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https://www.readbyqxmd.com/read/28817824/parametric-linkage-analysis-identifies-five-novel-genome-wide-significant-loci-for-familial-lung-cancer
#1
Anthony M Musolf, Claire L Simpson, Mariza de Andrade, Diptasri Mandal, Colette Gaba, Ping Yang, Yafang Li, Ming You, Elena Y Kupert, Marshall W Anderson, Ann G Schwartz, Susan M Pinney, Christopher I Amos, Joan E Bailey-Wilson
OBJECTIVE: One of four American cancer patients dies of lung cancer. Environmental factors such as tobacco smoking are known to affect lung cancer risk. However, there is a genetic factor to lung cancer risk as well. Here, we perform parametric linkage analysis on family-based genotype data in an effort to find genetic loci linked to the disease. METHODS: 197 individuals from families with a high-risk history of lung cancer were recruited and genotyped using an Illumina array...
August 18, 2017: Human Heredity
https://www.readbyqxmd.com/read/28817121/meganuclease-assisted-generation-of-stable-transgenics-in-the-sea-anemone-nematostella-vectensis
#2
Eduard Renfer, Ulrich Technau
The sea anemone Nematostella vectensis is a model system used by a rapidly growing research community for comparative genomics, developmental biology and ecology. Here, we describe a microinjection procedure for creating stable transgenic lines in Nematostella based on meganuclease (I-SceI)-assisted integration of a transgenic cassette into the genome. The procedure describes the preparation of the reagents, microinjection of the transgenesis vector and the husbandry of transgenic animals. The microinjection setup differs from those of previously published protocols by the use of a holding capillary mounted on an inverted fluorescence microscope...
September 2017: Nature Protocols
https://www.readbyqxmd.com/read/28816391/cytoskeleton-and-nucleoskeleton-involvement-in-processes-of-cytomixis-in-plants
#3
REVIEW
E A Kravets, A I Yemets, Ya B Blume
Cytomixis, is a form of cell-to-cell nuclear migration that involves the interaction of dynamic cytoskeletal components with the nucleus through signalling systems and linker complexes. In cytomixis two known mechanisms can be involved: actomyosin and/or microtubules and their associated motors. Perinuclear actin anchors and determines the direction of nuclear movement. In microsporogenesis cytomixis is probably initiated by a cascade of signals that trigger prophase reorganization of nucleus and cytoskeleton, and is a result of cytoskeletal protein activation, as well as a weakening of mechanisms responsible for anchoring the nucleus...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28815494/use-of-the-dice-dual-integrase-cassette-exchange-system
#4
Alfonso P Farruggio, Mital S Bhakta, Michele P Calos
When constructing transgenic cell lines via plasmid DNA integration, precise targeting to a desired genomic location is advantageous. It is also often advantageous to remove the bacterial backbone, since bacterial elements can lead to the epigenetic silencing of neighboring DNA. The least cumbersome method to remove the plasmid backbone is recombinase-mediated cassette exchange (RMCE). RMCE is accomplished by arranging recombinase sites in the genome and in a donor plasmid such that a recombinase can both integrate the donor plasmid and excise its bacterial backbone...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815138/integrative-network-and-transcriptomics-based-approach-predicts-genotype-specific-drug-combinations-for-melanoma
#5
Kelly E Regan, Philip R O Payne, Fuhai Li
Computational methods for drug combination predictions are needed to identify effective therapies that improve durability and prevent drug resistance in an efficient manner. In this paper, we present SynGeNet, a computational method that integrates transcriptomics data characterizing disease and drug z-score profiles with network mining algorithms in order to predict synergistic drug combinations. We compare SynGeNet to other available transcriptomics-based tools to predict drug combinations validated across melanoma cell lines in three genotype groups: BRAF-mutant, NRAS-mutant and combined...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28814796/crispr-cas9-mediated-labelling-allows-for-single-molecule-imaging-and-resolution
#6
Abdullah O Khan, Victoria A Simms, Jeremy A Pike, Steven G Thomas, Neil V Morgan
Single molecule imaging approaches like dSTORM and PALM resolve structures at 10-20 nm, and allow for unique insights into protein stoichiometry and spatial relationships. However, key obstacles remain in developing highly accurate quantitative single molecule approaches. The genomic tagging of PALM fluorophores through CRISPR-Cas9 offers an excellent opportunity for generating stable cell lines expressing a defined single molecule probe at endogenous levels, without the biological disruption and variability inherent to transfection...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814268/the-genomic-architecture-of-mastitis-resistance-in-dairy-sheep
#7
G Banos, G Bramis, S J Bush, E L Clark, M E B McCulloch, J Smith, G Schulze, G Arsenos, D A Hume, A Psifidi
BACKGROUND: Mastitis is the most prevalent disease in dairy sheep with major economic, hygienic and welfare implications. The disease persists in all dairy sheep production systems despite the implementation of improved management practises. Selective breeding for enhanced mastitis resistance may provide the means to further control the disease. In the present study, we investigated the genetic architecture of four mastitis traits in dairy sheep. Individual animal records for clinical mastitis occurrence and three mastitis indicator traits (milk somatic cell count, total viable bacterial count in milk and the California mastitis test) were collected monthly throughout lactation for 609 ewes of the Greek Chios breed...
