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| Open AccessC1 CAGE detects transcription start sites and enhancer activity at single-cell resolution
Single-cell transcriptomic profiling allows the exploration of cellular heterogeneity but commonly focuses on the 3′-end of the transcript. Here the authors introduce C1 CAGE, which detects the 5′ transcript end in a multiplexed microfluidic system.
- Tsukasa Kouno
- , Jonathan Moody
- & Jay W. Shin
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Article
| Open AccessLocal and global chromatin interactions are altered by large genomic deletions associated with human brain development
Copy number variants in the human genome (CNVs) are associated with neurodevelopmental and psychiatric disorders such as schizophrenia and autism. Here the authors investigate how the large deletion CNV on chromosome 22q11.2 alters chromatin organization.
- Xianglong Zhang
- , Ying Zhang
- & Alexander E. Urban
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| Open AccessThe genomic landscape of molecular responses to natural drought stress in Panicum hallii
Drought is a major factor limiting crop productivity. Here, via eQTL analysis and comparative genomics, the authors show compensatory evolution between trans-regulatory loci and transcription factor binding sites that shape the drought response networks in the model C4 grass Panicum hallii.
- John T. Lovell
- , Jerry Jenkins
- & Thomas E. Juenger
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| Open AccessChromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities
Multimorbidities of common diseases often have shared underlying predisposing factors. Here Fadason et al. study the pleiotropy of SNPs and their effects on target genes by integrating chromatin interaction and expression quantitative trait loci data to identify target genes shared between phenotypes.
- Tayaza Fadason
- , William Schierding
- & Justin M. O’Sullivan
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Article
| Open AccessArchitecture of gene regulatory networks controlling flower development in Arabidopsis thaliana
Homeotic transcription factors and miRNAs promote floral organ specification. Here Chen et al. reconstruct gene regulatory networks in Arabidopsis flowers and find evidence for feed forward loops between transcription factors, miRNAs and their targets that determine organ-specific gene expression.
- Dijun Chen
- , Wenhao Yan
- & Kerstin Kaufmann
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| Open AccessReprogramming of regulatory network using expression uncovers sex-specific gene regulation in Drosophila
For many applications knowledge of context-specific gene regulatory networks (GRNs) is desirable, but their inference remains a challenge. Here, the authors introduce a method for construction of context-specific GRNs, and apply it to construct sex-specific Drosophila GRNs.
- Yijie Wang
- , Dong-Yeon Cho
- & Teresa M. Przytycka
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| Open AccessA systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target
The identification of new drug targets is highly challenging, particularly for diseases of the brain. This study describes a general computational gene regulatory framework called CRAFT for drug target discovery, and the authors use CRAFT to identify the microglial membrane receptor Csf1R as a potential therapeutic target for epilepsy.
- Prashant K. Srivastava
- , Jonathan van Eyll
- & Michael R. Johnson
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| Open AccessGenome-wide identification of directed gene networks using large-scale population genomics data
Identification of causal drivers behind expression is essential for understanding gene function. Here authors develop a method for the large-scale inference of gene–gene interactions in observational population genomics data and characterize a network of trans-effects for 6600 genes.
- René Luijk
- , Koen F. Dekkers
- & Diana van Heemst
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| Open AccessCell fate potentials and switching kinetics uncovered in a classic bistable genetic switch
Bistable switches are a common regulatory motif in cell fate decision-making circuits with two mutually exclusive expression states. Here the authors develop a bistable reporter system and report two additional expression states.
- Xiaona Fang
- , Qiong Liu
- & Jie Xiao
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Article
| Open AccessA geometric approach to characterize the functional identity of single cells
Functional characterisation of single cells is crucial for uncovering the true extent of cellular heterogeneity. Here the authors offer an approach to infer functional identities of cells from their transcriptomes, identify their dominant function, and reconstruct the underlying regulatory networks.
