Articles

Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation

CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumor suppressors. Currently, for most cancers inclu...

Authors: Nisha Padmanabhan, Huang Kie Kyon, Arnoud Boot, Kevin Lim, Supriya Srivastava, Shuwen Chen, Zhiyuan Wu, Hyung-Ok Lee, Vineeth T. Mukundan, Charlene Chan, Yarn Kit Chan, Ong Xuewen, Jason J. Pitt, Zul Fazreen Adam Isa, Manjie Xing, Ming Hui Lee…

Impacts of allopolyploidization and structural variation on intraspecific diversification in Brassica rapa

Despite the prevalence and recurrence of polyploidization in the speciation of flowering plants, its impacts on crop intraspecific genome diversification are largely unknown. Brassica rapa is a mesopolyploid spec...

Authors: Xu Cai, Lichun Chang, Tingting Zhang, Haixu Chen, Lei Zhang, Runmao Lin, Jianli Liang, Jian Wu, Michael Freeling and Xiaowu Wang

diffBUM-HMM: a robust statistical modeling approach for detecting RNA flexibility changes in high-throughput structure probing data

Advancing RNA structural probing techniques with next-generation sequencing has generated demands for complementary computational tools to robustly extract RNA structural information amidst sampling noise and ...

Authors: Paolo Marangio, Ka Ying Toby Law, Guido Sanguinetti and Sander Granneman

GRiNCH: simultaneous smoothing and detection of topological units of genome organization from sparse chromatin contact count matrices with matrix factorization

High-throughput chromosome conformation capture assays, such as Hi-C, have shown that the genome is organized into organizational units such as topologically associating domains (TADs), which can impact gene r...

Authors: Da-Inn Lee and Sushmita Roy

scDesign2: a transparent simulator that generates high-fidelity single-cell gene expression count data with gene correlations captured

A pressing challenge in single-cell transcriptomics is to benchmark experimental protocols and computational methods. A solution is to use computational simulators, but existing simulators cannot simultaneousl...

Authors: Tianyi Sun, Dongyuan Song, Wei Vivian Li and Jingyi Jessica Li

Samplot: a platform for structural variant visual validation and automated filtering

Visual validation is an important step to minimize false-positive predictions from structural variant (SV) detection. We present Samplot, a tool for creating images that display the read depth and sequence ali...

Authors: Jonathan R. Belyeu, Murad Chowdhury, Joseph Brown, Brent S. Pedersen, Michael J. Cormier, Aaron R. Quinlan and Ryan M. Layer

Genome-wide DNA mutations in Arabidopsis plants after multigenerational exposure to high temperatures

Elevated temperatures can cause physiological, biochemical, and molecular responses in plants that can greatly affect their growth and development. Mutations are the most fundamental force driving biological e...

Authors: Zhaogeng Lu, Jiawen Cui, Li Wang, Nianjun Teng, Shoudong Zhang, Hon-Ming Lam, Yingfang Zhu, Siwei Xiao, Wensi Ke, Jinxing Lin, Chenwu Xu and Biao Jin

Characterization of structural variation in Tibetans reveals new evidence of high-altitude adaptation and introgression

Structural variation (SV) acts as an essential mutational force shaping the evolution and function of the human genome. However, few studies have examined the role of SVs in high-altitude adaptation and little...

Authors: Cheng Quan, Yuanfeng Li, Xinyi Liu, Yahui Wang, Jie Ping, Yiming Lu and Gangqiao Zhou

MichiGAN: sampling from disentangled representations of single-cell data using generative adversarial networks

Deep generative models such as variational autoencoders (VAEs) and generative adversarial networks (GANs) generate and manipulate high-dimensional images. We systematically assess the complementary strengths a...

Authors: Hengshi Yu and Joshua D. Welch

treeclimbR pinpoints the data-dependent resolution of hierarchical hypotheses

treeclimbR is for analyzing hierarchical trees of entities, such as phylogenies or cell types, at different resolutions. It proposes multiple candidates that capture the latent signal and pinpoints branches or le...

Authors: Ruizhu Huang, Charlotte Soneson, Pierre-Luc Germain, Thomas S.B. Schmidt, Christian Von Mering and Mark D. Robinson

A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks

Lung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the ...