August 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28814066/mice-expressing-human-erap1-variants-associated-with-ankylosing-spondylitis-have-altered-t-cell-repertoires-and-nk-cell-functions-as-well-as-increased-in-utero-and-perinatal-mortality
#8
David P W Rastall, Fadel S Alyaquob, Patrick O'Connell, Yuliya Pepelyayeva, Douglas Peters, Sarah Godbehere-Roosa, Cristiane Pereira-Hicks, Yasser A Aldhamen, Andrea Amalfitano
Specific variants of endoplasmic reticulum-associated aminopeptidase 1 (ERAP1) identified by genome-wide association study modify the risk for developing ankylosing spondylitis. We previously confirmed that disease-associated ERAP1 variants have altered enzymatic abilities that can impact upon the production of pro-inflammatory cytokines from cells expressing the same ERAP1 variants. To determine if these ERAP1 variants also impacted immune responses in vivo, we generated two strains of transgenic mice expressing human ERAP1 genes containing non-synonymous single-nucleotide polymorphisms associated with an increased (ERAP1-High) or decreased (ERAP1-Low) risk for developing autoimmune disease...
June 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28813413/polylox-barcoding-reveals-haematopoietic-stem-cell-fates-realized-in-vivo
#9
Weike Pei, Thorsten B Feyerabend, Jens Rössler, Xi Wang, Daniel Postrach, Katrin Busch, Immanuel Rode, Kay Klapproth, Nikolaus Dietlein, Claudia Quedenau, Wei Chen, Sascha Sauer, Stephan Wolf, Thomas Höfer, Hans-Reimer Rodewald
Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813177/how-single-cell-genomics-is-changing-evolutionary-and-developmental-biology
#10
John C Marioni, Detlev Arendt
The recent flood of single-cell data not only boosts our knowledge of cells and cell types, but also provides new insight into development and evolution from a cellular perspective. For example, assaying the genomes of multiple cells during development reveals developmental lineage trees-the kinship lineage-whereas cellular transcriptomes inform us about the regulatory state of cells and their gradual restriction in potency-the Waddington lineage. Beyond that, the comparison of single-cell data across species allows evolutionary changes to be tracked at all stages of development from the zygote, via different kinds of stem cells, to the differentiating cells...
August 16, 2017: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/28811753/characterization-of-the-rosellinia-necatrix-transcriptome-and-genes-related-to-pathogenesis-by-single-molecule-mrna-sequencing
#11
Hyeongmin Kim, Seung Jae Lee, Ick-Hyun Jo, Jinsu Lee, Wonsil Bae, Hyemin Kim, Kyungho Won, Tae Kyung Hyun, Hojin Ryu
White root rot disease, caused by the pathogen Rosellinia necatrix, is one of the world's most devastating plant fungal diseases and affects several commercially important species of fruit trees and crops. Recent global outbreaks of R. necatrix and advances in molecular techniques have both increased interest in this pathogen. However, the lack of information regarding the genomic structure and transcriptome of R. necatrix has been a barrier to the progress of functional genomic research and the control of this harmful pathogen...
August 2017: Plant Pathology Journal
https://www.readbyqxmd.com/read/28811315/quantitative-whole-genome-sequencing-of-circulating-tumor-cells-enables-personalized-combination-therapy-of-metastatic-cancer
#12
Natali Gulbahce, Mark Jesus M Magbanua, Robert Chin, Misha R Agarwal, Xuhao Luo, Jia Liu, Daniel M Hayden, Qing Mao, Serban Ciotlos, Zhenyu Li, Yanxiang Chen, Xingpeng Chen, Yuxiang Li, Rebecca Yu Zhang, Katharine Lee, Rick Tearle, Emily Park, Snezana Drmanac, Hope S Rugo, John W Park, Radoje Drmanac, Brock A Peters
Much effort has been dedicated to developing circulating tumor cells (CTC) as a noninvasive cancer biopsy, but with limited success as yet. In this study, we combine a method for isolation of highly pure CTCs using immunomagnetic enrichment/fluorescence-activated cell sorting with advanced whole genome sequencing (WGS), based on long fragment read technology, to illustrate the utility of an accurate, comprehensive, phased, and quantitative genomic analysis platform for CTCs. Whole genomes of 34 CTCs from a patient with metastatic breast cancer were analyzed as 3,072 barcoded subgenomic compartments of long DNA...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28810930/sex-differences-in-microrna-mrna-networks-examination-of-novel-epigenetic-programming-mechanisms-in-the-sexually-dimorphic-neonatal-hypothalamus
#13
Christopher P Morgan, Tracy L Bale
BACKGROUND: Sexual differentiation of the male brain, and specifically the stress circuitry in the hypothalamus, is primarily driven by estrogen exposure during the perinatal period. Surprisingly, this single hormone promotes diverse programs of sex-specific development that vary widely between different cell types and across the developing male brain. The complexity of this phenomenon suggests that additional layers of gene regulation, including microRNAs (miRNAs), must act downstream of estrogen to mediate this specificity...
