Tao Jiang, Yongzhuang Liu, Yue Jiang, Junyi Li, Yan Gao, Zhe Cui, Yadong Liu, Bo Liu and Yadong Wang

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