Articles

The evolution of relapse of adult T cell acute lymphoblastic leukemia

Adult T cell acute lymphoblastic leukemia (T-ALL) is a rare disease that affects less than 10 individuals in one million. It has been less studied than its cognate pediatric malignancy, which is more prevalent...

Authors: Inés Sentís, Santiago Gonzalez, Eulalia Genescà, Violeta García-Hernández, Ferran Muiños, Celia Gonzalez, Erika López-Arribillaga, Jessica Gonzalez, Lierni Fernandez-Ibarrondo, Loris Mularoni, Lluís Espinosa, Beatriz Bellosillo, Josep-Maria Ribera, Anna Bigas, Abel Gonzalez-Perez and Nuria Lopez-Bigas

A pitfall for machine learning methods aiming to predict across cell types

Machine learning models that predict genomic activity are most useful when they make accurate predictions across cell types. Here, we show that when the training and test sets contain the same genomic loci, th...

Authors: Jacob Schreiber, Ritambhara Singh, Jeffrey Bilmes and William Stafford Noble

Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease characterized by the development of anti-nuclear antibodies. Susceptibility to SLE is multifactorial, with a combination of g...

Authors: Prithvi Raj, Ran Song, Honglin Zhu, Linley Riediger, Dong-Jae Jun, Chaoying Liang, Carlos Arana, Bo Zhang, Yajing Gao, Benjamin E. Wakeland, Igor Dozmorov, Jinchun Zhou, Jennifer A. Kelly, Bernard R. Lauwerys, Joel M. Guthridge, Nancy J. Olsen…

Stairway Plot 2: demographic history inference with folded SNP frequency spectra

Inferring the demographic histories of populations has wide applications in population, ecological, and conservation genomics. We present Stairway Plot 2, a cross-platform program package for this task using S...

Authors: Xiaoming Liu and Yun-Xin Fu

A versatile toolkit for CRISPR-Cas13-based RNA manipulation in Drosophila

Advances in CRISPR technology have immensely improved our ability to manipulate nucleic acids, and the recent discovery of the RNA-targeting endonuclease Cas13 adds even further functionality. Here, we show th...

Authors: Nhan Huynh, Noah Depner, Raegan Larson and Kirst King-Jones

Navigating the crowd: visualizing coordination between genome dynamics, structure, and transcription

The eukaryotic genome is hierarchically structured yet highly dynamic. Regulating transcription in this environment demands a high level of coordination to permit many proteins to interact with chromatin fiber...

Authors: Haitham A. Shaban, Roman Barth and Kerstin Bystricky

A DNA methylation state transition model reveals the programmed epigenetic heterogeneity in human pre-implantation embryos

During mammalian early embryogenesis, expression and epigenetic heterogeneity emerge before the first cell fate determination, but the programs causing such determinate heterogeneity are largely unexplored.

Authors: Chengchen Zhao, Naiqian Zhang, Yalin Zhang, Nuermaimaiti Tuersunjiang, Shaorong Gao, Wenqiang Liu and Yong Zhang

Do malignant cells sleep at night?

Biological rhythms regulate the biology of most, if not all living creatures, from whole organisms to their constitutive cells, their microbiota, and also parasites. Here, we present the hypothesis that intern...

Authors: Luis Enrique Cortés-Hernández, Zahra Eslami-S, Antoine M. Dujon, Mathieu Giraudeau, Beata Ujvari, Frédéric Thomas and Catherine Alix-Panabières

Massive gene presence-absence variation shapes an open pan-genome in the Mediterranean mussel

The Mediterranean mussel Mytilus galloprovincialis is an ecologically and economically relevant edible marine bivalve, highly invasive and resilient to biotic and abiotic stressors causing recurrent massive morta...

Authors: Marco Gerdol, Rebeca Moreira, Fernando Cruz, Jessica Gómez-Garrido, Anna Vlasova, Umberto Rosani, Paola Venier, Miguel A. Naranjo-Ortiz, Maria Murgarella, Samuele Greco, Pablo Balseiro, André Corvelo, Leonor Frias, Marta Gut, Toni Gabaldón, Alberto Pallavicini…

SVFX: a machine learning framework to quantify the pathogenicity of structural variants

There is a lack of approaches for identifying pathogenic genomic structural variants (SVs) although they play a crucial role in many diseases. We present a mechanism-agnostic machine learning-based workflow, c...

