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https://www.readbyqxmd.com/read/29770330/the-prediction-of-drug-disease-correlation-based-on-gene-expression-data
#1
Hui Cui, Menghuan Zhang, Qingmin Yang, Xiangyi Li, Michael Liebman, Ying Yu, Lu Xie
The explosive growth of high-throughput experimental methods and resulting data yields both opportunity and challenge for selecting the correct drug to treat both a specific patient and their individual disease. Ideally, it would be useful and efficient if computational approaches could be applied to help achieve optimal drug-patient-disease matching but current efforts have met with limited success. Current approaches have primarily utilized the measureable effect of a specific drug on target tissue or cell lines to identify the potential biological effect of such treatment...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29767749/association-of-brca2-k3326-with-small-cell-lung-cancer-and-squamous-cell-cancer-of-the-skin
#2
Thorunn Rafnar, Gudbjorg R Sigurjonsdottir, Simon N Stacey, Gisli Halldorsson, Patrick Sulem, Luba M Pardo, Hannes Helgason, Stefan T Sigurdsson, Thorkell Gudjonsson, Laufey Tryggvadottir, Gudridur H Olafsdottir, Jon G Jonasson, Kristin Alexiusdottir, Asgeir Sigurdsson, Julius Gudmundsson, Jona Saemundsdottir, Jon K Sigurdsson, Hrefna Johannsdottir, Andre Uitterlinden, Sita H Vermeulen, Tessel E Galesloot, Dawn C Allain, Martin Lacko, Bardur Sigurgeirsson, Kristin Thorisdottir, Oskar T Johannsson, Fridbjorn Sigurdsson, Gunnar B Ragnarsson, Helgi Isaksson, Hronn Hardardottir, Tomas Gudbjartsson, Daniel F Gudbjartsson, Gisli Masson, Lambertus A M L Kiemeney, Amanda Ewart Toland, Tamar Nijsten, Wilbert H M Peters, Jon H Olafsson, Steinn Jonsson, Unnur Thorsteinsdottir, Gudmar Thorleifsson, Kari Stefansson
Background: Most pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population...
May 14, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29727590/determination-of-single-embryo-sex-in-macaca-mulatta-and-mus-musculus-rnaseq-transcriptome-profiles
#3
Uros Midic, Catherine A VandeVoort, Keith E Latham
To account for sex as a biological variable, it is sometimes necessary to identify the sex of an embryo or embryonic cell that was used to generate libraries for RNA sequencing, without the sex being known a priori. The preferred approach for this would take advantage of the mRNA data itself, rather than relying on other methods that require separation and analysis of genomic DNA or diversion of limiting RNA for other assays. We describe here a method that has been optimized for this purpose in samples of rhesus monkey and mouse embryos...
May 4, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29702224/sigemd-a-powerful-method-for-differential-gene-expression-analysis-in-single-cell-rna-sequencing-data
#4
Tianyu Wang, Sheida Nabavi
Differential gene expression analysis is one of the significant efforts in single cell RNA sequencing (scRNAseq) analysis to discover the specific changes in expression levels of individual cell types. Since scRNAseq exhibits multimodality, large amounts of zero counts, and sparsity, it is different from the traditional bulk RNA sequencing (RNAseq) data. The new challenges of scRNAseq data promote the development of new methods for identifying differentially expressed (DE) genes. In this study, we proposed a new method, SigEMD, that combines a data imputation approach, a logistic regression model and a nonparametric method based on the Earth Mover's Distance, to precisely and efficiently identify DE genes in scRNAseq data...
April 24, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29700068/advances-in-transcriptomics-investigating-cardiovascular-disease-at-unprecedented-resolution
#5
REVIEW
Robert C Wirka, Milos Pjanic, Thomas Quertermous
Whole-genome transcriptional profiling has become a standard genomic approach to investigate biological processes. RNA sequencing (RNAseq) in particular has witnessed myriad applications in genetics and various biomedical fields. RNAseq involves a relatively simple experimental protocol of RNA extraction and cDNA library preparation and, because of decreasing next-generation sequencing cost and lower computational burden for data processing, has obtained a central role in the modern biology. The recent application of RNAseq methodology to single-cell transcriptional profiling has enabled the more precise characterization of cell lineage and cell state genetic profiles...
