Article
|
Open Access
Featured
-
-
Article
| Open Access
Deciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level
Here, Kessler et al use single-cell RNA sequencing of the intestine and mesentery from H18N11 influenza-infected bats to show that viral infection is predominant in leukocytes and causes activation of immune cells and antiviral gene signatures.
- Susanne Kessler
- , Bradly Burke
- & Kevin Ciminski
-
Article
| Open Access
Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates
Orphan transporters can be found in over 20 families in the SLC superfamily. Here, the authors show that human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220; while in great apes, its orthologs transport sex steroid conjugates.
- Sook Wah Yee
- , Luis Ferrández-Peral
- & Kathleen M. Giacomini
-
Article
| Open Access
A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma
Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.
- Jamie L. Everman
- , Satria P. Sajuthi
- & Max A. Seibold
-
Article
| Open Access
Spatially revealed roles for lncRNAs in Drosophila spermatogenesis, Y chromosome function and evolution
In Drosophila, long noncoding RNAs (lncRNAs) are expressed most highly in male germline cells. Here the authors report the subcellular distributions of approximately 600 Drosophila lncRNAs in male reproductive tissues, indicating potential involvement in spermatogenesis, fertility and evolution.
- Zhantao Shao
- , Jack Hu
- & Henry M. Krause
-
Article
| Open Access
Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo
Here, the authors report that schizophrenia risk variants mapping to a striatal dopamine-related gene set are associated with increased striatal dopamine synthesis capacity and increased striatal activity during reward anticipation in humans.
- Leonardo Sportelli
- , Daniel P. Eisenberg
- & Giulio Pergola
-
Article
| Open Access
Multi-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease
Here, Drury et al study gene, microRNA and protein expression during COVID-19, in a randomised controlled trial of ChAdOx1 nCoV19 vaccine and find that ChAdOx1 nCoV-19 attenuates the inflammatory response, thought to be the basis for severe COVID-19.
- Ruth E. Drury
- , Susana Camara
- & Daniel O’Connor
-
Article
| Open Access
Massively parallel screen uncovers many rare 3′ UTR variants regulating mRNA abundance of cancer driver genes
The function of rare non-coding variants remains challenging to decipher. Here, the authors developed MapUTR to uncover 10,524 functional rare 3’ UTR variants regulating mRNA abundance, many of which reside in cancer driver genes.
- Ting Fu
- , Kofi Amoah
- & Xinshu Xiao
-
Article
| Open Access
Gene-expression memory-based prediction of cell lineages from scRNA-seq datasets
Combining experimental lineage tracing with single cell transcriptomics is technically demanding. Here, authors present GEMLI, a computational tool to annotate cell lineages in single cell RNA sequencing data solely based on gene expression.
- A. S. Eisele
- , M. Tarbier
- & D. M. Suter
-
Article
| Open Access
Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes
Leveraging the fact that eukaryotic genomes are organized into gene modules, FISHnCHIPs images multiple co-expressed genes simultaneously for sensitive and high throughput profiling of gene programs and cell types in tissues.
- Xinrui Zhou
- , Wan Yi Seow
- & Kok Hao Chen
-
Article
| Open Access
QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration
Here, the authors perform genome-wide mapping of DNA methylation and expression quantitative trait loci, revealing associations among genotype, epigenome and transcriptome, uncovering genes and gene-environment interactions contributing to age-related macular degeneration (AMD).
- Jayshree Advani
- , Puja A. Mehta
- & Anand Swaroop
-
Article
| Open Access
Evolution of chemosensory tissues and cells across ecologically diverse Drosophilids
Chemosensory tissues are remarkably variable between species but the cause of this diversity is unclear. Here, the authors conduct transcriptomic analyses of chemosensory tissues from diverse Drosophila species, revealing evidence of stabilizing selection and recent species- and sex-specific changes.