Authors: Sushant Kumar, Arif Harmanci, Jagath Vytheeswaran and Mark B. Gerstein

Pathway information extracted from 25 years of pathway figures

Thousands of pathway diagrams are published each year as static figures inaccessible to computational queries and analyses. Using a combination of machine learning, optical character recognition, and manual cu...

Authors: Kristina Hanspers, Anders Riutta, Martina Summer-Kutmon and Alexander R. Pico

Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage

Structural maintenance of chromosomes (SMC) complexes are central organizers of chromatin architecture throughout the cell cycle. The SMC family member condensin is best known for establishing long-range chrom...

Authors: Yasutaka Kakui, Christopher Barrington, David J. Barry, Tereza Gerguri, Xiao Fu, Paul A. Bates, Bhavin S. Khatri and Frank Uhlmann

Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Metastasis is the primary cause of cancer mortality accounting for 90% of cancer deaths. Our understanding of the molecular mechanisms driving metastasis is rudimentary.

Authors: Won-Chul Lee, Alexandre Reuben, Xin Hu, Nicholas McGranahan, Runzhe Chen, Ali Jalali, Marcelo V. Negrao, Shawna M. Hubert, Chad Tang, Chia-Chin Wu, Anthony San Lucas, Whijae Roh, Kenichi Suda, Jihye Kim, Aik-Choon Tan, David H. Peng…

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

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

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

Cis-acting lnc-eRNA SEELA directly binds histone H4 to promote histone recognition and leukemia progression

Long noncoding enhancer RNAs (lnc-eRNAs) are a subset of stable eRNAs identified from annotated lncRNAs. They might act as enhancer activity-related therapeutic targets in cancer. However, the underlying mecha...

Authors: Ke Fang, Wei Huang, Yu-Meng Sun, Tian-Qi Chen, Zhan-Cheng Zeng, Qian-Qian Yang, Qi Pan, Cai Han, Lin-Yu Sun, Xue-Qun Luo, Wen-Tao Wang and Yue-Qin Chen

RNA editing in cancer impacts mRNA abundance in immune response pathways

RNA editing generates modifications to the RNA sequences, thereby increasing protein diversity and shaping various layers of gene regulation. Recent studies have revealed global shifts in editing levels across...

Authors: Tracey W. Chan, Ting Fu, Jae Hoon Bahn, Hyun-Ik Jun, Jae-Hyung Lee, Giovanni Quinones-Valdez, Chonghui Cheng and Xinshu Xiao

Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions

One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes...

Authors: Enrique Navas-Pérez, Cristina Vicente-García, Serena Mirra, Demian Burguera, Noèlia Fernàndez-Castillo, José Luis Ferrán, Macarena López-Mayorga, Marta Alaiz-Noya, Irene Suárez-Pereira, Ester Antón-Galindo, Fausto Ulloa, Carlos Herrera-Úbeda, Pol Cuscó, Rafael Falcón-Moya, Antonio Rodríguez-Moreno, Salvatore D’Aniello…

High throughput single-cell detection of multiplex CRISPR-edited gene modifications

CRISPR-Cas9 gene editing has transformed our ability to rapidly interrogate the functional impact of somatic mutations in human cancers. Droplet-based technology enables the analysis of Cas9-introduced gene ed...

Authors: Elisa ten Hacken, Kendell Clement, Shuqiang Li, María Hernández-Sánchez, Robert Redd, Shu Wang, David Ruff, Michaela Gruber, Kaitlyn Baranowski, Jose Jacob, James Flynn, Keith W. Jones, Donna Neuberg, Kenneth J. Livak, Luca Pinello and Catherine J. Wu

The design and construction of reference pangenome graphs with minigraph

The recent advances in sequencing technologies enable the assembly of individual genomes to the quality of the reference genome. How to integrate multiple genomes from the same species and make the integrated ...

Authors: Heng Li, Xiaowen Feng and Chong Chu

Multiomics kaleidoscope to visualize cancer hallmarks

Authors: Shengtao Zhou

Clonal tracing reveals diverse patterns of response to immune checkpoint blockade

Immune checkpoint blockade (ICB) therapy has improved patient survival in a variety of cancers, but only a minority of cancer patients respond. Multiple studies have sought to identify general biomarkers of IC...

