Articles

Biologically relevant transfer learning improves transcription factor binding prediction

Deep learning has proven to be a powerful technique for transcription factor (TF) binding prediction but requires large training datasets. Transfer learning can reduce the amount of data required for deep lear...

Authors: Gherman Novakovsky, Manu Saraswat, Oriol Fornes, Sara Mostafavi and Wyeth W. Wasserman

Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation

Mammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentia...

Authors: Giancarlo Bonora, Vijay Ramani, Ritambhara Singh, He Fang, Dana L. Jackson, Sanjay Srivatsan, Ruolan Qiu, Choli Lee, Cole Trapnell, Jay Shendure, Zhijun Duan, Xinxian Deng, William S. Noble and Christine M. Disteche

ACE: a probabilistic model for characterizing gene-level essentiality in CRISPR screens

High-throughput CRISPR-Cas9 knockout screens are widely used to evaluate gene essentiality in cancer research. Here we introduce a probabilistic modeling framework, Analysis of CRISPR-based Essentiality (ACE),...

Authors: Elizabeth R. Hutton, Christopher R. Vakoc and Adam Siepel

SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs

Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs fo...

Authors: Avigayel Rabin, Michela Zaffagni, Reut Ashwal-Fluss, Ines Lucia Patop, Aarti Jajoo, Shlomo Shenzis, Liran Carmel and Sebastian Kadener

Genome and metabolome: chance and necessity

Authors: Emanuel Gonçalves and Christian Frezza

The influence of the gut microbiome on BCG-induced trained immunity

The bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in specific and nonspecific, or trained, immune responses. While...

Authors: Martin Stražar, Vera P. Mourits, Valerie A. C. M. Koeken, L. Charlotte J. de Bree, Simone J. C. F. M. Moorlag, Leo A. B. Joosten, Reinout van Crevel, Hera Vlamakis, Mihai G. Netea and Ramnik J. Xavier

Revisiting genetic artifacts on DNA methylation microarrays exposes novel biological implications

Illumina DNA methylation microarrays enable epigenome-wide analysis vastly used for the discovery of novel DNA methylation variation in health and disease. However, the microarrays’ probe design cannot fully c...

Authors: Benjamin Planterose Jiménez, Manfred Kayser and Athina Vidaki

Chromatin accessibility and regulatory vocabulary across indicine cattle tissues

Spatiotemporal changes in the chromatin accessibility landscape are essential to cell differentiation, development, health, and disease. The quest of identifying regulatory elements in open chromatin regions a...

Authors: Pâmela A. Alexandre, Marina Naval-Sánchez, Moira Menzies, Loan T. Nguyen, Laercio R. Porto-Neto, Marina R. S. Fortes and Antonio Reverter

Author Correction: Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network

Authors: Zhonghua Du, Xue Wen, Yichen Wang, Lin Jia, Shilin Zhang, Yudi Liu, Lei Zhou, Hui Li, Wang Yang, Cong Wang, Jingcheng Chen, Yajing Hao, Daniela Salgado Figueroa, Huiling Chen, Dan Li, Naifei Chen…

LightGBM: accelerated genomically designed crop breeding through ensemble learning

LightGBM is an ensemble model of decision trees for classification and regression prediction. We demonstrate its utility in genomic selection-assisted breeding with a large dataset of inbred and hybrid maize l...

Authors: Jun Yan, Yuetong Xu, Qian Cheng, Shuqin Jiang, Qian Wang, Yingjie Xiao, Chuang Ma, Jianbing Yan and Xiangfeng Wang

STAT: a fast, scalable, MinHash-based k-mer tool to assess Sequence Read Archive next-generation sequence submissions

Sequence Read Archive submissions to the National Center for Biotechnology Information often lack useful metadata, which limits the utility of these submissions. We describe the Sequence Taxonomic Analysis Too...

Authors: Kenneth S. Katz, Oleg Shutov, Richard Lapoint, Michael Kimelman, J. Rodney Brister and Christopher O’Sullivan

Mapping the evolving landscape of super-enhancers during cell differentiation

Super-enhancers are clusters of enhancer elements that play critical roles in the maintenance of cell identity. Current investigations on super-enhancers are centered on the established ones in static cell typ...

