Articles

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

Subtype-associated epigenomic landscape and 3D genome structure in bladder cancer

Muscle-invasive bladder cancers are characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival....

Authors: Tejaswi Iyyanki, Baozhen Zhang, Qixuan Wang, Ye Hou, Qiushi Jin, Jie Xu, Hongbo Yang, Tingting Liu, Xiaotao Wang, Fan Song, Yu Luan, Hironobu Yamashita, Ruby Chien, Huijue Lyu, Lijun Zhang, Lu Wang…

PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity

Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients w...

Authors: Shuang Qu, Zichen Jiao, Geng Lu, Bing Yao, Ting Wang, Weiwei Rong, Jiahan Xu, Ting Fan, Xinlei Sun, Rong Yang, Jun Wang, Yongzhong Yao, Guifang Xu, Xin Yan, Tao Wang, Hongwei Liang…

Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication

Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address ...

Authors: Gareth B. Gillard, Lars Grønvold, Line L. Røsæg, Matilde Mengkrog Holen, Øystein Monsen, Ben F. Koop, Eric B. Rondeau, Manu Kumar Gundappa, John Mendoza, Daniel J. Macqueen, Rori V. Rohlfs, Simen R. Sandve and Torgeir R. Hvidsten

A benchmark for RNA-seq deconvolution analysis under dynamic testing environments

Deconvolution analyses have been widely used to track compositional alterations of cell types in gene expression data. Although a large number of novel methods have been developed, due to a lack of understandi...

Authors: Haijing Jin and Zhandong Liu

Computational methods for chromosome-scale haplotype reconstruction

High-quality chromosome-scale haplotype sequences of diploid genomes, polyploid genomes, and metagenomes provide important insights into genetic variation associated with disease and biodiversity. However, who...

Authors: Shilpa Garg

Comparative genomics identifies thousands of candidate structured RNAs in human microbiomes

Structured RNAs play varied bioregulatory roles within microbes. To date, hundreds of candidate structured RNAs have been predicted using informatic approaches that search for motif structures in genomic seque...

Authors: Brayon J. Fremin and Ami S. Bhatt

ACME dissociation: a versatile cell fixation-dissociation method for single-cell transcriptomics

Single-cell sequencing technologies are revolutionizing biology, but they are limited by the need to dissociate live samples. Here, we present ACME (ACetic-MEthanol), a dissociation approach for single-cell tr...

Authors: Helena García-Castro, Nathan J. Kenny, Marta Iglesias, Patricia Álvarez-Campos, Vincent Mason, Anamaria Elek, Anna Schönauer, Victoria A. Sleight, Jakke Neiro, Aziz Aboobaker, Jon Permanyer, Manuel Irimia, Arnau Sebé-Pedrós and Jordi Solana

Response to correspondence on “Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation”

Authors: Channabasavaiah B. Gurumurthy, Aidan R. O’Brien, Rolen M. Quadros, John Adams Jr, Pilar Alcaide, Shinya Ayabe, Johnathan Ballard, Surinder K. Batra, Marie-Claude Beauchamp, Kathleen A. Becker, Guillaume Bernas, David Brough, Francisco Carrillo-Salinas, Wesley Chan, Hanying Chen, Ruby Dawson…

Response to “Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation”

Authors: Hui Yang, Haoyi Wang and Rudolf Jaenisch

PCIP-seq: simultaneous sequencing of integrated viral genomes and their insertion sites with long reads

The integration of a viral genome into the host genome has a major impact on the trajectory of the infected cell. Integration location and variation within the associated viral genome can influence both clonal...

Authors: Maria Artesi, Vincent Hahaut, Basiel Cole, Laurens Lambrechts, Fereshteh Ashrafi, Ambroise Marçais, Olivier Hermine, Philip Griebel, Natasa Arsic, Frank van der Meer, Arsène Burny, Dominique Bron, Elettra Bianchi, Philippe Delvenne, Vincent Bours, Carole Charlier…

Simplitigs as an efficient and scalable representation of de Bruijn graphs

de Bruijn graphs play an essential role in bioinformatics, yet they lack a universal scalable representation. Here, we introduce simplitigs as a compact, efficient, and scalable representation, and ProphAsm, a...

Authors: Karel Břinda, Michael Baym and Gregory Kucherov

Homopolish: a method for the removal of systematic errors in nanopore sequencing by homologous polishing

Nanopore sequencing has been widely used for the reconstruction of microbial genomes. Owing to higher error rates, errors on the genome are corrected via neural networks trained by Nanopore reads. However, the...

Authors: Yao-Ting Huang, Po-Yu Liu and Pei-Wen Shih

MTSplice predicts effects of genetic variants on tissue-specific splicing

We develop the free and open-source model Multi-tissue Splicing (MTSplice) to predict the effects of genetic variants on splicing of cassette exons in 56 human tissues. MTSplice combines MMSplice, which models...