Authors: Shengqing Stan Gu, Xiaoqing Wang, Xihao Hu, Peng Jiang, Ziyi Li, Nicole Traugh, Xia Bu, Qin Tang, Chenfei Wang, Zexian Zeng, Jingxin Fu, Cliff Meyer, Yi Zhang, Paloma Cejas, Klothilda Lim, Jin Wang…

Multiplex enCas12a screens detect functional buffering among paralogs otherwise masked in monogenic Cas9 knockout screens

Pooled library CRISPR/Cas9 knockout screening across hundreds of cell lines has identified genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the...

Authors: Merve Dede, Megan McLaughlin, Eiru Kim and Traver Hart

iMOKA: k-mer based software to analyze large collections of sequencing data

iMOKA (interactive multi-objective k-mer analysis) is a software that enables comprehensive analysis of sequencing data from large cohorts to generate robust classification models or explore specific genetic elem...

Authors: Claudio Lorenzi, Sylvain Barriere, Jean-Philippe Villemin, Laureline Dejardin Bretones, Alban Mancheron and William Ritchie

AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants

Stochastic changes in DNA methylation (i.e., spontaneous epimutations) contribute to methylome diversity in plants. Here, we describe AlphaBeta, a computational method for estimating the precise rate of such stoc...

Authors: Yadollah Shahryary, Aikaterini Symeonidi, Rashmi R. Hazarika, Johanna Denkena, Talha Mubeen, Brigitte Hofmeister, Thomas van Gurp, Maria Colomé-Tatché, Koen J.F. Verhoeven, Gerald Tuskan, Robert J. Schmitz and Frank Johannes

A genome assembly and the somatic genetic and epigenetic mutation rate in a wild long-lived perennial Populus trichocarpa

Plants can transmit somatic mutations and epimutations to offspring, which in turn can affect fitness. Knowledge of the rate at which these variations arise is necessary to understand how plant development con...

Authors: Brigitte T. Hofmeister, Johanna Denkena, Maria Colomé-Tatché, Yadollah Shahryary, Rashmi Hazarika, Jane Grimwood, Sujan Mamidi, Jerry Jenkins, Paul P. Grabowski, Avinash Sreedasyam, Shengqiang Shu, Kerrie Barry, Kathleen Lail, Catherine Adam, Anna Lipzen, Rotem Sorek…

An integrated peach genome structural variation map uncovers genes associated with fruit traits

Genome structural variations (SVs) have been associated with key traits in a wide range of agronomically important species; however, SV profiles of peach and their functional impacts remain largely unexplored.

Authors: Jian Guo, Ke Cao, Cecilia Deng, Yong Li, Gengrui Zhu, Weichao Fang, Changwen Chen, Xinwei Wang, Jinlong Wu, Liping Guan, Shan Wu, Wenwu Guo, Jia-Long Yao, Zhangjun Fei and Lirong Wang

Prime editing efficiently generates W542L and S621I double mutations in two ALS genes in maize

Prime editing is a novel and universal CRISPR/Cas-derived precision genome-editing technology that has been recently developed. However, low efficiency of prime editing has been shown in transgenic rice lines....

Authors: Yuan-Yuan Jiang, Yi-Ping Chai, Min-Hui Lu, Xiu-Li Han, Qiupeng Lin, Yu Zhang, Qiang Zhang, Yun Zhou, Xue-Chen Wang, Caixia Gao and Qi-Jun Chen

Mustache: multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation

We present Mustache, a new method for multi-scale detection of chromatin loops from Hi-C and Micro-C contact maps. Mustache employs scale-space theory, a technical advance in computer vision, to detect blob-shape...

Authors: Abbas Roayaei Ardakany, Halil Tuvan Gezer, Stefano Lonardi and Ferhat Ay

Tissue-specific usage of transposable element-derived promoters in mouse development

Transposable elements (TEs) are a significant component of eukaryotic genomes and play essential roles in genome evolution. Mounting evidence indicates that TEs are highly transcribed in early embryo developme...

Authors: Benpeng Miao, Shuhua Fu, Cheng Lyu, Paul Gontarz, Ting Wang and Bo Zhang

A systematic comparison of chloroplast genome assembly tools

Chloroplasts are intracellular organelles that enable plants to conduct photosynthesis. They arose through the symbiotic integration of a prokaryotic cell into an eukaryotic host cell and still contain their o...

Authors: Jan A. Freudenthal, Simon Pfaff, Niklas Terhoeven, Arthur Korte, Markus J. Ankenbrand and Frank Förster

GraphAligner: rapid and versatile sequence-to-graph alignment

Genome graphs can represent genetic variation and sequence uncertainty. Aligning sequences to genome graphs is key to many applications, including error correction, genome assembly, and genotyping of variants in ...