Authors: Yan Kai, Bin E. Li, Ming Zhu, Grace Y. Li, Fei Chen, Yingli Han, Hye Ji Cha, Stuart H. Orkin, Wenqing Cai, Jialiang Huang and Guo-Cheng Yuan

PRINCESS: comprehensive detection of haplotype resolved SNVs, SVs, and methylation

Long-read sequencing has been shown to have advantages in structural variation (SV) detection and methylation calling. Many studies focus either on SV, methylation, or phasing of SNV; however, only the combina...

Authors: Medhat Mahmoud, Harshavardhan Doddapaneni, Winston Timp and Fritz J. Sedlazeck

Pandora: nucleotide-resolution bacterial pan-genomics with reference graphs

We present pandora, a novel pan-genome graph structure and algorithms for identifying variants across the full bacterial pan-genome. As much bacterial adaptability hinges on the accessory genome, methods which an...

Authors: Rachel M. Colquhoun, Michael B. Hall, Leandro Lima, Leah W. Roberts, Kerri M. Malone, Martin Hunt, Brice Letcher, Jane Hawkey, Sophie George, Louise Pankhurst and Zamin Iqbal

Trycycler: consensus long-read assemblies for bacterial genomes

While long-read sequencing allows for the complete assembly of bacterial genomes, long-read assemblies contain a variety of errors. Here, we present Trycycler, a tool which produces a consensus assembly from m...

Authors: Ryan R. Wick, Louise M. Judd, Louise T. Cerdeira, Jane Hawkey, Guillaume Méric, Ben Vezina, Kelly L. Wyres and Kathryn E. Holt

Regulatory regions in natural transposable element insertions drive interindividual differences in response to immune challenges in Drosophila

Variation in gene expression underlies interindividual variability in relevant traits including immune response. However, the genetic variation responsible for these gene expression changes remains largely unk...

Authors: Anna Ullastres, Miriam Merenciano and Josefa González

Evaluation of some aspects in supervised cell type identification for single-cell RNA-seq: classifier, feature selection, and reference construction

Cell type identification is one of the most important questions in single-cell RNA sequencing (scRNA-seq) data analysis. With the accumulation of public scRNA-seq data, supervised cell type identification meth...

Authors: Wenjing Ma, Kenong Su and Hao Wu

Recovering genotypes and phenotypes using allele-specific genes

With the recent increase in RNA sequencing efforts using large cohorts of individuals, surveying allele-specific gene expression is becoming increasingly frequent. Here, we report that, despite not containing ...

Authors: Gamze Gürsoy, Nancy Lu, Sarah Wagner and Mark Gerstein

SUPERGNOVA: local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits

Local genetic correlation quantifies the genetic similarity of complex traits in specific genomic regions. However, accurate estimation of local genetic correlation remains challenging, due to linkage disequil...

Authors: Yiliang Zhang, Qiongshi Lu, Yixuan Ye, Kunling Huang, Wei Liu, Yuchang Wu, Xiaoyuan Zhong, Boyang Li, Zhaolong Yu, Brittany G. Travers, Donna M. Werling, James J. Li and Hongyu Zhao

NanoCaller for accurate detection of SNPs and indels in difficult-to-map regions from long-read sequencing by haplotype-aware deep neural networks

Long-read sequencing enables variant detection in genomic regions that are considered difficult-to-map by short-read sequencing. To fully exploit the benefits of longer reads, here we present a deep learning m...

Authors: Mian Umair Ahsan, Qian Liu, Li Fang and Kai Wang

Genomic basis underlying the metabolome-mediated drought adaptation of maize

Drought is a major environmental disaster that causes crop yield loss worldwide. Metabolites are involved in various environmental stress responses of plants. However, the genetic control of metabolomes underl...

Authors: Fei Zhang, Jinfeng Wu, Nir Sade, Si Wu, Aiman Egbaria, Alisdair R. Fernie, Jianbing Yan, Feng Qin, Wei Chen, Yariv Brotman and Mingqiu Dai

Gramtools enables multiscale variation analysis with genome graphs

Genome graphs allow very general representations of genetic variation; depending on the model and implementation, variation at different length-scales (single nucleotide polymorphisms (SNPs), structural varian...