- Gwénaëlle Bontonou
- , Bastien Saint-Leandre
- & J. Roman Arguello
-
Article
| Open Access
Haplotype-aware modeling of cis-regulatory effects highlights the gaps remaining in eQTL data
Genetic variants that influence gene expression play a major role in human phenotypic variability and disease susceptibility. Here, the authors introduce a computational method to estimate the regulatory effect size in genes with multiple conditionally independent regulatory variants.
- Nava Ehsan
- , Bence M. Kotis
- & Pejman Mohammadi
-
Article
| Open Access
GNTD: reconstructing spatial transcriptomes with graph-guided neural tensor decomposition informed by spatial and functional relations
Reconstructing transcriptome-wide spatially-resolved gene expressions requires modelling nonlinear patterns and spatial structures in RNA profiling data. Here, authors introduce a graph-guided neural hierarchical tensor decomposition model that incorporates spatial and functional relations for the task.
- Tianci Song
- , Charles Broadbent
- & Rui Kuang
-
Article
| Open Access
Deciphering triterpenoid saponin biosynthesis by leveraging transcriptome response to methyl jasmonate elicitation in Saponaria vaccaria
Methyl jasmonate triggers saponin production in Saponaria vaccaria. Using transcriptome data and heterologous expression, the authors identify P450s and glycosyltransferases that modify triterpenoids. They also discover the pathway for UDP-D-fucose biosynthesis.
- Xiaoyue Chen
- , Graham A. Hudson
- & Henrik V. Scheller
-
Article
| Open Access
eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk
Fetal development plays an important role in defining adult diabetes risk. Here, authors identified a genetic link between fetal pancreatic gene expression, obesity, and diabetes risk through eQTL mapping of iPSC-derived pancreatic progenitor cells.
- Jennifer P. Nguyen
- , Timothy D. Arthur
- & Kelly A. Frazer
-
Article
| Open Access
Genome-wide promoter responses to CRISPR perturbations of regulators reveal regulatory networks in Escherichia coli
Measuring gene expression responses for every transcription factor (TF)-gene pair in living prokaryotic cells is challenging. Here the authors report pooled promoter responses to TF perturbation sequencing (PPTP-seq) using CRISPRi, which they use to address this problem in E. coli.
- Yichao Han
- , Wanji Li
- & Fuzhong Zhang
-
Article
| Open Access
Activator-blocker model of transcriptional regulation by pioneer-like factors
How gene expression timing is regulated during development remains a key area of research. Here they show that zebrafish genome activators Pou5f3 and Nanog block each other’s activity on the enhancers of differentiation genes, preventing their premature expression.
- Aileen Julia Riesle
- , Meijiang Gao
- & Daria Onichtchouk
-
Article
| Open Access
Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands
The authors investigate the regulatory complexity of a multigene locus with 20 candidate regulatory elements, including an ancestral super-enhancer, active in mammary and salivary tissue and local enhancers and promoter elements unique to mammary tissue.
- Hye Kyung Lee
- , Michaela Willi
- & Lothar Hennighausen
-
Article
| Open Access
SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells
Linking proteins secreted from individual cells with other cellular information is challenging. Here, authors report a high-throughput method which uses hydrogel nanovials loaded with single cells to link the secretion profile of individual cells with their surface markers and transcriptomic data.
- Rene Yu-Hong Cheng
- , Joseph de Rutte
- & Richard G. James
-
Article
| Open Access
In vivo PAR-CLIP (viP-CLIP) of liver TIAL1 unveils targets regulating cholesterol synthesis and secretion
Here the authors develop viP-CLIP, a technique allowing the identification of RNA binding proteins (RBP) targets in mouse tissues, and identify the RBP Tial1 as a regulator of cholesterol metabolism in the liver.
