Articles

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

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

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…

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

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

3D genome architecture coordinates trans and cis regulation of differentially expressed ear and tassel genes in maize

Maize ears and tassels are two separate types of inflorescence which are initiated by similar developmental processes but gradually develop distinct architectures. However, coordinated trans and cis regulation of...

Authors: Yonghao Sun, Liang Dong, Ying Zhang, Da Lin, Weize Xu, Changxiong Ke, Linqian Han, Lulu Deng, Guoliang Li, David Jackson, Xingwang Li and Fang Yang

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

Dynamic rewiring of the human interactome by interferon signaling

The type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes. Comprehensive catalogs of IFN-stimulate...

Authors: Craig H. Kerr, Michael A. Skinnider, Daniel D. T. Andrews, Angel M. Madero, Queenie W. T. Chan, R. Greg Stacey, Nikolay Stoynov, Eric Jan and Leonard J. Foster

SURF: integrative analysis of a compendium of RNA-seq and CLIP-seq datasets highlights complex governing of alternative transcriptional regulation by RNA-binding proteins

Advances in high-throughput profiling of RNA-binding proteins (RBPs) have resulted inCLIP-seq datasets coupled with transcriptome profiling by RNA-seq. However, analysis methods that integrate both types of da...

Authors: Fan Chen and Sündüz Keleş

Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes

Glioblastoma (GBM) has one of the worst 5-year survival rates of all cancers. While genomic studies of the disease have been performed, alterations in the non-coding regulatory regions of GBM have largely rema...

Authors: Sharadha Sakthikumar, Ananya Roy, Lulu Haseeb, Mats E. Pettersson, Elisabeth Sundström, Voichita D. Marinescu, Kerstin Lindblad-Toh and Karin Forsberg-Nilsson

Analysis of 1321 Eubacterium rectale genomes from metagenomes uncovers complex phylogeographic population structure and subspecies functional adaptations

Eubacterium rectale is one of the most prevalent human gut bacteria, but its diversity and population genetics are not well understood because large-scale whole-genome investigations of this microbe have not been...

Authors: Nicolai Karcher, Edoardo Pasolli, Francesco Asnicar, Kun D. Huang, Adrian Tett, Serena Manara, Federica Armanini, Debbie Bain, Sylvia H. Duncan, Petra Louis, Moreno Zolfo, Paolo Manghi, Mireia Valles-Colomer, Roberta Raffaetà, Omar Rota-Stabelli, Maria Carmen Collado…

CB2 improves power of cell detection in droplet-based single-cell RNA sequencing data

An important challenge in pre-processing data from droplet-based single-cell RNA sequencing protocols is distinguishing barcodes associated with real cells from those binding background reads. Existing methods...

Authors: Zijian Ni, Shuyang Chen, Jared Brown and Christina Kendziorski

Direct-seq: programmed gRNA scaffold for streamlined scRNA-seq in CRISPR screen

CRISPR-based genome perturbation provides a new avenue to conveniently change DNA sequences, transcription, and epigenetic modifications in genetic screens. However, it remains challenging to assay the complex...

Authors: Qingkai Song, Ke Ni, Min Liu, Yini Li, Lixia Wang, Yingying Wang, Yingzheng Liu, Zhenxing Yu, Yinyao Qi, Zhike Lu and Lijia Ma

Molecular mechanisms of coronary disease revealed using quantitative trait loci for TCF21 binding, chromatin accessibility, and chromosomal looping

To investigate the epigenetic and transcriptional mechanisms of coronary artery disease (CAD) risk, as well as the functional regulation of chromatin structure and function, we create a catalog of genetic vari...

Authors: Quanyi Zhao, Michael Dacre, Trieu Nguyen, Milos Pjanic, Boxiang Liu, Dharini Iyer, Paul Cheng, Robert Wirka, Juyong Brian Kim, Hunter B. Fraser and Thomas Quertermous

MAUDE: inferring expression changes in sorting-based CRISPR screens

Improved methods are needed to model CRISPR screen data for interrogation of genetic elements that alter reporter gene expression readout. We create MAUDE (Mean Alterations Using Discrete Expression) for quant...

Authors: Carl G. de Boer, John P. Ray, Nir Hacohen and Aviv Regev

Author Correction: Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation

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

Authors: Mayilaadumveettil Nishana, Caryn Ha, Javier Rodriguez-Hernaez, Ali Ranjbaran, Erica Chio, Elphege P. Nora, Sana B. Badri, Andreas Kloetgen, Benoit G. Bruneau, Aristotelis Tsirigos and Jane A. Skok

Universal promoter scanning by Pol II during transcription initiation in Saccharomyces cerevisiae

The majority of eukaryotic promoters utilize multiple transcription start sites (TSSs). How multiple TSSs are specified at individual promoters across eukaryotes is not understood for most species. In Saccharomyc...

Authors: Chenxi Qiu, Huiyan Jin, Irina Vvedenskaya, Jordi Abante Llenas, Tingting Zhao, Indranil Malik, Alex M. Visbisky, Scott L. Schwartz, Ping Cui, Pavel Čabart, Kang Hoo Han, William K. M. Lai, Richard P. Metz, Charles D. Johnson, Sing-Hoi Sze, B. Franklin Pugh…

The promise and challenge of cancer microbiome research

Many microbial agents have been implicated as contributors to cancer genesis and development, and the search to identify and characterize new cancer-related organisms is ongoing. Modern developments in methodo...