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

Microbiome meta-analysis and cross-disease comparison enabled by the SIAMCAT machine learning toolbox

The human microbiome is increasingly mined for diagnostic and therapeutic biomarkers using machine learning (ML). However, metagenomics-specific software is scarce, and overoptimistic evaluation and limited cr...

Authors: Jakob Wirbel, Konrad Zych, Morgan Essex, Nicolai Karcher, Ece Kartal, Guillem Salazar, Peer Bork, Shinichi Sunagawa and Georg Zeller

Comprehensive identification of somatic nucleotide variants in human brain tissue

Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. How...

Authors: Yifan Wang, Taejeong Bae, Jeremy Thorpe, Maxwell A. Sherman, Attila G. Jones, Sean Cho, Kenneth Daily, Yanmei Dou, Javier Ganz, Alon Galor, Irene Lobon, Reenal Pattni, Chaggai Rosenbluh, Simone Tomasi, Livia Tomasini, Xiaoxu Yang…

Utilizing genomics to understand and respond to global climate change

Authors: Justin Borevitz

Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders

People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm...

Authors: Marta F. Nabais, Simon M. Laws, Tian Lin, Costanza L. Vallerga, Nicola J. Armstrong, Ian P. Blair, John B. Kwok, Karen A. Mather, George D. Mellick, Perminder S. Sachdev, Leanne Wallace, Anjali K. Henders, Ramona A. J. Zwamborn, Paul J. Hop, Katie Lunnon, Ehsan Pishva…

Author Correction: CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies

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

Authors: Rebecca Davies, Ling Liu, Sheng Taotao, Natasha Tuano, Richa Chaturvedi, Kie Kyon Huang, Catherine Itman, Amit Mandoli, Aditi Qamra, Changyuan Hu, David Powell, Roger J. Daly, Patrick Tan and Joseph Rosenbluh

Unraveling the cartography of the cancer ecosystem

Authors: Roy Rabbie, Doreen Lau, Richard M. White and David J. Adams

Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing

Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new...

Authors: Xi Gu, Daqi Wang, Zhijiao Xu, Jinghan Wang, Luo Guo, Renjie Chai, Genglin Li, Yilai Shu and Huawei Li

Histone lactylation drives oncogenesis by facilitating m⁶A reader protein YTHDF2 expression in ocular melanoma

Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in...

Authors: Jie Yu, Peiwei Chai, Minyue Xie, Shengfang Ge, Jing Ruan, Xianqun Fan and Renbing Jia

Kssd: sequence dimensionality reduction by k-mer substring space sampling enables real-time large-scale datasets analysis

Here, we develop k -mer substring space decomposition (Kssd), a sketching technique which is significantly faster and more accurate than current sketching methods. We show that it is the only method that can b...

Authors: Huiguang Yi, Yanling Lin, Chengqi Lin and Wenfei Jin

Prime editing in mice reveals the essentiality of a single base in driving tissue-specific gene expression

Most single nucleotide variants (SNVs) occur in noncoding sequence where millions of transcription factor binding sites (TFBS) reside. Here, a comparative analysis of CRISPR-mediated homology-directed repair (...

Authors: Pan Gao, Qing Lyu, Amr R. Ghanam, Cicera R. Lazzarotto, Gregory A. Newby, Wei Zhang, Mihyun Choi, Orazio J. Slivano, Kevin Holden, John A. Walker II, Anastasia P. Kadina, Rob J. Munroe, Christian M. Abratte, John C. Schimenti, David R. Liu, Shengdar Q. Tsai…

SRSF3 and SRSF7 modulate 3′UTR length through suppression or activation of proximal polyadenylation sites and regulation of CFIm levels

Alternative polyadenylation (APA) refers to the regulated selection of polyadenylation sites (PASs) in transcripts, which determines the length of their 3′ untranslated regions (3′UTRs). We have recently shown...

Authors: Oliver Daniel Schwich, Nicole Blümel, Mario Keller, Marius Wegener, Samarth Thonta Setty, Melinda Elaine Brunstein, Ina Poser, Igor Ruiz De Los Mozos, Beatrix Suess, Christian Münch, François McNicoll, Kathi Zarnack and Michaela Müller-McNicoll

gapseq: informed prediction of bacterial metabolic pathways and reconstruction of accurate metabolic models

Genome-scale metabolic models of microorganisms are powerful frameworks to predict phenotypes from an organism’s genotype. While manual reconstructions are laborious, automated reconstructions often fail to re...

Authors: Johannes Zimmermann, Christoph Kaleta and Silvio Waschina

Identification of pathogenic variants in cancer genes using base editing screens with editing efficiency correction

Millions of nucleotide variants are identified through cancer genome sequencing and it is clinically important to identify the pathogenic variants among them. By introducing base substitutions at guide RNA tar...

Authors: Changcai Huang, Guangyu Li, Jiayu Wu, Junbo Liang and Xiaoyue Wang

Genetic variation and microRNA targeting of A-to-I RNA editing fine tune human tissue transcriptomes

A-to-I RNA editing diversifies the transcriptome and has multiple downstream functional effects. Genetic variation contributes to RNA editing variability between individuals and has the potential to impact phe...