Authors: Mikko Rautiainen and Tobias Marschall

Haplotype threading: accurate polyploid phasing from long reads

Resolving genomes at haplotype level is crucial for understanding the evolutionary history of polyploid species and for designing advanced breeding strategies. Polyploid phasing still presents considerable cha...

Authors: Sven D. Schrinner, Rebecca Serra Mari, Jana Ebler, Mikko Rautiainen, Lancelot Seillier, Julia J. Reimer, Björn Usadel, Tobias Marschall and Gunnar W. Klau

Chromatin regulates expression of small RNAs to help maintain transposon methylome homeostasis in Arabidopsis

Eukaryotic genomes are partitioned into euchromatic and heterochromatic domains to regulate gene expression and other fundamental cellular processes. However, chromatin is dynamic during growth and development...

Authors: Ranjith K. Papareddy, Katalin Páldi, Subramanian Paulraj, Ping Kao, Stefan Lutzmayer and Michael D. Nodine

Removing reference bias and improving indel calling in ancient DNA data analysis by mapping to a sequence variation graph

During the last decade, the analysis of ancient DNA (aDNA) sequence has become a powerful tool for the study of past human populations. However, the degraded nature of aDNA means that aDNA molecules are short ...

Authors: Rui Martiniano, Erik Garrison, Eppie R. Jones, Andrea Manica and Richard Durbin

Bifrost: highly parallel construction and indexing of colored and compacted de Bruijn graphs

Memory consumption of de Bruijn graphs is often prohibitive. Most de Bruijn graph-based assemblers reduce the complexity by compacting paths into single vertices, but this is challenging as it requires the unc...

Authors: Guillaume Holley and Páll Melsted

Ultrasensitive deletion detection links mitochondrial DNA replication, disease, and aging

Acquired human mitochondrial genome (mtDNA) deletions are symptoms and drivers of focal mitochondrial respiratory deficiency, a pathological hallmark of aging and late-onset mitochondrial disease.

Authors: Scott A. Lujan, Matthew J. Longley, Margaret H. Humble, Christopher A. Lavender, Adam Burkholder, Emma L. Blakely, Charlotte L. Alston, Grainne S. Gorman, Doug M. Turnbull, Robert McFarland, Robert W. Taylor, Thomas A. Kunkel and William C. Copeland

Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation

The three-dimensional genome organization is critical for gene regulation and can malfunction in diseases like cancer. As a key regulator of genome organization, CCCTC-binding factor (CTCF) has been characteri...

Authors: Celestia Fang, Zhenjia Wang, Cuijuan Han, Stephanie L. Safgren, Kathryn A. Helmin, Emmalee R. Adelman, Valentina Serafin, Giuseppe Basso, Kyle P. Eagen, Alexandre Gaspar-Maia, Maria E. Figueroa, Benjamin D. Singer, Aakrosh Ratan, Panagiotis Ntziachristos and Chongzhi Zang

AuthentiCT: a model of ancient DNA damage to estimate the proportion of present-day DNA contamination

Contamination from present-day DNA is a fundamental issue when studying ancient DNA from historical or archaeological material, and quantifying the amount of contamination is essential for downstream analyses....

Authors: Stéphane Peyrégne and Benjamin M. Peter

Merqury: reference-free quality, completeness, and phasing assessment for genome assemblies

Recent long-read assemblies often exceed the quality and completeness of available reference genomes, making validation challenging. Here we present Merqury, a novel tool for reference-free assembly evaluation...

Authors: Arang Rhie, Brian P. Walenz, Sergey Koren and Adam M. Phillippy

Primo: integration of multiple GWAS and omics QTL summary statistics for elucidation of molecular mechanisms of trait-associated SNPs and detection of pleiotropy in complex traits

To provide a comprehensive mechanistic interpretation of how known trait-associated SNPs affect complex traits, we propose a method, Primo, for integrative analysis of GWAS summary statistics with multiple set...

Authors: Kevin J. Gleason, Fan Yang, Brandon L. Pierce, Xin He and Lin S. Chen

sn-spMF: matrix factorization informs tissue-specific genetic regulation of gene expression

Genetic regulation of gene expression, revealed by expression quantitative trait loci (eQTLs), exhibits complex patterns of tissue-specific effects. Characterization of these patterns may allow us to better un...