Authors: Brice Letcher, Martin Hunt and Zamin Iqbal

Analytic Pearson residuals for normalization of single-cell RNA-seq UMI data

Standard preprocessing of single-cell RNA-seq UMI data includes normalization by sequencing depth to remove this technical variability, and nonlinear transformation to stabilize the variance across genes with ...

Authors: Jan Lause, Philipp Berens and Dmitry Kobak

PUMAS: fine-tuning polygenic risk scores with GWAS summary statistics

Polygenic risk scores (PRSs) have wide applications in human genetics research, but often include tuning parameters which are difficult to optimize in practice due to limited access to individual-level data. H...

Authors: Zijie Zhao, Yanyao Yi, Jie Song, Yuchang Wu, Xiaoyuan Zhong, Yupei Lin, Timothy J. Hohman, Jason Fletcher and Qiongshi Lu

Oncogene Concatenated Enriched Amplicon Nanopore Sequencing for rapid, accurate, and affordable somatic mutation detection

We develop the Oncogene Concatenated Enriched Amplicon Nanopore Sequencing (OCEANS) method, in which variants with low variant allele frequency (VAFs) are amplified and subsequently concatenated for Nanopore S...

Authors: Deepak Thirunavukarasu, Lauren Y. Cheng, Ping Song, Sherry X. Chen, Mitesh J. Borad, Lawrence Kwong, Phillip James, Daniel J. Turner and David Yu Zhang

LeafGo: Leaf to Genome, a quick workflow to produce high-quality de novo plant genomes using long-read sequencing technology

Currently, different sequencing platforms are used to generate plant genomes and no workflow has been properly developed to optimize time, cost, and assembly quality. We present LeafGo, a complete de novo plan...

Authors: Patrick Driguez, Salim Bougouffa, Karen Carty, Alexander Putra, Kamel Jabbari, Muppala Reddy, Richard Soppe, Ming Sin Cheung, Yoshinori Fukasawa and Luca Ermini

Author Correction: Avocado: a multi-scale deep tensor factorization method learns a latent representation of the human epigenome

Authors: Jacob Schreiber, Timothy Durham, Jeffrey Bilmes and William Stafford Noble

Introgression among North American wild grapes (Vitis) fuels biotic and abiotic adaptation

Introgressive hybridization can reassort genetic variants into beneficial combinations, permitting adaptation to new ecological niches. To evaluate evolutionary patterns and dynamics that contribute to introgr...

Authors: Abraham Morales-Cruz, Jonas A. Aguirre-Liguori, Yongfeng Zhou, Andrea Minio, Summaira Riaz, Andrew M. Walker, Dario Cantu and Brandon S. Gaut

H2A ubiquitination is essential for Polycomb Repressive Complex 1-mediated gene regulation in Marchantia polymorpha

Polycomb repressive complex 1 (PRC1) and PRC2 are chromatin regulators maintaining transcriptional repression. The deposition of H3 lysine 27 tri-methylation (H3K27me3) by PRC2 is known to be required for tran...

Authors: Shujing Liu, Minerva S. Trejo-Arellano, Yichun Qiu, D. Magnus Eklund, Claudia Köhler and Lars Hennig

AMULET: a novel read count-based method for effective multiplet detection from single nucleus ATAC-seq data

Detecting multiplets in single nucleus (sn)ATAC-seq data is challenging due to data sparsity and limited dynamic range. AMULET (ATAC-seq MULtiplet Estimation Tool) enumerates regions with greater than two uniq...

Authors: Asa Thibodeau, Alper Eroglu, Christopher S. McGinnis, Nathan Lawlor, Djamel Nehar-Belaid, Romy Kursawe, Radu Marches, Daniel N. Conrad, George A. Kuchel, Zev J. Gartner, Jacques Banchereau, Michael L. Stitzel, A. Ercument Cicek and Duygu Ucar

BRIE2: computational identification of splicing phenotypes from single-cell transcriptomic experiments

RNA splicing is an important driver of heterogeneity in single cells through the expression of alternative transcripts and as a determinant of transcriptional kinetics. However, the intrinsic coverage limitati...