April 27, 2018: Circulation Research
https://www.readbyqxmd.com/read/29682616/human-ccl3l1-copy-number-variation-gene-expression-and-the-role-of-the-ccl3l1-ccr5-axis-in-lung-function
#6
Adeolu B Adewoye, Nick Shrine, Linda Odenthal-Hesse, Samantha Welsh, Anders Malarstig, Scott Jelinsky, Iain Kilty, Martin D Tobin, Edward J Hollox, Louise V Wain
Background: The CCL3L1-CCR5 signaling axis is important in a number of inflammatory responses, including macrophage function, and T-cell-dependent immune responses. Small molecule CCR5 antagonists exist, including the approved antiretroviral drug maraviroc, and therapeutic monoclonal antibodies are in development. Repositioning of drugs and targets into new disease areas can accelerate the availability of new therapies and substantially reduce costs. As it has been shown that drug targets with genetic evidence supporting their involvement in the disease are more likely to be successful in clinical development, using genetic association studies to identify new target repurposing opportunities could be fruitful...
2018: Wellcome Open Research
https://www.readbyqxmd.com/read/29672674/trumicount-correctly-counting-absolute-numbers-of-molecules-using-unique-molecular-identifiers
#7
Florian G Pflug, Arndt von Haeseler
Motivation: Counting molecules using next-generation sequencing (NGS) suffers from PCR amplification bias, which reduces the accuracy of many quantitative NGS-based experimental methods such as RNASeq. This is true even if molecules are made distinguishable using unique molecular identifiers (UMIs) before PCR amplification, and distinct UMIs are counted instead of reads: Molecules that are lost entirely during the sequencing process will still cause underestimation of the molecule count, and amplification artifacts like PCR chimeras create phantom UMIs and thus cause over-estimation...
April 16, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29672343/polygenic-risk-score-for-schizophrenia-is-not-strongly-associated-with-the-expression-of-specific-genes-or-gene-sets
#8
David Curtis
BACKGROUND: The polygenic risk score (PRS) is derived from single nucleotide polymorphisms (SNPs) including those that are genome-wide significant and also including a large number of others more weakly associated with schizophrenia. Such variants are widely dispersed, though concentrated near genes expressed in the brain, and it has been proposed that these SNP associations result from impacts on cell regulatory networks that ultimately affect the expression or function of a modest number of 'core' genes...
April 18, 2018: Psychiatric Genetics
https://www.readbyqxmd.com/read/29670881/impact-of-transcriptomics-on-our-understanding-of-pulmonary-fibrosis
#9
REVIEW
Milica Vukmirovic, Naftali Kaminski
Idiopathic pulmonary fibrosis (IPF) is a lethal fibrotic lung disease characterized by aberrant remodeling of the lung parenchyma with extensive changes to the phenotypes of all lung resident cells. The introduction of transcriptomics, genome scale profiling of thousands of RNA transcripts, caused a significant inversion in IPF research. Instead of generating hypotheses based on animal models of disease, or biological plausibility, with limited validation in humans, investigators were able to generate hypotheses based on unbiased molecular analysis of human samples and then use animal models of disease to test their hypotheses...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29529099/gene-expression-profiling-in-a-mouse-model-of-retinal-vein-occlusion-induced-by-laser-treatment-reveals-a-predominant-inflammatory-and-tissue-damage-response
#10
Gottfried Martin, David Conrad, Bertan Cakir, Günther Schlunck, Hansjürgen T Agostini
PURPOSE: Retinal vein occlusion (RVO) has been investigated in several laser-induced animal models using pigs, rabbits and rats. However, laser-induced RVO has been rarely reported in mice, despite the impressive number of available mutants, ease of handling and cost effectiveness. The aim of this study was to further assess the feasibility of a RVO mouse model for gene expression analysis and its possible use to investigate effects of hypoxia. METHODS: C57Bl/6J mice were injected with eosin Y for photo-sensitization...