Authors: Chongze Yuan, Haojie Chen, Shiqi Tu, Hsin-Yi Huang, Yunjian Pan, Xiuqi Gui, Muyu Kuang, Xuxia Shen, Qiang Zheng, Yang Zhang, Chao Cheng, Hui Hong, Xiaoting Tao, Yizhou Peng, Xingxin Yao, Feilong Meng…

PEPPRO: quality control and processing of nascent RNA profiling data

Nascent RNA profiling is growing in popularity; however, there is no standard analysis pipeline to uniformly process the data and assess quality. Here, we introduce PEPPRO, a comprehensive, scalable workflow f...

Authors: Jason P. Smith, Arun B. Dutta, Kizhakke Mattada Sathyan, Michael J. Guertin and Nathan C. Sheffield

Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune regulatory pathways

The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed at the metastatic stage, and standard therapies have limited activity with a dismal 5-year survival rate of only 8%. The liver and lung ar...

Authors: Won Jin Ho, Rossin Erbe, Ludmila Danilova, Zaw Phyo, Emma Bigelow, Genevieve Stein-O’Brien, Dwayne L. Thomas II, Soren Charmsaz, Nicole Gross, Skylar Woolman, Kayla Cruz, Rebecca M. Munday, Neeha Zaidi, Todd D. Armstrong, Marcelo B. Sztein, Mark Yarchoan…

Novel predictions arise from contradictions

Authors: Itai Yanai and Martin Lercher

On the optimistic performance evaluation of newly introduced bioinformatic methods

Most research articles presenting new data analysis methods claim that “the new method performs better than existing methods,” but the veracity of such statements is questionable. Our manuscript discusses and ...

Authors: Stefan Buchka, Alexander Hapfelmeier, Paul P. Gardner, Rory Wilson and Anne-Laure Boulesteix

Cellular and transcriptomic analyses reveal two-staged chloroplast biogenesis underpinning photosynthesis build-up in the wheat leaf

The developmental gradient in monocot leaves has been exploited to uncover leaf developmental gene expression programs and chloroplast biogenesis processes. However, the relationship between the two is barely ...

Authors: Naresh Loudya, Priyanka Mishra, Kotaro Takahagi, Yukiko Uehara-Yamaguchi, Komaki Inoue, Laszlo Bogre, Keiichi Mochida and Enrique López-Juez

Super-resolution visualization and modeling of human chromosomal regions reveals cohesin-dependent loop structures

The 3D organization of the chromatin fiber in cell nuclei plays a key role in the regulation of gene expression. Genome-wide techniques to score DNA-DNA contacts, such as Hi-C, reveal the partitioning of chrom...

Authors: Xian Hao, Jyotsana J. Parmar, Benoît Lelandais, Andrey Aristov, Wei Ouyang, Christian Weber and Christophe Zimmer

Functional mapping of androgen receptor enhancer activity

Androgen receptor (AR) is critical to the initiation, growth, and progression of prostate cancer. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there ...

Authors: Chia-Chi Flora Huang, Shreyas Lingadahalli, Tunc Morova, Dogancan Ozturan, Eugene Hu, Ivan Pak Lok Yu, Simon Linder, Marlous Hoogstraat, Suzan Stelloo, Funda Sar, Henk van der Poel, Umut Berkay Altintas, Mohammadali Saffarzadeh, Stephane Le Bihan, Brian McConeghy, Bengul Gokbayrak…

The genetic mechanism of heterosis utilization in maize improvement

In maize hybrid breeding, complementary pools of parental lines with reshuffled genetic variants are established for superior hybrid performance. To comprehensively decipher the genetics of heterosis, we prese...

Authors: Yingjie Xiao, Shuqin Jiang, Qian Cheng, Xiaqing Wang, Jun Yan, Ruyang Zhang, Feng Qiao, Chuang Ma, Jingyun Luo, Wenqiang Li, Haijun Liu, Wenyu Yang, Wenhao Song, Yijiang Meng, Marilyn L. Warburton, Jiuran Zhao…

Endogenous retroviruses in the origins and treatment of cancer

Endogenous retroviruses (ERVs) are emerging as promising therapeutic targets in cancer. As remnants of ancient retroviral infections, ERV-derived regulatory elements coordinate expression from gene networks, i...