- Hasan Vatandaslar
- , Aitor Garzia
- & Markus Stoffel
-
Article
| Open Access
O2 partitioning of sulfur oxidizing bacteria drives acidity and thiosulfate distributions in mining waters
Microbial genomics is a widely under-utilized tool in mining in understanding water quality drivers. Here the authors show early acid generation and thiosulfate concentrations are driven by O2 dependent microbial sulfur oxidizing bacterial niches in a mine tailings impoundment
- Kelly J. Whaley-Martin
- , Lin-Xing Chen
- & Lesley A. Warren
-
Article
| Open Access
Chance promoter activities illuminate the origins of eukaryotic intergenic transcriptions
It is debated whether the pervasive intergenic transcription from eukaryotic genomes has functional significance. Here, Xu et al. find that only 1–5% of yeast intergenic transcription is unattributable to chance promoter activity or neighboring gene expression.
- Haiqing Xu
- , Chuan Li
- & Jianzhi Zhang
-
Article
| Open Access
A-MYB and BRDT-dependent RNA Polymerase II pause release orchestrates transcriptional regulation in mammalian meiosis
During spermatogenic meiosis, chromatin changes due to transcription, homologous recombination, and chromosome synapsis must be coordinated. Here they show that A-MYC and BRDT regulate release of paused RNA PolII to induce a transcriptional burst during pachytene of prophase I.
- Adriana K. Alexander
- , Edward J. Rice
- & Charles G. Danko
-
Article
| Open Access
Spatial transcriptomics using multiplexed deterministic barcoding in tissue
Examining the spatially resolved transcriptome of tissue sections promises advances in biomedical research. Here, the authors present xDBiT, a versatile, microfluidics-based approach to cost-effectively measure the spatial transcriptome of multiple tissue sections in parallel.
- Johannes Wirth
- , Nina Huber
- & Matthias Meier
-
Article
| Open Access
Widespread perturbation of ETS factor binding sites in cancer
Few cancer drivers in non-coding regions have been identified so far. Here, the authors develop a transcription factor-aware burden test to predict non-coding variants and analyze the impact on transcription factor binding - especially ETS factors - as well as their impact on transcriptional activity.
- Sebastian Carrasco Pro
- , Heather Hook
- & Juan Ignacio Fuxman Bass
-
Article
| Open Access
A molecular atlas reveals the tri-sectional spinning mechanism of spider dragline silk
The genetic basis of spider major ampullate (Ma) gland silk production remains unknown. Hu et al. unveil a molecular atlas of this gland for the golden orb-weaving spider combining genome assembly and multiomics, revealing the single-cell spatial architecture of silk production in the Ma gland.
- Wenbo Hu
- , Anqiang Jia
- & Yi Wang
-
Article
| Open Access
Molecular mechanisms of coronary artery disease risk at the PDGFD locus
Genes encode risk for coronary disease, identifying how they function is critical to developing new therapies. In work reported the authors have identified one culprit gene, PDGFD, and studied how it functions to promote disease risk.
- Hyun-Jung Kim
- , Paul Cheng
- & Thomas Quertermous
-
Article
| Open Access
Analysis of transcriptional changes in the immune system associated with pubertal development in a longitudinal cohort of children with asthma
Puberty is an important developmental period marked by hormonal, metabolic and immunological changes. Here the authors report gene expression changes in immune cells associated with age and puberty, and that may be relevant for sex differences in susceptibility to asthma, in a longitudinal cohort of 251 children with asthma.
- Justyna A. Resztak
- , Jane Choe
- & Francesca Luca
-
Article
| Open Access
Deep autoencoder for interpretable tissue-adaptive deconvolution and cell-type-specific gene analysis
Traditional bulk sequencing data lack information about cell-type-specific gene expression. Here, the authors develop a Tissue-AdaPtive autoEncoder (TAPE), a deep learning method connecting bulk RNA-seq and single-cell RNA-seq, and apply it to analyze the cell type fractions and cell-type-specific gene expression in clinical data.
- Yanshuo Chen
- , Yixuan Wang
- & Yu Li
-
Article
| Open Access
GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements
Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.