2018: PloS One
https://www.readbyqxmd.com/read/29484588/identification-of-new-bacterial-small-rna-targets-using-ms2-affinity-purification-coupled-to-rna-sequencing
#11
Marie-Claude Carrier, Guillaume Laliberté, Eric Massé
Small regulatory RNAs (sRNAs) are ubiquitous regulatory molecules expressed in living cells. In prokaryotes, sRNAs usually bind to target mRNAs to either promote their degradation or interfere with translation initiation. Because a single sRNA can regulate a considerable number of target mRNAs, we seek to identify those targets rapidly and reliably. Here, we present a robust method based on the co-purification of target mRNAs bound to MS2-tagged sRNAs expressed in vivo. After purification of the tagged-sRNA, we use RNAseq to determine the identity of all RNA interacting partners and their enrichment level...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29483513/clonally-diverse-cd38-hla-dr-cd8-t-cells-persist-during-fatal-h7n9-disease
#12
Zhongfang Wang, Lingyan Zhu, Thi H O Nguyen, Yanmin Wan, Sneha Sant, Sergio M Quiñones-Parra, Jeremy Chase Crawford, Auda A Eltahla, Simone Rizzetto, Rowena A Bull, Chenli Qiu, Marios Koutsakos, E Bridie Clemens, Liyen Loh, Tianyue Chen, Lu Liu, Pengxing Cao, Yanqin Ren, Lukasz Kedzierski, Tom Kotsimbos, James M McCaw, Nicole L La Gruta, Stephen J Turner, Allen C Cheng, Fabio Luciani, Xiaoyan Zhang, Peter C Doherty, Paul G Thomas, Jianqing Xu, Katherine Kedzierska
Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8+ T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38+ HLA-DR+ PD-1+ CD8+ T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αβ analyses of activated CD38+ HLA-DR+ CD8+ T cells show similar TCRαβ diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients...
February 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29483303/single-cell-rnaseq-reveals-seven-classes-of-colonic-sensory-neuron
#13
James R F Hockley, Toni S Taylor, Gerard Callejo, Anna L Wilbrey, Alex Gutteridge, Karsten Bach, Wendy J Winchester, David C Bulmer, Gordon McMurray, Ewan St John Smith
OBJECTIVE: Integration of nutritional, microbial and inflammatory events along the gut-brain axis can alter bowel physiology and organism behaviour. Colonic sensory neurons activate reflex pathways and give rise to conscious sensation, but the diversity and division of function within these neurons is poorly understood. The identification of signalling pathways contributing to visceral sensation is constrained by a paucity of molecular markers. Here we address this by comprehensive transcriptomic profiling and unsupervised clustering of individual mouse colonic sensory neurons...
February 26, 2018: Gut
https://www.readbyqxmd.com/read/29456968/alternative-splicing-of-differentiated-myeloid-cell-transcripts-after-infection-by-anaplasma-phagocytophilum-impacts-a-selective-group-of-cellular-programs
#14
J Stephen Dumler, Sara H Sinclair, Amol C Shetty
Eukaryotic proteome diversity exceeds that encoded within individual genes, and results in part from alternative splicing events of pre-messenger RNA. The diversity of these splicing events can shape the outcome in development and differentiation of normal tissues, and is important in pathogenic circumstances such as cancer and some heritable conditions. A role for alternative splicing of eukaryotic genes in response to viral and intracellular bacterial infections has only recently been recognized, and plays an important role in providing fitness for microbial survival, while potentially enhancing pathogenicity...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29444188/switching-and-loss-of-cellular-cytokine-producing-capacity-characterize-in-vivo-viral-infection-and-malignant-transformation-in-human-t-lymphotropic-virus-type-1-infection
#15
Huseini Kagdi, Maria Antonietta Demontis, Juan Carlos Ramos, Graham P Taylor
Adult T-cell leukaemia/lymphoma (ATL) arises from chronic non-malignant human T lymphotropic virus type-1 (HTLV-1) infection which is characterized by high plasma pro-inflammatory cytokines whereas ATL is characterized by high plasma anti-inflammatory (IL-10) concentrations. The poor prognosis of ATL is partly ascribed to disease-associated immune suppression. ATL cells have a CD4+CCR4+CD26-CD7- immunophenotype but infected cells with this immunophenotype ('ATL-like' cells) are also present in non-malignant HTLV-1 infection...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29439658/high-fidelity-hypothermic-preservation-of-primary-tissues-in-organ-transplant-preservative-for-single-cell-transcriptome-analysis
#16
Wanxin Wang, Lolita Penland, Ozgun Gokce, Derek Croote, Stephen R Quake
BACKGROUND: High-fidelity preservation strategies for primary tissues are in great demand in the single cell RNAseq community. A reliable method would greatly expand the scope of feasible multi-site collaborations and maximize the utilization of technical expertise. When choosing a method, standardizability and fidelity are important factors to consider due to the susceptibility of single-cell RNAseq analysis to technical noise. Existing approaches such as cryopreservation and chemical fixation are less than ideal for failing to satisfy either or both of these standards...