Authors: Yuan He, Surya B. Chhetri, Marios Arvanitis, Kaushik Srinivasan, François Aguet, Kristin G. Ardlie, Alvaro N. Barbeira, Rodrigo Bonazzola, Hae Kyung Im, Christopher D. Brown and Alexis Battle

A vast resource of allelic expression data spanning human tissues

Allele expression (AE) analysis robustly measures cis-regulatory effects. Here, we present and demonstrate the utility of a vast AE resource generated from the GTEx v8 release, containing 15,253 samples spanning ...

Authors: Stephane E. Castel, François Aguet, Pejman Mohammadi, Kristin G. Ardlie and Tuuli Lappalainen

Impact of admixture and ancestry on eQTL analysis and GWAS colocalization in GTEx

Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings. The Genotype-Tissue Expression (GTEx) project largely contains i...

Authors: Nicole R. Gay, Michael Gloudemans, Margaret L. Antonio, Nathan S. Abell, Brunilda Balliu, YoSon Park, Alicia R. Martin, Shaila Musharoff, Abhiram S. Rao, François Aguet, Alvaro N. Barbeira, Rodrigo Bonazzola, Farhad Hormozdiari, Kristin G. Ardlie, Christopher D. Brown, Hae Kyung Im…

PTWAS: investigating tissue-relevant causal molecular mechanisms of complex traits using probabilistic TWAS analysis

We propose a new computational framework, probabilistic transcriptome-wide association study (PTWAS), to investigate causal relationships between gene expressions and complex traits. PTWAS applies the establis...

Authors: Yuhua Zhang, Corbin Quick, Ketian Yu, Alvaro Barbeira, Francesca Luca, Roger Pique-Regi, Hae Kyung Im and Xiaoquan Wen

Estimating the quality of eukaryotic genomes recovered from metagenomic analysis with EukCC

Microbial eukaryotes constitute a significant fraction of biodiversity and have recently gained more attention, but the recovery of high-quality metagenomic assembled eukaryotic genomes is limited by the curre...

Authors: Paul Saary, Alex L. Mitchell and Robert D. Finn

STARR-seq identifies active, chromatin-masked, and dormant enhancers in pluripotent mouse embryonic stem cells

Enhancers are distal regulators of gene expression that shape cell identity and control cell fate transitions. In mouse embryonic stem cells (mESCs), the pluripotency network is maintained by the function of a...

Authors: Tianran Peng, Yanan Zhai, Yaser Atlasi, Menno ter Huurne, Hendrik Marks, Hendrik G. Stunnenberg and Wout Megchelenbrink

Metalign: efficient alignment-based metagenomic profiling via containment min hash

Metagenomic profiling, predicting the presence and relative abundances of microbes in a sample, is a critical first step in microbiome analysis. Alignment-based approaches are often considered accurate yet com...

Authors: Nathan LaPierre, Mohammed Alser, Eleazar Eskin, David Koslicki and Serghei Mangul

GetOrganelle: a fast and versatile toolkit for accurate de novo assembly of organelle genomes

GetOrganelle is a state-of-the-art toolkit to accurately assemble organelle genomes from whole genome sequencing data. It recruits organelle-associated reads using a modified “baiting and iterative mapping” ap...

Authors: Jian-Jun Jin, Wen-Bin Yu, Jun-Bo Yang, Yu Song, Claude W. dePamphilis, Ting-Shuang Yi and De-Zhu Li

Natural display of nuclear-encoded RNA on the cell surface and its impact on cell interaction

Compared to proteins, glycans, and lipids, much less is known about RNAs on the cell surface. We develop a series of technologies to test for any nuclear-encoded RNAs that are stably attached to the cell surfa...

Authors: Norman Huang, Xiaochen Fan, Kathia Zaleta-Rivera, Tri C. Nguyen, Jiarong Zhou, Yingjun Luo, Jie Gao, Ronnie H. Fang, Zhangming Yan, Zhen Bouman Chen, Liangfang Zhang and Sheng Zhong

The Tug1 lncRNA locus is essential for male fertility

Several long noncoding RNAs (lncRNAs) have been shown to function as components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has grea...

Authors: Jordan P. Lewandowski, Gabrijela Dumbović, Audrey R. Watson, Taeyoung Hwang, Emily Jacobs-Palmer, Nydia Chang, Christian Much, Kyle M. Turner, Christopher Kirby, Nimrod D. Rubinstein, Abigail F. Groff, Steve C. Liapis, Chiara Gerhardinger, Assaf Bester, Pier Paolo Pandolfi, John G. Clohessy…