Authors: Natasha Jansz and Geoffrey J. Faulkner

Long-read cDNA sequencing identifies functional pseudogenes in the human transcriptome

Pseudogenes are gene copies presumed to mainly be functionless relics of evolution due to acquired deleterious mutations or transcriptional silencing. Using deep full-length PacBio cDNA sequencing of normal hu...

Authors: Robin-Lee Troskie, Yohaann Jafrani, Tim R. Mercer, Adam D. Ewing, Geoffrey J. Faulkner and Seth W. Cheetham

SpatialDWLS: accurate deconvolution of spatial transcriptomic data

Recent development of spatial transcriptomic technologies has made it possible to characterize cellular heterogeneity with spatial information. However, the technology often does not have sufficient resolution...

Authors: Rui Dong and Guo-Cheng Yuan

HDAC4 degradation during senescence unleashes an epigenetic program driven by AP-1/p300 at selected enhancers and super-enhancers

Cellular senescence is a permanent state of replicative arrest defined by a specific pattern of gene expression. The epigenome in senescent cells is sculptured in order to sustain the new transcriptional requi...

Authors: Eros Di Giorgio, Harikrishnareddy Paluvai, Emiliano Dalla, Liliana Ranzino, Alessandra Renzini, Viviana Moresi, Martina Minisini, Raffaella Picco and Claudio Brancolini

scSNV: accurate dscRNA-seq SNV co-expression analysis using duplicate tag collapsing

Identifying single nucleotide variants has become common practice for droplet-based single-cell RNA-seq experiments; however, presently, a pipeline does not exist to maximize variant calling accuracy. Furtherm...

Authors: Gavin W. Wilson, Mathieu Derouet, Gail E. Darling and Jonathan C. Yeung

Promoter G-quadruplex folding precedes transcription and is controlled by chromatin

Four-stranded G-quadruplexes (G4s) are DNA secondary structures in the human genome that are primarily found in active promoters associated with elevated transcription. Here, we explore the relationship betwee...

Authors: Jiazhen Shen, Dhaval Varshney, Angela Simeone, Xiaoyun Zhang, Santosh Adhikari, David Tannahill and Shankar Balasubramanian

Tejaas: reverse regression increases power for detecting trans-eQTLs

Trans-acting expression quantitative trait loci (trans-eQTLs) account for ≥70% expression heritability and could therefore facilitate uncovering mechanisms underlying the origination of complex diseases. Identify...

Authors: Saikat Banerjee, Franco L. Simonetti, Kira E. Detrois, Anubhav Kaphle, Raktim Mitra, Rahul Nagial and Johannes Söding

Transgenerational effect of mutants in the RNA-directed DNA methylation pathway on the triploid block in Arabidopsis

Hybridization of plants that differ in number of chromosome sets (ploidy) frequently causes endosperm failure and seed arrest, a phenomenon referred to as triploid block. In Arabidopsis, loss of function of NRPD1

Authors: Zhenxing Wang, Nicolas Butel, Juan Santos-González, Lauriane Simon, Cecilia Wärdig and Claudia Köhler

Embryo CHH hypermethylation is mediated by RdDM and is autonomously directed in Brassica rapa

RNA-directed DNA methylation (RdDM) initiates cytosine methylation in all contexts and maintains asymmetric CHH methylation. Mature plant embryos show one of the highest levels of CHH methylation, and it has b...

Authors: Tania Chakraborty, Timmy Kendall, Jeffrey W. Grover and Rebecca A. Mosher

Determination of complete chromosomal haplotypes by bulk DNA sequencing

Haplotype phase represents the collective genetic variation between homologous chromosomes and is an essential feature of non-haploid genomes. Here we describe a computational strategy to reliably determine co...

Authors: Richard W. Tourdot, Gregory J. Brunette, Ricardo A. Pinto and Cheng-Zhong Zhang

Genetic and environmental modulation of transposition shapes the evolutionary potential of Arabidopsis thaliana

How species can adapt to abrupt environmental changes, particularly in the absence of standing genetic variation, is poorly understood and a pressing question in the face of ongoing climate change. Here we lev...