- Peter H. Dixon
- , Adam P. Levine
- & Catherine Williamson
-
Article
| Open Access
ChIP-Hub provides an integrative platform for exploring plant regulome
A comprehensive data portal to explore plant regulomes is still unavailable. Here, the authors develop a web-based platform ChIP-Hub in the ENCODE standards and demonstrate its applications in the identification of hierarchical regulatory network, tissue-specific chromatin dynamics, putative enhancers and chromatin states.
- Liang-Yu Fu
- , Tao Zhu
- & Dijun Chen
-
Article
| Open Access
Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder
Cerebral organoids can be used to gain insights into neuropsychiatric disorders. Here the authors carry out RNAseq characterization from organoids derived from donors with autism spectrum disorder to identify associated cell type specific driver genes.
- Elaine T. Lim
- , Yingleong Chan
- & George M. Church
-
Comment
| Open Access
The case for increasing diversity in tissue-based functional genomics datasets to understand human disease susceptibility
Tissue-based functional genomics resources including molecular quantitative trait loci datasets lack diversity in ancestry and tissue types and thus are inadequate for comprehensively investigating gene regulation. Global efforts to increase the tissue diversity will help achieve more equitable medical care.
- Erping Long
- , Montserrat García-Closas
- & Jiyeon Choi
-
Article
| Open Access
Xenogeneic silencing strategies in bacteria are dictated by RNA polymerase promiscuity
Bacteria use specific silencing proteins to prevent spurious transcription of horizontally acquired DNA. Here, Forrest et al. describe differences in silencing strategies between E. coli and Bacillus subtilis, driven by the respective specificities of the silencing protein and the RNA polymerase in each organism.
- David Forrest
- , Emily A. Warman
- & David C. Grainger
-
Article
| Open Access
Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm
Perturbations of the cardiopharyngeal mesoderm can lead to congenital defects in individuals with 22q11.2 deletion syndrome. Here the authors use single cell RNA-sequencing to identify a multilineage primed population within the mesoderm, marked by Tbx1, which has bipotent properties to form cardiac and branchiomeric muscle cells.
- Hiroko Nomaru
- , Yang Liu
- & Bernice E. Morrow
-
Article
| Open Access
Enhancer-associated H3K4 methylation safeguards in vitro germline competence
While inductive signals controlling germline specification are well characterized, the intrinsic factors that allow epiblast cells to respond to such signals remain largely unknown. Here the authors use in vitro differentiated primordial germ cells to show that partial retention of histone H3K4 monomethylation within relevant enhancers is important for germline competence and specification.
- Tore Bleckwehl
- , Giuliano Crispatzu
- & Álvaro Rada-Iglesias
-
Article
| Open Access
High-throughput RNA sequencing of paraformaldehyde-fixed single cells
Current high-throughput single-cell transcriptomic methods are incompatible with paraformaldehyde, a common cell fixation technique. Here the authors present FD-seq, a method for droplet-based RNA sequencing of paraformaldehyde-fixed, stained and sorted single cells.
- Hoang Van Phan
- , Michiel van Gent
- & Savaş Tay
-
Article
| Open Access
Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia
Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here the authors perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways in each somatic cell type in testes of men with idiopathic germ cell aplasia.
- Massimo Alfano
- , Anna Sofia Tascini
- & Andrea Salonia
-
Article
| Open Access
Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases
Alcohol use disorder and drinks per week both have been studied genetically and have different correlations with psychiatric diseases. Here the authors integrate multi-omics data to identify unique and shared variants, genes and pathways for alcohol use disorder and drinks per week.
- Manav Kapoor
- , Michael J. Chao
- & Alison Goate
-
Article
| Open Access
Development and implementation of a scalable and versatile test for COVID-19 diagnostics in rural communities
Here, the authors report the development of a versatile academic, SARSCoV-2 RT-qPCR molecular diagnostic test that uses 3D printed technology for sample collection, is implemented in rural setting in the US state of Virginia and validated in its population.