- Shahin Mohammadi
- , Vikram Ravindra
- & Ananth Grama
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| Open AccessA comprehensive evaluation of module detection methods for gene expression data
Modules composed of groups of genes with similar expression profiles tend to be functionally related and co-regulated. Here, Saelens et al evaluate the performance of 42 computational methods and provide practical guidelines for module detection in gene expression data.
- Wouter Saelens
- , Robrecht Cannoodt
- & Yvan Saeys
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| Open AccessDissecting super-enhancer hierarchy based on chromatin interactions
Super-enhancers (SEs) are important regulatory elements for gene expression, but their intrinsic properties remain poorly understood. Here the authors analyse Hi-C and ChIP-seq data and find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers.
- Jialiang Huang
- , Kailong Li
- & Guo-Cheng Yuan
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Article
| Open AccessIdentifying noncoding risk variants using disease-relevant gene regulatory networks
Current methods for prioritization of non-coding genetic risk variants are based on sequence and chromatin features. Here, Gao et al. develop ARVIN, which predicts causal regulatory variants using disease-relevant gene-regulatory networks, and validate this approach in reporter gene assays.
- Long Gao
- , Yasin Uzun
- & Kai Tan
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Article
| Open AccessSingle-cell variability in multicellular organisms
While gene expression noise in single-celled organisms is well understood, it is less so in the context of tissues. Here the authors show that coupling between cells in tissues can increase or decrease cell-to-cell variability depending on the level of noise intrinsic to the regulatory networks.
- Stephen Smith
- & Ramon Grima
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Article
| Open AccessExperimental noise cutoff boosts inferability of transcriptional networks in large-scale gene-deletion studies
Reliable inference of gene interactions from perturbation experiments remains a challenge. Here, the authors quantify the upper limits of transcriptional network inference from knockout screens, identify the key determinants of accuracy, and introduce an unbiased and scalable inference algorithm.
- C. F. Blum
- , N. Heramvand
- & M. Kollmann
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Article
| Open AccessIntegrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions
Rising rates of peanut allergy pose a public health problem. Here, the authors profile blood transcriptomes during double-blind, placebo-controlled oral challenge in peanut-allergic children to identify gene and cell composition changes, and construct causal networks to detect key allergic reaction drivers.
- C. T. Watson
- , A. T. Cohain
- & S. Bunyavanich
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Article
| Open AccessDecoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition
The role of lncRNA is unclear with respect to epithelial-to-mesenchymal transition (EMT), which is linked to ovarian cancer metastasis. Here, the authors show lncRNA DNM3OS expression contributes to ovarian cancer EMT, cell migration/invasion, and correlates with worse overall patient survival.
- Ramkrishna Mitra
- , Xi Chen
- & Christine M. Eischen
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Article
| Open AccessAn integrative method to decode regulatory logics in gene transcription
Existing transcriptional regulatory networks models fall short of deciphering the cooperation between multiple transcription factors on dynamic gene expression. Here the authors develop an integrative method that combines gene expression and transcription factor-DNA binding data to decode transcription regulatory logics.
- Bin Yan
- , Daogang Guan
- & Hailong Zhu
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| Open AccessInference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer’s disease
“mRNA abundance is determined by the rates of transcription and decay. Here, the authors propose a method for estimating the rate of differential mRNA decay from RNA-seq data and model mRNA stability in the brain, suggesting a link between mRNA stability and Alzheimer’s disease.”
- Rached Alkallas
- , Lisa Fish
- & Hamed S. Najafabadi
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Article
| Open AccessTranscriptional regulation of endothelial cell behavior during sprouting angiogenesis
Angiogenesis is a complex process that requires coordinated changes in endothelial cell behavior. Here the authors use Ribo-tag and RNA-Seq to determine temporal profiles of transcriptional activity during postnatal retinal angiogenesis, identifying transcriptional regulators of the process.
- Hyun-Woo Jeong
- , Benjamín Hernández-Rodríguez
- & Ralf H. Adams
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| Open AccessIntegrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants
Inflammation mediated by microglia plays a key role in brain injury associated with preterm birth, but little is known about the microglial response in preterm infants. Here, the authors integrate molecular and imaging data from animal models and preterm infants, and find that microglial expression of DLG4 plays a role.