Authors: Pierre Baduel, Basile Leduque, Amandine Ignace, Isabelle Gy, José Gil Jr, Olivier Loudet, Vincent Colot and Leandro Quadrana

Limited haplotype diversity underlies polygenic trait architecture across 70 years of wheat breeding

Selection has dramatically shaped genetic and phenotypic variation in bread wheat. We can assess the genomic basis of historical phenotypic changes, and the potential for future improvement, using experimental...

Authors: Michael F. Scott, Nick Fradgley, Alison R. Bentley, Thomas Brabbs, Fiona Corke, Keith A. Gardner, Richard Horsnell, Phil Howell, Olufunmilayo Ladejobi, Ian J. Mackay, Richard Mott and James Cockram

Intergenic RNA mainly derives from nascent transcripts of known genes

Eukaryotic genomes undergo pervasive transcription, leading to the production of many types of stable and unstable RNAs. Transcription is not restricted to regions with annotated gene features but includes alm...

Authors: Federico Agostini, Julian Zagalak, Jan Attig, Jernej Ule and Nicholas M. Luscombe

geneshot: gene-level metagenomics identifies genome islands associated with immunotherapy response

Researchers must be able to generate experimentally testable hypotheses from sequencing-based observational microbiome experiments to discover the mechanisms underlying the influence of gut microbes on human h...

Authors: Samuel S. Minot, Kevin C. Barry, Caroline Kasman, Jonathan L. Golob and Amy D. Willis

Role of epigenetics in unicellular to multicellular transition in Dictyostelium

The evolution of multicellularity is a critical event that remains incompletely understood. We use the social amoeba, Dictyostelium discoideum, one of the rare organisms that readily transits back and forth betwe...

Authors: Simon Yuan Wang, Elizabeth Ann Pollina, I-Hao Wang, Lindsay Kristina Pino, Henry L. Bushnell, Ken Takashima, Colette Fritsche, George Sabin, Benjamin Aaron Garcia, Paul Lieberman Greer and Eric Lieberman Greer

Functional and genetic determinants of mutation rate variability in regulatory elements of cancer genomes

Cancer genomes are shaped by mutational processes with complex spatial variation at multiple scales. Entire classes of regulatory elements are affected by local variations in mutation frequency. However, the u...

Authors: Christian A. Lee, Diala Abd-Rabbo and Jüri Reimand

Deep sequencing of pre-translational mRNPs reveals hidden flux through evolutionarily conserved alternative splicing nonsense-mediated decay pathways

Alternative splicing, which generates multiple mRNA isoforms from single genes, is crucial for the regulation of eukaryotic gene expression. The flux through competing splicing pathways cannot be determined by...

Authors: Carrie Kovalak, Scott Donovan, Alicia A. Bicknell, Mihir Metkar and Melissa J. Moore

Schema: metric learning enables interpretable synthesis of heterogeneous single-cell modalities

A complete understanding of biological processes requires synthesizing information across heterogeneous modalities, such as age, disease status, or gene expression. Technological advances in single-cell profil...

Authors: Rohit Singh, Brian L. Hie, Ashwin Narayan and Bonnie Berger

A generalization of t-SNE and UMAP to single-cell multimodal omics

Emerging single-cell technologies profile multiple types of molecules within individual cells. A fundamental step in the analysis of the produced high-dimensional data is their visualization using dimensionali...

Authors: Van Hoan Do and Stefan Canzar

MARS: leveraging allelic heterogeneity to increase power of association testing

In standard genome-wide association studies (GWAS), the standard association test is underpowered to detect associations between loci with multiple causal variants with small effect sizes. We propose a statist...

Authors: Farhad Hormozdiari, Junghyun Jung, Eleazar Eskin and Jong Wha J. Joo

Genetic impacts on DNA methylation: research findings and future perspectives

Multiple recent studies highlight that genetic variants can have strong impacts on a significant proportion of the human DNA methylome. Methylation quantitative trait loci, or meQTLs, allow for the exploration...