- A. Ceci
- , C. Muñoz-Ballester
- & C. V. Finkielstein
-
Article
| Open Access
Hotspot exons are common targets of splicing perturbations
Splicing-disrupting mutations are linked to diseases. By employing a machine learning approach, the authors show that certain exons, termed hotspot exons, are enriched for splicing-disruption variants and susceptible to splicing perturbations.
- David T. Glidden
- , Jeramiah L. Buerer
- & William G. Fairbrother
-
Article
| Open Access
Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures
The correlation between brain structural changes in major depressive disorder (MDD) and gene expression is unclear. Here, the authors explore the correlation between cell type-specific gene expression changes and cortical structural difference in individuals with major depressive disorder.
- Jiao Li
- , Jakob Seidlitz
- & Wei Liao
-
Article
| Open Access
Aptardi predicts polyadenylation sites in sample-specific transcriptomes using high-throughput RNA sequencing and DNA sequence
Short read RNA sequencing and DNA sequence contain useful information for profiling polyadenylation sites, but each also possesses inherent limitations when examined independently. Aptardi combines these data and significantly improves annotation of polyadenylation sites in the expressed transcriptome.
- Ryan Lusk
- , Evan Stene
- & Laura M. Saba
-
Article
| Open Access
A molecular quantitative trait locus map for osteoarthritis
Understanding the molecular effects of disease variants in relevant tissues is essential to understanding and treating disease. Here, the authors discover expression and protein quantitative trait loci in cartilage and synovium from 115 osteoarthritis patients to pinpoint genes of action and potential drug treatments.
- Julia Steinberg
- , Lorraine Southam
- & Eleftheria Zeggini
-
Article
| Open Access
LETR1 is a lymphatic endothelial-specific lncRNA governing cell proliferation and migration through KLF4 and SEMA3C
Long noncoding RNAs regulate tissue-specific gene expression. Here the authors profile lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs) and show a role of LEC-specific lncRNA, LETR1, in cell proliferation and migration.
- Luca Ducoli
- , Saumya Agrawal
- & Michael Detmar
-
Article
| Open Access
Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin-associated proteins reveal an O-GlcNAc-regulated genotoxic stress response
Protein O-GlcNAcylation is involved in regulating gene expression and maintaining cellular homeostasis. Here, the authors develop a chemical reporter-based strategy for the proteomic profiling and genome-wide mapping of genotoxic stress-induced O-GlcNAcylated chromatin-associated proteins.
- Yubo Liu
- , Qiushi Chen
- & Jianing Zhang
-
Article
| Open Access
Analysis of chromatin organization and gene expression in T cells identifies functional genes for rheumatoid arthritis
Although genome-wide association studies have identified genetic variation contributing to disease risk, assigning causal genes is challenging. Here, the authors generate ATAC-seq, Hi-C, Capture Hi-C and RNA-seq data in stimulated CD4+ T cells to identify functional enhancers and demonstrate interactions of expression quantitative trait loci with target genes in rheumatoid arthritis.
- Jing Yang
- , Amanda McGovern
- & Stephen Eyre
-
Article
| Open Access
The genomic landscape of Mongolian hepatocellular carcinoma
Mongolia has the highest incidence of—and mortality from—hepatocellular carcinoma (HCC) in the world. Here, the authors examine the genomic and transcriptomic landscape of Mongolian HCC, uncover novel driver mutations, and suggest distinct disease etiologies.
- Julián Candia
- , Enkhjargal Bayarsaikhan
- & Xin Wei Wang
-
Article
| Open Access
Multiplexed single-cell transcriptional response profiling to define cancer vulnerabilities and therapeutic mechanism of action
Large-scale screens of chemical and genetic vulnerabilities in cancer are typically limited to simple readouts of cell viability. Here, the authors develop a method for profiling post-perturbation transcriptional responses across large pools of cancer cell lines, enabling deep characterization of shared and context-specific responses.
- James M. McFarland
- , Brenton R. Paolella
- & Aviad Tsherniak
Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms