scholarly journals Whole-Genome Analysis of Temporal Gene Expression during Early Transdifferentiation of Human Lung Alveolar Epithelial Type 2 Cells In Vitro

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e93413 ◽  
Author(s):  
Helena Morales Johansson ◽  
Donna R. Newman ◽  
Philip L. Sannes
Keyword(s):  
Gene Expression ◽  
Genome Analysis ◽  
Human Lung ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Alveolar Epithelial ◽  
Temporal Gene Expression

scholarly journals Whole-Genome Analysis of Temporal Gene Expression during Foregut Development

PLoS Biology ◽  
2004 ◽  
Vol 2 (11) ◽  
pp. e352 ◽  
Author(s):  
Jeb Gaudet ◽  
Srikanth Muttumu ◽  
Michael Horner ◽  
Susan E Mango
Keyword(s):  
Gene Expression ◽  
Genome Analysis ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Temporal Gene Expression

Association of SLC15A2 genomic variation with the response to sorafenib treatment: Whole-genome analysis in patients with hepatocellular carcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 308-308
Author(s):  
Bo Hyun Kim ◽  
Yeon-Su Lee ◽  
Byung Chul Kim ◽  
Aesun Shin ◽  
Jin Sook Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Functional Analysis ◽  
Genome Analysis ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Single Nucleotide ◽  
Sorafenib Treatment ◽  
Genomic Variations ◽  
Validation Tests

308 Background: Reliable biomarkers are required to predict patient response to sorafenib. We attempted to investigate genomic variations associated with responsiveness to sorafenib treatment in patients with unresectable hepatocellular carcinoma (HCC) and their functional relevance. Methods: We obtained blood samples from 4 strong and 3 poor responders to sorafenib treatment and subjected these samples to whole-genome analysis. Next, we performed validation tests for candidate single-nucleotide polymorphisms (SNPs) in the samples of 174 HCC patients who were treated with sorafenib, followed by in vitro functional analysis and in silico analyses of candidate SNPs. Results: On average, 90 gigabases/sample was generated at ~34X sequencing depth. In total, 1813 genomic variations were perfectly matched to sorafenib responses in the clinical data; 708 were located within regions for sorafenib-target genes or drug absorption, distribution, metabolism, and excretion (ADME)-related genes—36 within the coding regions and 6 identified as non-synonymous single-nucleotide variants from 4 ADME-related genes (ABCB1, FMO3, MUSK, and SLC15A2), which potentially cause functional alterations. Validation tests of 174 patients confirmed sequencing results and revealed that patients with the C/C genotype for rs2257212 in SCL15A2 displayed higher risk for cancer progression than did patients with C/T or T/T genotypes (HR: 2.18; 95% CI, 1.15–4.15; P = 0.018). In vitro functional analysis revealed that cells harboring C/C genotype for this SNP displayed lower response to sorafenib treatment than did cells harboring the T/T genotype. Structural prediction analysis revealed change in protein phosphorylation levels, potentially affecting sorafenib-associated enzymatic activity. Conclusions: SLC15A2 could be a robust biomarker of response to sorafenib treatment in HCC patients.

scholarly journals Whole-Genome Analysis of Porcine Circovirus Type 2 in Russia

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1631
Author(s):  
Sergei Raev ◽  
Anton Yuzhakov ◽  
Taras Aliper
Keyword(s):  
Genetic Diversity ◽  
Genome Analysis ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Porcine Circovirus ◽  
Economic Losses ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Reading Frame

Porcine circovirus type 2 (PCV2) is the causative agent of porcine circovirus-associated diseases (PCVAD) that bring about significant economic losses in the pig industry all over the world. The aim of this study was to investigate the genetic diversity of PCV2 in Russia and characterize the available complete genome sequences. PCV2 DNA was detected at all investigated farms located in different regions of Russia. Whole-genome analysis demonstrated that the majority of PCV2 strains belonged to genotype PCV2d (12 out of 14), while PCV2a and PCV2b were only detected at 2 farms (one at each). Further analysis revealed that all antibody recognition sites in Russian PCV2 strains were different from the corresponding epitopes in a PCV2a vaccine strain, suggesting that PCV2a-based vaccines may only provide limited protection against these strains. PCV2d strains could be grouped into 3 distinct lines which shared 98.7–100% identity within open reading frame 2 (ORF2). It is the first study reporting the genetic diversity of PCV2 strains in Russia. Our data indicated that, similarly to China, Europe, and USA, PCV2a and PCV2b have largely been replaced by PCV2d.

scholarly journals In Vitro Whole-Genome Analysis Identifies a Susceptibility Locus for HIV-1

PLoS Biology ◽  
2008 ◽  
Vol 6 (2) ◽  
pp. e32 ◽  
Author(s):  
Corinne Loeuillet ◽  
Samuel Deutsch ◽  
Angela Ciuffi ◽  
Daniel Robyr ◽  
Patrick Taffé ◽  
...  
Keyword(s):  
Genome Analysis ◽  
Susceptibility Locus ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Hiv 1

scholarly journals SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response

2020 ◽  
Author(s):  
Jessie Huang ◽  
Adam J. Hume ◽  
Kristine M. Abo ◽  
Rhiannon B. Werder ◽  
Carlos Villacorta-Martin ◽  
...  
Keyword(s):  
Target Genes ◽  
Human Lung ◽  
Human Model ◽  
Alveolar Type ◽  
Alveolar Cells ◽  
Protease Inhibition ◽  
Alveolar Epithelial ◽  
Distal Lung

ABSTRACTThe most severe and fatal infections with SARS-CoV-2 result in the acute respiratory distress syndrome, a clinical phenotype of coronavirus disease 2019 (COVID-19) that is associated with virions targeting the epithelium of the distal lung, particularly the facultative progenitors of this tissue, alveolar epithelial type 2 cells (AT2s). Little is known about the initial responses of human lung alveoli to SARS-CoV-2 infection due in part to inability to access these cells from patients, particularly at early stages of disease. Here we present an in vitro human model that simulates the initial apical infection of the distal lung epithelium with SARS-CoV-2, using AT2s that have been adapted to air-liquid interface culture after their derivation from induced pluripotent stem cells (iAT2s). We find that SARS-CoV-2 induces a rapid global transcriptomic change in infected iAT2s characterized by a shift to an inflammatory phenotype predominated by the secretion of cytokines encoded by NF-kB target genes, delayed epithelial interferon responses, and rapid loss of the mature lung alveolar epithelial program. Over time, infected iAT2s exhibit cellular toxicity that can result in the death of these key alveolar facultative progenitors, as is observed in vivo in COVID-19 lung autopsies. Importantly, drug testing using iAT2s confirmed an antiviral dose-response to remdesivir and demonstrated the efficacy of TMPRSS2 protease inhibition, validating a putative mechanism used for viral entry in human alveolar cells. Our model system reveals the cell-intrinsic responses of a key lung target cell to infection, providing a physiologically relevant platform for further drug development and facilitating a deeper understanding of COVID-19 pathogenesis.

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