February 13, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29433896/generating-tissue-resident-macrophages-from-pluripotent-stem-cells-lessons-learned-from-microglia
#17
Christel Claes, Johanna Van den Daele, Catherine M Verfaillie
Over the past decades, the importance of the immune system in a broad scope of pathologies, has drawn attention towards tissue-resident macrophages, such as microglia in the brain. To enable the study of for instance microglia, it is crucial to recreate in vitro (and in vivo) assays. However, very fast loss of tissue-specific features of primary tissue resident macrophages, including microglia, upon in vitro culture has complicated such studies. Moreover, limited knowledge of macrophage developmental pathways and the role of local 'niche factors', has hampered the generation of tissue-resident macrophages from pluripotent stem cells (PSC)...
February 2, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29408715/single-cell-profiling-of-peanut-responsive-t-cells-in-patients-with-peanut-allergy-reveals-heterogeneous-effector-t-h-2-subsets
#18
David Chiang, Xintong Chen, Stacie M Jones, Robert A Wood, Scott H Sicherer, A Wesley Burks, Donald Y M Leung, Charuta Agashe, Alexander Grishin, Peter Dawson, Wendy F Davidson, Leah Newman, Robert Sebra, Miriam Merad, Hugh A Sampson, Bojan Losic, M Cecilia Berin
BACKGROUND: The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood. OBJECTIVES: Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of subjects with and without peanut allergy (PA). METHODS: We obtained samples from patients with PA, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (Consortium of Food Allergy Research [CoFAR] 6)...
January 31, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29392698/single-cell-rna-sequencing-of-glioblastoma-cells
#19
Rajeev Sen, Igor Dolgalev, N Sumru Bayin, Adriana Heguy, Aris Tsirigos, Dimitris G Placantonakis
Single-cell RNA sequencing (sc-RNASeq) is a recently developed technique used to evaluate the transcriptome of individual cells. As opposed to conventional RNASeq in which entire populations are sequenced in bulk, sc-RNASeq can be beneficial when trying to better understand gene expression patterns in markedly heterogeneous populations of cells or when trying to identify transcriptional signatures of rare cells that may be underrepresented when using conventional bulk RNASeq. In this method, we describe the generation and analysis of cDNA libraries from single patient-derived glioblastoma cells using the C1 Fluidigm system...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29281100/antiviral-response-in-the-nasopharynx-identifies-patients-with-respiratory-virus-infection
#20
Marie L Landry, Ellen F Foxman
Background: Despite the high burden of respiratory infection and the importance of early and accurate diagnosis, there is no simple diagnostic test to rule in viral infection as a cause of respiratory symptoms. Methods: We performed RNA sequencing on human nasal epithelial cells following stimulation of the intracellular viral recognition receptor RIG-I. Next, we evaluated whether measuring identified host mRNAs and proteins from patient nasopharyngeal swabs could predict the presence of a respiratory virus in the sample...
March 5, 2018: Journal of Infectious Diseases
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