Authors: Yuanhua Huang and Guido Sanguinetti

NucHMM: a method for quantitative modeling of nucleosome organization identifying functional nucleosome states distinctly associated with splicing potentiality

We develop a novel computational method, NucHMM, to identify functional nucleosome states associated with cell type-specific combinatorial histone marks and nucleosome organization features such as phasing, sp...

Authors: Kun Fang, Tianbao Li, Yufei Huang and Victor X. Jin

Technology dictates algorithms: recent developments in read alignment

Aligning sequencing reads onto a reference is an essential step of the majority of genomic analysis pipelines. Computational algorithms for read alignment have evolved in accordance with technological advances...

Authors: Mohammed Alser, Jeremy Rotman, Dhrithi Deshpande, Kodi Taraszka, Huwenbo Shi, Pelin Icer Baykal, Harry Taegyun Yang, Victor Xue, Sergey Knyazev, Benjamin D. Singer, Brunilda Balliu, David Koslicki, Pavel Skums, Alex Zelikovsky, Can Alkan, Onur Mutlu…

Sfaira accelerates data and model reuse in single cell genomics

Single-cell RNA-seq datasets are often first analyzed independently without harnessing model fits from previous studies, and are then contextualized with public data sets, requiring time-consuming data wrangli...

Authors: David S. Fischer, Leander Dony, Martin König, Abdul Moeed, Luke Zappia, Lukas Heumos, Sophie Tritschler, Olle Holmberg, Hananeh Aliee and Fabian J. Theis

Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability

Genome-wide association studies have reported more than 100 risk loci for rheumatoid arthritis (RA). These loci are shown to be enriched in immune cell-specific enhancers, but the analysis so far has excluded ...

Authors: Xiangyu Ge, Mojca Frank-Bertoncelj, Kerstin Klein, Amanda McGovern, Tadeja Kuret, Miranda Houtman, Blaž Burja, Raphael Micheroli, Chenfu Shi, Miriam Marks, Andrew Filer, Christopher D. Buckley, Gisela Orozco, Oliver Distler, Andrew P. Morris, Paul Martin…

Author Correction: Community-wide hackathons to identify central themes in single-cell multi-omics

Authors: Kim-Anh Lê Cao, Al J. Abadi, Emily F. Davis-Marcisak, Lauren Hsu, Arshi Arora, Alexis Coullomb, Atul Deshpande, Yuzhou Feng, Pratheepa Jeganathan, Melanie Loth, Chen Meng, Wancen Mu, Vera Pancaldi, Kris Sankaran, Dario Righelli, Amrit Singh…

Absent from DNA and protein: genomic characterization of nullomers and nullpeptides across functional categories and evolution

Nullomers and nullpeptides are short DNA or amino acid sequences that are absent from a genome or proteome, respectively. One potential cause for their absence could be their having a detrimental impact on an ...

Authors: Ilias Georgakopoulos-Soares, Ofer Yizhar-Barnea, Ioannis Mouratidis, Martin Hemberg and Nadav Ahituv

Acute depletion of CTCF rewires genome-wide chromatin accessibility

The transcription factor CTCF appears indispensable in defining topologically associated domain boundaries and maintaining chromatin loop structures within these domains, supported by numerous functional studi...

Authors: Beisi Xu, Hong Wang, Shaela Wright, Judith Hyle, Yang Zhang, Ying Shao, Mingming Niu, Yiping Fan, Wojciech Rosikiewicz, Mohamed Nadhir Djekidel, Junmin Peng, Rui Lu and Chunliang Li

Deterministic transition of enterotypes shapes the infant gut microbiome at an early age

The succession of the gut microbiota during the first few years plays a vital role in human development. We elucidate the characteristics and alternations of the infant gut microbiota to better understand the ...

Authors: Liwen Xiao, Jinfeng Wang, Jiayong Zheng, Xiaoqing Li and Fangqing Zhao

Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus

To date, the locus with the most robust human genetic association to COVID-19 severity is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to...