- Michelle L. Krishnan
- , Juliette Van Steenwinckel
- & Pierre Gressens
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| Open AccessSimilarity in viral and host promoters couples viral reactivation with host cell migration
The coevolution of viruses and host cells can be mapped with interactomics. Here the authors identify coupling of human and viral promoters, and show that HIV-reactivation from dormancy is coincident with migration of HIV-infected cells owing to coupling of human CXCR4 and HIV LTR promoters.
- Kathrin Bohn-Wippert
- , Erin N. Tevonian
- & Roy D. Dar
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| Open AccessA computational systems approach identifies synergistic specification genes that facilitate lineage conversion to prostate tissue
The identification of master regulator genes that may be manipulatedin vitro to regulate reprogramming has been difficult. Here, the authors use a computational systems approach to identify three genes (FoxA1, Nkx3.1and the androgen receptor) that can reprogramme fibroblasts to prostate tissue.
- Flaminia Talos
- , Antonina Mitrofanova
- & Michael M. Shen
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| Open AccessComputational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer
Dysregulation of microRNAs is thought to be important for metastasis in castration-resistant prostate cancer (CRPC), but its drivers are unknown. Here, the authors use computational analysis to identify HOXC6 and NKX2-2 in addition to AR as alternative drivers of dysregulated miRNA expression in CRPC.
- Mengzhu Xue
- , Haiyue Liu
- & Peng Wang
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Article
| Open AccessMicroRNA filters Hox temporal transcription noise to confer boundary formation in the spinal cord
In the spinal cord, someHox genes are transcribed in progenitors while their proteins are only detected in differentiating postmitotic motor neurons. Here, the authors show that miRNAs (specifically mir-27) regulate post-transcriptional Hoxa5 expression in motor neurons.
- Chung-Jung Li
- , Tian Hong
- & Jun-An Chen
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Article
| Open AccessTissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival
Cancer cells reprogramme their metabolism with unclear clinical implications. Here, the authors analyse the expression of metabolic genes across 20 types of solid cancers and find that clinical aggressiveness, poor survival and metastasis are associated with the deregulation of mitochondrial metabolism.
- Edoardo Gaude
- & Christian Frezza
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Article
| Open AccessTemporal and spatial dynamics of scaling-specific features of a gene regulatory network in Drosophila
How pattern formation is regulated relative to the size of an organism is unclear. Here, Wu et al.take data from gap gene expression in flies of different sizes together with simulations, identifying how scaling emerges dynamically and that local patterning influences global gene regulatory networks.
- Honggang Wu
- , Manu
- & Jun Ma
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Article
| Open AccessDecoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state
The key regulators that allow transition from proliferative to invasive phenotype in melanoma cells have not been identified yet. The authors perform chromatin and transcriptome profiling followed by comprehensive bioinformatics analysis identifying new candidate regulators for two distinct cell states of melanoma.
- Annelien Verfaillie
- , Hana Imrichova
- & Stein Aerts
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| Open AccessCpG island-mediated global gene regulatory modes in mouse embryonic stem cells
CpG islands are high GC content DNA elements that surround the majority of transcriptional start sites in eukaryotes. Here, the authors analyse over 200 genomic data sets to provide new insight into global CpG islands-dependent regulatory mechanisms in differentiated and pluripotent stem cells.
- Samuel Beck
- , Bum-Kyu Lee
- & Jonghwan Kim
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Gene network reconstruction reveals cell cycle and antiviral genes as major drivers of cervical cancer
As cervical tumours become more invasive, levels of episomal human papillomavirus paradoxically tend to decrease. Here the authors identify a network of antiviral and cell cycle genes that is amplified by chromosomal aberrations and promotes cervical tumour progression.
- Karina L. Mine
- , Natalia Shulzhenko
- & Andrey Morgun