Authors: Sumeed Syed Manzoor, Annemiek Doedens and Michael B. Burns

Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows

Single-cell RNA sequencing has been widely adopted to estimate the cellular composition of heterogeneous tissues and obtain transcriptional profiles of individual cells. Multiple approaches for optimal sample ...

Authors: Elena Denisenko, Belinda B. Guo, Matthew Jones, Rui Hou, Leanne de Kock, Timo Lassmann, Daniel Poppe, Olivier Clément, Rebecca K. Simmons, Ryan Lister and Alistair R. R. Forrest

Assembly and annotation of an Ashkenazi human reference genome

Thousands of experiments and studies use the human reference genome as a resource each year. This single reference genome, GRCh38, is a mosaic created from a small number of individuals, representing a very sm...

Authors: Alaina Shumate, Aleksey V. Zimin, Rachel M. Sherman, Daniela Puiu, Justin M. Wagner, Nathan D. Olson, Mihaela Pertea, Marc L. Salit, Justin M. Zook and Steven L. Salzberg

Developmental regulation of canonical and small ORF translation from mRNAs

Ribosomal profiling has revealed the translation of thousands of sequences outside annotated protein-coding genes, including small open reading frames of less than 100 codons, and the translational regulation ...

Authors: Pedro Patraquim, Muhammad Ali Shahzad Mumtaz, José Ignacio Pueyo, Julie Louise Aspden and Juan-Pablo Couso

CICERO: a versatile method for detecting complex and diverse driver fusions using cancer RNA sequencing data

To discover driver fusions beyond canonical exon-to-exon chimeric transcripts, we develop CICERO, a local assembly-based algorithm that integrates RNA-seq read support with extensive annotation for candidate r...

Authors: Liqing Tian, Yongjin Li, Michael N. Edmonson, Xin Zhou, Scott Newman, Clay McLeod, Andrew Thrasher, Yu Liu, Bo Tang, Michael C. Rusch, John Easton, Jing Ma, Eric Davis, Austyn Trull, J. Robert Michael, Karol Szlachta…

FORK-seq: replication landscape of the Saccharomyces cerevisiae genome by nanopore sequencing

Genome replication mapping methods profile cell populations, masking cell-to-cell heterogeneity. Here, we describe FORK-seq, a nanopore sequencing method to map replication of single DNA molecules at 200-nucle...

Authors: Magali Hennion, Jean-Michel Arbona, Laurent Lacroix, Corinne Cruaud, Bertrand Theulot, Benoît Le Tallec, Florence Proux, Xia Wu, Elizaveta Novikova, Stefan Engelen, Arnaud Lemainque, Benjamin Audit and Olivier Hyrien

Personalized and graph genomes reveal missing signal in epigenomic data

Epigenomic studies that use next generation sequencing experiments typically rely on the alignment of reads to a reference sequence. However, because of genetic diversity and the diploid nature of the human ge...

Authors: Cristian Groza, Tony Kwan, Nicole Soranzo, Tomi Pastinen and Guillaume Bourque

Accounting for cell type hierarchy in evaluating single cell RNA-seq clustering

Cell clustering is one of the most common routines in single cell RNA-seq data analyses, for which a number of specialized methods are available. The evaluation of these methods ignores an important biological...

Authors: Zhijin Wu and Hao Wu

Lifestyle and the presence of helminths is associated with gut microbiome composition in Cameroonians

African populations provide a unique opportunity to interrogate host-microbe co-evolution and its impact on adaptive phenotypes due to their genomic, phenotypic, and cultural diversity. We integrate gut microb...

Authors: Meagan A. Rubel, Arwa Abbas, Louis J. Taylor, Andrew Connell, Ceylan Tanes, Kyle Bittinger, Valantine N. Ndze, Julius Y. Fonsah, Eric Ngwang, André Essiane, Charles Fokunang, Alfred K. Njamnshi, Frederic D. Bushman and Sarah A. Tishkoff

Gapless assembly of maize chromosomes using long-read technologies

Creating gapless telomere-to-telomere assemblies of complex genomes is one of the ultimate challenges in genomics. We use two independent assemblies and an optical map-based merging pipeline to produce a maize...

Authors: Jianing Liu, Arun S. Seetharam, Kapeel Chougule, Shujun Ou, Kyle W. Swentowsky, Jonathan I. Gent, Victor Llaca, Margaret R. Woodhouse, Nancy Manchanda, Gernot G. Presting, David A. Kudrna, Magdy Alabady, Candice N. Hirsch, Kevin A. Fengler, Doreen Ware, Todd P. Michael…

RNA structural dynamics regulate early embryogenesis through controlling transcriptome fate and function

Vertebrate early embryogenesis is initially directed by a set of maternal RNAs and proteins, yet the mechanisms controlling this program remain largely unknown. Recent transcriptome-wide studies on RNA structu...

Authors: Boyang Shi, Jinsong Zhang, Jian Heng, Jing Gong, Ting Zhang, Pan Li, Bao-Fa Sun, Ying Yang, Ning Zhang, Yong-Liang Zhao, Hai-Lin Wang, Feng Liu, Qiangfeng Cliff Zhang and Yun-Gui Yang