Authors: Eddie Park, Yan Jiang, Lili Hao, Jingyi Hui and Yi Xing

riboCIRC: a comprehensive database of translatable circRNAs

riboCIRC is a translatome data-oriented circRNA database specifically designed for hosting, exploring, analyzing, and visualizing translatable circRNAs from multi-species. The database provides a comprehensive...

Authors: Huihui Li, Mingzhe Xie, Yan Wang, Ludong Yang, Zhi Xie and Hongwei Wang

Giotto: a toolbox for integrative analysis and visualization of spatial expression data

Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive and open-source toolbox for spat...

Authors: Ruben Dries, Qian Zhu, Rui Dong, Chee-Huat Linus Eng, Huipeng Li, Kan Liu, Yuntian Fu, Tianxiao Zhao, Arpan Sarkar, Feng Bao, Rani E. George, Nico Pierson, Long Cai and Guo-Cheng Yuan

Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells

The discovery that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) has provided a foundation for in vitro human disease modelling, drug development and population genetics studies. ...

Authors: Drew Neavin, Quan Nguyen, Maciej S. Daniszewski, Helena H. Liang, Han Sheng Chiu, Yong Kiat Wee, Anne Senabouth, Samuel W. Lukowski, Duncan E. Crombie, Grace E. Lidgerwood, Damián Hernández, James C. Vickers, Anthony L. Cook, Nathan J. Palpant, Alice Pébay, Alex W. Hewitt…

seqQscorer: automated quality control of next-generation sequencing data using machine learning

Controlling quality of next-generation sequencing (NGS) data files is a necessary but complex task. To address this problem, we statistically characterize common NGS quality features and develop a novel qualit...

Authors: Steffen Albrecht, Maximilian Sprang, Miguel A. Andrade-Navarro and Jean-Fred Fontaine

simATAC: a single-cell ATAC-seq simulation framework

Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) identifies regulated chromatin accessibility modules at the single-cell resolution. Robust evaluation is critical to the developme...

Authors: Zeinab Navidi, Lin Zhang and Bo Wang

Pluripotent stem cell-derived models of neurological diseases reveal early transcriptional heterogeneity

Many neurodegenerative diseases develop only later in life, when cells in the nervous system lose their structure or function. In many forms of neurodegenerative diseases, this late-onset phenomenon remains la...

Authors: Matan Sorek, Walaa Oweis, Malka Nissim-Rafinia, Moria Maman, Shahar Simon, Cynthia C. Hession, Xian Adiconis, Sean K. Simmons, Neville E. Sanjana, Xi Shi, Congyi Lu, Jen Q. Pan, Xiaohong Xu, Mahmoud A. Pouladi, Lisa M. Ellerby, Feng Zhang…

2passtools: two-pass alignment using machine-learning-filtered splice junctions increases the accuracy of intron detection in long-read RNA sequencing

Transcription of eukaryotic genomes involves complex alternative processing of RNAs. Sequencing of full-length RNAs using long reads reveals the true complexity of processing. However, the relatively high erro...

Authors: Matthew T. Parker, Katarzyna Knop, Geoffrey J. Barton and Gordon G. Simpson

Re-evaluating experimental validation in the Big Data Era: a conceptual argument

Authors: Mohieddin Jafari, Yuanfang Guan, David C. Wedge and Naser Ansari-Pour

MEDALT: single-cell copy number lineage tracing enabling gene discovery

We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine...

Authors: Fang Wang, Qihan Wang, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jincheng Han, Darlan Conterno Minussi, Ruli Gao, Li Ding, Nicholas Navin and Ken Chen

scSorter: assigning cells to known cell types according to marker genes

On single-cell RNA-sequencing data, we consider the problem of assigning cells to known cell types, assuming that the identities of cell-type-specific marker genes are given but their exact expression levels a...

Authors: Hongyu Guo and Jun Li

Megabase-scale methylation phasing using nanopore long reads and NanoMethPhase

The ability of nanopore sequencing to simultaneously detect modified nucleotides while producing long reads makes it ideal for detecting and phasing allele-specific methylation. However, there is currently no ...

Authors: Vahid Akbari, Jean-Michel Garant, Kieran O’Neill, Pawan Pandoh, Richard Moore, Marco A. Marra, Martin Hirst and Steven J. M. Jones

FlsnRNA-seq: protoplasting-free full-length single-nucleus RNA profiling in plants

The broad application of single-cell RNA profiling in plants has been hindered by the prerequisite of protoplasting that requires digesting the cell walls from different types of plant tissues. Here, we presen...

Authors: Yanping Long, Zhijian Liu, Jinbu Jia, Weipeng Mo, Liang Fang, Dongdong Lu, Bo Liu, Hong Zhang, Wei Chen and Jixian Zhai

Promoting reproducibility with Code Ocean

Authors: Barbara Cheifet