Authors: Silva Kasela, Zharko Daniloski, Sailalitha Bollepalli, Tristan X. Jordan, Benjamin R. tenOever, Neville E. Sanjana and Tuuli Lappalainen

INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants

Genome-wide association studies reveal many non-coding variants associated with complex traits. However, model organism studies largely remain as an untapped resource for unveiling the effector genes of non-co...

Authors: Chenyang Dong, Shane P. Simonett, Sunyoung Shin, Donnie S. Stapleton, Kathryn L. Schueler, Gary A. Churchill, Leina Lu, Xiaoxiao Liu, Fulai Jin, Yan Li, Alan D. Attie, Mark P. Keller and Sündüz Keleş

Systematic functional interrogation of human pseudogenes using CRISPRi

The human genome encodes over 14,000 pseudogenes that are evolutionary relics of protein-coding genes and commonly considered as nonfunctional. Emerging evidence suggests that some pseudogenes may exert import...

Authors: Ming Sun, Yunfei Wang, Caishang Zheng, Yanjun Wei, Jiakai Hou, Peng Zhang, Wei He, Xiangdong Lv, Yao Ding, Han Liang, Chung-Chau Hon, Xi Chen, Han Xu and Yiwen Chen

ExOrthist: a tool to infer exon orthologies at any evolutionary distance

Several bioinformatic tools have been developed for genome-wide identification of orthologous and paralogous genes. However, no corresponding tool allows the detection of exon homology relationships. Here, we ...

Authors: Yamile Márquez, Federica Mantica, Luca Cozzuto, Demian Burguera, Antonio Hermoso-Pulido, Julia Ponomarenko, Scott W. Roy and Manuel Irimia

Bedshift: perturbation of genomic interval sets

Functional genomics experiments, like ChIP-Seq or ATAC-Seq, produce results that are summarized as a region set. There is no way to objectively evaluate the effectiveness of region set similarity metrics. We p...

Authors: Aaron Gu, Hyun Jae Cho and Nathan C. Sheffield

Megabase-scale presence-absence variation with Tripsacum origin was under selection during maize domestication and adaptation

Structural variants (SVs) significantly drive genome diversity and environmental adaptation for diverse species. Unlike the prevalent small SVs (< kilobase-scale) in higher eukaryotes, large-size SVs rarely ex...

Authors: Yumin Huang, Wei Huang, Zhuang Meng, Guilherme Tomaz Braz, Yunfei Li, Kai Wang, Hai Wang, Jinsheng Lai, Jiming Jiang, Zhaobin Dong and Weiwei Jin

Effective control of large deletions after double-strand breaks by homology-directed repair and dsODN insertion

After repairing double-strand breaks (DSBs) caused by CRISPR-Cas9 cleavage, genomic damage, such as large deletions, may have pathogenic consequences.

Authors: Wei Wen, Zi-Jun Quan, Si-Ang Li, Zhi-Xue Yang, Ya-Wen Fu, Feng Zhang, Guo-Hua Li, Mei Zhao, Meng-Di Yin, Jing Xu, Jian-Ping Zhang, Tao Cheng and Xiao-Bing Zhang

Easy-Prime: a machine learning–based prime editor design tool

Prime editing is a revolutionary genome-editing technology that can make a wide range of precise edits in DNA. However, designing highly efficient prime editors (PEs) remains challenging. We develop Easy-Prime...

Authors: Yichao Li, Jingjing Chen, Shengdar Q. Tsai and Yong Cheng

Keeping your lab together in the COVID-19 era

Authors: Timothy R. Sands

MultiK: an automated tool to determine optimal cluster numbers in single-cell RNA sequencing data

Single-cell RNA sequencing (scRNA-seq) provides new opportunities to characterize cell populations, typically accomplished through some type of clustering analysis. Estimation of the optimal cluster number (K) is...

Authors: Siyao Liu, Aatish Thennavan, Joseph P. Garay, J. S. Marron and Charles M. Perou

VariantStore: an index for large-scale genomic variant search

Efficiently scaling genomic variant search indexes to thousands of samples is computationally challenging due to the presence of multiple coordinate systems to avoid reference biases. We present VariantStore, ...

Authors: Prashant Pandey, Yinjie Gao and Carl Kingsford