August 15, 2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28810700/a-single-mini-barcode-test-to-screen-for-australian-mammalian-predators-from-environmental-samples
#14
Elodie Modave, Anna J MacDonald, Stephen D Sarre
Identification of species from trace samples is now possible through the comparison of diagnostic DNA fragments against reference DNA sequence databases. DNA detection of animals from non-invasive samples, such as predator faeces (scats) that contain traces of DNA from their species of origin, has proved to be a valuable tool for the management of elusive wildlife. However, application of this approach can be limited by the availability of appropriate genetic markers. Scat DNA is often degraded, meaning that longer DNA sequences, including standard DNA barcoding markers, are difficult to recover...
August 1, 2017: GigaScience
https://www.readbyqxmd.com/read/28809760/the-milestone-of-non-invasive-prenatal-identification-of-chromosomal-abnormalities-in-fetal-trophoblasts-recovered-from-maternal-blood
#15
Jaime Garcia-Heras
Two recent studies demonstrated that array CGH and NGS allow identification of chromosomal abnormalities in fetal trophoblasts circulating in maternal blood. This remarkable breakthrough paves the way for an improved assay that supersedes the performance of non-invasive prenatal testing (NIPT) in cell-free fetal DNA. Furthermore, it is foreseeable to expand the use of this new genomic analysis in trophoblasts to uncover single gene mutations of clinical significance prenatally.
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28809135/detecting-signatures-of-past-pathogen-selection-on-human-hla-loci-are-there-needles-in-the-haystack
#16
Bridget S Penman, Sunetra Gupta
Human leucocyte antigens (HLAs) are responsible for the display of peptide fragments for recognition by T-cell receptors. The gene family encoding them is thus integral to human adaptive immunity, and likely to be under strong pathogen selection. Despite this, it has proved difficult to demonstrate specific examples of pathogen-HLA coevolution. Selection from multiple pathogens simultaneously could explain why the evolutionary signatures of particular pathogens on HLAs have proved elusive. Here, we present an individual-based model of HLA evolution in the presence of two mortality-causing pathogens...
August 15, 2017: Parasitology
https://www.readbyqxmd.com/read/28808970/genome-wide-crispr-cas9-screening-for-high-throughput-functional-genomics-in-human-cells
#17
Shiyou Zhu, Yuexin Zhou, Wensheng Wei
It is highly desirable to identify gene's function in a high-throughput fashion, and the CRISPR/Cas9 system has been harnessed to meet such a need. Here, we describe a general method to generate genome-scale lentiviral single-guide RNA (sgRNA) library and conduct a pooled function-based screening in human cells. This protocol would be of interest to researchers to rapidly identify genes in a variety of biological processes.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28807314/a-candidate-gene-approach-to-study-nematode-resistance-traits-in-naturally-infected-sheep
#18
Hazel Wilkie, Valentina Riggio, Oswald Matika, Louise Nicol, Kathryn A Watt, Rona Sinclair, Alexandra M Sparks, Daniel H Nussey, Josephine M Pemberton, Ross D Houston, John Hopkins
Sheep naturally acquire a degree of resistant immunity to parasitic worm infection through repeated exposure. However, the immune response and clinical outcome vary greatly between animals. Genetic polymorphisms in genes integral to differential T helper cell polarization may contribute to variation in host response and disease outcome. A total of twelve single nucleotide polymorphisms (SNPs) were sequenced in IL23R, RORC2 and TBX21 from genomic DNA of Scottish Blackface lambs. Of the twelve SNPs, six were non-synonymous (missense), four were within the 3' UTRs and two were intronic...
August 30, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28806726/replication-fork-slowing-and-stalling-are-distinct-checkpoint-independent-consequences-of-replicating-damaged-dna
#19
Divya Ramalingam Iyer, Nicholas Rhind
In response to DNA damage during S phase, cells slow DNA replication. This slowing is orchestrated by the intra-S checkpoint and involves inhibition of origin firing and reduction of replication fork speed. Slowing of replication allows for tolerance of DNA damage and suppresses genomic instability. Although the mechanisms of origin inhibition by the intra-S checkpoint are understood, major questions remain about how the checkpoint regulates replication forks: Does the checkpoint regulate the rate of fork progression? Does the checkpoint affect all forks, or only those encountering damage? Does the checkpoint facilitate the replication of polymerase-blocking lesions? To address these questions, we have analyzed the checkpoint in the fission yeast Schizosaccharomyces pombe using a single-molecule DNA combing assay, which allows us to unambiguously separate the contribution of origin and fork regulation towards replication slowing, and allows us to investigate the behavior of individual forks...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28806616/parvovirus-b19-integration-into-human-cd36-erythroid-progenitor-cells
#20
Tyler Janovitz, Susan Wong, Neal S Young, Thiago Oliveira, Erik Falck-Pedersen
The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome...
August 11, 2017: Virology
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