Authors: Sergio Villicaña and Jordana T. Bell

nPhase: an accurate and contiguous phasing method for polyploids

While genome sequencing and assembly are now routine, we do not have a full, precise picture of polyploid genomes. No existing polyploid phasing method provides accurate and contiguous haplotype predictions. W...

Authors: Omar Abou Saada, Andreas Tsouris, Chris Eberlein, Anne Friedrich and Joseph Schacherer

Ten-eleven translocation protein 1 modulates medulloblastoma progression

Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB hig...

Authors: Hyerim Kim, Yunhee Kang, Yujing Li, Li Chen, Li Lin, Nicholas D. Johnson, Dan Zhu, M. Hope Robinson, Leon McSwain, Benjamin G. Barwick, Xianrui Yuan, Xinbin Liao, Jie Zhao, Zhiping Zhang, Qiang Shu, Jianjun Chen…

PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data

To investigate molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along the pseudotime inferred from single-cell RNA-sequencing data. Howe...

Authors: Dongyuan Song and Jingyi Jessica Li

Next-generation microbiology: from comparative genomics to gene function

Microbiology is at a turning point in its 120-year history. Widespread next-generation sequencing has revealed genetic complexity among bacteria that could hardly have been imagined by pioneers such as Pasteur...

Authors: Carolin M. Kobras, Andrew K. Fenton and Samuel K. Sheppard

The impact of cell type and context-dependent regulatory variants on human immune traits

The vast majority of trait-associated variants identified using genome-wide association studies (GWAS) are noncoding, and therefore assumed to impact gene regulation. However, the majority of trait-associated ...

Authors: Zepeng Mu, Wei Wei, Benjamin Fair, Jinlin Miao, Ping Zhu and Yang I. Li

Best practices on the differential expression analysis of multi-species RNA-seq

Advances in transcriptome sequencing allow for simultaneous interrogation of differentially expressed genes from multiple species originating from a single RNA sample, termed dual or multi-species transcriptom...

Authors: Matthew Chung, Vincent M. Bruno, David A. Rasko, Christina A. Cuomo, José F. Muñoz, Jonathan Livny, Amol C. Shetty, Anup Mahurkar and Julie C. Dunning Hotopp

Complete vertebrate mitogenomes reveal widespread repeats and gene duplications

Modern sequencing technologies should make the assembly of the relatively small mitochondrial genomes an easy undertaking. However, few tools exist that address mitochondrial assembly directly.

Authors: Giulio Formenti, Arang Rhie, Jennifer Balacco, Bettina Haase, Jacquelyn Mountcastle, Olivier Fedrigo, Samara Brown, Marco Rosario Capodiferro, Farooq O. Al-Ajli, Roberto Ambrosini, Peter Houde, Sergey Koren, Karen Oliver, Michelle Smith, Jason Skelton, Emma Betteridge…

Cotton pan-genome retrieves the lost sequences and genes during domestication and selection

Millennia of directional human selection has reshaped the genomic architecture of cultivated cotton relative to wild counterparts, but we have limited understanding of the selective retention and fractionation...

Authors: Jianying Li, Daojun Yuan, Pengcheng Wang, Qiongqiong Wang, Mengling Sun, Zhenping Liu, Huan Si, Zhongping Xu, Yizan Ma, Boyang Zhang, Liuling Pei, Lili Tu, Longfu Zhu, Ling-Ling Chen, Keith Lindsey, Xianlong Zhang…

Drosophila primary microRNA-8 encodes a microRNA-encoded peptide acting in parallel of miR-8

Recent genome-wide studies of many species reveal the existence of a myriad of RNAs differing in size, coding potential and function. Among these are the long non-coding RNAs, some of them producing functional...

Authors: Audrey Montigny, Patrizia Tavormina, Carine Duboe, Hélène San Clémente, Marielle Aguilar, Philippe Valenti, Dominique Lauressergues, Jean-Philippe Combier and Serge Plaza

G-quadruplexes are transcription factor binding hubs in human chromatin

The binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many qu...

Authors: Jochen Spiegel, Sergio Martínez Cuesta, Santosh Adhikari, Robert Hänsel-Hertsch, David Tannahill and Shankar Balasubramanian