Articles

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

Human brain region-specific variably methylated regions are enriched for heritability of distinct neuropsychiatric traits

DNA methylation dynamics in the brain are associated with normal development and neuropsychiatric disease and differ across functionally distinct brain regions. Previous studies of genome-wide methylation diff...

Authors: Lindsay F. Rizzardi, Peter F. Hickey, Adrian Idrizi, Rakel Tryggvadóttir, Colin M. Callahan, Kimberly E. Stephens, Sean D. Taverna, Hao Zhang, Sinan Ramazanoglu, Kasper D. Hansen and Andrew P. Feinberg

AFLAP: assembly-free linkage analysis pipeline using k-mers from genome sequencing data

Our assembly-free linkage analysis pipeline (AFLAP) identifies segregating markers as k-mers in the raw reads without using a reference genome assembly for calling variants and provides genotype tables for the...

Authors: Kyle Fletcher, Lin Zhang, Juliana Gil, Rongkui Han, Keri Cavanaugh and Richard Michelmore

scMET: Bayesian modeling of DNA methylation heterogeneity at single-cell resolution

High-throughput single-cell measurements of DNA methylomes can quantify methylation heterogeneity and uncover its role in gene regulation. However, technical limitations and sparse coverage can preclude this t...

Authors: Chantriolnt-Andreas Kapourani, Ricard Argelaguet, Guido Sanguinetti and Catalina A. Vallejos

Genomic insights into the origin, domestication and genetic basis of agronomic traits of castor bean

Castor bean (Ricinus communis L.) is an important oil crop, which belongs to the Euphorbiaceae family. The seed oil of castor bean is currently the only commercial source of ricinoleic acid that can be used for p...

Authors: Wei Xu, Di Wu, Tianquan Yang, Chao Sun, Zaiqing Wang, Bing Han, Shibo Wu, Anmin Yu, Mark A. Chapman, Sammy Muraguri, Qing Tan, Wenbo Wang, Zhigui Bao, Aizhong Liu and De-Zhu Li

Personalized genome structure via single gamete sequencing

Genetic maps have been fundamental to building our understanding of disease genetics and evolutionary processes. The gametes of an individual contain all of the information required to perform a de novo chromo...

Authors: Ruqian Lyu, Vanessa Tsui, Davis J. McCarthy and Wayne Crismani

A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency

Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference...

Authors: Wendell Jones, Binsheng Gong, Natalia Novoradovskaya, Dan Li, Rebecca Kusko, Todd A. Richmond, Donald J. Johann Jr, Halil Bisgin, Sayed Mohammad Ebrahim Sahraeian, Pierre R. Bushel, Mehdi Pirooznia, Katherine Wilkins, Marco Chierici, Wenjun Bao, Lee Scott Basehore, Anne Bergstrom Lucas…

Identification of X-chromosomal genes that drive sex differences in embryonic stem cells through a hierarchical CRISPR screening approach

X-chromosomal genes contribute to sex differences, in particular during early development, when both X chromosomes are active in females. Double X-dosage shifts female pluripotent cells towards the naive stem ...

Authors: Oriana Genolet, Anna A. Monaco, Ilona Dunkel, Michael Boettcher and Edda G. Schulz

Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions

Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and ...

Authors: Binsheng Gong, Dan Li, Rebecca Kusko, Natalia Novoradovskaya, Yifan Zhang, Shangzi Wang, Carlos Pabón-Peña, Zhihong Zhang, Kevin Lai, Wanshi Cai, Jennifer S. LoCoco, Eric Lader, Todd A. Richmond, Vinay K. Mittal, Liang-Chun Liu, Donald J. Johann Jr…

Mechanisms of enhancer action: the known and the unknown

Differential gene expression mechanisms ensure cellular differentiation and plasticity to shape ontogenetic and phylogenetic diversity of cell types. A key regulator of differential gene expression programs ar...

Authors: Anil Panigrahi and Bert W. O’Malley

Publisher Correction: MTSplice predicts effects of genetic variants on tissue-specific splicing

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

Authors: Jun Cheng, Muhammed Hasan Çelik, Anshul Kundaje and Julien Gagneur

Improving the completeness of public metadata accompanying omics studies

Authors: Anushka Rajesh, Yutong Chang, Malak S. Abedalthagafi, Annie Wong-Beringer, Michael I. Love and Serghei Mangul